# Evidence: crystallization inhibition

Parent: — · class: kinetics · names merged here: crystallization inhibition; crystallization inhibitor

87 papers measured or used it, 33 only mentioned it (of 207 kept papers). Papers in year order; each section heading ends with the paper's category / subcategory. Generated by tools/build_evidence.py from registry/concepts.csv and the cards; do not edit.

## 1997 Taylor — Spectroscopic Characterization of Interactions Between PVP and Indomethacin in Amorphous Molecular Dispersions · Solid state stability / Miscibility and drug-polymer interactions

[1997-taylor-pvp-indomethacin-amorphous-molecular-dispersions](../../../cards/1997-taylor-pvp-indomethacin-amorphous-molecular-dispersions/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C3 | claim, prior hypothesis, authors: asserted; mechanism: "it has been suggested" | PVP inhibits crystallisation in solution and in amorphous solid dispersions; in solution PVP interacts with many organic molecules and the inhibition has been suggested to relate to the extent of drug-polymer interaction [rests on: cited: refs 6, 7] | p.1691 |
| C5 | claim, prior hypothesis, authors: asserted | Yoshioka et al. found significant inhibition of indomethacin crystallisation at relatively low PVP levels, which could not be explained solely by the antiplasticising effect of the polymer [rests on: cited: ref 7] | p.1691 |
| C43 | claim, mechanism, authors: asserted ("immediately apparent"; "would require") | The PVP-indomethacin hydrogen bond breaks the dimer and engages the proton donor needed for dimer formation; since γ consists of dimers, forming a critical nucleus would require breaking PVP-indomethacin bonds so that molecules can dimerise and order [rests on: C35; M1] | p.1697 |
| C44 | claim, generalisation, authors: "would thus also be anticipated" | Because α also appears to hydrogen-bond in a non-dimer pattern, probably chains, hydrogen bonding with PVP would likewise be anticipated to inhibit crystallisation to α [rests on: C17, C35] | p.1697 |
| C45 | claim, generalisation, authors: abstract: "may influence"; summary: "offers an explanation" | PVP may influence crystallisation kinetics by preventing the self-association of indomethacin; the hydrogen bond offers an explanation of how PVP inhibits crystallisation from the amorphous phase at levels where its antiplasticising effect is minimal [rests on: C35, C5; cited: ref 7] | p.1691, p.1697 |

## 2001 Broman — A comparison of alternative polymer excipients and processing methods for making solid dispersions of a poorly water soluble drug · ASD process / ASD process

[2001-broman-polymer-excipients-processing-probucol-solid-dispersions](../../../cards/2001-broman-polymer-excipients-processing-probucol-solid-dispersions/paper.html) · ASD process / ASD process · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | physical stability of amorphous probucol alone — melt-quenched probucol (P6), room temperature — crystallisation within hours to days, depending on sample handling | p.147 |
| R4 | record, measured | DSC thermal events (°C) and Raman form of probucol in the dispersions — Table 1 compositions; code 1) solvent method (P4), 2) compression moulding (P3); DSC P2, Raman P1 — sub-table below | Table 2, p.145 |
| C30 | claim, mechanism, authors: "presumably"; "to some extent" | PVP inhibits probucol crystallisation, probably through molecular-level interaction with the drug, whereas PEO does not [rests on: R4, R5] | p.147 |
| C31 | claim, prior hypothesis, authors: "it has been suggested" | PVP's inhibition of crystallisation from the amorphous state has been linked to raising the Tg and forming hydrogen-bonded complexes [rests on: cited: Yoshioka et al. 1995; Taylor & Zografi 1997] | p.147 |
| C33 | claim, mechanism, authors: "Presumably" | Neither PAA nor PEO stabilised amorphous probucol, after melting or after solvent evaporation; probably neither forms a single-phase system with probucol at room temperature [rests on: R4.c, R4.d, R4.e, R4.f, R3] | p.147-148 |

## 2006 Konno — Influence of Different Polymers on the Crystallization Tendency of Molecularly Dispersed Amorphous Felodipine · Solid state stability / Physical stability

[2006-konno-felodipine-polymer-crystallization-nucleation-solid-dispersions](../../../cards/2006-konno-felodipine-polymer-crystallization-nucleation-solid-dispersions/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | steady-state nucleation rate (m⁻³ s⁻¹, log axis; mean, error bars SD, n = 3) — felodipine films with PVP, HPMCAS or HPMC (P1, P2), 22 °C, 0% RH — sub-table below; text: 3% w/w polymer lowered the rate by around 1.5 orders of magnitude and 25% w/w by approximately 2.5 orders; within experimental error no difference between the polymers at any concentration | Fig. 4, p.2697; text p.2697 |
| C14 | claim, conclusion, authors: asserted ("Interestingly") | Within experimental error the polymers do not differ in stabilizing ability at any concentration; abstract: similar extent at an equivalent weight fraction; discussion: equally effective for all compositions between 0 and 25% w/w; conclusions: equally effective at a given weight percentage in the absence of moisture [rests on: R4] | p.2692, p.2697, p.2701, p.2703 |
| C23 | claim, conclusion, authors: asserted ("clearly show") | The three polymers inhibit crystallization of amorphous felodipine by reducing the nucleation rate [rests on: R4] | p.2701 |

## 2006 Marsac — Theoretical and Practical Approaches for Prediction of Drug–Polymer Miscibility and Solubility · Solid state stability / Miscibility and drug-polymer interactions

[2006-marsac-drug-polymer-miscibility-solubility](../../../cards/2006-marsac-drug-polymer-miscibility-solubility/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: "generally considered" | Crystallization of low-Tg amorphous APIs can be prevented by a polymeric crystallization inhibitor; the stabilization mechanism is debated without consensus, but achieving miscibility is generally considered important [rests on: cited: refs 1-13] | p.2417 |
| C56 | claim, generalisation, authors: abstract: "suggesting"; p.2424: "also suggests"; p.2425: "can therefore be attributed predominantly" | Physical stabilization of APIs in amorphous molecular-level solid dispersions is largely due to altered kinetics; abstract: kinetic rather than thermodynamic stabilization plays a significant role; conclusions: crystallization inhibition can be attributed predominantly to kinetic stabilization [rests on: R17, R12, R16] | p.2417, p.2424, p.2425 |

## 2008 Konno — Ability of Different Polymers to Inhibit the Crystallization of Amorphous Felodipine in the Presence of Moisture · Solid state stability / Physical stability

[2008-konno-polymers-inhibit-amorphous-felodipine-moisture-crystallization](../../../cards/2008-konno-polymers-inhibit-amorphous-felodipine-moisture-crystallization/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, cited (ref 11; "reproduced" in Fig. 1a) | nucleation rate (m⁻³ sec⁻¹, mean, n = 3) versus polymer content — spin-coated films (P1), 0% RH, 22 °C (P3, P4) — sub-table below | Fig. 1a, p.971; Fig. 2 (0% RH points); text p.971 |
| R2 | record, measured | nucleation rate (m⁻³ sec⁻¹, mean, n = 3) versus polymer content — spin-coated films (P1), 33% RH, 22 °C (P3, P4) — sub-table below | Fig. 1b, p.971 |
| R3 | record, measured | nucleation rate (m⁻³ sec⁻¹, mean, n = 3) versus polymer content — spin-coated films (P1), 75% RH, 22 °C (P3, P4) — sub-table below | Fig. 1c, p.971 |
| R4 | record, measured | nucleation rate (m⁻³ sec⁻¹, mean, n = 3) at the two RHs shown only in Fig. 2 — spin-coated films (P1), 11% and 58% RH, 22 °C (P3, P4) — sub-table below; text: in all cases the rate rises with storage RH, highest for drug alone | Fig. 2, p.972; text p.972-973 |
| C9 | claim, conclusion, authors: asserted | Without moisture there was very little difference in the stabilizing ability of the three polymers as a function of concentration [rests on: R1] | p.971 |
| C10 | claim, conclusion, authors: results: asserted ("seen most clearly", "apparent"); discussion: "varied quite considerably" | On exposure to water vapour the polymers' stabilizing abilities diverge: PVP is a less effective nucleation inhibitor than the cellulose polymers at the same RH; the divergence is greatest at low polymer content (3% PVP at 75% RH lowers the rate only slightly, the same amount of HPMC or HPMCAS much more) and the polymers converge as content rises, becoming similar at 25% [rests on: R2, R3, R4; cited: ref 11] | p.971-972, p.976 |
| C13 | claim, conclusion, authors: asserted (abstract; discussion; conclusions "in spite of") | Polymer (crystallization inhibitor) and water (crystallization enhancer) compete: at any given storage RH the polymer-containing systems nucleated more slowly than the drug alone, although they absorbed more water [rests on: R1, R2, R3, R4, R8, R9] | p.969, p.975-976, p.977 |

## 2008 Marsac — Recrystallization of Nifedipine and Felodipine from Amorphous Molecular Level Solid Dispersions Containing Poly(vinylpyrrolidone) and Sorbed Water · Solid state stability / Physical stability

[2008-marsac-nifedipine-felodipine-pvp-sorbed-water-recrystallization](../../../cards/2008-marsac-nifedipine-felodipine-pvp-sorbed-water-recrystallization/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | nucleation rate (#/m³/s; error bars one SD, n = 3) — spin-coated films (P1), 0-25 wt% PVP, stored at 0, 11, 33, 58, 75% RH (P2), 25 °C per Fig. 1 caption; counted per P3 — text: from 0% to 75% RH the rate of the 7% PVP dispersion rises by a factor of about 400 for nifedipine and about 100 for felodipine; 25% PVP: nifedipine about 2,000 → 400,000 #/m³/s, felodipine roughly 300 → 2,000 #/m³/s. Figure readings in the sub-table below; Fig. 2 replots the same values against RH (readings agree within plot precision) | Fig. 1, p.649; Fig. 2, p.650; text p.649 |
| C8 | claim, conclusion, authors: asserted | At 0% RH the nucleation rate of both drugs falls dramatically with only 7% PVP and less steeply with further PVP, as described previously [rests on: R1; cited: refs 22, 29] | p.649 |
| C27 | claim, conclusion, authors: asserted ("it is clear") | For these nifedipine and felodipine systems the benefits of the polymer outweigh the drawbacks of the increased water content, which stays below 6% [rests on: R1, R5, R2] | p.652 |

## 2009 Rumondor — Effects of Polymer Type and Storage Relative Humidity on the Kinetics of Felodipine Crystallization from Amorphous Solid Dispersions · Solid state stability / Physical stability

[2009-rumondor-polymer-rh-felodipine-crystallization-kinetics](../../../cards/2009-rumondor-polymer-rh-felodipine-crystallization-kinetics/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | % felodipine crystallized at the last time point analysed, mean (SD), n = 3; storage time in days — all quantified systems, room temperature; — = cell blank in Table I (not stored at that RH) — sub-table below | Table I, p.2602 |
| R10 | record, derived (P6) | F-test outcomes, PVP dispersions — final common assay time point, 95% confidence — 0% RH: no statistically significant difference between the PVP levels; 33% RH: extent at long times significantly lower for 25% and 50% PVP than for 10% PVP; 0, 33 and 52% RH: no significant difference between 25% and 50% PVP; every dispersion at 66% RH and above: significantly higher extent than the corresponding samples at lower RHs; plateau values at 86 and 93% RH: no significant difference between 10, 25 and 50% PVP | p.2601-2602 |
| R19 | record, derived (P6) | F-test outcome, PVP versus HPMCAS — 0, 33 and 52% RH, same polymer concentration — no statistically significant difference in stabilizing ability between the two polymers | p.2602 |
| C12 | claim, conclusion, authors: asserted; discussion: "in general comparable" | At low storage RH (0, 33, 52%) PVP and HPMCAS are similar in their ability to inhibit felodipine crystallization, and both are effective inhibitors when the dispersions are protected from moisture; similar to nucleation-rate results for these polymers at 0 or 33% RH [rests on: R9, R19, R22] | p.2599, p.2602, p.2605 |
| C13 | claim, conclusion, authors: asserted ("clearly") | At 75% RH and above HPMCAS is clearly a better stabilizer of amorphous felodipine than PVP, crystallization from PVP dispersions proceeding much faster [rests on: R9, R6-R8, R15, R16] | p.2599, p.2602, p.2605 |

## 2010 Alonzo — Understanding the Behavior of Amorphous Pharmaceutical Systems during Dissolution · Dissolution / B. Supersaturation from ASD dissolution

[2010-alonzo-amorphous-pharmaceutical-dissolution-crystallization-polymers](../../../cards/2010-alonzo-amorphous-pharmaceutical-dissolution-crystallization-polymers/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | felodipine concentration–time with polymer pre-dissolved at 500 µg/mL (µg/mL) — P2; 37 °C; 500 µg amorphous solid per mL; crystalline felodipine without polymer as reference — sub-table below. Text: with PVP a peak of about 7.5 µg/mL followed by rapid desupersaturation; HPMC and HPMC-AS kept the concentration above 7 and 10 µg/mL respectively for at least 4 h, with a slow decline after the maximum | Fig. 4, p.611-612 |
| R5 | record, measured | PXRD of amorphous felodipine 15 min after wetting — P8; medium without polymer or with 1 mg/mL PVP or HPMC-AS — no polymer: sharp crystalline felodipine peaks (strongest at ≈10.2° 2θ; others at ≈10.8, 13.1, 16.3, 16.6, 20.5, 23.2, 24.5, 25.3, 26.5 and 29.6° 2θ, read from Fig. 5); PVP: no observable crystalline peaks; HPMC-AS: largely amorphous halo with a small peak at 10° 2θ (text); unexposed amorphous felodipine: halo only | Fig. 5, p.612 |
| R6 | record, measured | % crystalline felodipine in aqueous slurry with polymer (Raman PLS) — P5, P6; 37 °C; polymer 500 µg/mL in pH 6.8 buffer; no-polymer series is the 37 °C series of Fig. 3 — sub-table below. Text: with every polymer a sigmoidal profile with a lag phase, a transformation period and a plateau | Fig. 6, p.613 |
| R14 | record, measured | indomethacin concentration–time with PVP pre-dissolved at 250 µg/mL (µg/mL) — P3; 300 µg solid per mL — sub-table below. Text: at 25 °C a maximum around 23.5 µg/mL, maintained for the 4 h experiment; at 37 °C the maximum equals that at 25 °C and is not maintained | Fig. 11, p.614 |
| R15 | record, measured | indomethacin concentration–time with HPMC pre-dissolved at 250 µg/mL (µg/mL) — P3; 300 µg solid per mL — sub-table below. Text: at 37 °C the peak is much lower than with PVP | Fig. 12, p.614 |
| R17 | record, measured | indomethacin concentration–time after solvent shift, 37 °C (µg/mL) — P4; pH 2 buffer — sub-table below. Text: without polymer the concentration drops rapidly; with HPMC the initial concentration is held for about 2.5 h, then decreases; with PVP an initial drop to about 33 µg/mL, fairly steady until 160 min, then decreasing | Fig. 13, p.615 |
| R18 | record, measured | indomethacin concentration–time after solvent shift, 25 °C (µg/mL) — P4; pH 2 buffer — sub-table below. Text: initial concentration around 25 µg/mL; without polymer a 25 min delay before desupersaturation; with either polymer a very slow desupersaturation over the 4 h experiment to approximately 20 µg/mL | Fig. 14, p.615 |
| C11 | claim, conclusion, authors: "These results indicate"; "excellent agreement" | For felodipine, PVP is a poor inhibitor of crystallization from supersaturated solution, whereas HPMC and HPMC-AS inhibit it at the supersaturation generated by the amorphous solid, in excellent agreement with ref 25 [rests on: R4, R20] | p.612 |
| C38 | claim, conclusion, authors: asserted | PVP is much less effective than the cellulosic polymers at maintaining felodipine supersaturation, in agreement with ref 25, but at least as effective at delaying crystallization of the solid [rests on: R4, R6, R20] | p.616 |

## 2010 Kestur — Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine · Solid state stability / Miscibility and drug-polymer interactions

[2010-kestur-polymer-chemistry-felodipine-crystal-growth-inhibition](../../../cards/2010-kestur-polymer-chemistry-felodipine-crystal-growth-inhibition/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, derived (P4) | ratio of the growth rate of felodipine alone to that with 3% w/w polymer (all values ≈, read from Fig. 5) — 70-110 °C; linear regression lines drawn by the authors — sub-table below; text: at 70 °C approximately 4-fold (HPMCAS), 7-fold (PVP/VA) and 10-fold (PVP) decrease in growth rate | Fig. 5, p.2393; text p.2393 |
| R8 | record, measured | growth rate versus polymer concentration (m s⁻¹; all values ≈, read from the log axis of Fig. 6) — 90 °C; 0, 0.5, 1.5, 3 and 4.5% w/w polymer (P1-P4); one shared point at 0%; linear regression lines on the log scale drawn by the authors — sub-table below; text: log-linear relationship with concentration | Fig. 6, p.2393; text p.2393 |
| C17 | claim, conclusion, authors: asserted | Inhibition effectiveness follows PVP > PVP/VA > HPMCAS > PVAc at equivalent concentration across 0.5-4.5% w/w; PVP is the most and PVAc the least effective [rests on: R6, R8] | p.2390, p.2393, p.2397 |
| C38 | claim, conclusion, authors: discussion: "corresponds well", "further supported"; conclusions: "appeared to correlate well" | The polymers with the strongest drug–polymer interactions, PVP and PVP/VA, are the best growth inhibitors, and the IR order corresponds well with the inhibition order; PVP/VA, in which 40% of the pyrrolidone groups are replaced by weakly interacting acetate, is less effective than an equal amount of PVP, and PVAc has essentially no effect [rests on: R9, R6, R8, R5] | p.2396, p.2397 |
| C40 | claim, generalisation, authors: discussion: "strongly suggest"; abstract: "appear"; conclusions: "appeared to correlate well" | Drug–polymer specific interactions play a key role in a polymer's effectiveness as a crystal growth inhibitor; polymers that form stronger or more extensive hydrogen bonds with the drug appear to be better crystallization inhibitors [rests on: R6, R8, R9, C38] | p.2390, p.2396, p.2397 |

## 2010 Rumondor — Effects of Moisture on the Growth Rate of Felodipine Crystals in the Presence and Absence of Polymers · Solid state stability / Physical stability

[2010-rumondor-moisture-felodipine-crystal-growth-pvp-hpmcas](../../../cards/2010-rumondor-moisture-felodipine-crystal-growth-pvp-hpmcas/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | crystal growth rate (mm/min) versus storage RH — felodipine with 2.5, 5, 10% w/w HPMCAS (M3, P2), saturated-salt storage at room temperature (P4), growth rate by P5; drug alone (R1) plotted for comparison — sub-table below; error bars plotted but overlapping at several RH, not transcribed | Fig. 3, p.749 |
| R5 | record, measured | crystal growth rate (mm/min) versus storage RH — felodipine with 2.5, 5, 10% w/w PVP (M2, P2), saturated-salt storage at room temperature (P4), growth rate by P5; drug alone (R1) plotted for comparison — sub-table below; error bars plotted but overlapping at several RH, not transcribed | Fig. 5, p.750 |
| C12 | claim, conclusion, authors: abstract: asserted; conclusions: asserted | Polymeric additives decreased crystal growth rates, more so with increasing polymer concentration [rests on: R3, R5] | p.747, p.753 |
| C14 | claim, conclusion, authors: abstract: asserted; discussion (low RH): "appears to be a better crystal growth inhibitor"; conclusions (below 52%): asserted | Below 52% RH PVP was the better crystal growth inhibitor; above 64% RH HPMCAS inhibited growth more effectively [rests on: R3, R5] | p.747, p.752, p.753 |
| C45 | claim, generalisation, authors: asserted | Polymeric additives inhibit felodipine crystal growth in the presence of moisture, to an extent that depends on several factors [rests on: R3, R5] | p.747 |

## 2010 Eerdenbrugh — Small Scale Screening To Determine the Ability of Different Polymers To Inhibit Drug Crystallization upon Rapid Solvent Evaporation · Solid state stability / Miscibility and drug-polymer interactions

[2010-van-eerdenbrugh-polymer-crystallization-inhibition-spin-coating-screen](../../../cards/2010-van-eerdenbrugh-polymer-crystallization-inhibition-spin-coating-screen/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured (category, P2); derived (AI, E1) | category time course and AI of each composition (three replicate films scored together) — 8 drugs × 7 polymers × 7 drug/polymer weight ratios (w/w), spin coated (P1), stored dry — sub-table below; each code gives the number of C letters in the category at day 0, 1, 3 and 7 (0 = AAAA, 1 = AAAC, 2 = AACC, 3 = ACCC, 4 = CCCC), read from the grey shades of Table S1; the AI in parentheses is the value printed in Table S2 | Table S1, SI p.1-2; Table S2, SI p.3 |
| R3 | record, derived (E2) | average AI (%) of each drug-polymer combination over the 7 weight ratios — spin-coated films, days 0-7 (R2) — sub-table below | Table 1, p.1334 |
| R4 | record, derived (E4) | average AI (%) per drug over all polymers and ratios — spin-coated films (R3) — PH 47 (class I), CZ 47 (class I), BD 48 (class I), LI 55 (class I), FFA 59 (class I), FB 68 (class I/II), CP 73 (class II), BI 97 (class II); Fig. 4 bars at the same heights | text p.1333; Fig. 4, p.1333 |
| R5 | record, derived (E3) | average AI (%) per polymer over all drugs — spin-coated films (R3) — PVP 70, PVPVA 70, E100 67, HPMC 66, HPMCAS 62, PAA 49, PSSA 48; Fig. 5 bars at the same heights | text p.1334; Fig. 5, p.1334 |
| C20 | claim, conclusion, authors: results: asserted ("clearly no"; "readily apparent"); conclusions: asserted ("highly compound dependent") | No polymer is universally superior at inhibiting crystallization during rapid solvent evaporation; a polymer's inhibiting ability is highly dependent on the compound [rests on: R3] | p.1334; p.1337 |
| C27 | claim, conclusion, authors: asserted; "tend to show the best performance" | For the acidic drugs FB, FFA, CP and CZ, PAA and PSSA are very poor inhibitors; HPMCAS, with only 1.0 mmol/g COOH, is less poor but the next worse; HPMC is somewhat better than HPMCAS but, except for CP, worse than E100, PVP and PVPVA, which tend to perform best [rests on: R3.c-f; M15] | p.1334 |

## 2011 Alonzo — Dissolution and Precipitation Behavior of Amorphous Solid Dispersions · Dissolution / B. Supersaturation from ASD dissolution

[2011-alonzo-asd-dissolution-precipitation-nanoparticles](../../../cards/2011-alonzo-asd-dissolution-precipitation-nanoparticles/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | DLS average particle diameter versus time (nm) — 25 °C (P3, P5): methanol shift to 30 µg/mL without polymer; 90:10 PVP–felodipine ASD at nominal 40 µg/mL; 90:10 HPMC–felodipine ASD at 30 and 50 µg/mL plotted with the R8 values — no polymer: 450 nm immediately after the supersaturation was generated (figure ≈447 nm at ≈2 min), 936 nm at 7 min with significant settling; PVP ASD: ≈218, ≈248, ≈302, ≈362, ≈407, ≈459 nm at 10, 20, 30, 45, 60, 90 min (read from Fig. 8); PVP 5-min point removed from the data set (bimodal distribution with a peak at about 5 µm) | Fig. 8, p.3323 |
| R11 | record, measured | DLS average particle diameter versus time (nm) — 37 °C (P3, P5): 90:10 HPMC–felodipine ASD at nominal 40 and 60 µg/mL; 90:10 PVP–felodipine ASD at 50 µg/mL; methanol shift with HPMC at 40 and 60 µg/mL (HPMC concentration not printed); methanol shift without polymer at 40 µg/mL — sub-table below; text: ASD-derived initial size consistently larger (250–260 nm) than the same ASD at 25 °C and than methanol-shift particles at 37 °C (∼200 nm); methanol-shift profiles almost identical to 25 °C; at 37 °C slower rise and earlier levelling off; PVP ASD rise much faster than HPMC ASD | Fig. 9, p.3323-3324 |
| R5 | record, measured | apparent felodipine concentration versus time (µg/mL; mean ± SD, n = 3; 50:50 error bars smaller than symbols) — 90:10 and 50:50 HPMC– and PVP–felodipine ASDs, pH 6.8, 25 °C (P2); nominal felodipine not printed — sub-table below; text: very high apparent concentrations for 90% HPMC and 90% PVP ASDs; 50:50 HPMC maximum just above the predicted amorphous solubility of 5–6 µg/mL (M1); initial dissolution much faster for 90% PVP than for 50% PVP | Fig. 5, p.3321 |
| C18 | claim, conclusion, authors: "suggests"; "as would be expected" | Settling at 7 min means very rapid particle growth from supersaturated solution without any crystallization inhibitor; growth with the PVP ASD was considerably faster than with HPMC, as expected from earlier data [rests on: R10, R24] | p.3323 |
| C51 | claim, conclusion, authors: HPMC: asserted; PVP: "appeared to be" | The supersaturation generated on dissolution was maintained for biologically relevant timeframes for the HPMC dispersions, whereas PVP was a less effective crystallization inhibitor [rests on: R1, R5, R10, R11, R12] | p.3316 |

## 2011 Eerdenbrugh — An ab initio polymer selection methodology to prevent crystallization in amorphous solid dispersions by application of crystal engineering principles · Solid state stability / Miscibility and drug-polymer interactions

[2011-van-eerdenbrugh-ab-initio-polymer-selection-asd-crystallization](../../../cards/2011-van-eerdenbrugh-ab-initio-polymer-selection-asd-crystallization/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | amorphicity index AI (%) of each drug–polymer combination (mean over weight ratios, E1); no error bars — spin-coated films (P1), dry storage 7 days (P2), polarized light microscopy (P3) — sub-table below; all values ≈, read from Fig. 3 (bar tops measured on the embedded figure image; read-out step ≈0.3 AI unit) | Fig. 3, p.6175 |
| C20 | claim, conclusion, authors: asserted ("Indeed") | For the carboxylic acids the best results come from polymers with strong acceptors and no donors (E100, PVP, PVPVA) and the worst from the acidic polymers (PAA, PSSA); HPMC and HPMCAS are variable, good for flurbiprofen and flufenamic acid and extremely poor for 4-biphenylcarboxylic acid and 4-biphenylacetic acid [rests on: R3.a–e] | p.6175 |
| C25 | claim, conclusion, authors: asserted | For the acidic N–H drugs, as for the acids, polymers with strong accepting groups (E100, PVP, PVPVA) inhibit best, offering a competitive hydrogen bond for the acidic N–H; HPMC and HPMCAS perform somewhat lower, except chlorpropamide-HPMC; the acidic polymers again perform poorly [rests on: R3.f–h] | p.6175 |
| C33 | claim, conclusion, authors: "in line with" | For benzamide and phenacetin, polymers with strong donors (PSSA, PAA) are the best inhibitors, and polymers with the very strong pyrrolidone acceptor (PVP, PVPVA) also perform well [rests on: R3.k–l] | p.6176 |

## 2012 Trasi — Effect of Additives on Crystal Growth and Nucleation of Amorphous Flutamide · Solid state stability / Physical stability

[2012-trasi-flutamide-additives-growth-nucleation](../../../cards/2012-trasi-flutamide-additives-growth-nucleation/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | diameter growth rate (µm/s, log axis; triplicate, error bars shown, type not stated) — flutamide alone and with 10 mol% additives (P1 rows a-g), 40-70 °C (P2) — sub-table below. Text: pure flutamide rate falls by nearly 2 orders of magnitude from 70 to 40 °C; with PVP about 1 order of magnitude lower than pure drug; with PAA average slightly higher than pure drug, difference not significant | Fig. 2, p.3223; text p.3223 |
| R5 | record, measured | diameter growth rate (µm/s, log axis) — flutamide alone and with 5% w/w polymers (P1 rows h-l), 40-70 °C (P2) — sub-table below. Text: all pharmaceutical polymers lowered the rate; PVP by more than 1 order of magnitude; HPMCAS by around 4 times; HPMC by around 2.5 times | Fig. 3, p.3223; text p.3223 |
| C40 | claim, generalisation, authors: asserted ("strongly support") | Both pieces of evidence strongly support the hypothesis that specific drug-polymer interactions are extremely important in determining the extent of crystal growth inhibition [rests on: R14, R25, R3] | p.3228 |
| C50 | claim, conclusion, authors: asserted ("verified") | Effective growth reduction was seen only for polymers with good hydrogen-bond acceptor groups, and hydrogen bond formation with these polymers was verified by infrared spectroscopy [rests on: R3, R5, R14, R15, R16] | p.3229 |
| C53 | claim, generalisation, authors: "points to"; "highlights" | Drug-polymer interactions matter for reducing crystallization rates in amorphous formulations, and one must consider not only the molecular structure of the crystallizing compound but also whether its functional groups are available for intermolecular interactions [rests on: R3, R14, R23] | p.3229 |

## 2013 Ilevbare — Influence of Additives on the Properties of Nanodroplets Formed in Highly Supersaturated Aqueous Solutions of Ritonavir · Dissolution / B. Supersaturation from ASD dissolution

[2013-ilevbare-ritonavir-nanodroplets-additives-asd-llps](../../../cards/2013-ilevbare-ritonavir-nanodroplets-additives-asd-llps/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, measured | aggregate size range before crystallization (diameter, nm) and crystallization induction time (min, mean ± SD; triplicate per P6) — solvent shift, ritonavir 20 µg/mL, additive 5 µg/mL (butyl-6-CO2HPull 2 µg/mL), 100 mM phosphate buffer pH 6.8, 37 °C (P6) — sub-table below | Table 4, p.3400 |
| R14 | record, measured | classification of additives by colloidal size stabilization and crystallization inhibition — solvent shift (P6), from R12 and R13 — sub-table below; asterisk (footnote): these polymers promote crystallization | Table 5, p.3400 |
| C30 | claim, generalisation, authors: asserted ("In summary"; "Interestingly") | The more hydrophilic uncharged additives were ineffective or less effective against crystal formation and/or coalescence, the more hydrophobic negatively charged cellulose-based polymers inhibited both, and certain additives promoted nucleation [rests on: R12, R14] | p.3400 |

## 2013 Wegiel — Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions · Solid state stability / Miscibility and drug-polymer interactions

[2013-wegiel-mid-ir-polymer-selection-polyphenol-asd-stability](../../../cards/2013-wegiel-mid-ir-polymer-selection-polyphenol-asd-stability/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, measured | highest polyphenol content (% w/w) giving an X-ray amorphous dispersion by rotary evaporation — P6; 1:1 (w/w) dichloromethane:ethanol — sub-table below (bars read from Fig. 7); text: only 15% and 30% E100 were needed for naringenin and quercetin, and 70% and 80% PAA | Fig. 7, p.6; text p.6 |
| R9 | record, measured | onset Tg of the dry dispersions (°C, ± as printed; triplicate per P5) and days before crystalline material was observed by PXRD at five storage conditions — P3, P5; polymer content (w/w) of each dispersion in the first column; polymer Tg in B1 (M3-M8) — sub-table below; >X = monitoring stopped after X days; a = only partially crystallized; NA as printed | Table 3, p.7 |
| C20 | claim, generalisation, authors: "strong indicator"; "likely" | The highest polyphenol content that gives an X-ray amorphous dispersion is a strong indicator of crystallization-inhibiting performance; a polymer that needs less polymer to form the amorphous dispersion is likely the better inhibitor [rests on: R8] | p.6 |
| C22 | claim, conclusion, authors: asserted ("It is clear") | The polymers differed widely as crystallization inhibitors: E100 and PVP dispersions were the most resistant, with no crystallization for over 200 days even at 90 °C (0% RH), 25 °C (84% RH) and 40 °C (75% RH), whereas cellulosic and PAA dispersions began to crystallize within a few days under the same conditions [rests on: R9] | p.7 |
| C25 | claim, conclusion, authors: p.7: "a good correlation"; abstract: asserted | Overall the observed crystallization behaviour correlated well with the mid-IR predictions, E100 and PVP being the best stabilizers and the cellulosics and PAA giving less inhibition; abstract: stability followed the IR prediction, strongly interacting dispersions were stable at high RH and temperature, weakly interacting ones were unstable at moderate conditions [rests on: R9, R8, C18] | p.1, p.7 |
| C37 | claim, conclusion, authors: asserted ("correlates particularly well") | The mid-IR order of potential inhibition (E100 > PVP > HPMCAS > HPMC ≥ CMCAB > PAA) correlates particularly well with the stability data: PVP and E100 dispersions were extremely stable at all conditions and PAA was a poor inhibitor [rests on: R9, C18] | p.9 |

## 2013 Wegiel — Crystallization of Amorphous Solid Dispersions of Resveratrol during Preparation and Storage—Impact of Different Polymers · Solid state stability / Physical stability

[2013-wegiel-resveratrol-asd-polymer-crystallization-stability](../../../cards/2013-wegiel-resveratrol-asd-polymer-crystallization-stability/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | highest resveratrol content giving an X-ray amorphous dispersion after rotary evaporation — P1, P4; dichloromethane:ethanol 1:1; 5% steps — sub-table below | Fig. 2, p.174; text p.174 |
| R12 | record, measured | days before crystallization was observed by XRPD — P3, P4; polymer content of each dispersion in parentheses — sub-table below | Table 3, p.179 |
| C7 | claim, conclusion, authors: asserted ("stood out"; "Clearly") | Polymers are effective crystallization inhibitors for resveratrol but differ greatly: E100 stood out as the best during solvent evaporation, PAA needed so much polymer that little resveratrol remained, and some polymers are much less effective than others [rests on: R2] | p.174 |
| C45 | claim, generalisation, authors: abstract: "could be correlated", "suggested", "it is rationalized"; conclusions: asserted ("strongly related") | Manufacturability and physical stability of resveratrol dispersions are strongly related to the specific resveratrol-polymer interactions, polymers forming weaker hydrogen bonds being less effective inhibitors; abstract: polymer influence could be correlated with polymer structure, polymers with good acceptor groups performing better, stability was suggested to be linked to the type and strength of interactions, and inhibitor effectiveness is rationalized by them [rests on: R2, R11, R12, R17] | p.171, p.183 |

## 2014 Hsieh — Assessing the Impact of Polymers on the pH-Induced Precipitation Behavior of Poorly Water-Soluble Compounds using Synchrotron Wide Angle X-Ray Scattering · Dissolution / D. Crystallization from solution

[2014-hsieh-polymers-ph-induced-precipitation-waxs](../../../cards/2014-hsieh-polymers-ph-induced-precipitation-waxs/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | crystalline ("Intrinsic") solubility, concentration after precipitation, birefringence and WAXS phase — P2–P7. Drug and polymer 1 mg/mL starting concentration. Final pH: papaverine 8.4–9.0, dipyridamole 8.2–9.0, glyburide 1.9–2.9, warfarin 2.2–3.3 (pH adjusted so that compounds are unionized). Standard deviation of solubility and concentration within 20%. Concentration within approximately 1 h after precipitation. WAXS read at 15 min unless noted. Triplicate samples (P2). Glyburide solubility: row u from pH-metric titration; rows v–ad set equal to row u (C19). Warfarin birefringence images for rows af–an in Fig. 4. — sub-table R4 | Table 2, p.4; Fig. 4, p.7 |
| R12 | record, measured | WAXS of glyburide and warfarin precipitates with HPMC — P4; HPMC; 15 min, 30 min, 1 h, 3 h, 6 h; amorphous, blank and crystalline reference traces — Broad halo only at all five time points for both drugs (Fig. 8c, d). Text: slight peaks in the patterns are also present in the blank. | Fig. 8c–d, p.8; WAXS Results, p.6 |
| R13 | record, measured | WAXS of other amorphous-coded systems — P4; glyburide and warfarin with PVP, PVPVA, HPMCAS or Eudragit E100; glyburide with PAA or CMCAB — Text: amorphous halos at 15 min with no crystallization over 6 h for the PVP, PVPVA, HPMCAS and Eudragit E100 systems. Glyburide with PAA and CMCAB coded A at 15 min (R4.aa, R4.ab); no duration given. Patterns not shown. | WAXS Results, p.6–7 |
| C4 | claim, conclusion, authors: abstract: asserted ("more than 6 h"); results: "indicating"; conclusions: asserted ("at least 6 h") | For glyburide and warfarin, WAXS and PLM point to several polymers (PVP, PVPVA, HPMC, both HPMCAS grades, Eudragit E100) preventing crystallization, with the precipitate staying amorphous for at least 6 h; PAA and CMCAB were also effective for glyburide. Some polymers thus promoted precipitation to a noncrystalline solid and a supersaturated solution. [rests on: R4, R12, R13] | Abstract, p.1; WAXS Results, p.6–7; Discussion, p.9; Conclusions, p.10 |
| C10 | claim, conclusion, authors: asserted (papaverine, dipyridamole, glyburide); "suggesting" (warfarin) | By birefringence: no polymer inhibited crystallization of papaverine or dipyridamole; all polymers except CAP-adipate were effective inhibitors for glyburide; for warfarin, birefringence pointed to crystallization with PAA, CMCAB and CAP-adipate and to a noncrystalline precipitate with PVP, PVPVA, HPMC, HPMCAS and Eudragit E100. [rests on: R4] | Results, p.5–6 |

## 2014 Jackson — Impact of Polymers on the Precipitation Behavior of Highly Supersaturated Aqueous Danazol Solutions · Dissolution / D. Crystallization from solution

[2014-jackson-polymers-precipitation-supersaturated-danazol](../../../cards/2014-jackson-polymers-precipitation-supersaturated-danazol/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R17 | record, measured | crystallization induction time Ti (min) by UV absorbance, UV extinction and fluorescence — P8; danazol 10, 15, 20 µg/mL with or without 10 µg/mL polymer; ± as printed, n not printed; N/A as printed — sub-table below; Fig. 12 plots the same values | Table 4, p.3033; Fig. 12, p.3035 |
| C2 | claim, conclusion, authors: abstract: asserted ("greatly"); conclusions: asserted ("dramatically") | Small amounts of polymer greatly extend the lifetime of the supersaturated two-phase solution, delaying the onset of crystallization from a few minutes to a few hours [rests on: R17] | p.3027, p.3028, p.3036 |
| C27 | claim, conclusion, authors: "suggesting" | With any of the three polymers the constant, low I1/I3 over 15 min shows that crystallization was inhibited and the probe stayed in the drug-rich phase [rests on: R12] | p.3032 |
| C32 | claim, conclusion, authors: "around"; "approximately"; "Clearly" (HPMC-AS longest); discussion: "huge increase" | With polymer the induction time rises to hours, longest with HPMC-AS: around 1.5 h for PVP, approximately 2.5 h for HPMC and 4 h or more for HPMC-AS (p.3033); approximately 100 and 150 min for PVP and HPMC and 6 h for HPMC-AS (p.3034); the large variation is typical of stochastic nucleation [rests on: R17] | p.3033, p.3034, p.3036 |

## 2014 Mosqueragiraldo — Impact of surfactants on the crystal growth of amorphous celecoxib · Solid state stability / Physical stability

[2014-mosquera-giraldo-surfactants-crystal-growth-amorphous-celecoxib](../../../cards/2014-mosquera-giraldo-surfactants-crystal-growth-amorphous-celecoxib/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | radial growth rate versus temperature (µm/s; triplicate per P3; no error bars plotted) — celecoxib alone and with 10% (w/w) additive (P1, P3) — sub-table below; text: 10 wt.% PVP reduced the growth rate by more than one order of magnitude; TPGS raised it by approximately two orders of magnitude at 70 °C | Fig. 2, p.253; text p.253 |
| R2 | record, measured | radial growth rate versus temperature (µm/s; no error bars plotted) — 10% surfactant + 10% PVP + 80% celecoxib (P1, P3); the PVP-only series of Fig. 3 is plotted at the same points as R1.b — sub-table below | Fig. 3, p.253 |
| C8 | claim, conclusion, authors: asserted | 10 wt.% PVP reduced the growth rate of celecoxib by more than one order of magnitude [rests on: R1.a, R1.b] | p.253 |
| C13 | claim, conclusion, authors: asserted; "at least at higher temperatures" | The combined effect of TPGS and PVP was unexpected: growth was considerably lower than with PVP alone, making this the most stable of all the systems, at least at higher temperatures; the Fig. 3 caption calls it a synergistic effect [rests on: R1.b, R2.b] | p.253 |
| C3 | claim, prior hypothesis, authors: "strongly support" | Studies of polymer chemistry support a correlation between the strength of drug–polymer hydrogen bonding and the extent of crystal growth rate inhibition in supercooled liquids [rests on: cited: Kestur and Taylor 2010; Kestur et al. 2011] | p.251 |

## 2014 Raina — Enhancements and Limits in Drug Membrane Transport Using Supersaturated Solutions of Poorly Water Soluble Drugs · Bioperformance / Bioperformance

[2014-raina-llps-limits-drug-membrane-transport-supersaturated-solutions](../../../cards/2014-raina-llps-limits-drug-membrane-transport-supersaturated-solutions/paper.html) · Bioperformance / Bioperformance · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | onset concentration of LLPS or crystallization by UV extinction (µg/mL, mean ± 1 SD, n = 3) — felodipine and nifedipine in 50 mM pH 6.8 phosphate buffer, without or with HPMC (P7) — sub-table below | Table 1, p.2741; Fig. 4, p.2742 |
| R5 | record, measured | phase formed by nifedipine with and without HPMC — nifedipine, buffer with 1 mg/mL HPMC versus buffer alone (P6, P7) — with HPMC: diffuse phase without birefringence on rotating the plane of polarized light; without HPMC: crystalline particulates under PLM, and the onset recorded is spontaneous nucleation followed by crystal growth (R1 column 3) | p.2740 |
| C14 | claim, conclusion, authors: asserted | Nifedipine shows LLPS only with polymer dissolved in solution; without HPMC it crystallizes [rests on: R5, R1] | p.2740 |
| C18 | claim, conclusion, authors: asserted | Without polymer nifedipine spontaneously crystallizes before the LLPS concentration is reached; with polymer higher concentrations are reached before crystallization and LLPS is observed [rests on: R1, R5] | p.2740 |
| C31 | claim, mechanism, authors: "it is clear" | Felodipine, a slow crystallizer, can exceed its amorphous solubility and undergo LLPS; nifedipine, a faster crystallizer, crystallizes just below the coexistence curve without inhibitor; HPMC, a nucleation inhibitor, allows higher supersaturation and LLPS of nifedipine [rests on: R1, R5, R20] | p.2744 |
| C41 | claim, recommendation, authors: "is expected to" | Crystallization-inhibiting polymers are expected to convert a crystallizing system into an LLPS system and so promote drug uptake [rests on: R1, R5] | p.2745 |

## 2014 Raina — Impact of Polymers on the Crystallization and Phase Transition Kinetics of Amorphous Nifedipine during Dissolution in Aqueous Media · Dissolution / B. Supersaturation from ASD dissolution

[2014-raina-polymers-nifedipine-crystallization-phase-transition-dissolution](../../../cards/2014-raina-polymers-nifedipine-crystallization-phase-transition-dissolution/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | crystallization of neat amorphous nifedipine particles in buffer (PLM) — neat amorphous nifedipine (P1) in 50 mM pH 6.8 phosphate buffer at 25 °C, 15 min after exposure, without polymer (Fig. 3B) and with 1 mg/mL PVP (C), HPMC (D) or HPMCAS (E) predissolved — birefringent crystalline material on the particles in all four media; text: crystallization rapid, primarily in the solid matrix, onset and route the same with and without predissolved polymer; matrix-crystallized material 1−300 µm | Fig. 3, p.3568; text p.3568, p.3571 |
| R9 | record, derived (E1) | MCR relative concentration of γ versus time with and without predissolved polymer — neat amorphous nifedipine in 50 mM pH 6.8 phosphate buffer alone or with 1 mg/mL PVP, HPMC or HPMCAS; 25 °C (Fig. 7A) and 37 °C (Fig. 7B) (P6, P10) — sub-table below; text: lag time before γ-to-α conversion at 25 °C about 10 min in buffer and nearly 2 h with HPMCAS (Fig. 7A) | Fig. 7, p.3571; text p.3569, p.3574 |
| R10 | record, derived (E1) | MCR relative concentration of α versus time with and without predissolved polymer — as R9; 25 °C (Fig. 8A) and 37 °C (Fig. 8B) — sub-table below | Fig. 8, p.3571 |
| C11 | claim, conclusion, authors: asserted | Predissolved PVP, HPMC and HPMCAS did not change the onset or the route of crystallization of neat amorphous nifedipine; matrix crystallization was instantaneous even with dissolved polymer [rests on: R2, R7, R9] | p.3565, p.3568 |
| C16 | claim, conclusion, authors: results: "did appear to have a stabilizing effect"; conclusions: asserted ("did have a significant impact") | Predissolved polymers did not impede the onset of crystallization at 25 or 37 °C (the amorphous material disappeared within a few minutes) but stabilized γ and delayed its conversion to α [rests on: R7, R9, R10] | p.3569, p.3574 |

## 2014 Trasi — Nucleation and crystal growth of amorphous nilutamide – unusual low temperature behavior · Solid state stability / Crystallization tendency

[2014-trasi-taylor-amorphous-nilutamide-low-temperature-nucleation](../../../cards/2014-trasi-taylor-amorphous-nilutamide-low-temperature-nucleation/paper.html) · Solid state stability / Crystallization tendency · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | radial growth rate of the stable form (µm s−1, triplicate; log scale) — seeded melt-quenched films (P2, P3); pure nilutamide, with 10% molar PAA, with PVP — sub-table below; text: both polymers reduce the growth rate, marginally for PAA, much more for PVP, particularly at lower temperature | Fig. 2, p.7188; text p.7189-7190 |
| C14 | claim, conclusion, authors: asserted | Both polymers reduce the stable-form growth rate, marginally for PAA and much more for PVP, particularly at lower temperature; PVP, with a good acceptor and no donor, is a much better growth inhibitor than PAA, with a strong donor and a medium-weak acceptor [rests on: R3] | p.7189-7190 |
| C19 | claim, generalisation, authors: asserted ("correlates well"); "in general agreement" | The nilutamide-polymer interaction strength correlates with the relative impact of each polymer on crystal growth, in general agreement with other studies [rests on: R3, R11, R12] | p.7190 |

## 2014 Wegiel — Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability · Solid state stability / Physical stability

[2014-wegiel-curcumin-asd-intramolecular-bonding-physical-stability](../../../cards/2014-wegiel-curcumin-asd-intramolecular-bonding-physical-stability/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R13 | record, measured | Tg (°C) and days before crystalline material is observed by PXRD — 75% w/w curcumin dispersions (P2, P3) and amorphous curcumin (P3) under the storage conditions (P5, P6) — sub-table below; text p.982 gives 10 d for amorphous curcumin at 84% RH, 25 °C | Table 3, p.982; text p.982 |
| C2 | claim, conclusion, authors: asserted ("proved to be") | Polymers were effective curcumin crystallization inhibitors that enabled amorphous solid dispersions, but their ability to inhibit crystallization during long-term storage differed widely [rests on: R13] | p.976 |
| C24 | claim, conclusion, authors: asserted; "to some extent" | PVP was the poorest crystallization inhibitor: it delayed crystallization to some extent relative to amorphous curcumin but crystallized faster than every other dispersion at comparable conditions [rests on: R13.a, R13.c] | p.982 |
| C25 | claim, conclusion, authors: asserted ("much better physical stability") | The E100 dispersions were the most stable at intermediate conditions, the only ones stable at both 84% RH, 25 °C and 75% RH, 40 °C, and at 60 °C/98% RH and 90 °C/0% RH remained X-ray amorphous considerably longer than the other dispersions [rests on: R13.b] | p.982 |
| C26 | claim, conclusion, authors: asserted | The cellulosic polymers gave some enhancement of stability; HPMC was the most effective cellulosic inhibitor; CMCAB and HPMCAS were similar [rests on: R13.d-f] | p.982 |

## 2015 Sousa — Assessment of the Amorphous “Solubility” of a Group of Diverse Drugs Using New Experimental and Theoretical Approaches · Dissolution / C. Amorphous solubility and LLPS

[2015-almeida-sousa-amorphous-solubility-diverse-drugs-llps-cp-method](../../../cards/2015-almeida-sousa-amorphous-solubility-diverse-drugs-llps-cp-method/paper.html) · Dissolution / C. Amorphous solubility and LLPS · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | extinction and probe fluorescence against drug concentration — P1 and P2, 25 °C; drug and medium per row — sub-table below | Fig. 4, p.490 |
| R4 | record, measured | visual and text-stated observations for griseofulvin — pH 6.8 without polymer; pH 6.8 + 100 μg/mL HPMCAS-HF; P1, P2 — without polymer: extinction increase around 150 μg/mL with no change in the intensity of the 4-di-2-ASP emission peak; small solid particles seen at around 150 μg/mL. With polymer: extinction increase around 350 μg/mL and increase in 4-di-2-ASP emission intensity around the same concentration; solutions at this concentration free of visible particles and uniformly turbid | p.491 |
| C19 | claim, mechanism, authors: "This result by itself suggests" | HPMCAS-HF delays the crystallization of griseofulvin, the extinction rising only at much higher concentrations (around 350 μg/mL) [rests on: R3.g, R4] | p.491 |

## 2015 Chen — Bile Salts as Crystallization Inhibitors of Supersaturated Solutions of Poorly Water-Soluble Compounds · Dissolution / D. Crystallization from solution

[2015-chen-bile-salts-crystallization-inhibitors-supersaturated-solutions](../../../cards/2015-chen-bile-salts-crystallization-inhibitors-supersaturated-solutions/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | nucleation induction time (min), average of three runs; error bars plotted for some bars, type not printed — 11 drugs at the C/Ceq of the P2 sub-table in buffer, buffer + 0.1% SDS, buffer + 0.1% STC; 25 °C, telaprevir 37 °C (P2, P3) — sub-table below; text: no crystallization event detected during the measurement for celecoxib, griseofulvin, warfarin and naproxen in 0.1% STC, plotted as greater than the experimental duration; SDS not tested for bifonazole and compound 1 | Fig. 3, p.2596; text p.2595-2596 |
| R4 | record, measured | nucleation induction time (min) with three bile salts — celecoxib (HCl solution, pH 3, C/Ceq 5) and nevirapine (phosphate buffer pH 6.5, 50 mM, C/Ceq 4), 0.1% bile salt, 25 °C (P4) — sub-table below; text: with SGC no nucleation event of celecoxib was detected during the experiment; nevirapine induction times with SGC and SGDC longer than with 0.1% STC | Fig. 4, p.2596; text p.2596 |
| C13 | claim, conclusion, authors: results: asserted ("quite dramatic"); conclusions: "was demonstrated to prolong" | For all 11 drugs the induction time with 0.1% STC was longer than in buffer, and for most compounds the increase was quite dramatic [rests on: R3] | p.2596 |
| C23 | claim, conclusion, authors: results: asserted; conclusions: "showed promise as nucleation inhibitors" | SGC and SGDC gave similar or better nucleation inhibition than STC: SGC greatly inhibited celecoxib nucleation (no event detected), and with SGC or SGDC nevirapine induction times were longer than with 0.1% STC [rests on: R4] | p.2596 |
| C25 | claim, generalisation, authors: abstract: "suggested other members of the bile salt family may also have crystallization inhibition properties"; conclusions: "suggest", "potentially" | Bile salts, naturally present in the GI tract, potentially represent a family of additives that can delay nucleation of a variety of poorly water-soluble drugs from aqueous solution and deserve further investigation for supersaturating formulations [rests on: R3, R4] | p.2593, p.2596 |

## 2015 Chen — Impact of Surfactants on the Crystallization of Aqueous Suspensions of Celecoxib Amorphous Solid Dispersion Spray Dried Particles · Dissolution / B. Supersaturation from ASD dissolution

[2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions](../../../cards/2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, measured (P9) | mean nucleation induction time, at least three runs — eight media, S = 5, 25 °C — sub-table R12 | Results p. 13; Fig. 4, p. 14 |
| R19 | record, measured (P9) | induction time with and without 3 µg/mL HPMCAS — SDS, Polysorbate 80, Poloxamer 188 media, S = 5 — sub-table R19 | Discussion pp. 22–23; Fig. 9, p. 24 |
| C4 | claim, conclusion, authors: asserted | Polysorbate 80, Poloxamer 188 and SDS accelerate celecoxib nucleation relative to the surfactant-free medium, in the order Polysorbate 80 > Poloxamer 188 > SDS; Triton X100 and STC inhibit nucleation. [rests on: R12] | Results p. 13; Discussion p. 21 |
| C27 | claim, conclusion, authors: asserted ("within experimental error"; "significantly") | 3 µg/mL HPMCAS does not change τ for SDS and Polysorbate 80 within experimental error but makes τ significantly longer for Poloxamer 188. [rests on: R19] | Discussion p. 23 |
| C28 | claim, mechanism, authors: "most likely"; "is likely to be" | The HPMCAS-prolonged induction time most likely explains the extended stability of Poloxamer 188 suspensions, especially as the real HPMCAS concentration is likely higher than tested. [rests on: R19.c, R14.d] | Discussion p. 23 |

## 2015 Jackson — Dissolution of Danazol Amorphous Solid Dispersions: Supersaturation and Phase Behavior as a Function of Drug Loading and Polymer Type · Dissolution / B. Supersaturation from ASD dissolution

[2015-jackson-danazol-asd-dissolution-llps-drug-loading-polymer-type](../../../cards/2015-jackson-danazol-asd-dissolution-llps-drug-loading-polymer-type/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured per row; cited (ref 30) for pre-dissolved polymer rows | crystallization induction time and LLPS onset concentration (bar height, with error-bar ends in brackets; error-bar type and n not printed) — ASD dissolution (P2, P3); antisolvent solutions with pre-dissolved polymer (P7) — sub-table below (all values ≈, read from Fig. 4); text: pyrene response marking LLPS when the concentration exceeded 6-10 µg/mL for all dispersions except 50:50 HPMCAS; 50:50 HPMC and HPMCAS showed no desupersaturation over the experiments | Fig. 4, p.18; text p.18-19 |
| C2 | claim, prior hypothesis, authors: asserted | Polymers are added to ASDs to stabilise against crystallization during storage and dissolution; inhibiting crystallization during dissolution lets a supersaturated solution form under non-sink conditions [rests on: cited: refs 7-12] | p.3 |
| C19 | claim, conclusion, authors: asserted | Crystallization induction times after ASD dissolution are similar to those of antisolvent solutions with the same polymer pre-dissolved, except for 50:50 HPMC and HPMCAS, which do not desupersaturate during the experiments; all PVP systems have the shortest and the HPMCAS systems the longest induction times [rests on: R5] | p.18 |

## 2015 Mosqueragiraldo — Glass–Liquid Phase Separation in Highly Supersaturated Aqueous Solutions of Telaprevir · Dissolution / C. Amorphous solubility and LLPS

[2015-mosquera-giraldo-telaprevir-glass-liquid-phase-separation](../../../cards/2015-mosquera-giraldo-telaprevir-glass-liquid-phase-separation/paper.html) · Dissolution / C. Amorphous solubility and LLPS · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | appearance of telaprevir solutions versus added concentration — stock added to pH 6.8 buffer (P12) — clear until the concentration exceeded around 90 μg/mL; above, visually turbid with no obvious particles; visible particles after approximately 15 min, birefringent under polarized light; turbid solutions maintained for several hours with a small quantity of HPMCAS; without a polymeric inhibitor, solutions crystallized within approximately 15 min (p.502) | p.499, p.502 |
| M2 | material | HPMCAS-MF hydroxypropyl methyl cellulose acetate succinate grade AS-MF; Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) | p.497 |
| C31 | claim, conclusion, authors: asserted | Crystallization occurs fairly quickly from solutions containing drug-rich amorphous particles; without a polymeric inhibitor telaprevir solutions crystallized within approximately 15 min [rests on: R1] | p.502 |

## 2015 Purohit — Miscibility of Itraconazole-Hydroxypropyl Methylcellulose Blends- Insights with High Resolution Analytical Methodologies · Solid state stability / Miscibility and drug-polymer interactions

[2015-purohit-itraconazole-hpmc-miscibility-high-resolution-methods](../../../cards/2015-purohit-itraconazole-hpmc-miscibility-high-resolution-methods/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C51 | claim, mechanism, authors: "would be expected"; "may also be altered" | A partially miscible ASD with drug-rich domains would crystallize more readily, because less polymer surrounds the drug, and may dissolve differently, because the polymer-rich phase dissolves first and leaves a poorly wettable drug-rich phase [rests on: argument only] | p.18 |
| C2 | claim, prior hypothesis, authors: "would be expected" | A phase-separated system would be expected to be less stable, with faster drug crystallization during storage and dissolution and loss of performance, so miscibility evaluation is essential [rests on: cited: ref 8] | p.3 |

## 2015 Raina — Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds · Characterization methods / Solution methods

[2015-raina-fluorescent-probes-llps-supersaturated-solutions](../../../cards/2015-raina-fluorescent-probes-llps-supersaturated-solutions/paper.html) · Characterization methods / Solution methods · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C38 | claim, mechanism, authors: "is known to" | HPMC in solution impedes nucleation of dihydropyridines, which lets nifedipine and nimodipine reach LLPS [rests on: R4; argument only] | pdf p.12 |
| R4 | record, measured | phase formed at the extinction onset (visual and PLM classification, P7) — six compounds in buffer without and with HPMC, 25 and 37 °C — without HPMC: LLPS for cilnidipine, felodipine, nisoldipine and nitrendipine at 25 and 37 °C and for nimodipine at 25 °C; visually observed crystallization (asterisks in Fig. 5) for nifedipine at 25 and 37 °C and nimodipine at 37 °C, just below the LLPS onset concentration; with HPMC: LLPS for nifedipine and nimodipine | text pdf p.6-7, p.12; Fig. 5, pdf p.7 |
| M7 | material | hydroxypropylmethyl cellulose (HPMC) Pharmacoat grade 606, Shin-Etsu Chemical Co. (Tokyo, Japan) | pdf p.2, p.8, p.10 |

## 2015 Raina — Trends in the Precipitation and Crystallization Behavior of Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs Assessed Using Synchrotron Radiation · Dissolution / D. Crystallization from solution

[2015-raina-precipitation-crystallization-supersaturated-dihydropyridines-synchrotron](../../../cards/2015-raina-precipitation-crystallization-supersaturated-dihydropyridines-synchrotron/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | first sampled time at which crystallinity was detected, with predissolved polymer — P1, P4; polymer 4.5 mg/mL (CMCAB, CAPAdp 100 µg/mL); sampling at 0.25, 0.5, 1, 3, 6, 12, 24 h; ">24" = amorphous at all time points up to 24 h — sub-table below; PAA low molecular weight grade identical to the high grade (only high grade shown) | Fig. 8, p.8 |
| C14 | claim, conclusion, authors: asserted | PAA and P2VP were ineffective inhibitors for all compounds, with no difference between the PAA grades; PVPVA, HPMC and HPMCAS were the most effective for all compounds, with small differences (cilnidipine amorphous beyond 24 h, nifedipine crystallizing between 1 and 3 h) [rests on: R9] | p.5 |
| C16 | claim, conclusion, authors: "On the basis of the observed trends"; conclusions: "was found to be" | Polymer effectiveness against dihydropyridine crystallization ranks PVPVA = HPMC = HPMCAS > PVP > CMCAB = CAPAdp > P2VP = PAA [rests on: R9] | p.6, p.11 |
| C38 | claim, conclusion, authors: asserted ("largely ineffective") | HPMC, HPMCAS and PVPVA were effective for all compounds, PVP had some impact, and PAA, P2VP, CMCAB and CAPAdp were largely ineffective [rests on: R9] | p.10 |

## 2015 Raina — Impact of Solubilizing Additives on Supersaturation and Membrane Transport of Drugs · Bioperformance / Bioperformance

[2015-raina-solubilizing-additives-supersaturation-membrane-transport](../../../cards/2015-raina-solubilizing-additives-supersaturation-membrane-transport/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| M3 | material | HPMC Pharmacoat grade 606; Shin-Etsu Chemical Co., Ltd (Tokyo, Japan) | pdf p.3, p.4, p.5 |
| C11 | claim, prior hypothesis, authors: "do not generally"; "typically" | Polymers at low concentration do not generally raise crystalline solubility but inhibit nucleation and crystal growth and so stabilize supersaturated solutions, whereas surfactants and complexing agents typically raise equilibrium solubility [rests on: cited: refs 5, 28–36] | pdf p.2 |
| C47 | claim, assumption, authors: "typically" | Between crystalline and amorphous solubility the solution is a single supersaturated phase; above the amorphous solubility LLPS or crystallization can occur, and slowly crystallizing systems typically show LLPS, as here where polymer impedes crystallization [rests on: argument only] | pdf p.12 |

## 2015 Sato — Chiral discrimination by a cellulose polymer: differential crystallization inhibition of enantiomers in amorphous dispersions · Solid state stability / Physical stability

[2015-sato-cellulose-polymer-chiral-crystallization-inhibition-enantiomers](../../../cards/2015-sato-cellulose-polymer-chiral-crystallization-inhibition-enantiomers/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | spherulite growth rate (μm s−1, log axis; values ≈, read from Fig. 6; S filled markers, R markers with a light centre per the legend; mean of triplicates, error bars not read) — ATP(S) and ATP(R) without polymer and with 5% w/w PHB, PVP, HPMCP, HPMCAS-LF or HPMCAS-HF (P1, P3, P4) — sub-table below; blank = not measured; "both" = R and S markers overlap | Fig. 6, p.5049 |
| R1 | record, measured | onset Tg, Tc (recrystallization on heating) and Tm by DSC at 10 °C min−1 (°C) — pure and 5% w/w polymer samples (P1, P2, P6); n not printed — sub-table below; footnote: melting point during first heating in parentheses | Table 1, p.5049; Figs. 3–5, p.5048 |
| R15 | record, measured | IR NH/OH region during storage at 40 °C — ATP(S) and ATP(R) with 5% HPMCAS HF (P7) — ATP(S): spectra at 15 h and 30 h match the crystallized pure ATP(S) pattern (sharp band ≈3365 cm−1 plus bands ≈3425 and ≈3300 cm−1, read from Fig. 15); ATP(R): at 15 h and 30 h a weak sharp band on the broad amorphous background, a mixture of crystalline and amorphous material | p.5051; Fig. 15, p.5052 |
| C10 | claim, conclusion, authors: asserted; discussion: PVP result "as expected" | The polymer effect on growth depended on both polymer and enantiomer: PHB had minimal impact on either enantiomer; achiral PVP inhibited growth equally for both; HPMCP was even more effective but showed no differential effect; HPMCAS inhibited to a similar extent as HPMCP but differently for the two enantiomers; of the three chiral polymers only HPMCAS discriminated [rests on: R5, R7, R8] | p.5049; p.5052 |
| C11 | claim, conclusion, authors: asserted ("clearly") | With HPMCAS-HF, ATP(R) grew twice as fast as ATP(S); with HPMCAS-LF, ATP(S) grew twice as fast as ATP(R); HPMCAS clearly has a differential impact on each enantiomer, i.e. the same mass fraction of HPMCAS inhibited growth of the enantiomers to different extents [rests on: R7, R8] | p.5050; abstract p.5046; conclusions p.5052 |

## 2015 Trasi — Thermodynamics of Highly Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs—Impact of a Second Drug on the Solution Phase Behavior and Implications for Combination Products · Dissolution / C. Amorphous solubility and LLPS

[2015-trasi-second-drug-supersaturated-solutions-drug-rich-phase](../../../cards/2015-trasi-second-drug-supersaturated-solutions-drug-rich-phase/paper.html) · Dissolution / C. Amorphous solubility and LLPS · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C9 | claim, assumption, authors: asserted | HPMC at 10 µg/mL prevents nucleation and crystallization for the duration of the experiments; the reported values are for solutions containing a small amount of polymer [rests on: R4] | p.2584-2585 |
| R4 | record, measured | LLPS concentration by ultracentrifugation without HPMC — P2 without polymer — ritonavir and lopinavir: no change in concentration; paclitaxel crystallized | p.2584-2585 |

## 2015 Trasi — Dissolution performance of binary amorphous drug combinations—Impact of a second drug on the maximum achievable supersaturation · Dissolution / B. Supersaturation from ASD dissolution

[2015-trasi-taylor-binary-amorphous-drug-combinations-supersaturation](../../../cards/2015-trasi-taylor-binary-amorphous-drug-combinations-supersaturation/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R15 | record, measured | pyrene I3/I1 versus time in drug-rich phase suspensions (error bars drawn, meaning and n not printed) — suspensions made by antisolvent addition (P11) — sub-table below; text: I3/I1 of LPV fell between 1 and 2 h; no fall reported for RTV alone or for the two mixtures up to 5 h | Fig. 7, p.288; text p.288 |
| R16 | record, measured | average free drug concentration in the supernatant of drug-rich phase suspensions (µg/mL; standard deviation in parentheses) — P11 suspensions, ultracentrifuged at 0 h and after 5 h stirring (P12) — sub-table below | Table 2, p.289 |
| C34 | claim, conclusion, authors: "indicating" | The two RTV-LPV drug-rich phase suspensions did not crystallize for up to 5 h, so RTV stabilized LPV against crystallization [rests on: R15.c-d] | p.288 |
| C51 | claim, mechanism, authors: "can be attributed, at least in part" | Two drugs in the same droplet lowered the crystallization tendency relative to the pure components, at least partly through the lower supersaturation that follows from the lower amorphous solubility of each drug [rests on: R15, R16] | p.290 |

## 2015 Wegiel — Phase Behavior of Resveratrol Solid Dispersions Upon Addition to Aqueous media · Dissolution / B. Supersaturation from ASD dissolution

[2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior](../../../cards/2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R13 | record, measured | Raman ratio vs time at different polymer contents — PB 6.8, 37°C, n=3 (P7) — sub-table R13 | Fig. 6, pdf p.8; text, pdf p.6 |
| R14 | record, measured | minimum polymer wt% needed to inhibit crystallization during dissolution — 50 mM PB pH 6.8, 37°C — sub-table R14 | Table IV, pdf p.9 |
| C11 | claim, conclusion, authors: asserted | Raising polymer content reduced the extent of crystallization; for every polymer a minimum polymer level completely inhibited crystallization in aqueous slurry; at low resveratrol loadings crystallization was inhibited for 24 h. [rests on: R13, R14] | Results, pdf p.6; Discussion, pdf p.11 |
| C37 | claim, mechanism, authors: most probably | The dependence of crystallization extent on polymer amount most probably reflects the limited number of polymer functional groups (e.g., hydroxyls) available to hydrogen bond with resveratrol, which falls as polymer content falls. [rests on: R13, R21] | Discussion, pdf p.11 |

## 2015 Xie — Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations · Dissolution / B. Supersaturation from ASD dissolution

[2015-xie-taylor-celecoxib-high-drug-loading-asd-polymer-combinations](../../../cards/2015-xie-taylor-celecoxib-high-drug-loading-asd-polymer-combinations/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | nucleation induction time (onset: rise in 350 nm extinction with fall in 249 nm absorbance) — CEX 22 µg/mL in SPB pH 6.8, 37 °C, each polymer 5 µg/mL (P4) — text: no polymer, crystallization commenced within 5 min and the solution became increasingly turbid with macroscopic crystals; PVP-K12 approximately 1 h (discussion: desupersaturation commencing after 60 min); PVP-K29/32 approximately 2 h; HPMCAS and HPMC, no substantial nucleation or crystal growth and initial supersaturation maintained for more than 8 h; PVP-K12 + HPMCAS and PVP-K29/32 + HPMCAS, no significant desupersaturation | text pdf p.4, p.10; Fig. 2 pdf p.5 |
| R2 | record, measured | CEX concentration (µg/mL) versus time, mean with error bars (triplicate), values read from Fig. 2 — as R1 — sub-table below | Fig. 2 pdf p.5 |
| R6 | record, measured | CEX concentration (µg/mL) versus time from ASDs, mean with error bars (triplicate), values read from Figs. 5-7 — 17.6 mg ASD in 400 mL SPB pH 6.8, 37 °C, 300 rpm, 16 h (P5); medium with or without 5 µg/mL pre-dissolved polymer — sub-table below | Figs. 5-7 pdf p.7-8; text pdf p.5-8 |
| C3 | claim, conclusion, authors: asserted | Cellulosic polymers were more effective than PVP in maintaining supersaturation [rests on: R1, R2, R6] | pdf p.1 |
| C49 | claim, conclusion, authors: asserted ("Interestingly") | The higher tendency of PVP-K12 dispersions to crystallize from solution can be mitigated by adding a small amount of HPMCAS or HPMC to the dispersion [rests on: R6.a, R6.e, R6.g] | pdf p.11 |
| C57 | claim, conclusion, authors: "it is apparent" | The polymer added against crystallization need not be in the dispersion: trace amounts (5 µg/mL) of HPMC and HPMCAS pre-dissolved in buffer effectively inhibit crystallization from CEX:PVP-K12 dispersions [rests on: R6.i-j] | pdf p.11 |

## 2016 Sousa — Supersaturation Potential of Salt, Co-Crystal, and Amorphous Forms of a Model Weak Base · Dissolution / C. Amorphous solubility and LLPS

[2016-almeida-sousa-supersaturation-salt-cocrystal-amorphous-weak-base](../../../cards/2016-almeida-sousa-supersaturation-salt-cocrystal-amorphous-weak-base/paper.html) · Dissolution / C. Amorphous solubility and LLPS · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, measured | apparent un-ionized concentration versus time without polymer (mean ± SD, triplicate) — P11, A1; pH 4.6 citrate, no predissolved polymer; grey band = estimated amorphous solubility ≈11.2-12.5 µg/mL — sub-table below. Text: free base dissolved very slowly to a plateau at the crystalline solubility, its UV value similar to the HPLC equilibrium solubility (~1.5 µg/mL); co-crystal, glass, HCl and HBr salts dissolved much faster, reached their maximum in less than 30 min and then decreased, never reaching the band; glass never exceeded 4 µg/mL; the ASD was the only form above the band | Fig. 5, pdf p.6; text pdf p.7 |
| R9 | record, measured | apparent un-ionized concentration versus time with 20 µg/mL predissolved HPMC (mean ± SD, triplicate) — P11, A1, A2; pH 4.6 citrate + 20 µg/mL HPMC; ASD data from buffer without polymer, added for comparison (caption); grey band ≈11.2-12.5 µg/mL — sub-table below. Text: co-crystal, glass, HBr and HCl salts dissolved initially at a similar rate but reached different maxima; crystallization induction time differed between the triplicate runs and the error bars widen after the maximum | Fig. 6, pdf p.7; text pdf p.8 |
| R10 | record, measured | choice of crystallization inhibitor for the medium — P17 — HPMC selected for its ability to delay crystallization significantly and its solubility at pH 4.6; HPMC above 20 µg/mL gave no significant further delay of crystallization; data not shown | pdf p.7 |
| C25 | claim, mechanism, authors: asserted ("Clearly"; "significantly") | HPMC in the ASD is important: it facilitated dissolution and delayed crystallization from the supersaturated solution and/or the dissolving matrix, giving a higher maximum and a larger AUC than the other forms [rests on: R8; cited: ref 36] | pdf p.7 |
| C27 | claim, conclusion, authors: asserted | Among the polymers tested, HPMC delayed crystallization significantly and is soluble at pH 4.6; concentrations above 20 µg/mL gave no significant improvement [rests on: R10] | pdf p.7 |
| C44 | claim, conclusion, authors: asserted ("clearly essential") | A crystallization inhibitor is essential for CRH1 salts or co-crystals to yield supersaturated solutions [rests on: R8, R9] | pdf p.10 |

## 2016 Indulkar — Exploiting the phenomenon of liquid-liquid phase separation for enhanced and sustained membrane transport of a poorly water soluble drug · Bioperformance / Bioperformance

[2016-indulkar-llps-nanodroplet-reservoir-membrane-transport](../../../cards/2016-indulkar-llps-nanodroplet-reservoir-membrane-transport/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| P7 | method | diffusion set 2 (16 h) | p.8-9; Fig. 4B |
| M3 | material | HPMC-606 (hydroxypropyl methylcellulose-606) Shin-Etsu Chemical Co. Ltd. (Tokyo, Japan) | p.5, p.9 |

## 2016 Jackson — Characterization of Supersaturated Danazol Solutions – Impact of Polymers on Solution Properties and Phase Transitions · Dissolution / D. Crystallization from solution

[2016-jackson-supersaturated-danazol-polymer-phase-transitions](../../../cards/2016-jackson-supersaturated-danazol-polymer-phase-transitions/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R16 | record, measured | UV apparent concentration versus time (μg/mL) — 15 μg/mL added danazol; no polymer or 10 μg/mL polymer (P10) — all ≈, read from Fig. 6: DNZ only falls from ≈15 within the first minutes to ≈6 at ≈20 min, ≈2 at ≈40 min and ≈0.7 at ≈90 min (end of trace); PVP ≈14 until ≈100 min, ≈13 at 120 min, ≈6 at ≈180 min, ≈3.4 at ≈230 min, ≈2.3 at ≈390 min (end of trace); HPMC ≈14.7 at start, ≈13.8 at 120 min, ≈7 at ≈270 min, ≈4 at ≈420 min, ≈2.8 at 600 min; HPMCAS ≈14.3 at start, ≈13 at 240 min, ≈9 at ≈360 min, ≈6.6 at ≈400 min, ≈3.8 at 600 min | Fig. 6, pdf p.7 |
| R17 | record, measured | average crystallization induction time (min) — 15 μg/mL danazol, 25 °C buffer, polymer 0-1000 μg/mL (P10); n and error-bar definition not stated — sub-table below; text: danazol without polymer crystallizes within 10-15 min; with polymer, crystallization inhibited for 30 min to 6 h; at 10 μg/mL and above HPMCAS much more effective than PVP and HPMC; 10 → 1000 μg/mL no further extension | Fig. 7, pdf p.7; text pdf p.7 |
| C21 | claim, conclusion, authors: asserted | All three polymers prolong supersaturation, to different extents; PVP is the least effective and HPMCAS is highly effective at preventing crystallization [rests on: R16, R17] | pdf p.7 |
| C23 | claim, conclusion, authors: asserted ("clear") | At 10 μg/mL and above the polymers differ clearly, HPMCAS being much more effective than PVP and HPMC [rests on: R17] | pdf p.7 |
| C46 | claim, generalisation, authors: asserted ("extremely small"); "fairly minimal" | The largest gain in inhibition comes from raising polymer from 1 to 10 μg/mL, with fairly minimal further gains up to 1 mg/mL; extremely small polymer quantities suffice, even with a drug-rich phase present [rests on: R17] | pdf p.10-11 |
| C52 | claim, conclusion, authors: conclusion: asserted ("dramatically"); abstract: "to some extent" | The dissolved polymers dramatically improve the stability of supersaturated solutions against crystallization, with inhibition from 1 μg/mL [rests on: R17] | pdf p.1, p.11 |

## 2016 Li — A Comparison of the Crystallization Inhibition Properties of Bile Salts · Dissolution / D. Crystallization from solution

[2016-li-crystallization-inhibition-properties-bile-salts](../../../cards/2016-li-crystallization-inhibition-properties-bile-salts/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | nucleation induction time (min, mean ± SD, triplicate) with 0.1% (w/v) bile salt at 37 °C — P4; COX 20, NVP 800, FLB 45 µg/mL; media pH as in R1 — sub-table below; ">16hr" as printed; ** = insoluble compounds formed; * = footnote on ionization (wording in C18); source shading marks the six bile salts abundant in human bile (rows h-j, l-n) | Table 4, p.45; text p.15-16 |
| C2 | claim, conclusion, authors: abstract: "Most"; results: "It is apparent"; conclusions: "to some extent"; TOC: "Several ... very effective" | Most bile salts extended the nucleation induction times of the three drugs relative to the bile-salt-free controls; exceptions: SGDC and STDC for COX, SLC for NVP (insoluble particles), STDC for FLB, and SDC, SCDC, SLC formed insoluble particles with FLB [rests on: R6, R4] | p.2, p.15-16, p.30, p.54 |
| C3 | claim, generalisation, authors: abstract: asserted; results: "appear to vary greatly"; conclusions: asserted | The inhibitory effects vary with the structure (and, abstract, the concentration) of both the bile salt and the drug; the same bile salt acts differently on different drugs, e.g. SC good for COX but modest for NVP and FLB [rests on: R6, R8, R10] | p.2, p.16, p.30 |
| C21 | claim, conclusion, authors: asserted | Most effective inhibitors: for COX SDC and STCDC, then SC and SGC; for NVP SHDC and SDC, then STCDC, then SCDC and SGC; for FLB STCDC, SHDC, SGUDC and SGC [rests on: R6] | p.16 |

## 2016 Mosqueragiraldo — Mechanistic Design of Chemically Diverse Polymers with Applications in Oral Drug Delivery · Dissolution / D. Crystallization from solution

[2016-mosquera-giraldo-chemically-diverse-cellulose-polymers-telaprevir-crystallization](../../../cards/2016-mosquera-giraldo-chemically-diverse-cellulose-polymers-telaprevir-crystallization/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | nucleation induction time (min), commercial polymers, values read from Fig. 2a (n = 3) — pH 6.8, 100 mM phosphate, 37 °C (P7) — sub-table below; text: at 80 µg/mL TPV HPMC and HPMCAS held supersaturation for more than 700 min; at 150 µg/mL HPMCAS longer at 50 than at 5 µg/mL; HPMC unchanged between 5 and 50 µg/mL | Fig. 2a, p.3663 |
| R5 | record, measured | nucleation induction time (min), cellulose ω-carboxyalkanoates and CP-Tod-202, values read from Fig. 2b (n = 3; polymers ordered from high to low SP) — as R4 — sub-table below | Fig. 2b, p.3663 |
| R6 | record, measured | nucleation induction time (min), chemically diverse polymers, values read from Fig. 2c (n = 3) — 150 µg/mL TPV, 5 µg/mL polymer, pH 6.8, 37 °C (P7) — sub-table below; graphical abstract repeats rows a, g, h (≈15, ≈90, ≈12 min; arrows "t ~ 90 min" and "t ~ 12 min") | Fig. 2c, p.3663; graphical abstract, p.3659 |
| C61 | claim, conclusion, authors: abstract: asserted ("show that the only effective polymers"); conclusion: "it was concluded" | The only effective polymers contained carboxylate groups combined with an optimal hydrocarbon chain length [rests on: R5, R6, R7] | p.3659, p.3669-3670 |

## 2016 Tian — Investigating the Correlation between Miscibility and Physical Stability of Amorphous Solid Dispersions Using Fluorescence-based Techniques · Solid state stability / Physical stability

[2016-tian-indomethacin-polymer-miscibility-physical-stability-fluorescence](../../../cards/2016-tian-indomethacin-polymer-miscibility-physical-stability-fluorescence/paper.html) · Solid state stability / Physical stability · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C4 | claim, mechanism, authors: introduction: "is anticipated"; discussion: "would be anticipated" | Above the miscibility limit amorphous-amorphous phase separation is thermodynamically favoured and forms a drug-rich phase; with less polymer in that phase, crystallization inhibition is less effective, so crystallization occurs more readily, lowering dissolution performance and bioavailability [rests on: cited: refs 4, 12, 13; argument only] | p.3, p.21 |
| C39 | claim, prior hypothesis, authors: asserted | A miscible ASD is a homogeneous single amorphous phase mixed at the molecular level; it keeps the drug amorphous by kinetic inhibition of crystallization although it is metastable with respect to the crystal [rests on: cited: ref 19] | p.21 |
| C57 | claim, mechanism, authors: conclusion: asserted ("led to"); abstract: "suggesting" | Drug-rich domains formed above the miscibility limit led to enhanced susceptibility to crystallization, whereas homogeneous dispersions resisted crystallization for long periods [rests on: R17, R21] | p.2, p.25 |

## 2017 Elkhabaz — Variation in the Supersaturation and Phase Behavior of Ezetimibe Amorphous Solid Dispersions Upon Dissolution in Different Biorelevant Media · Bioperformance / Bioperformance

[2017-elkhabaz-ezetimibe-asd-phase-behavior-biorelevant-media](../../../cards/2017-elkhabaz-ezetimibe-asd-phase-behavior-biorelevant-media/paper.html) · Bioperformance / Bioperformance · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | nucleation induction time (min; n = 3) — P5; pH 6.8 buffer, ezetimibe 21 µg/mL, 37 °C — sub-table below; text: PAA (10 or 100 µg/mL) did not delay the onset of crystallization | Fig. 4A, p.12; text p.10-11 |
| R7 | record, measured | nucleation induction time (min; n = 3; 350 nm scattering only) — P5; FeSSIF, ezetimibe 123 µg/mL, 37 °C — sub-table below; text: 50 µg/mL HPMC-AS inhibited crystallization completely for up to 6 hours | Fig. 4B, p.12; text p.11 |
| C35 | claim, conclusion, authors: "seemed to be highly dependent on the medium employed" | The relative effectiveness of PVP and HPMC-AS and the resulting supersaturation profiles depend on the medium: PVP gave the greatest crystallization inhibition in buffer, HPMC-AS was more efficient (particularly against nucleation) in FeSSIF [rests on: R6, R7, R14] | p.24 |
| C46 | claim, mechanism, authors: "appeared to be" | HPMC-AS is an effective crystallization inhibitor in the presence of the drug-rich colloidal phase of ezetimibe, and FeSSIF components did not reduce its inhibition as they did for PVP; despite desupersaturation after 2 h the HPMC-AS ASD gave better concentration-time profiles than the others [rests on: R14, R7, R18] | p.26 |

## 2017 Hate — Absorptive Dissolution Testing of Supersaturating Systems: Impact of Absorptive Sink Conditions on Solution Phase Behavior and Mass Transport · Bioperformance / Bioperformance

[2017-hate-absorptive-dissolution-supersaturating-systems](../../../cards/2017-hate-absorptive-dissolution-supersaturating-systems/paper.html) · Bioperformance / Bioperformance · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | nucleation induction time — nevirapine 500 µg/mL (P2) — no polymer: around 5 min; 0.05% HPMC-AS: crystallization inhibited for more than 4 h; 0.1% PVPVA: crystallization at around 60 min; n not stated | p.15 |
| R9 | record, measured | crystals in donor samples — dissolution-absorption runs (P7, P9) — powder without polymer: crystals seen by polarized light microscopy after the pH shift; HPMC-AS arms: no crystals observed in the donor for up to 160 min (p.20); powder + HPMC-AS: no crystallization observed for 4 h (p.28); tablet + HPMC-AS: crystallization inhibited for only 120 min (p.29; run type not specified) | p.20, p.28-29 |
| C13 | claim, conclusion, authors: asserted; PVPVA: "some impact" | Nevirapine at 500 µg/mL (S 3.9) crystallizes within minutes; 0.05% HPMC-AS inhibits crystallization for more than 4 h, and 0.1% PVPVA has some inhibitory effect [rests on: R2] | p.15, p.24 |
| C46 | claim, mechanism, authors: "expected"; asserted | With HPMC-AS both powder and tablet were expected to sustain supersaturation; the powder showed no crystallization for 4 h, a slower decline and a higher Cmax than without polymer, where drug was lost to crystallization as well as transport [rests on: R2, R7, R8, R9] | p.28 |

## 2017 Lu — Impact of Bile Salts on Solution Crystal Growth Rate and Residual Supersaturation of an Active Pharmaceutical Ingredient · Dissolution / D. Crystallization from solution

[2017-lu-bile-salts-telaprevir-crystal-growth-residual-supersaturation](../../../cards/2017-lu-bile-salts-telaprevir-crystal-growth-residual-supersaturation/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, derived (E3) | E_C at δ 12.5 — P2; five bile salts at 1.86 and 12 mM; sub-table below — values read from Fig. 5(b) only | Fig. 5(b) pdf p.27 |
| R9 | record, derived (E3) | R₀/R at δ 7.9, 1.86 mM — P2; sub-table below — δ 2.4 and δ 12.5 bars of Fig. 7 equal the 1.86 mM values of R7 and R8; STC across δ 2.4 → 7.9 → 12.5: ≈3.2 → ≈9.8 → ≈14.4 (read from Fig. 7) | pdf p.13; Fig. 7 pdf p.29 |
| C19 | claim, conclusion, authors: asserted | At δ 12.5 the bile salts follow a similar pattern of inhibition: monomeric STCDC remains the most effective inhibitor of combined growth and secondary nucleation, and SGC, STDC and SGDC inhibit comparably at both concentrations. [rests on: R8, R10] | pdf p.12 |
| C47 | claim, generalisation, authors: asserted | Bile salts are not interchangeable from a crystallization-inhibition standpoint. [rests on: R7, R8, R12, R14] | conclusions pdf p.18 |

## 2017 Lu — Maintaining Supersaturation of Active Pharmaceutical Ingredient Solutions with Biologically Relevant Bile Salts · Dissolution / D. Crystallization from solution

[2017-lu-bile-salts-telaprevir-supersaturation](../../../cards/2017-lu-bile-salts-telaprevir-supersaturation/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | t_ind at δ = 11.5 (min; mean ± SD, n = 3; ">960" = no crystallization detected within 960 min, bar drawn at 960) — buffer or 1.86 or 12 mM bile salt (P2, P3) — sub-table below; text: buffer crystallized within 30 minutes ("~30 minutes", pdf p.15); at 1.86 mM no crystallization over 16 hours and no visible crystals under cross-polarized light; at 12 mM STDC, SGDC and STCDC crystallized at "about 2 hours" | Fig. 4, pdf p.28; same values in Figs. 8, 9, 13; text pdf p.10-11 |
| R4 | record, measured | t_ind at δ = 28.8 (min; mean ± SD, n = 3) — solutions containing a telaprevir-rich amorphous phase; buffer or 1.86 or 12 mM bile salt (P2, P3) — sub-table below; buffer labelled "Immediately"; STCDC and SGCDC not reported (δ 28.8 not reached, R1.b, R1.c, R1.f); text: crystallized much faster than the homogeneous solutions | Fig. 5, pdf p.28-29; same values in Figs. 8, 9, 13; text pdf p.11 |
| R6 | record, measured | t_ind versus STC concentration below the CMC (min; mean ± SD; ">720" = no event within 720 min) — 60 µg/mL telaprevir, δ 11.5 (P4) — sub-table below; text: 0.47 mM STC ("less than 0.025% (w/w)") changed t_ind from within 30 minutes to "approximately 3 hours" | Fig. 7, pdf p.30; text pdf p.12 |
| R11 | record, measured | t_ind with HPMCAS-MF (min; mean ± SD, n = 3) — HPMCAS-MF 5 µg/mL or 1 mg/mL, δ 11.5 and 28.8 (P3) — sub-table below; buffer and 1.86 mM bile salt bars in the same figure repeat R3.a-e and R4.a-e | Fig. 13, pdf p.33; text pdf p.21-22 |
| C28 | claim, conclusion, authors: abstract: asserted; discussion: "it is evident"; summary: "suggest"; conclusions: "extremely effective" | Monomeric bile salts are effective crystallization inhibitors for telaprevir, extremely effective below the amorphous solubility, as also noted in earlier studies [rests on: R3, R6; cited: refs 11-13] | pdf p.3, p.16, p.20, p.22 |
| C47 | claim, conclusion, authors: asserted | Monomeric bile salts inhibited comparably to HPMCAS-MF in homogeneous solutions, where all additives were extremely effective; with a drug-rich phase HPMCAS-MF was better than the least effective bile salt but not as effective as the best; celecoxib studies likewise show comparable inhibition by bile salts and polymers [rests on: R11, R3, R4; cited: refs 10, 13, 50] | pdf p.21-22 |

## 2017 Tres — Monitoring the Phase Behavior of Supersaturated Solutions of Poorly Water-Soluble Drugs Using Fluorescence Techniques · Characterization methods / Solution methods

[2017-tres-fluorescence-supersaturated-drug-phase-behavior](../../../cards/2017-tres-fluorescence-supersaturated-drug-phase-behavior/paper.html) · Characterization methods / Solution methods · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| M5 | material | polymer printed as "Hydroxypropyl methylcellulose (HPMC) AS-MF grade" Shin-Etsu Chemicals (Niigata, Japan) | pdf p.8 |
| P1 | method | solvent-shift supersaturated solution for fluorescence | pdf p.8; Tables 1, 3, 4 pdf p.32, p.34-35 |

## 2017 Xie — Impact of Eudragit EPO and Hydroxypropyl Methylcellulose on Drug Release Rate, Supersaturation, Precipitation Outcome and Redissolution Rate of Indomethacin Amorphous Solid Dispersions · Dissolution / B. Supersaturation from ASD dissolution

[2017-xie-eudragit-epo-hpmc-indomethacin-asd-supersaturation-redissolution](../../../cards/2017-xie-eudragit-epo-hpmc-indomethacin-asd-supersaturation-redissolution/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | A319 and E450 versus time after the 16 min addition — as R4, 240 min — text: high supersaturation held for about 1.5 h, then absorbance decreased and extinction changed; figure: plateau A319 ≈2.5, A319 − E450 ≈2.2, E450 ≈0.33 from ≈16 to ≈110 min; at 240 min A319 ≈0.52, A319 − E450 ≈0.32, E450 ≈0.20 (read from Fig. 2 right) | Fig. 2 right, pdf p.27; text pdf p.12 |
| R8 | record, measured | A319 and E450 during stock addition and over time with EPO alone — EPO 100 µg/mL, pH 2.2, 37 °C (P4) — text: during injection a simultaneous nonlinear increase in extinction and decrease in absorbance; numerous very small IND crystals seen by eye; UV absorption much higher than expected for a solution at the crystalline solubility; LLPS onset not determinable (Table 3 "NA"); figure: A319 linear to ≈70 µg/mL, maximum ≈1.33 near ≈77 µg/mL, ≈1.31 at 80; E450 rises from ≈65 µg/mL to ≈0.14 at 80; over time A319 peaks ≈1.33 at ≈16 min, falls to ≈0.8 by ≈25 min, then ≈0.76-0.84 to 240 min; E450 ≈0.33-0.42 from ≈17 min (read from Fig. 4) | Fig. 4, pdf p.28; text pdf p.13 |
| R10 | record, measured | UV apparent IND concentration, two-stage dissolution pH 2.2 → 5 (µg/mL) — P7 sub-table formulations; 50 mL pH 2.2 → 100 mL pH 5 at 60 min; 37 °C, 300 rpm — sub-table below | Fig. 5, pdf p.29 |
| R13 | record, measured | acid-stage course of IND:HPMC ASDs — R10.c-e — release rate increased as drug loading decreased; 30% DL: supersaturation rose gradually, no crystallization during the experiment; 10% DL: biphasic profile, fast initial rate then much slower, concentration reaching about the amorphous solubility by 60 minutes ("appeared to just reach"); 30% and 50% DL: concentrations well below the amorphous solubility before the shift | text pdf p.14 |
| C1 | claim, conclusion, authors: abstract: "could maintain"; results: asserted | At acidic pH HPMC maintained IND supersaturation by effectively inhibiting solution crystallization [rests on: R3, R5, R10.c-e, R13] | pdf p.3, p.12 |
| C2 | claim, conclusion, authors: asserted | EPO increased both the crystalline and the amorphous solubility of IND but did not inhibit crystallization [rests on: R1, R2, R3, R8, R11] | pdf p.3, p.12-13 |

## 2017 Xie — Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib · Solid state stability / Physical stability

[2017-xie-temperature-moisture-celecoxib-binary-ternary-asd-stability](../../../cards/2017-xie-temperature-moisture-celecoxib-binary-ternary-asd-stability/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R22 | record, measured | crystallinity by PXRD after storage at 80 °C/0% RH — 80% DL: 8:2 binaries and 8:1.6:0.4 ternaries (P5 row a) — text: CEX:PVP-K29/32, CEX:PVP/VA and the ternaries with PVP and a small amount of HPMCAS or HPMC show signs of crystallization only after ~120 days; CEX:HPMCAS and CEX:HPMC show crystallinity after 6 days; figure at 6 days: halo only for CEX:PVP/VA, CEX:PVP-K29/32:HPMC, CEX:PVP-K29/32:HPMCAS and CEX:PVP-K29/32; sharp peaks on the halo for CEX:HPMCAS (strongest) and CEX:HPMC | Fig. 9a, p.9; text p.7 |
| R23 | record, measured | crystallinity by PXRD after storage at RT/94% RH — 60% DL: 6:4 binaries and 6:3.5:0.5 ternaries (P5 row f) — text: CEX:PVP/VA amorphous for up to 150 days and crystallized thereafter; CEX:HPMCAS stable for up to 115 days; binary ASDs with HPMC or PVP and the PVP-major ternaries show some diffraction peaks within a month; figure at 28 days: strong sharp peaks for CEX:PVP-K29/32:HPMC 6:3.5:0.5 (largest near ≈15, ≈16, ≈18-19.7, ≈21.5, ≈22.3, ≈23.4, ≈25.4 and ≈29.6° 2θ), smaller clear peaks for CEX:PVP-K29/32 6:4, weak features for CEX:PVP-K29/32:HPMCAS 6:3.5:0.5, at most faint features for CEX:HPMC 6:4, halo only for CEX:PVP-K12 6:4, CEX:HPMCAS 6:4 and CEX:PVP/VA 6:4 (read from Fig. 9b) | Fig. 9b, p.9; text p.8 |
| R24 | record, measured | crystallinity by PXRD after storage at 40 °C/75% RH — 80% DL: 8:2 binaries and the 8:1.6:0.4 HPMCAS ternary (P5 row g) — text: crystallization at an earlier time point in all systems (comparator not stated); CEX:PVP/VA 8:2 amorphous for up to 4 months; CEX:HPMCAS stable for up to 33 days, crystallization detected thereafter; CEX:PVP-K29/32 and the corresponding ternary amorphous for up to 70 days; figure at 33 days: halo only for CEX:PVP/VA, CEX:PVP-K29/32:HPMCAS and CEX:PVP-K29/32; small sharp features on the halo of CEX:HPMCAS 8:2 near ≈18.5-21.5, ≈23.5, ≈25.3 and ≈29.5° 2θ (read from Fig. 9c) | Fig. 9c, p.9; text p.8 |
| C38 | claim, conclusion, authors: asserted | At 80 °C/0% RH and 80% DL the most stable ASDs were CEX:PVP-K29/32, CEX:PVP/VA and the PVP ternaries with a little HPMCAS or HPMC, and the least stable were CEX:HPMCAS and CEX:HPMC [rests on: R22] | p.7 |
| C41 | claim, conclusion, authors: asserted | At RT/94% RH and 60% DL CEX:PVP/VA was the most stable binary ASD, CEX:HPMCAS next, and the binaries with HPMC or PVP and the PVP-major ternaries were much less stable [rests on: R23] | p.8 |
| C42 | claim, conclusion, authors: asserted ("Interestingly") | At 40 °C/75% RH crystallization occurred earlier in all systems; CEX:PVP/VA 8:2 was the most stable, and CEX:PVP-K29/32 and its ternary outperformed CEX:HPMCAS [rests on: R24] | p.8 |

## 2018 Dening — Supersaturation Potential of Ordered Mesoporous Silica Delivery Systems. Part 1: Dissolution Performance and Drug Membrane Transport Rates · Mesoporous silica / Mesoporous silica

[2018-dening-ordered-mesoporous-silica-supersaturation-dissolution-flux](../../../cards/2018-dening-ordered-mesoporous-silica-supersaturation-dissolution-flux/paper.html) · Mesoporous silica / Mesoporous silica · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| M4 | material | hydroxypropyl methylcellulose (HPMC) Pharmacoat 606; Shin-Etsu Chemical Co. Ltd. (Tokyo, Japan) | p.3490 |
| R3 | record, measured | amorphous solubility of ritonavir with SBA-15 or HPMC present — P2; 100 µg/mL SBA-15 or 5 µg/mL HPMC; pH 6.8 buffer, 37 °C — with SBA-15: 27.5 ± 0.1 µg/mL, not significantly different (p > 0.05) from 27.9 ± 0.3 µg/mL (M1); with HPMC: no impact (value not printed) | p.3492 |
| P12 | method | side-by-side diffusion cell | p.3491, p.3493, p.3496 |

## 2018 Indulkar — Crystallization from Supersaturated Solutions: Role of Lecithin and Composite Simulated Intestinal Fluid · Dissolution / D. Crystallization from solution

[2018-indulkar-lecithin-composite-sif-crystallization-supersaturation](../../../cards/2018-indulkar-lecithin-composite-sif-crystallization-supersaturation/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R16 | record, measured | NIT of atazanavir versus lecithin (min) — 3 mM STC with 0 to 0.75 mM lecithin (P2), pH 6.5 buffer reference; initial concentration = amorphous solubility of each medium; 37 °C (P9) — sub-table below; text: 170 min in buffer; up to 600 min in STC alone; NIT decreases as lecithin rises | Fig. 6, p.9; text p.7 |
| R18 | record, measured | NIT of atazanavir in single bile salts with lecithin (min) — 3 mM bile salt with 0.75 mM lecithin (P3); initial concentration = amorphous solubility; 37 °C (P9) — sub-table below; caption: ~170 min without additives | Fig. 7, p.9 |
| R20 | record, measured | NIT in Composite-SIF and FaSSIF-V1 (min) — four drugs at the amorphous solubility of each medium, 37 °C (P9) — sub-table below | Fig. 8, p.9 |
| C20 | claim, conclusion, authors: asserted; discussion: "highlights" | STC alone is an effective crystallization inhibitor of atazanavir (NIT prolonged, inhibition up to 600 min); adding lecithin shortens NIT, more so at higher lecithin; lecithin as low as 0.01 mM diminishes the STC effect and higher lecithin makes it worse than buffer alone; abstract: crystallization was accelerated as lecithin rose [rests on: R16] | p.1, p.7, p.11 |
| C22 | claim, conclusion, authors: "It is evident" | Single bile salts with lecithin differ in their effect on atazanavir nucleation: chenodehydroxy salts (SGCDC, STCDC) give the longest NIT, then dehydroxy salts (SGDC, STDC), trihydroxy salts (SGC, STC) the shortest [rests on: R18] | p.8, p.12 |
| C23 | claim, conclusion, authors: "readily apparent"; abstract: asserted | NITs of atazanavir, ritonavir and tacrolimus are longer in Composite-SIF than in FaSSIF-V1, so supersaturation is maintained longer, at equivalent supersaturation ratios (abstract); no significant difference for cilnidipine [rests on: R20, R12] | p.1, p.8, p.12 |

## 2018 Li — Tailoring supersaturation from amorphous solid dispersions · Dissolution / B. Supersaturation from ASD dissolution

[2018-li-tailoring-supersaturation-lopinavir-insoluble-polymer-asd](../../../cards/2018-li-tailoring-supersaturation-lopinavir-insoluble-polymer-asd/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | LPV concentration versus time without crystallization inhibitor (μg/mL; mean with error bars) — 50% DL ASD films, amorphous LPV film (P4), pH 3 buffer without HPMC, 25 °C (P6) — sub-table below (all values ≈, read from Fig. 3; "–" = no point plotted; the LPV curve is the same in panels A-C) | Fig. 3, p.118 |
| R7 | record, measured | matrix appearance under polarized light — 50% DL ASD particles and amorphous LPV in pH 3 buffer without HPMC (P7) — sub-table below (circled regions are drawn in the figure without explanation in the caption); text: EUD and CAP least effective at inhibiting matrix crystallization; HPMCP no crystallization | Fig. 4, p.119; text p.118 |
| C25 | claim, conclusion, authors: asserted | The 50% DL systems fall into fast, intermediate and slow crystallization despite different supersaturation: EUD and CAP are poor inhibitors whose supersaturation is short-lived and which crystallize in a similar time frame to amorphous LPV; HPMCAS, CA and EC retained supersaturation for 12 h, longer than amorphous LPV; HPMCP ASDs did not crystallize during the experiment, with a lower but protracted supersaturation [rests on: R6] | p.118 |
| C26 | claim, conclusion, authors: asserted ("Similar trends") | Matrix crystallization followed the solution trends: EUD and CAP least effective inhibitors, HPMCP ASDs no crystallization [rests on: R7] | p.118 |
| C69 | claim, conclusion, authors: asserted ("was also found to be highly dependent") | Crystallization stability of the ASDs suspended in aqueous media depends strongly on these factors, on the level of supersaturation generated and on the polymer's effectiveness as a solution crystallization inhibitor [rests on: R6, R7] | p.125 |

## 2018 Lu — Compositional Effect of Complex Biorelevant Media on the Crystallization Kinetics of an Active Pharmaceutical Ingredient · Dissolution / D. Crystallization from solution

[2018-lu-biorelevant-media-telaprevir-crystallization-kinetics](../../../cards/2018-lu-biorelevant-media-telaprevir-crystallization-kinetics/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibitor

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | crystallization induction time (min; values ≈, read from Fig. 7; error bars as drawn) — δ = 28.8 (GLPS), 37 °C, 150 µg/mL predissolved HPMCAS-MF unless stated (P2) — sub-table below | Fig. 7, pdf p.26; text pdf p.14 |
| R9 | record, measured | crystallization induction time (min; values ≈, read from Fig. 8; error bars as drawn) — δ = 28.8 (GLPS), 37 °C, 150 µg/mL HPMCAS-MF in all media (P2) — sub-table below; rows a, b and d agree with Fig. 7 rows b, c and e within reading | Fig. 8, pdf p.26-27; text pdf p.15-16 |
| C33 | claim, prior hypothesis, authors: asserted | Whether an effective polymeric inhibitor overrides the media differences is an important question; HPMCAS-MF is one of the most potent polymeric inhibitors of telaprevir crystallization [rests on: cited: ref 9; R16] | pdf p.14 |
| C36 | claim, conclusion, authors: asserted ("it is apparent") | At its amorphous solubility telaprevir is highly unstable in buffer and crystallizes immediately; with HPMCAS-MF the solution containing a telaprevir-rich second phase can be stabilized for more than 6 hours [rests on: R7.a-e] | pdf p.14 |

## 2018 Mosqueragiraldo — Crystallization Inhibition Properties of Cellulose Esters and Ethers for a Group of Chemically Diverse Drugs - Experimental and Computational Insight · Dissolution / D. Crystallization from solution

[2018-mosquera-giraldo-cellulose-esters-ethers-crystallization-inhibition-computational-insight](../../../cards/2018-mosquera-giraldo-cellulose-esters-ethers-crystallization-inhibition-computational-insight/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | nucleation induction time (min), bar height and error bar (± half-length; error type not stated), n = 3 — nine drugs at the P4 concentrations, pH 6.8, 100 mM phosphate buffer, 37 °C, 300 rpm, without polymer or with 5 µg/mL A5a or A5b; broken y axis (lower part 0 to ≈130, upper part 160 to 300) — sub-table below; text: A5a longer than A5b for all nine drugs; TOC graphic prints the atazanavir values 40 (no polymer), >300 (A5a) and 65 (A5b) | Fig. 4, p.15-16; text p.15; TOC p.36 |
| R2 | record, measured | nucleation induction time (min), bar height and error bar (± half-length; error type not stated), n = 3 — as R1, without polymer or with 5 µg/mL ECA, ECB or ECD; continuous y axis 0-350 — sub-table below | Fig. 5, p.16; text p.15, p.25-26 |
| C48 | claim, conclusion, authors: asserted ("strongly influenced") | Small changes in the chemical structure of the polymer strongly influenced its ability to inhibit crystallization [rests on: R1, R2] | p.30 |

## 2018 Mosqueragiraldo — Influence of Polymer and Drug Loading on the Release Profile and Membrane Transport of Telaprevir · Bioperformance / Bioperformance

[2018-mosquera-giraldo-telaprevir-asd-polymer-loading-release-membrane-transport](../../../cards/2018-mosquera-giraldo-telaprevir-asd-polymer-loading-release-membrane-transport/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R24 | record, cited | TPV crystallization inhibition by the polymers in induction-time experiments — ref 25 — HPMCAS, HPMC and CA Sub highly effective; PVPVA less effective; CA Sub good solution crystallization inhibition | p.12, p.18 |
| C55 | claim, mechanism, authors: "can be attributed"; "possible" | The poor performance of the PVPVA ASDs is attributed to possible solid-state phase separation between polymer and drug and to PVPVA being a weak solution crystallization inhibitor because its hydrophilicity favours interaction with water rather than with hydrophobic TPV [rests on: R22, R23, R24] | p.26 |
| C61 | claim, generalisation, authors: asserted ("strongly") | Polymer selection strongly affects drug-polymer interactions, giving different release profiles, different inhibition of crystallization in the matrix and in solution, complex formation and polymer-drug mixing in the drug-rich phase [rests on: R5, R8, R13, R14, R22] | p.28 |

## 2018 Sugihara — Evaluation of Pazopanib Phase Behavior Following pH-induced Supersaturation · Dissolution / C. Amorphous solubility and LLPS

[2018-sugihara-pazopanib-ph-induced-supersaturation-phase-behavior](../../../cards/2018-sugihara-pazopanib-ph-induced-supersaturation-phase-behavior/paper.html) · Dissolution / C. Amorphous solubility and LLPS · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R21 | record, measured | intestinal apparent concentration versus time, intermediate dose at four HPMC levels — P6; 0, 5, 20, 50 µg/mL HPMC — 0 and 50 µg/mL traces as R13 and R12. 5 µg/mL: maximum ≈19 µg/mL at ≈28 min, ≈10 at ≈32 min, ≈1 at ≈55 min, ≈0.16 at 200 min. 20 µg/mL: ≈25 µg/mL from ≈20 to ≈33 min, ≈10 at ≈41 min, ≈1 at ≈71 min, ≈0.18 at 200 min (read from Fig. 8a). Text: even 5 µg/mL HPMC gave notable improvement | Fig. 8a, p.45; text p.18-19 |
| R22 | record, measured | supersaturation maintenance (text: induction time) versus HPMC concentration in the intestinal compartment, intermediate dose — criterion, n and error-bar type not stated — sub-table below; text: approximately 8-fold prolongation at the highest HPMC concentration | Fig. 8b, p.45; text p.19 |
| C32 | claim, conclusion, authors: asserted ("Interestingly"; "notable") | Without HPMC crystallization is very rapid; even 5 µg/mL HPMC notably improves the supersaturation profile, and the highest HPMC concentration prolongs the induction time about 8-fold [rests on: R21, R22] | p.19 |
| C39 | claim, conclusion, authors: asserted ("clearly") | HPMC clearly extends the supersaturation duration and is an effective crystallization inhibitor both with and without amorphous pazopanib particles; it also lowers the rate of desupersaturation [rests on: R12, R13, R18, R19, R21, R22] | p.25-26 |

## 2019 Elkhabaz — Characterization of Phase Transformations for Amorphous Solid Dispersions of a Weakly Basic Drug upon Dissolution in Biorelevant Media · Dissolution / B. Supersaturation from ASD dissolution

[2019-elkhabaz-posaconazole-asd-phase-transformations-biorelevant-media](../../../cards/2019-elkhabaz-posaconazole-asd-phase-transformations-biorelevant-media/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: asserted; "not fully understood" | Polymers such as HPMC and HPMC-AS delay crystallization by acting on nucleation and/or crystal growth; the mechanisms are not fully understood; in the ASD matrix polymers can raise Tg, lower molecular mobility and hydrogen-bond the drug [rests on: cited: refs 5, 20-23] | p.2 |
| C52 | claim, generalisation, authors: "suggests"; "potentially" | HPMC-AS in itself is potentially an effective solution-crystallization inhibitor for posaconazole when matrix crystallization is absent and the polymer is soluble in the medium [rests on: R6, R7] | p.14-15 |
| C53 | claim, recommendation, authors: "suggest"; "should be assessed" | The crystallization-inhibiting ability of ASD polymers should be assessed in different environments, varying drug and polymer ionization by pH and evaluating crystallization from both the matrix and supersaturated solutions [rests on: argument only] | p.15 |

## 2019 Elkhabaz — Interplay of supersaturation and solubilization: Lack of correlation between concentration-based supersaturation measurements and membrane transport rates in simulated and aspirated human fluids · Bioperformance / Bioperformance

[2019-elkhabaz-supersaturation-solubilization-activity-flux-biorelevant-media](../../../cards/2019-elkhabaz-supersaturation-solubilization-activity-flux-biorelevant-media/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| M3 | material | HPMC-AS MF grade; Shin-Etsu Chemical Co. (Tokyo, Japan) | p.5, p.8, p.9 |
| P6 | method | amorphous solubility by solvent shift and ultracentrifugation | p.8; Table 3, p.11 |
| P9 | method | side-by-side diffusion cell flux | p.9-10, p.14; Figs. 4-5, p.15; Table S1, SI p.1 |
| X10 | extractor note | comparability warning — HPMC-AS (10 µg/mL for atazanavir, 100 µg/mL for posaconazole) was present in the amorphous solubility, fluorescence, SEM (posaconazole) and J_amph experiments but is not stated for the crystalline solubility or J_eq; the no-effect control covers only atazanavir flux in buffer-V1 (R10) — M3, P3, P6, P9, R2, R10, C11 — read amorphous solubilities as values in medium plus dissolved HPMC-AS |  |

## 2019 Indulkar — Impact of monomeric vs. micellar surfactant and surfactant-polymer interactions on nucleation-induction times of atazanavir from supersaturated solutions · Dissolution / D. Crystallization from solution

[2019-indulkar-sds-polymer-hemimicelle-atazanavir-nucleation](../../../cards/2019-indulkar-sds-polymer-hemimicelle-atazanavir-nucleation/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | NIT of ATZ with 1 mg/mL polymer, without and with 0.1 mg/mL SDS — ATZ at SRamorph, 37 °C (P5); bars for "> 1000 min" drawn to 1000 min — text: each polymer alone inhibited crystallization for at least 1000 min; 0.1 mg/mL SDS without polymer reduced onset to 130 min; with SDS, PVPVA 350 min, cellulosic polymers at least 1000 min. Sub-table below (values read from Fig. 4) | Fig. 4, p.22; text p.12 |
| C22 | claim, conclusion, authors: abstract: "lost some of its inhibitory effect"; results: "to some extent", "does not seem", "at least for the experimental duration"; discussion: "substantially reduced (from 1000 to 350 min)", "at least at the concentration ratios employed" | With 0.1 mg/mL SDS the inhibitory effect of PVPVA on crystallization onset decreases, whereas SDS does not seem to affect the cellulosic polymers over the duration studied [rests on: R4] | p.2, p.12, p.16 |
| C23 | claim, conclusion, authors: asserted | Each polymer alone (1 mg/mL) effectively prolongs the crystallization time of ATZ (abstract: inhibited detectable nucleation for >1000 min) [rests on: R4] | p.2, p.12, p.18 |

## 2019 Purohit — Assessing the impact of endogenously derived crystalline drug on the in vivo performance of amorphous formulations · Bioperformance / Bioperformance

[2019-purohit-endogenous-crystallinity-in-vivo-amorphous-tacrolimus](../../../cards/2019-purohit-endogenous-crystallinity-in-vivo-amorphous-tacrolimus/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C1 | claim, prior hypothesis, authors: asserted | ASDs can release drug to supersaturated solutions; the polymer improves wetting and dissolution, which can give concentrations above the crystalline and even the amorphous solubility at low drug load, and it helps reach and keep supersaturation by inhibiting crystallization in the matrix and in solution [rests on: cited: refs 1-10] | p.3 |
| C6 | claim, prior hypothesis, authors: "might be"; "plausible" | Reference crystals come from solvent crystallization under ideal conditions, whereas crystals forming in an ASD matrix form under very different conditions; with crystallization-inhibiting polymers present they might be imperfect or poisoned at growth sites, so it becomes plausible that such endogenously derived crystals behave differently from reference crystals [rests on: cited: refs 13-15] | p.4 |
| C39 | claim, mechanism, authors: "can be explained"; "This provides an explanation" | The lack of crystallization of the maximally crystallized sample can be explained by its low supersaturation and by HPMC from the dosage form being present in the medium; crystallization inhibitors work better at low than at high supersaturation, which explains why HPMC fails for fresh Accord (high supersaturation) but succeeds for the nearly fully crystallized sample [rests on: R4; cited: refs 12, 34-37] | p.13 |

## 2020 Enright — Impact of phospholipid digests and bile acid pool variations on the crystallization of atazanavir from supersaturated solutions · Dissolution / D. Crystallization from solution

[2020-enright-phospholipid-digests-bile-acid-pool-atazanavir-crystallization](../../../cards/2020-enright-phospholipid-digests-bile-acid-pool-atazanavir-crystallization/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, measured | NIT in media with equal lipid fraction and different bile salts (n ≥ 3) — FaSSIFMod, Composite-SIFMod, FaSSIF-V3 — 39 ± 12, 74 ± 11, 23 ± 6; pairwise marks: FaSSIFMod versus Composite-SIFMod *, FaSSIFMod versus FaSSIF-V3 *, Composite-SIFMod versus FaSSIF-V3 *** | Fig. 7(b), p.23; text p.22 |
| R18 | record, measured | NIT in volunteer pools with a fixed lipid fraction (n ≥ 3) — V1-V6 (Table 4) — text only (Fig. 9(b) blank in the supplied file): low group (0.57-2.2 mM) 23-33; high group (3.6-5.1 mM) 112-144; V6 23 ± 2 versus V5 144 ± 19 (6-fold) | text p.24; Fig. 9(b), p.25 |
| R28 | record, measured | NIT of V5 and V6 media with and without HPMC 1 mg/mL (n = 3) — as R27 — without HPMC: V5 134 ± 23, V6 45 ± 7 (V5 versus V6 **); with HPMC: > 360 for both (bars drawn to 360 and labelled "> 360") | Fig. 12(b), p.28; text p.28, p.35 |
| C57 | claim, generalisation, authors: asserted ("were determined") | Bile acids are crystallization inhibitors; mixed tri- and dihydroxy bile acid media prolong supersaturation more than trihydroxy media, cholesterol slightly delays nucleation, phospholipids promote crystallization onset and their digests more so (summary schematic, with in vivo 7α-dehydroxylation of trihydroxy bile acids drawn as the source of the mixture) [rests on: R14, R18, R10, R12] | Fig. 14 caption, p.30 |
| C40 | claim, mechanism, authors: "can be attributed to either"; "and/or" | Longer induction times at higher bile salt levels come from more bile salt available for crystallization inhibition and/or more micellar uptake of phospholipids and digests, which leaves less of them to adsorb on the emerging nucleus [rests on: R18, R22; cited: R40] | p.34 |

## 2020 Mccarthy — A Comparison of Drug Release and Adsorption Under Supersaturating Conditions for Ordered Mesoporous Silica with Indomethacin or Indomethacin Methyl Ester · Mesoporous silica / Mesoporous silica

[2020-mccarthy-indomethacin-indme-sba15-adsorption-release](../../../cards/2020-mccarthy-indomethacin-indme-sba15-adsorption-release/paper.html) · Mesoporous silica / Mesoporous silica · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| M4 | material | hydroxypropyl methylcellulose (HPMC) Pharmacoat 606; Shin-Etsu Chemical Co. Ltd. (Tokyo) | p.6 |
| R9 | record, measured | isotherm range, limits and stability — P7 — Ci spanned 1 µg/mL to beyond the amorphous solubility; Ce always lower than the amorphous solubility; Qa begins to exceed theoretical monolayer coverage at the highest Ci (60 µg/mL IND, 14 µg/mL INDME); monolayer lines in Fig. 4 at ≈287 (IND) and ≈270 mg/g (INDME); no crystallization observed during the adsorption experiments | p.10, p.20-22; Fig. 4, p.21 |

## 2020 Saboo — Congruent release of drug and polymer from amorphous solid dispersions: insights into the role of drug-polymer hydrogen bonding, surface crystallization and glass transition · Dissolution / A. Release mechanism and LoC

[2020-saboo-congruent-release-hbond-crystallization-tg-pvpva-asd](../../../cards/2020-saboo-congruent-release-hbond-crystallization-tg-pvpva-asd/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C8 | claim, assumption, authors: asserted | HPMC-606 at 200 µg/mL (IND) and 1000 µg/mL (INDester, a relatively fast crystallizer) prevents crystallization for the duration of the experiment; pH 2.1 keeps IND unionized and pH 6.8 avoids ester hydrolysis [rests on: argument only] | p.5 |
| C37 | claim, conclusion, authors: "indicating"; "it is apparent" | Interface crystallization produces no measurable net desupersaturation, indicating that these crystals cannot grow enough to consume the supersaturation; crystallization is not triggered by the evolving supersaturation nor occurring from solution, rather the polymer cannot prevent crystallization at the hydrated compact interface [rests on: R8] | p.28 |

## 2020 Trasi — Physical stability and release properties of lumefantrine amorphous solid dispersion granules prepared by a simple solvent evaporation approach · Solid state stability / Physical stability

[2020-trasi-lumefantrine-asd-granules-solvent-evaporation](../../../cards/2020-trasi-lumefantrine-asd-granules-solvent-evaporation/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | XRPD after preparation — 6:4 rotary-evaporated dispersions, same five polymers — HPMCAS and PVPVA: sharp peaks (≈5.6, ≈15.0, ≈18.7, ≈21.6, ≈23.0, ≈25.4° 2θ, read from Fig. 2b); CAP, HPMCP and L100: halo only | Fig. 2b, p.4; text p.4 |
| R3 | record, measured | XRPD after open-dish storage at 40 °C/75% RH — 4:6 rotary-evaporated dispersions (P14) — sub-table below | Fig. 3a, p.5; text p.4 |
| R4 | record, measured | XRPD after open-dish storage at 40 °C/75% RH — 6:4 rotary-evaporated dispersions with CAP, HPMCP, L100 (P14) — sub-table below | Fig. 3b, p.5; text p.4 |
| C6 | claim, conclusion, authors: asserted ("In summary") | The most stable systems under 40 °C/75% RH were the 4:6 CAP, L100 and HPMCP dispersions [rests on: R3, R4] | p.4 |
| C28 | claim, generalisation, authors: asserted ("clearly") | The polymer clearly has a critical impact both on obtaining a completely amorphous lumefantrine formulation and on its resistance to crystallization under high-stress storage [rests on: R1, R2, R3, R4] | p.9 |
| C33 | claim, conclusion, authors: asserted | Of the four acidic polymers, HPMCP, L100 and CAP are highly effective crystallization inhibitors and HPMCAS is a poorer one [rests on: R3, R4] | p.10-11 |

## 2020 Ueda — Impact of hypromellose acetate succinate grade on drug amorphous solubility and in vitro membrane transport · Bioperformance / Bioperformance

[2020-ueda-hpmcas-grade-amorphous-solubility-membrane-transport](../../../cards/2020-ueda-hpmcas-grade-amorphous-solubility-membrane-transport/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C1 | claim, prior hypothesis, authors: asserted | ASDs improve the oral absorption of poorly water-soluble drugs and typically give supersaturation under non-sink conditions; polymer properties and ASD composition must be optimized to inhibit crystallization, and HPMC-AS is widely studied for its crystallization inhibition [rests on: cited: refs 1-19] | p.3 |
| C44 | claim, generalisation, authors: "may outweigh" | More polymer in the drug-rich phase aids crystallization inhibition in that phase, but the lowered amorphous solubility is disadvantageous for membrane transport; when the absorption window is sufficient, longer-lasting supersaturation from better crystallization inhibition may outweigh the reduced flux [rests on: cited: ref 48; argument only] | p.17-18 |
| C45 | claim, recommendation, authors: "Clearly"; "should" | Improved crystallization inhibition should be balanced against the amorphous-solubility decrease, and polymer selection should consider both the polymer's tendency to distribute into the drug-rich phase and the polymer concentration reached after formulation dissolution [rests on: argument only] | p.18 |

## 2020 Wilson — Amorphous solid dispersions of enzalutamide and novel polysaccharide derivatives: investigation of relationships between polymer structure and performance · Bioperformance / Bioperformance

[2020-wilson-enzalutamide-polysaccharide-asd-polymer-performance](../../../cards/2020-wilson-enzalutamide-polysaccharide-asd-polymer-performance/paper.html) · Bioperformance / Bioperformance · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | time to crystallization (h; average of triplicate, error bars as plotted, meaning not stated; colour class per caption: red 0-30 min, orange 30 min-2 h, blue 2-6 h, green >6 h) — enzalutamide 70 µg/mL with pre-dissolved polymer, pH 6.5 buffer, 37 °C (P5) — sub-table below; text: no polymer ~15 min; HPMCAS at least 16 h at all three concentrations; CAAd 3CES HE, CA Sub and ECCP-B >16 h at 50 µg/mL; CA Sub approximately 5 h at 5 µg/mL and >16 h at higher concentrations; CPHPC-106 ~1 h | Fig. 1, p.3; text p.3, p.6 |
| C13 | claim, conclusion, authors: asserted | Inhibition depended on polymer concentration for some polymers, in particular CA Sub; CAAd 0.67, CA Ph, PVPVA, PVP, HPMCAS and HPMC showed no dependence on polymer concentration [rests on: R1] | p.3 |
| C32 | claim, conclusion, authors: asserted ("virtually all") | Of the 24 polymers, 4 (HPMCAS, CA Sub, CAAd 3CES HE, ECCP-B) inhibited crystallization for longer than 5 h, ample time for transit through the small intestine; virtually all polymers showed some inhibitory effect [rests on: R1, R3] | p.6 |
| C52 | claim, conclusion, authors: asserted | Several effective solution crystallization inhibitors of enzalutamide were identified among the newly synthesized cellulose derivatives [rests on: R1] | p.7 |

## 2021 Bhujbal — Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation · Solid state stability / Physical stability

[2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation](../../../cards/2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation/paper.html) · Solid state stability / Physical stability · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | PXRD right after drying — 4:6 ASDs with HPMCAS, HPMCP, CAP, EL100 (P1, P3) — HPMCAS, HPMCP, CAP: no diffraction peaks; broad halos at ≈8 and ≈21° 2θ; EL100: small peaks at ≈24.8 and ≈26.5° 2θ on a trace without the ≈21° halo (read from Fig. 2) | Fig. 2, p.2426; text p.2426 |
| R2 | record, measured | PXRD right after preparation — 2:8 and 3:7 EL100 ASDs (P1, P3) — diffraction peaks present (data not shown) | p.2426 |
| R4 | record, measured | PXRD after storage at 40 °C/75% RH — seven ASDs (P4) — sub-table below | Fig. 4, p.2427; text p.2426 |
| R5 | record, measured | PXRD after storage under vacuum — 4:6 Lum:CAP, 3 months — no crystallinity (data not shown) | p.2426 |
| C1 | claim, conclusion, authors: abstract: asserted ("demonstrated"); results: "indicating"; "relatively stable" | HPMCP- and HPMCAS-based ASDs had satisfactory physical stability, with no PXRD peaks for up to 3 months at 40 °C/75% RH (prolonged retention of the amorphous state) [rests on: R3, R4] | p.2423, p.2426 |
| C5 | claim, generalisation, authors: abstract: asserted ("crucial role"); discussion: "The study demonstrated" ("critically affected", stability); conclusions: "The results indicate" ("important role") | Polymer choice and drug:polymer ratio play a crucial role in solubility enhancement and an important role in physical stability and dissolution of lumefantrine ASDs [rests on: R1, R4, R15, R16, R17] | p.2423, p.2429, p.2430 |
| C17 | claim, conclusion, authors: asserted | The 4:6 CAP ASD began to crystallize within the first day of storage without further growth of peak area over 3 months, and stayed amorphous for 3 months under vacuum [rests on: R4.a, R5] | p.2426 |

## 2021 Elkhabaz — Crystallization Kinetics in Fasted-State Simulated and Aspirated Human Intestinal Fluids · Dissolution / D. Crystallization from solution

[2021-elkhabaz-crystallization-kinetics-fasted-simulated-aspirated-human-intestinal-fluids](../../../cards/2021-elkhabaz-crystallization-kinetics-fasted-simulated-aspirated-human-intestinal-fluids/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | nucleation induction time of atazanavir (min, mean ± SD, n = 3 except where noted; values read from Fig. 3 unless marked text) — P7; six media; without and with 10 μg/mL HPMC-AS — sub-table below | Fig. 3, p.2810; text p.2810-2811 |
| R7 | record, measured | nucleation induction time of posaconazole (min, mean ± SD, n = 3; values read from Fig. 4 unless marked text) — P7; six media; without and with 10 or 50 μg/mL HPMC-AS — sub-table below | Fig. 4, p.2811; text p.2811 |
| R8 | record, measured | desupersaturation rate after onset of nucleation (μg/mL·min, mean ± SD, n = 3) — P8; buffer-V1, FaSSIF-V1, composite-FaSSIF — sub-table below | Table 2, p.2811 |
| R14 | record, measured | estimated nucleation rate from SHG counts (SHG signal count/min, mean ± SD, n = 3; values read from Fig. 8 unless marked text) — P10; six media; posaconazole also with 10 μg/mL HPMC-AS — sub-table below; posaconazole with 50 μg/mL HPMC-AS: SHG signals too low for reliable assessment; atazanavir with polymer: not performed | Fig. 8, p.2812; text p.2812 |
| R15 | record, measured | estimated crystal growth rate from SHG signal size (nm/min, mean ± SD, n = 3; values read from Fig. 9) — P10; six media; posaconazole also with 10 μg/mL HPMC-AS — sub-table below | Fig. 9, p.2812; text p.2812-2813 |
| C31 | claim, conclusion, authors: asserted ("apparent"; "clearly") | HPMC-AS is an effective nucleation and growth inhibitor even at low concentration for both compounds, and for posaconazole the suppression clearly depends on polymer concentration [rests on: R6, R7, R8, R14, R15] | p.2816 |
| C57 | claim, conclusion, authors: asserted ("albeit variable") | Adding a polymer led to favourable, albeit variable, inhibitory effects in the different media [rests on: R6, R7, R8, R14, R15] | p.2817 |

## 2021 Hate — A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes · Bioperformance / Bioperformance

[2021-hate-drug-mass-transport-supersaturated-pampa-membranes](../../../cards/2021-hate-drug-mass-transport-supersaturated-pampa-membranes/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| P1 | method | side-by-side diffusion cell mass flow rate | p.104 |
| M16 | material | hydroxypropyl methylcellulose acetate succinate (HPMCAS) MF grade, Shin-Etsu | p.103, p.104 |

## 2021 Wilson — Interaction of Polymers with Enzalutamide Nanodroplets—Impact on Droplet Properties and Induction Times · Dissolution / D. Crystallization from solution

[2021-wilson-enzalutamide-nanodroplets-polymer-interactions-induction-times](../../../cards/2021-wilson-enzalutamide-nanodroplets-polymer-interactions-induction-times/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | nucleation induction time with polymer (min, mean ± SD, n = 3); 720 = no crystallization by the 12 h end (NC) — enzalutamide 30-120 μg/mL with HPMCAS, Eudragit E PO or P177 at 2.5-100 μg/mL, pH 6.5 buffer (P3); 180 min line drawn by the authors — sub-table below; Eudragit E PO not tested above 70 μg/mL enzalutamide (text p.843) | Fig. 3, p.841 |
| R6 | record, derived (P4) | regression of inhibition probability on drug concentration, above/below GLPS, polymer and polymer concentration — all R1 and R3 data; base case 30 μg/mL enzalutamide, above GLPS, Eudragit, no polymer — sub-table below; SI summary bullets: inhibition more likely below than above GLPS; likely not inhibited with Eudragit or without polymer; likely inhibited with HPMCAS or P177; raising polymer 10-fold (5 to 50 μg/mL) likely inhibits | Table S3-2, SI p.6-7 |
| C10 | claim, conclusion, authors: asserted; "a trend can be seen" | Eudragit E PO is the least effective inhibitor, not significantly different from no polymer over all drug concentrations, and effective only at higher polymer and low drug concentrations [rests on: R3, R6.k] | p.840 |
| C12 | claim, conclusion, authors: asserted | HPMCAS is more effective than the other polymers and at ≥50 μg/mL maintained supersaturation for several hours both with a large amount of droplets and without droplets [rests on: R3] | p.840 |
| C37 | claim, conclusion, authors: asserted ("we do not observe a link"); "far less effective" (p.846) | For HPMCAS and Eudragit E PO no link is seen between the amount of polymer associated with the droplets and inhibition: Eudragit E PO associated more but was a less effective inhibitor with droplets, unlike the correlations of Ueda et al. and Wang et al. [rests on: R3, R7, C19] | p.836, p.845, p.846 |

## 2021 Yang — Drug Release and Nanodroplet Formation from Amorphous Solid Dispersions: Insight into the Roles of Drug Physicochemical Properties and Polymer Selection · Dissolution / A. Release mechanism and LoC

[2021-yang-asd-nanodroplet-release-drug-properties-polymer-selection](../../../cards/2021-yang-asd-nanodroplet-release-drug-properties-polymer-selection/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | nanodroplet z-average and PDI vs time — elbasvir ASDs, 2.5% DL, three media (P16) — sub-table R3 below | Fig. 2 and text, p.2071 |
| R9 | record, measured | total released drug vs DL — danazol ASDs, powder, 15 min (caption: API crystallization beyond 15 min) — PVPVA: ≈2% ≈91; ≈2.5% ≈96; 5% ≈78; 10% ≈9.5; 20% ≈9; 50% ≈8. HPMCAS: 5% ≈98; 10% ≈75; 20% ≈36; 30% ≈25; 50% ≈14; 70% ≈8 (read from Fig. 3c). Text: PVPVA cliff DL 5% | Fig. 3c, p.2071; text p.2073 |
| C4 | claim, conclusion, authors: abstract: "was found"; results: asserted ("Therefore"); discussion: asserted | HPMCAS inhibited nanodroplet crystallization and size growth better than PVPVA, regardless of which ASD produced the nanodroplets; similar trends held for loratadine, danazol and miconazole; PVPVA is poor at inhibiting crystallization of fast crystallizers [rests on: R3–R6] | Abstract p.2066; Results p.2071; Discussion p.2078; Conclusions p.2079 |

## 2022 Duong — Combining enabling formulation strategies to generate supersaturated solutions of delamanid: In situ salt formation during amorphous solid dispersion fabrication for more robust release profiles · Dissolution / B. Supersaturation from ASD dissolution

[2022-duong-delamanid-in-situ-salt-asd-release](../../../cards/2022-duong-delamanid-in-situ-salt-asd-release/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | nucleation induction time with polymer (min) — PBS pH 6.5, 37 °C, polymer 300 µg/mL, DLM at its amorphous solubility 0.76 µg/mL (P4) — sub-table below | Fig. 2A, p.135; text p.134 |
| C11 | claim, prior hypothesis, authors: asserted ("have been demonstrated") | Some polymers inhibit drug crystallization in solution, attributed to drug-polymer intermolecular interactions, and polymers can also stabilize drug-rich droplets formed above the amorphous solubility [rests on: cited: refs 35-37] | p.134-135 |
| C12 | claim, conclusion, authors: asserted ("highly effective") | PVPVA showed good crystallization inhibition, HPMC delayed crystallization to about 50 min, Eud-L100 was ineffective, and HPMCP and HPMCAS were highly effective [rests on: R4] | p.134 |
| C51 | claim, prior hypothesis, authors: "are thought to" | ASD polymers kinetically stabilize the supersaturated solution and are thought to inhibit crystallization through non-specific drug-polymer interactions; not all polymers are equally effective [rests on: cited: refs 35, 36, 51, 52] | p.141 |

## 2022 Hiew — Balancing Solid-State Stability and Dissolution Performance of Lumefantrine Amorphous Solid Dispersions: The Role of Polymer Choice and Drug−Polymer Interactions · Solid state stability / Miscibility and drug-polymer interactions

[2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice](../../../cards/2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | crystallinity of ASDs by PXRD — P5, P8; as prepared and after open-dish storage at 40 °C/75% RH — as prepared: all ASDs X-ray amorphous (Fig. 2a, c, e, g, i); storage: sub-table below | p.397; Fig. 2, p.398 |
| C10 | claim, conclusion, authors: asserted | PVPVA ASDs were the least stable at 40 °C/75% RH, whereas ASDs with enteric polymers showed much greater resistance to crystallization [rests on: R6] | p.392, p.397 |
| C62 | claim, mechanism, authors: "a potential explanation" | Enteric polymers can hydrogen bond to the lumefantrine acceptor and form an acid−base interaction with its tertiary amine; protonation was seen with all enteric polymers at 25% DL, unlike the earlier report for HPMCAS (R30); acid−base interaction is a potential explanation for their better physical stability [rests on: R20, R6, R30; cited: refs 36, 37] | p.411 |

## 2022 Moseson — Atomic Layer Coating to Inhibit Surface Crystallization of Amorphous Pharmaceutical Powders · ASD process / ASD process

[2022-moseson-atomic-layer-coating-surface-crystallization-asd-powders](../../../cards/2022-moseson-atomic-layer-coating-surface-crystallization-asd-powders/paper.html) · ASD process / ASD process · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | crystallization onset by SEM (Fig. 9 bars; Fig. 10 table) — 40 °C, RH as listed, open dish (P15); up to 48 weeks — sub-table R11. Text: abstract "within 1−2 weeks for all uncoated samples"; results "within 1−4 weeks for each uncoated system"; discussion: EP50 2 → 6 weeks (43% RH), EH60 2 → 3 weeks (75% RH) and 2 → more than 48 weeks (43% RH) | Figs. 9 and 10, p. 40705; text pp. 40698, 40703, 40706 |
| C2 | claim, conclusion, authors: asserted ("effectively delayed or completely inhibited") | Coating delayed crystallization or, in many systems, completely inhibited it for up to 48 weeks at highly accelerated conditions; 5−25 nm Al2O3 and ZnO coatings on SD and HME particles were effective crystallization inhibitors [rests on: R10, R11, R13] | p. 40698; pp. 40703−40704; p. 40708 |
| C3 | claim, generalisation, authors: abstract, results, conclusions: asserted; discussion: "Our observations indicate" | The observations indicate that the crystallization delay holds regardless of polymer hygroscopicity, hydroxyl groups in drug and/or polymer, manufacturing technique and particle size, and coating properties [rests on: R11] | p. 40698; p. 40704; p. 40706; p. 40708 |
| C4 | claim, mechanism, authors: abstract: "attributed primarily"; discussion: asserted ("mobility was successfully reduced") | Crystallization inhibition is attributed mainly to decreased surface molecular mobility; the coating reduced mobility, as other coating materials have [rests on: argument only; R11; cited: refs 30−34] | p. 40698; p. 40707 |

## 2022 Moseson — Formulation and processing strategies which underpin susceptibility to matrix crystallization in amorphous solid dispersions · ASD process / ASD process

[2022-moseson-processing-strategies-matrix-crystallization-bcl-pvpva-asd](../../../cards/2022-moseson-processing-strategies-matrix-crystallization-bcl-pvpva-asd/paper.html) · ASD process / ASD process · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C1 | claim, prior hypothesis, authors: asserted; "may" | ASDs aim to create and maintain supersaturation; because both the amorphous solid and the supersaturated solution are metastable, crystallization in either phase can reduce it; polymers can inhibit solution crystallization, whereas in matrix crystallization the amorphous solid converts to the crystal before entering solution and so lowers the driving force for dissolution [rests on: cited: refs 1-11] | p.4 |
| C7 | claim, assumption, authors: asserted | A dose giving at most 30 µg/mL BCL is not susceptible to solution-mediated nucleation with PVPVA and has near-zero solution growth, so concentration losses at this dose report on matrix crystallization [rests on: R22] | p.9 |
| R22 | record, cited | solution crystallization at the dose concentration — 30 µg/mL BCL with PVPVA, ref 11 — not susceptible to solution-mediated nucleation; near-zero rates of solution-mediated crystal growth | text p.9 (ref 11) |

## 2022 Duong — Surface nanocoating of high drug-loading spray-dried amorphous solid dispersions by atomic layer coating: Excellent physical stability under accelerated storage conditions for two years · ASD process / ASD process

[2022-van-duong-surface-nanocoating-high-drug-loading-asd-alc-stability](../../../cards/2022-van-duong-surface-nanocoating-high-drug-loading-asd-alc-stability/paper.html) · ASD process / ASD process · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R19 | record, measured | ezetimibe crystallinity (%) from the 19.6° 2θ peak (mean ± SD, n = 3) — six samples, P16, P13 — sub-table below; 50% Thin coated, 50% Thick coated and 70% Thick coated ≈0 at every point to 270 days | Fig. 13 p.11 |
| R20 | record, measured | DSC thermograms during storage (initial, 1, 3, 6, 9, 12, 24 months) — six samples, P16 (P11) — sub-table below; the 1-month traces of the coated samples have strongly sloping baselines | Fig. 14 p.11; text p.9 |
| C52 | claim, conclusion, authors: discussion: asserted ("Importantly"; "striking"); abstract: asserted; conclusions: asserted ("Strikingly") | A small coating amount gives an outstanding improvement in stability: coated samples showed no evidence of crystallization after two years of storage (except 70% Thin coated, from 7 months), ALC prolonging the amorphous state of ezetimibe from about two weeks to at least two years; the abstract and conclusions state two years without physical instability, or with crystallization prevented, without the exception [rests on: R16, R17, R18, R19, R20] | p.1, p.13 |
| C34 | claim, conclusion, authors: asserted | All coated samples kept their amorphous nature for two years without detectable crystallization, except 70% Thin coated, which showed a few surface crystals after 7 months and more after 24 months [rests on: R16, R17] | p.9 |

## 2023 Hiew — Improving Dissolution Performance and Drug Loading of Amorphous Dispersions Through a Hierarchical Particle Approach · Dissolution / A. Release mechanism and LoC

[2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release](../../../cards/2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| P2 | method | UV extinction amorphous solubility | p.2059, p.2061 |
| M5 | material | copovidone Kollidon VA64, BASF Corporation (Ludwigshafen, Germany) | p.2058, p.2059 |

## 2023 Nguyen — Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release · Dissolution / B. Supersaturation from ASD dissolution

[2023-nguyen-enteric-coating-delamanid-hpmcp-asd-release](../../../cards/2023-nguyen-enteric-coating-delamanid-hpmcp-asd-release/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C6 | claim, prior hypothesis, authors: asserted | Preventing crystallization during release maintains supersaturation; cellulose-derivative and anionic polymers delay nucleation and inhibit crystal growth in the solid state and in solution; HPMCAS acts through limited mobility from a higher ASD Tg, drug-polymer interactions and polymer dilution [rests on: cited: refs 2, 4, 10, 16, 57, 59, 60, 64, 69] | p.1-2 |
| C36 | claim, prior hypothesis, authors: "appear"; "may" | HPMCAS and HPMCP are effective solution crystallization inhibitors near neutral pH, where they are ionized and soluble, but appear less effective at lower pH where they are insoluble; polymers with the same functional groups may inhibit or accelerate heteronucleation depending on hydrophobicity and solubility [rests on: cited: refs 2, 10, 12, 15, 43, 44, 52, 64] | p.8-9 |
| C37 | claim, mechanism, authors: "can be attributed" | The rapid surface crystallization at low pH can be attributed to the enteric polymer being a poor crystallization inhibitor when unionized and/or to the drug crystallizing more readily at certain pH; drug at the ASD surface is more vulnerable because of higher molecular mobility [rests on: R3, R4] | p.9 |

## 2023 Nguyen — Impact of Gastric pH Variations on the Release of Amorphous Solid Dispersion Formulations Containing a Weakly Basic Drug and Enteric Polymers · Dissolution / B. Supersaturation from ASD dissolution

[2023-nguyen-gastric-ph-variations-delamanid-enteric-polymer-asd](../../../cards/2023-nguyen-gastric-ph-variations-delamanid-enteric-polymer-asd/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R22 | record, measured | DLM release with (1 mg/mL) and without predissolved PVPVA, pH 3.0 → 6.5 (%) — P16 — gastric stage ≈2-5% for all; at 90 min: HPMCP-50 ≈44 with versus ≈41 without; HPMCP-55 ≈82 with (≈82-86 from 63 min) versus ≈80.5 without; HPMCAS-MF ≈7 with versus ≈10 without (values ≈, read from Fig. S6); text: PVPVA did not affect release of the HPMCAS-MF and HPMCP-50 ASDs | Fig. S6, SI p.8; text p.1691 |
| C4 | claim, conclusion, authors: abstract: "appeared more extensive"; results: "In general"; conclusions: asserted ("were found to be poor inhibitors"; HPMCP "generally better") | Drug crystallization in acid was more extensive for HPMCAS than for HPMCP ASDs; the HPMCAS grades were poor inhibitors of matrix crystallization at all pH conditions, the HPMCP grades generally better [rests on: R18, R19, R20] | p.1681, p.1688, p.1692 |
| C38 | claim, mechanism, authors: "may be due to" | The lack of solution crystallization may be due to a minor amount of dissolved polymer at all pH; cellulose derivatives inhibit DLM solution crystallization even at high supersaturation (R27); at pH 5.0, where the driving force was highest, polymer solubility exceeded 100 µg/mL except for HPMCAS-HF [rests on: R4, R12, R27] | p.1691 |

## 2023 Nguyen — Fed- and Fasted-State Performance of Pretomanid Amorphous Solid Dispersions Formulated with an Enteric Polymer · Bioperformance / Bioperformance

[2023-nguyen-pretomanid-hpmcas-asd-fed-fasted-performance](../../../cards/2023-nguyen-pretomanid-hpmcas-asd-fed-fasted-performance/paper.html) · Bioperformance / Bioperformance · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | nucleation induction time with predissolved polymer (min, mean ± SD, n = 3) — PTM 80 µg/mL (supersaturation ratio 5, E1) in PB pH 6.5 with polymer 100 µg/mL, 37 °C (P3) — sub-table below; text: Eudragit L-100, CAP, HPMCP and HPMCAS-LF 2-5 min; HPMCAS-MF ~22 min; HPMC similar to MF; no crystallization with HPMCAS-HF for up to 1000 min | Fig. 1, p.3174; text p.3174 |
| R6 | record, measured | nucleation induction time at 160 µg/mL with HPMCAS-HF (min, mean ± SD) — PTM 160 µg/mL, HPMCAS-HF 1 mg/mL, 37 °C (P3) — PB pH 6.5: 43.8 ± 1.3; FaSSIF V1: 77.6 ± 13.6; text: approximately 44 and 77 min; the no-polymer rows of Table S1 repeat R1.d and R1.f | Table S1, SI p.3; text p.3174 |
| C11 | claim, conclusion, authors: asserted | Most enteric polymers (Eudragit L-100, CAP, HPMCP, HPMCAS-LF) do not inhibit PTM crystallization (2-5 min), whereas the more hydrophobic HPMCAS grades do: MF ~22 min, HPMC similar, HF no crystallization up to 1000 min [rests on: R5] | p.3174 |
| C14 | claim, conclusion, authors: abstract and results: asserted; discussion: "the only realistic"; conclusions: asserted | HPMCAS-HF was selected for PTM ASDs on its crystallization inhibition; discussion: "the only realistic polymeric candidate"; conclusions: the only viable choice from a crystallization inhibition perspective, the paucity of effective inhibitors having limited polymer choice [rests on: R5, R6] | p.3170, p.3174, p.3182, p.3183 |

## 2024 Polyzois — Amorphous Solid Dispersion Formation for Enhanced Release Performance of Racemic and Enantiopure Praziquantel · Dissolution / B. Supersaturation from ASD dissolution

[2024-polyzois-praziquantel-racemic-enantiopure-asd-release](../../../cards/2024-polyzois-praziquantel-racemic-enantiopure-asd-release/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | nucleation induction time of RS-PZQ by polymer (mean ± SD, n = 3) — RS-PZQ at its amorphous solubility in PBS pH 6.5 (R2.c), polymer 300 µg/mL, 37 °C, 400 rpm (P3) — sub-table below (text values; the Fig. 2a bars agree) | Section 3.3, p.5288; Fig. 2a, p.5288 |
| R4 | record, measured | nucleation induction time, R-PZQ compared with RS-PZQ — each drug at its own amorphous solubility in PBS pH 6.5 (R2.a, R2.c), polymer 300 µg/mL, 37 °C (P3); n = 2 for R-PZQ (mean ± SD) — sub-table below; RS-PZQ bars in Fig. 2b repeat R3.a, R3.g and R3.h | Section 3.3, p.5289; Fig. 2b, p.5288 |
| C5 | claim, prior hypothesis, authors: "are known to" | Polymers inhibit drug crystallization in solution through drug-polymer interactions that suppress nucleation and/or crystal growth, and crystallization inhibition is a key criterion for choosing an ASD polymer [rests on: cited: refs 51, 52] | p.5288, p.5291 |
| C7 | claim, conclusion, authors: asserted | Without polymer, RS-PZQ and R-PZQ crystallized quickly; every polymer prolonged the RS-PZQ induction time, and HPMCAS-MF and HPMC E5 LV were the most potent inhibitors (at least 83 min, the run length) and were selected as the most suitable polymers for stable RS-PZQ ASDs by SE and HME [rests on: R3, R4] | p.5288-5289, p.5291 |
| C8 | claim, conclusion, authors: asserted ("significantly") | HPMCAS-MF and HPMC E5 LV were significantly less potent inhibitors of R-PZQ crystallization than of RS-PZQ crystallization [rests on: R4, R3.g-h] | p.5289, p.5291 |

## 2025 Junior — Release performance and crystallization of racemic and enantiopure praziquantel amorphous solid dispersion in various media · Dissolution / B. Supersaturation from ASD dissolution

[2025-alvarenga-praziquantel-racemic-enantiopure-asd-release-crystallization-media](../../../cards/2025-alvarenga-praziquantel-racemic-enantiopure-asd-release-crystallization-media/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | release, single-stage PBS pH 6.5, 0.667 mg mL−1 — P9 — see R6 sub-table | Fig. 2A, p. 1129; Section 3.2.1, p. 1129 |
| R14 | record, measured | release, single-stage FaSSIF, 1.5 mg mL−1 — P9; Fig. 3C panel not printed (X1); text values only — HPMCAS ASDs: more than 85% within 60 min; (R,S)-PZQ-HPMC SE maximum 82% (∼40 min), (R)-PZQ-HPMC SE maximum 75% (∼19 min), each followed by a 30% drop in release | Section 3.2.2, p. 1130 |
| R24 | record, measured | PLM of HPMCAS ASDs during release — 1.5 mg mL−1; SE and HME; aqueous (Figs. S2–S3), fasted (S4A), fed (S4B, S5, S6, S7); neat HPMCAS controls in fed media — text: no birefringence in any HPMCAS sample, including fed-state two-stage tests with release below 32%; figure: irregular particles without interference colours; at 120 min, (R,S)-PZQ-HPMCAS SE in FeSSIF-V2 shows numerous angular particles without visible interference colours (read from Fig. S6); neat HPMCAS at pH 4.5 shows many dark particles at 5 and 60 min (read from Fig. S7) | Figs. S2–S7, SI p. 3–6; Section 3.3, p. 1131 |
| C26 | claim, conclusion, authors: asserted ("demonstrated", "clearly observed") | HPMC is not sufficiently effective in preventing PZQ crystallization during dissolution; crystals of both drug forms with HPMC were seen by PLM and found by PXRD; HPMC formulations are less stable to crystallization than HPMCAS formulations [rests on: R20–R23, R25–R27] | Section 4.2, p. 1134; Section 4.3, p. 1135; Section 5, p. 1135–1136 |
| C28 | claim, mechanism, authors: 4.2: consistent with; suggesting; conclusions: asserted | The absence of a concentration decrease with time for HPMCAS ASDs (except in fed-state media) suggests that HPMCAS MF inhibits crystallization from supersaturated PZQ solution better than HPMC, consistent with it being a better nucleation inhibitor [rests on: R6–R19; cited: refs 47, 54, 55] | Section 4.2, p. 1134; Section 5, p. 1136 |
| C32 | claim, conclusion, authors: asserted | HPMCAS ASDs show no evidence of crystallization except in fed-state media and release well (near-complete with crystallization inhibition) at intestinal pH, in PBS pH 6.5 and in fasted-state media [rests on: R6–R8, R12–R15, R24] | Abstract, p. 1125; Section 5, p. 1136 |

## 2025 Kaur — Impact of drug-polymer complexation and media properties on the release performance of amorphous solid dispersions containing a weakly basic drug and hydroxypropyl methylcellulose acetate succinate · Dissolution / A. Release mechanism and LoC

[2025-kaur-bdq-hpmcas-complexation-media-asd-release](../../../cards/2025-kaur-bdq-hpmcas-complexation-media-asd-release/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R18 | record, measured | nucleation induction time and particle size of BDQ (100 µg/mL), with and without HPMCAS (400 µg/mL) — P13, 37 °C — sub-table below; text: without polymer BDQ precipitated in <1 min from pH 5.8 and 6.5 buffers, precipitates >5000 nm, no birefringence up to 2 h, birefringence by 3 h; with polymer BDQ precipitated immediately, precipitates <1000 nm, amorphous for 12-24 h; in FaSSIF-V1 and FeSSIF-V2 with polymer no crystallization for 12-24 h | Table 3, p.8; text p.7 |
| C22 | claim, conclusion, authors: asserted | Without polymer BDQ precipitated within 1 min at pH 5.8 and 6.5 as large amorphous particles that crystallized by 3 h; with polymer the precipitates were smaller than 1000 nm and amorphous for 12-24 h; in FaSSIF-V1 and FeSSIF-V2 with polymer no crystallization occurred for 12-24 h [rests on: R18] | p.7 |
| C4 | claim, prior hypothesis, authors: asserted | HPMCAS is of interest as an ASD polymer because of excellent crystallization inhibition for many drugs [rests on: cited: ref 9] | p.2 |

## 2025 Shah — Chemistry and ionization of HPMCAS influences the dissolution and solution-mediated crystallization of posaconazole amorphous solid dispersions · Dissolution / D. Crystallization from solution

[2025-shah-hpmcas-ionization-posaconazole-asd-crystallization](../../../cards/2025-shah-hpmcas-ionization-posaconazole-asd-crystallization/paper.html) · Dissolution / D. Crystallization from solution · measured · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | nucleation induction time (min) — 10 µg/mL PCZ by solvent shift, buffer alone or 90 µg/mL HPMCAS, 37 °C, 240 min window (P4) — sub-table below | Fig. 3, p.226; text p.226-227 |
| R4 | record, measured | PCZ concentration in the supernatant vs time during ASD dissolution (µg/mL; stated target 100 µg/mL at complete release) — ASD powder 106-250 µm, 100 mL buffer, 37 °C, 50 rpm (P5, P6) — sub-table below (all values ≈, read from Fig. 4; error bars not transcribed) | Fig. 4, p.227 |
| C13 | claim, conclusion, authors: asserted | All three grades lengthened the nucleation induction time, in the order L, M, H; for a given grade induction times were shorter at higher pH; effectiveness in delaying nucleation was H > M > L [rests on: R3] | p.226-227 |
| C49 | claim, generalisation, authors: asserted ("were found to be") | Solution crystallization kinetics of posaconazole were markedly influenced by HPMCAS; the A/S ratio and the extent of polymer ionization are key parameters for the effectiveness of HPMCAS as a crystallization inhibitor [rests on: R3, R4] | p.232 |

## 2026 Alkalla — Coadministration of a crystalline drug compromises supersaturation and membrane transport of an amorphous drug · Bioperformance / Bioperformance

[2026-alkalla-crystalline-darunavir-compromises-amorphous-atazanavir-supersaturation-transport](../../../cards/2026-alkalla-crystalline-darunavir-compromises-amorphous-atazanavir-supersaturation-transport/paper.html) · Bioperformance / Bioperformance · used · as: crystallization inhibition

| id | kind | content | locator |
|---|---|---|---|
| C14 | claim, assumption, authors: asserted ("was used to stabilize all systems") | HPMCAS at 400 µg/mL stabilises all supersaturated systems against crystallization in the supersaturation and diffusion-cell experiments [rests on: argument only] | p.4; Fig. 5 caption, p.7 |
| P9 | method | maximum achievable concentration by antisolvent addition and ultracentrifugation | p.4; Fig. 5, p.7 |
| P10 | method | side-by-side diffusion cell flux | p.4 |

## Mentioned only

- 2009 Rumondor — [2009-rumondor-drug-polymer-miscibility-asd-dsc-ir-pxrd](../../../cards/2009-rumondor-drug-polymer-miscibility-asd-dsc-ir-pxrd/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref C2 C3)
- 2010 Rumondor — [2010-rumondor-moisture-sorption-amorphous-drug-polymer-blends](../../../cards/2010-rumondor-moisture-sorption-amorphous-drug-polymer-blends/paper.html) · Solid state stability / Physical stability (ref C1)
- 2010 Rumondor — [2010-rumondor-polymer-hygroscopicity-moisture-phase-separation-asd](../../../cards/2010-rumondor-polymer-hygroscopicity-moisture-phase-separation-asd/paper.html) · Solid state stability / Physical stability (ref C21)
- 2010 Wanapun — [2010-wanapun-sonicc-amorphous-api-crystallization-detection](../../../cards/2010-wanapun-sonicc-amorphous-api-crystallization-detection/paper.html) · Characterization methods / Solid-state methods (ref C3)
- 2012 Kestur — [2012-kestur-sonicc-sensitive-crystal-detection-amorphous-powders](../../../cards/2012-kestur-sonicc-sensitive-crystal-detection-amorphous-powders/paper.html) · Characterization methods / Solid-state methods (ref 9)
- 2012 Eerdenbrugh — [2012-van-eerdenbrugh-dextran-maltodextrin-pvp-molecular-weight-miscibility](../../../cards/2012-van-eerdenbrugh-dextran-maltodextrin-pvp-molecular-weight-miscibility/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref 2)
- 2012 Eerdenbrugh — [2012-van-eerdenbrugh-nanoscale-mid-ir-dextran-maltodextrin-pvp-miscibility](../../../cards/2012-van-eerdenbrugh-nanoscale-mid-ir-dextran-maltodextrin-pvp-miscibility/paper.html) · Characterization methods / Solid-state methods (ref 4)
- 2012 Zhu — [2012-zhu-api-peg-solid-dispersion-crystallization-behavior](../../../cards/2012-zhu-api-peg-solid-dispersion-crystallization-behavior/paper.html) · Solid state stability / PEG dispersions (ref C8 C36)
- 2016 Li — [2016-li-lopinavir-asd-leaching-acidic-media](../../../cards/2016-li-lopinavir-asd-leaching-acidic-media/paper.html) · Dissolution / B. Supersaturation from ASD dissolution (ref 15)
- 2016 Lu — [2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid](../../../cards/2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid/paper.html) · Solid state stability / Crystallization tendency (ref C1)
- 2017 Indulkar — [2017-indulkar-origin-nanodroplet-formation-asd-isotope-scrambling](../../../cards/2017-indulkar-origin-nanodroplet-formation-asd-isotope-scrambling/paper.html) · Dissolution / A. Release mechanism and LoC (ref 31)
- 2017 Lu — [2017-lu-endogenous-bile-salts-telaprevir-supersaturation-thermodynamics](../../../cards/2017-lu-endogenous-bile-salts-telaprevir-supersaturation-thermodynamics/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref 11)
- 2017 Purohit — [2017-purohit-itraconazole-hpmc-asd-phase-separation-fluorescence-ssnmr](../../../cards/2017-purohit-itraconazole-hpmc-asd-phase-separation-fluorescence-ssnmr/paper.html) · Characterization methods / Solid-state methods (ref C23)
- 2017 Purohit — [2017-purohit-ritonavir-asd-hydration-dissolution-phase-behavior](../../../cards/2017-purohit-ritonavir-asd-hydration-dissolution-phase-behavior/paper.html) · Dissolution / A. Release mechanism and LoC (ref C9 C12)
- 2017 Saboo — [2017-saboo-water-induced-miconazole-pvpva-asd-phase-separation](../../../cards/2017-saboo-water-induced-miconazole-pvpva-asd-phase-separation/paper.html) · Solid state stability / Physical stability (ref C1 C2 C31)
- 2018 Mugheirbi — [2018-mugheirbi-itz-hpmc-asd-solvent-phase-behavior](../../../cards/2018-mugheirbi-itz-hpmc-asd-solvent-phase-behavior/paper.html) · ASD process / ASD process (ref 40)
- 2019 Indulkar — [2019-indulkar-ritonavir-copovidone-asd-congruent-release-loc](../../../cards/2019-indulkar-ritonavir-copovidone-asd-congruent-release-loc/paper.html) · Dissolution / A. Release mechanism and LoC (ref C13)
- 2019 Saboo — [2019-saboo-congruent-drug-polymer-release-asd-sweet-spot](../../../cards/2019-saboo-congruent-drug-polymer-release-asd-sweet-spot/paper.html) · Dissolution / A. Release mechanism and LoC (ref 1)
- 2020 Que — [2020-que-halogen-bonding-amorphous-solid-dispersions](../../../cards/2020-que-halogen-bonding-amorphous-solid-dispersions/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref 9)
- 2020 Ueda — [2020-ueda-polymer-type-amorphous-solubility-drug-rich-phase-colloidal-stability](../../../cards/2020-ueda-polymer-type-amorphous-solubility-drug-rich-phase-colloidal-stability/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref 22)
- 2021 Que — [2021-que-drug-polymer-interactions-loc-copovidone-asd](../../../cards/2021-que-drug-polymer-interactions-loc-copovidone-asd/paper.html) · Dissolution / A. Release mechanism and LoC (ref 12)
- 2021 Saboo — [2021-saboo-tpgs-felodipine-pvpva-asd-release-high-loading](../../../cards/2021-saboo-tpgs-felodipine-pvpva-asd-release-high-loading/paper.html) · Dissolution / A. Release mechanism and LoC (ref C4 C5)
- 2021 Ueda — [2021-ueda-polymer-species-maximum-aqueous-supersaturation-nmr](../../../cards/2021-ueda-polymer-species-maximum-aqueous-supersaturation-nmr/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref C43)
- 2022 Jr — [2022-alvarenga-polymer-type-thermal-degradation-ritonavir-asd](../../../cards/2022-alvarenga-polymer-type-thermal-degradation-ritonavir-asd/paper.html) · ASD process / ASD process (ref 12)
- 2022 Duong — [2022-duong-posaconazole-phase-behavior-crystallization-kinetics-media](../../../cards/2022-duong-posaconazole-phase-behavior-crystallization-kinetics-media/paper.html) · Dissolution / D. Crystallization from solution (ref 26)
- 2022 Indulkar — [2022-indulkar-surfactants-ritonavir-copovidone-asd-release-performance](../../../cards/2022-indulkar-surfactants-ritonavir-copovidone-asd-release-performance/paper.html) · Dissolution / A. Release mechanism and LoC (ref 19)
- 2022 Ueda — [2022-ueda-polymer-partitioning-ibuprofen-drug-rich-phase-nmr](../../../cards/2022-ueda-polymer-partitioning-ibuprofen-drug-rich-phase-nmr/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref 31)
- 2023 Bapat — [2023-bapat-hpmcas-asd-media-choice-buffer-capacity-release](../../../cards/2023-bapat-hpmcas-asd-media-choice-buffer-capacity-release/paper.html) · Dissolution / A. Release mechanism and LoC (ref C6)
- 2023 Deac — [2023-deac-asd-dissolution-interface](../../../cards/2023-deac-asd-dissolution-interface/paper.html) · Dissolution / A. Release mechanism and LoC (ref 4)
- 2023 Yang — [2023-yang-surfactant-containing-asd-release-enhancement](../../../cards/2023-yang-surfactant-containing-asd-release-enhancement/paper.html) · Dissolution / A. Release mechanism and LoC (ref 37)
- 2024 Bapat — [2024-bapat-hpmcas-drug-polymer-complexation-release-performance](../../../cards/2024-bapat-hpmcas-drug-polymer-complexation-release-performance/paper.html) · Dissolution / A. Release mechanism and LoC (ref 11)
- 2025 Bapat — [2025-bapat-hpmcas-grade-weak-base-asd-release-complexation](../../../cards/2025-bapat-hpmcas-grade-weak-base-asd-release-complexation/paper.html) · Dissolution / A. Release mechanism and LoC (ref C1)
- 2025 Hiew — [2025-hiew-surface-composition-wettability-high-drug-loading-asd](../../../cards/2025-hiew-surface-composition-wettability-high-drug-loading-asd/paper.html) · Dissolution / A. Release mechanism and LoC (ref 16)