# Evidence: molecular mobility

Parent: — · class: kinetics · names merged here: molecular mobility

51 papers measured or used it, 21 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.

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: "is considered"; "has been attributed" | Tg is considered a key parameter separating high and low molecular mobility, and the stabilizing effect of polymers with high Tg relative to the drug has been attributed to antiplasticization [rests on: cited: refs 14-16] | p.2692-2693 |
| C24 | claim, prior hypothesis, authors: asserted ("lack of consensus") | Suggested mechanisms of polymer inhibition include raising Tg (antiplasticization) and lowering mobility, disrupting critical drug-drug interactions and forming drug-polymer interactions; there is no consensus on the dominant one, with Van den Mooter et al. stressing Tg and other studies finding inhibition without a Tg increase [R21] [rests on: cited: refs 14-20, 33, 34; R21] | p.2701 |
| C38 | claim, mechanism, authors: "might be expected"; "hard to assess" | Specific interactions might lower drug diffusivity by coupling drug and polymer motion, but this is hard to assess because drug molecules bonded to polymer and to other drug molecules coexist [rests on: R11; argument only] | p.2703 |
| R9 | record, derived (E7) | KWW average relaxation time τ and stretch exponent β — 9:1 dispersions at 2 °C (P6); nonlinear regression, R² > 0.9 — PVP τ 208 h, β 0.42; HPMCAS τ 687 h, β 0.45; HPMC τ 319 h, β 0.47; no τ for felodipine alone reported | p.2698 |

## 2006 Marsac — A Comparison of the Physical Stability of Amorphous Felodipine and Nifedipine Systems · Solid state stability / Physical stability

[2006-marsac-physical-stability-amorphous-felodipine-nifedipine](../../../cards/2006-marsac-physical-stability-amorphous-felodipine-nifedipine/paper.html) · Solid state stability / Physical stability · measured · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured or derived per row | properties of amorphous and crystalline nifedipine and felodipine; SD in parentheses, n = 3 — pure drugs; nucleation rate at 22 °C, 0% RH (P4); thermal data by DSC/MDSC (P7, P8); β and τ from enthalpy recovery at 23.5 °C (P9) — sub-table below; text p.2309 gives the same β and τ with τ in h | Table II, p.2310; text p.2309 |
| R6 | record, measured | enthalpy recovered versus aging time (mJ/mg; error bars one SD); lines are KWW fits — nifedipine, felodipine, and their dispersions with 10 wt% PVP, 23.5 °C, dry (P9) — sub-table below | Fig. 4, p.2310 |
| R7 | record, derived (E7) | KWW β and τ of dispersions — 10 wt% PVP dispersions, 23.5 °C, dry — nifedipine with 10% PVP: β 0.57 (±0.03), τ 42.1 (±0.6) h; felodipine with 10% PVP: β 0.45 (±0.04), τ 16.7 (±0.5) h | p.2310-2311 |
| R8 | record, measured and derived (E8) | enthalpy recovered after 16 h and expected maximum enthalpy recovery — felodipine and felodipine with 10% PVP, 23.5 °C; Tg 43.1 (±0.5) °C pure and 40.5 (±0.5) °C with 10% PVP — felodipine: about 5.4 (±0.3) mJ/mg after 16 h, maximum 6.3 (±0.3) mJ/mg, stated total recovery 84%; felodipine with 10% PVP: about 3.4 (±0.1) mJ/mg, maximum 5.3 (±0.3) mJ/mg, stated 65%; absolute enthalpy recovered by the two 10 wt% PVP dispersions virtually the same (Fig. 4: ≈3.55 and ≈3.4 mJ/mg at 16 h) | p.2311; Fig. 4, p.2310 |
| C13 | claim, conclusion, authors: asserted ("It is immediately obvious"; "clearly") | Molecular mobility of the two pure glasses at 23.5 °C (β, τ) is very similar, so the difference in crystallization tendency cannot be explained by mobility estimated this way; nifedipine crystallizes clearly faster despite virtually identical Tg and average relaxation time [rests on: R4.c-e, R4.m-n, R6.a-b, R1] | p.2309, p.2312 |
| C25 | claim, conclusion, authors: asserted ("virtually identical") | PVP decreases enthalpy recovery (molecular mobility) of both drugs at 23.5 °C under dry conditions, and the absolute enthalpy recovered is virtually identical for the two 10 wt% PVP dispersions [rests on: R6, R7, R8] | p.2311 |
| C26 | claim, generalisation, authors: asserted ("highlighting the fact") | For felodipine with 10% PVP mobility is reduced although Tg is slightly lower, which shows that Tg alone does not completely describe the reduction in molecular mobility, in agreement with other binary small molecule-polymer studies [rests on: R8, R6.b, R6.d; cited: ref 28] | p.2311 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C1 | claim, prior hypothesis, authors: asserted | Amorphous solids are more hygroscopic than their crystals because water is absorbed into their internal structure as well as adsorbed at the surface; absorbed water lowers Tg (plasticization) and so raises molecular mobility at room temperature [rests on: cited: refs 1-8] | p.647 |
| C16 | claim, prior hypothesis, authors: "expected"; "presumably" | Moisture is expected to depress Tg and raise molecular mobility, which presumably lowers the activation energy for crystallization [rests on: cited: refs 3-8] | p.650-651 |
| C29 | claim, mechanism, authors: "potentially"; "Presumably"; "may" | Without moisture the polymer raises the activation energy for crystallization and may act as a physical barrier; presumably it does the same with water present; mobility may also be reduced by coupling of molecular motions through molecular interactions [rests on: cited: refs 22, 29, 40] | p.652 |
| C30 | claim, prior hypothesis, authors: "it has been argued" | Tg is a common metric of the mobility barrier to crystallization, and crystallization tendency falls below Tg, but modes of mobility not reflected by Tg must also be considered; binary systems can be less mobile than the pure drug at a similar Tg [rests on: cited: refs 20, 22, 29, 35, 37, 41, 42] | p.652-653 |

## 2008 Marsac — Spontaneous Crystallinity Loss of Drugs in the Disordered Regions of Poly(Ethylene Oxide) in the Presence of Water · Solid state stability / PEG dispersions

[2008-marsac-peo-water-spontaneous-drug-crystallinity-loss](../../../cards/2008-marsac-peo-water-spontaneous-drug-crystallinity-loss/paper.html) · Solid state stability / PEG dispersions · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C17 | claim, mechanism, authors: "may"; "this supposition" | The dissolution of drug into PEO is kinetically slow (no transformation at 25 °C and 0% RH); raised temperature or moisture, while altering the driving force, may give the amorphous regions enough mobility to reach the thermodynamic end-state; the temperature effect is supported by ref 31, and the mobility increase by water is widely accepted [rests on: R8, R19] | p.3188-3189 |
| C25 | claim, mechanism, authors: discussion: "it can be argued", "two potential mechanisms"; conclusions: "is thought to"; abstract: asserted ("it was found") | Water facilitates the transformation by two mechanisms: raising the molecular mobility (lowering the viscosity) of the disordered PEO regions, and lowering PEO crystallinity (through deliquescence) so that more polymer can act as solvent [rests on: R9, R11, R13] | p.3190; p.3192; p.3182 |

## 2008 Towler — An Investigation into the Influence of Counterion on the Properties of Some Amorphous Organic Salts · Solid state stability / Crystallization tendency

[2008-towler-counterion-amorphous-organic-salts](../../../cards/2008-towler-counterion-amorphous-organic-salts/paper.html) · Solid state stability / Crystallization tendency · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C21 | claim, prior hypothesis, authors: asserted; "would be anticipated" | Stronger intermolecular interactions give a higher Tg, since more thermal energy is needed for the mobility of the transition; some of the polymer parameters would be anticipated to apply to small molecules; structural factors add through free volume and packing [rests on: cited: refs 36, 37] | p.951 |
| C3 | claim, prior hypothesis, authors: asserted ("was attributed"; "was cited as a cause") | Amorphous sodium indomethacin has a much higher Tg than amorphous indomethacin; Tg of alkali-metal indomethacin salts decreases from lithium to cesium and all exceed the neutral form, attributed to stronger electrostatic interaction of smaller ions with the carboxylate; similar effects are known for inorganic salts and for loperamide-poly(acrylic acid) salt formation [rests on: cited: refs 19-23] | p.947-948 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C18 | claim, prior hypothesis, authors: "can be expected" | Kinetically, mixing a polymer with an amorphous drug reduces molecular mobility (raises Tg), which can be expected to reduce the crystallization rate; molecular motif recognition and specific drug-polymer interactions also affect crystallization [rests on: cited: refs 5, 10, 17, 39-41] | p.2603 |
| C22 | claim, mechanism, authors: abstract: "It is hypothesized"; discussion: "supporting the supposition", "can be explained in part", "can be explained by"; conclusions: "can be attributed" | The rapid and PVP-level-independent crystallization of PVP dispersions at high RH, and their faster crystallization than HPMCAS dispersions, are explained by the greater moisture sorption of PVP dispersions, which causes moisture-induced drug-polymer immiscibility (amorphous-amorphous phase separation) in addition to raising molecular mobility (lowering Tg) [rests on: R6-R9, R21, R23, R24, R25] | p.2599, p.2604, p.2605 |

## 2009 Rumondor — Phase Behavior of Poly(vinylpyrrolidone) Containing Amorphous Solid Dispersions in the Presence of Moisture · Solid state stability / Physical stability

[2009-rumondor-pvp-asd-moisture-induced-immiscibility](../../../cards/2009-rumondor-pvp-asd-moisture-induced-immiscibility/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C34 | claim, mechanism, authors: asserted ("there must be"); Fig. 10 caption: "it is likely that water impacts both" | Moisture-induced AAPS needs both a thermodynamic driving force (the phase-separated state must have lower free energy than the one-phase ternary mixture) and enough molecular mobility for diffusion on the time scale of observation; water affects both [rests on: argument only] | p.1502, p.1503 |
| C38 | claim, conclusion, authors: "appears" | Ketoprofen-PVP at 94% RH was well above its Tg (−23 °C) with enough mobility to separate, yet did not; its thermodynamics favoured one phase at all times, which is evidence against a purely kinetic route [rests on: R16, R25] | p.1502-1503 |
| C41 | claim, conclusion, authors: "clearly important"; "These results suggest" | Mobility matters: pimozide-PVP still separated at 4 °C but much more slowly than at 22 °C (also seen for felodipine-PVP); thermodynamic factors decide whether moisture induces AAPS, and the rate depends at least partly on mobility [rests on: R11, R27] | p.1503 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| E1 | equation | crystal growth rate from the supercooled liquid (viscosity-limited normal growth law): u = (k/η)[1 − exp(−ΔG/(RT))] | p.2396 |
| E2 | equation | normalization of growth rate to undercooling and to distance from Tg (Wu et al.): growth rate normalized to the degree of supercooling (Tm − T) and to (T − Tg) | p.2396 |
| C31 | claim, prior hypothesis, authors: asserted; normalization "to a first approximation" | A decrease in Tm signals a reduced chemical potential of the crystallizing component in the liquid, i.e. a smaller ΔG, and a Tg change arises when an additive of different Tg is present in a quantity sufficient to plasticize or antiplasticize; normalizing growth rates to Tm − T and T − Tg separates these factors [rests on: E2, R16; cited: ref 37] | p.2396 |
| C32 | claim, conclusion, authors: asserted; "in good agreement" | Because dispersion Tg did not differ significantly from that of the drug, increases in Tg cannot account for the slower growth; this agrees with studies showing inhibition without a Tg increase, or even with a Tg decrease [rests on: R1, M1, R20] | p.2396, p.2397 |

## 2010 Kestur — Effects of the Molecular Weight and Concentration of Polymer Additives, and Temperature on the Melt Crystallization Kinetics of a Small Drug Molecule · Solid state stability / Physical stability

[2010-kestur-pvp-mw-concentration-temperature-felodipine-melt-crystallization](../../../cards/2010-kestur-pvp-mw-concentration-temperature-felodipine-melt-crystallization/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C24 | claim, conclusion, authors: "which suggests"; "suggests" | The fitted slope of ln(vη) versus 1/(TΔT) is significantly lower for the PVP K-12 dispersion than for pure felodipine, which under Eq. 5 (slope proportional to γ²/ΔHv) would mean a larger driving force with PVP and so a higher viscosity-corrected growth rate; the data show the opposite, so viscosity cannot be used as a precise measure of felodipine mobility [rests on: R16, E5] | p.3592 |
| C29 | claim, conclusion, authors: asserted; "again suggesting" | The impact of PVP molecular weight on growth rate is not nearly as large as the impact of adding the polymer, and the incremental gain is small; this trend is opposite to the viscosity change (K-12 small, K-90 10-20-fold), so there is no simple correlation between inhibition and viscosity, again making viscosity of limited value as a measure of felodipine mobility [rests on: R7, R8, R10] | p.3592-3593 |
| C35 | claim, mechanism, authors: "We speculate"; "It has been suggested"; conclusions: "favors the idea" | The main cause of the lower felodipine mobility with PVP is drug-polymer hydrogen bonding, which may couple the motions of polymer and drug (conclusions: the model analysis favours reduced mobility through drug-polymer specific interactions) [rests on: R9; cited: refs 10, 14, 37] | p.3593, p.3595 |

## 2010 Marsac — Effect of Temperature and Moisture on the Miscibility of Amorphous Dispersions of Felodipine and Poly(vinyl pyrrolidone) · Solid state stability / Physical stability

[2010-marsac-temperature-moisture-miscibility-felodipine-pvp-asd](../../../cards/2010-marsac-temperature-moisture-miscibility-felodipine-pvp-asd/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C3 | claim, prior hypothesis, authors: "well known"; "may" | Raised temperature can lower the stability of amorphous systems through molecular mobility (ref 8); dispersions meet temperature excursions in melt extrusion, accelerated stability testing and storage [rests on: cited: ref 8] | p.170 |
| C44 | claim, mechanism, authors: "most likely" | Water most likely also raises molecular mobility, letting molecules diffuse into drug-rich and polymer-rich regions (a dual role) [rests on: argument only] | p.182 |
| C46 | claim, mechanism, authors: "presumably"; "a reasonable assumption" | The persistence is related to both metastable phases being glassy at room temperature (felodipine Tg around 46 °C, PVP about 150 °C), so two metastable phases persist after drying, as in solvent-cast polymer blends [rests on: argument only; cited: refs 20, 21] | p.182 |
| C47 | claim, conclusion, authors: "supports the supposition" | At 125 °C, well above the Tg of felodipine and of the one-phase dispersion (about 80 °C), remixing takes place over several hours, which supports miscibility of amorphous felodipine and PVP in the absence of moisture [rests on: R16, R17, R21] | p.182 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| E1 | equation | Adam-Gibbs-Vogel equation: τ = τ0 exp[D T0 / (T − T(T0/Tf))] | Eq. 1, p.750 |
| R7 | record, derived (E1, E2) | log(τTg/τ)^ξ and log(crystal growth rate) + 1 versus T/Tg — drug alone (R1 data, shifted by +1 on the log scale); τ from E1 with M1 constants; Tg at each RH from M1 — sub-table below; text: good correlation obtained with a coupling constant of 0.5 | Fig. 7, p.751; text p.750-751 |
| C24 | claim, mechanism, authors: "is expected"; "indeed observed" | Because crystal growth rate depends on molecular mobility, water uptake by amorphous felodipine should raise its growth rate, and this trend was observed for drug alone up to 80% RH [rests on: R1, R10, R19] | p.749-750 |
| C26 | claim, conclusion, authors: asserted ("The results show") | Growth rate versus T/Tg follows a different trend from molecular mobility: below Tg crystals grew faster than the AGV mobility predicts [rests on: R7] | p.751 |

## 2010 Rumondor — Effect of Polymer Hygroscopicity on the Phase Behavior of Amorphous Solid Dispersions in the Presence of Moisture · Solid state stability / Physical stability

[2010-rumondor-polymer-hygroscopicity-moisture-phase-separation-asd](../../../cards/2010-rumondor-polymer-hygroscopicity-moisture-phase-separation-asd/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C25 | claim, prior hypothesis, authors: asserted ("it was concluded") | Higher molecular mobility from water plasticization alone did not induce immiscibility in PVP dispersions, so the thermodynamics of the system must be considered [rests on: cited: ref 10; R22] | p.488 |
| C32 | claim, mechanism, authors: "it is possible that" | Alternatively, HPMCAS dispersions may not demix because they absorb less water and are less plasticized (lower molecular mobility), as the Tg values after 75% RH of ref 9 illustrate [rests on: R21; cited: ref 9] | p.489 |
| C37 | claim, mechanism, authors: asserted ("was found to") | Water disrupted drug-polymer interactions and, together with its ability to raise molecular mobility, led to phase separation [rests on: R4-R11] | p.490 |

## 2010 Eerdenbrugh — Crystallization Tendency of Active Pharmaceutical Ingredients Following Rapid Solvent Evaporation—Classification and Comparison with Crystallization Tendency from Undercooled Melts · Solid state stability / Crystallization tendency

[2010-van-eerdenbrugh-api-crystallization-tendency-rapid-solvent-evaporation](../../../cards/2010-van-eerdenbrugh-api-crystallization-tendency-rapid-solvent-evaporation/paper.html) · Solid state stability / Crystallization tendency · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C3 | claim, prior hypothesis, authors: asserted ("Factors known") | Crystallization from the amorphous state combines nucleation and growth and is affected by thermodynamic (ΔGv), kinetic (molecular mobility, with Tg as indicator) and molecular (hydrogen bonding) factors, by moisture and by the method used to make the amorphous form [rests on: cited: ref 15] | p.3826-3827 |
| C41 | claim, mechanism, authors: "can be readily understood" | The Tg difference can be readily understood: the Class III criterion (little crystallization during days of room-temperature storage) selects compounds with a higher Tg that are glassy at storage temperature, whereas the melt procedure is short and exposes all samples to temperatures above Tg [rests on: R20.g, P9, P10] | p.3836 |

## 2010 Wanapun — Selective Detection and Quantitation of Organic Molecule Crystallization by Second Harmonic Generation Microscopy · Characterization methods / Solid-state methods

[2010-wanapun-sonicc-amorphous-api-crystallization-detection](../../../cards/2010-wanapun-sonicc-amorphous-api-crystallization-detection/paper.html) · Characterization methods / Solid-state methods · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C6 | claim, prior hypothesis, authors: is expected | At 120 °C griseofulvin is a supercooled liquid, so crystallization is expected to be rapid given both a thermodynamic driving force and sufficient molecular mobility [rests on: argument only] | Results, pp. 5427–5428 |

## 2012 Baird — Role of Viscosity in Influencing the Glass-Forming Ability of Organic Molecules from the Undercooled Melt State · Solid state stability / Crystallization tendency

[2012-baird-viscosity-glass-forming-ability-undercooled-melts](../../../cards/2012-baird-viscosity-glass-forming-ability-undercooled-melts/paper.html) · Solid state stability / Crystallization tendency · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C3 | claim, prior hypothesis, authors: asserted | Viscosity is a critical processing parameter for melt extrusion and a transport property, related to molecular rotation time and mobility above Tg, that influences crystallization between Tm and Tg; few studies have measured viscosity of pharmaceutical amorphous materials in this range, with little focus on links to crystallization tendency [rests on: cited: refs 9-11] | p.272 |
| C26 | claim, generalisation, authors: "likely plays a role" | A trend links crystallization tendency to the temperature dependence of viscosity, so mobility of the undercooled melt likely plays a role in crystallization tendency [rests on: R9, R3, R7] | p.277 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: "have been proposed" | Proposed mechanisms of polymer crystallization inhibition are a higher dispersion Tg (lower mobility), dilution that lowers the drug chemical potential, and specific drug-polymer interactions that restrict local drug mobility [rests on: cited: refs 9, 10] | p.3221 |
| C33 | claim, conclusion, authors: "suggesting"; "indicated" | The small Tg increases reduce mobility and growth, but the Tg differences between dispersions are too small to explain the growth differences; nilutamide, with the largest Tg effect, was not the best inhibitor, so mobility as reflected by Tg cannot completely explain the growth effects; the small Tm changes mean the polymers do not substantially change the degree of supercooling [rests on: R7, R3] | p.3227 |

## 2012 Trasi — Effect of polymers on nucleation and crystal growth of amorphous acetaminophen · Solid state stability / Physical stability

[2012-trasi-taylor-polymers-nucleation-growth-amorphous-acetaminophen](../../../cards/2012-trasi-taylor-polymers-nucleation-growth-amorphous-acetaminophen/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: "are thought to" | Polymers are thought to stabilise amorphous solids against crystallization by raising the Tg of the molecular blend (lower drug mobility) and by drug-polymer specific interactions that disrupt self-assembly; the specific interactions are thought to be particularly important [rests on: cited: refs 4-7] | p.5188 |
| C14 | claim, mechanism, authors: "appears to level off"; "is expected to decrease"; rest asserted | The APAP growth rate appears to level off at 110 °C and is expected to fall towards the form III melting point (134 °C) as the driving force decreases; above 110 °C it stays the same because form II forms and grows; below 100 °C it falls because molecular mobility drops sharply with temperature [rests on: R6.a, R7; cited: ref 24] | p.5190-5191 |

## 2012 Eerdenbrugh — Nanoscale Mid-Infrared Evaluation of the Miscibility Behavior of Blends of Dextran or Maltodextrin with Poly(vinylpyrrolidone) · Characterization methods / Solid-state methods

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C21 | claim, mechanism, authors: "likely" | The lower-MW PVP likely has higher mobility and lower viscosity than higher-MW PVP, which facilitates phase separation into smaller, more localized domains [rests on: argument only] | p.1464 |
| C45 | claim, mechanism, authors: "tends to"; "may be due to" | Formation of discrete domains during spin-coating tends to be favoured by the lower-MW component, which may be due to its higher mobility and lower viscosity; overall structure formation during spin-coating is complex [rests on: R15, R17, R23; argument only] | p.1468 |

## 2013 Kestur — Evaluation of the crystal growth rate of felodipine polymorphs in the presence and absence of additives as a function of temperature · Solid state stability / Physical stability

[2013-kestur-felodipine-polymorph-crystal-growth-pvp-additives](../../../cards/2013-kestur-felodipine-polymorph-crystal-growth-pvp-additives/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C16 | claim, mechanism, authors: "may be attributed" | Faster surface growth may be attributed to mobile molecules at the surface, the surface behaving more liquid-like and the interior more solid-like; indomethacin surface diffusion far exceeds bulk diffusion, and a thin gold coating makes surface crystals grow more like bulk crystals [rests on: cited: refs 5, 10, 12, 16; R17] | p.10 |
| R17 | record, cited | surface vs bulk growth and mobility in other organic glasses — indomethacin, nifedipine, griseofulvin (refs 3, 5, 11); indomethacin glass (ref 16) — surface-enhanced growth one to two orders of magnitude faster than bulk growth; surface diffusion a million times faster than bulk diffusion | p.10 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C40 | claim, mechanism, authors: "presents evidence"; "should be favoured" | The stability of flavonoid-PVP dispersions in moisture is evidence for strong hydrogen bonding, because PVP is very hygroscopic and high RH should favour crystallization through higher molecular mobility, as for felodipine-PVP (R14) [rests on: R9.b, R9.h, R14; cited: ref 45] | p.10 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C26 | claim, assumption, authors: "is expected to be" | All growth rates were measured in the bulk, with the free surface removed by sandwiching, and in a temperature range where growth is mainly controlled by the molecular mobility of the drug [rests on: argument only] | p.254 |
| C29 | claim, generalisation, authors: "It is well known"; "can consequently enhance" | Low-molecular-weight compounds with a low Tg increase molecular mobility and can therefore enhance crystal growth rates, as water does for felodipine and indomethacin [rests on: R18] | p.255 |
| C30 | claim, mechanism, authors: "appear to behave"; "fairly close"; "indicating"; "most likely" | The miscible surfactants appear to behave like small-molecule additives that depress the Tg of the system and enhance growth; after correction for Tg the growth rates of the surfactant systems are fairly close, so their main effect is most likely on the mobility of celecoxib molecules [rests on: R5, R12] | p.255 |

## 2014 Trasi — Factors Influencing Crystal Growth Rates from Undercooled Liquids of Pharmaceutical Compounds · Solid state stability / Crystallization tendency

[2014-trasi-crystal-growth-rates-undercooled-pharmaceutical-liquids](../../../cards/2014-trasi-crystal-growth-rates-undercooled-pharmaceutical-liquids/paper.html) · Solid state stability / Crystallization tendency · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C5 | claim, assumption, authors: asserted ("assuming") | Normalizing to Tg corrects for molecular mobility on the assumption that all compounds have the same mobility at Tg; normalizing to Tm corrects for the extent of undercooling and hence driving force [rests on: argument only] | p.9976 |
| C22 | claim, mechanism, authors: asserted | Thermodynamic driving force and viscosity (molecular mobility) are the two main factors in eq 1; near Tm mobility is high and driving force low, at lower temperature the reverse since ΔG ∝ Tm − T; their combination gives a growth-rate maximum, the MCV at Tcryst,max (Fig. 5); below Tcryst,max bulk growth is dominated by viscosity and above it is under thermodynamic control [rests on: argument only (E1)] | p.9978 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C37 | claim, mechanism, authors: "This suggests"; "unsurprising"; "is likely to be higher" | The new phase of griseofulvin and sorafenib is much more relaxed than the melt-quenched glass, with a heat capacity closer to that of the supercooled liquid; this is unsurprising since it forms in water, where molecular mobility is likely higher and relaxation rapid [rests on: R5, R6, R11] | p.494 |

## 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: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C46 | claim, mechanism, authors: "would be expected to persist"; "would reduce" | After solvent removal the domains are glassy at room temperature (Tg 60 and 140 °C), so the system is kinetically trapped: even with favourable mixing thermodynamics, mixing at room temperature is very slow, and heating above Tg lets the system move to the miscible state [rests on: argument only; M1, M2] | p.17 |
| C47 | claim, mechanism, authors: "An alternative explanation"; "very likely trap" | Alternatively ITZ and HPMC have limited miscibility at room temperature that increases with temperature (UCST behaviour): near the drug melting point mixing is favoured by entropy and mobility, and on cooling the glassy blend is trapped in a miscible state [rests on: argument only; cited: ref 77] | p.17 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C12 | claim, mechanism, authors: "This suggests"; "should" | RTV has a Tg about 30° lower than LPV, so amorphous LPV should be more stable than RTV through lower molecular mobility at room temperature [rests on: R2.a-b] | p.285 |
| C2 | claim, prior hypothesis, authors: "can be often circumvented" | Crystallization of the amorphous form is the main drawback; blending with high-Tg polymers often prevents it by drug-polymer interactions and lower molecular mobility [rests on: cited: refs 13, 19, 21] | p.282 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C8 | claim, prior hypothesis, authors: "are thought to" | Polymers inhibit crystallization by reducing drug molecular mobility through a higher Tg and/or by hydrogen bonding with the drug [rests on: cited: refs 5-7] | pdf p.2 |
| C32 | claim, mechanism, authors: asserted | Water absorption lowers the glass transition temperature, raising molecular mobility and so causing rapid crystallization of pure amorphous CEX [rests on: argument only] | pdf p.9 |

## 2016 Lu — Vemurafenib: A Tetramorphic System Displaying Concomitant Crystallization from the Supercooled Liquid · Solid state stability / Crystallization tendency

[2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid](../../../cards/2016-lu-vemurafenib-tetramorphic-cold-crystallization-supercooled-liquid/paper.html) · Solid state stability / Crystallization tendency · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C17 | claim, mechanism, authors: "can be readily explained" | The bell-shaped growth-rate profile of α-needles, with a maximum at 250 °C, is explained by a rising thermodynamic driving force and falling molecular mobility as temperature decreases [rests on: R12; cited: ref 20] | p.12-13 |
| C3 | claim, prior hypothesis, authors: asserted | Research on amorphous pharmaceuticals has focused on molecular mobility, polymeric additives and water, but crystallization mechanisms remain poorly understood and few studies address how different crystal phases evolve from amorphous drugs [rests on: cited: refs 5-16] | p.2-3 |

## 2016 Sato — Acceleration of the crystal growth rate of low molecular weight organic compounds in supercooled liquids in the presence of polyhydroxybutylate · Solid state stability / Physical stability

[2016-sato-phb-crystal-growth-supercooled-organic-compounds](../../../cards/2016-sato-phb-crystal-growth-supercooled-organic-compounds/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C19 | claim, mechanism, authors: "most likely"; "support the conjecture" | The polymers most likely change the growth rate by changing the mobility of the crystallizing solute in the supercooled liquid; the variation of Tg with polymer content supports the conjecture that viscosity changes play a role [rests on: R7, R8; C18] | p.7 |
| C24 | claim, mechanism, authors: "broad agreement"; abstract: "rationalized" | The observations agree broadly with Yu's explanation: the PHB-compound mobility difference is greatest for the high-Tg compounds, which leads to acceleration; as the difference decreases (APAP, ATP, FLU, with much lower Tg) PHB no longer accelerates and begins to retard growth (abstract: observations rationalized by the extent of mobility differences) [rests on: R11, R3, R4; cited: ref 22] | p.1, p.7 |
| C28 | claim, mechanism, authors: "suggesting" | The acceleration suggests that PHB increased the molecular mobility of the crystallizing compound [rests on: R4, R11] | p.7 |
| X7 | extractor note | claim-data gap — C24, C25 and C28 attribute acceleration and retardation to the mobility of PHB and of the compound, or to impeded transport; no mobility, viscosity, relaxation or diffusion measurement was made, Tg being the only proxy, which the authors themselves call "a crude indicator" (C26) — C24, C25, C28, C19, C26 — treat the mobility mechanisms as untested interpretation |  |

## 2017 Indulkar — Origin of Nanodroplet Formation upon Dissolution of an Amorphous Solid Dispersion: A Mechanistic Isotope Scrambling Study · Dissolution / A. Release mechanism and LoC

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C18 | claim, mechanism, authors: "can be attributed"; "presumably"; "appears" | The fast exchange at 25 °C is attributed to the droplets being above their Tg (~17 °C), with higher molecular mobility presumably giving faster equilibrium; at 15 °C and below the droplets are glassy, which appears to slow equilibration [rests on: R3, M1] | pdf p.13 |

## 2017 Li — Understanding the impact of water on the miscibility and microstructure of amorphous solid dispersions – An AFM/LCR and TEM/EDX study · ASD process / ASD process

[2017-li-water-miscibility-microstructure-asd-afm-tem-edx](../../../cards/2017-li-water-miscibility-microstructure-asd-afm-tem-edx/paper.html) · ASD process / ASD process · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C34 | claim, mechanism, authors: "This is to be expected"; "appear to lead"; "perhaps explains" | Route-dependent shape, size and composition of domains are expected: in solution, highly mobile solvated drug and polymer in a changing solvent-water mixture, plus the antisolvent effect, appear to form spherical drug-rich particles in a polymer-rich matrix; in the humid film, with only water and lower mobility, the different microstructure is perhaps explained by that lower mobility [rests on: R18, R19, R22] | p.31 |
| C44 | claim, prior hypothesis, authors: "suggesting" | Thermodynamic factors decide whether an ASD undergoes moisture-induced phase separation on storage, while molecular mobility limits its rate [rests on: R27; cited: ref 35] | p.36 |

## 2017 Saboo — Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy · Solid state stability / Physical stability

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C43 | claim, mechanism, authors: "is likely"; "evidence is provided" | Water acts by altering the thermodynamics of the ASD on uptake (the delta chi effect) rather than only by raising mobility in a system already thermodynamically unstable: during film formation by solvent evaporation mobility is likely high at both low and high RH, which provides evidence for a thermodynamic role of water [rests on: R5, R6; cited: refs 10, 31, 36] | pdf p.20 |
| C44 | claim, mechanism, authors: "This suggests"; "conjecture"; "consistent with" | Annealing at 100 °C, about 75 °C above the Tg, did not produce two Tgs, so mobility is not the sole criterion for phase separation; this conjecture is consistent with miscible melt-extruded ASDs and with remixing on compression [rests on: R22, R24] | pdf p.20 |

## 2017 Tian — Impact of Polymers on the Melt Crystal Growth Rate of Indomethacin Polymorphs · Solid state stability / Physical stability

[2017-tian-polymers-melt-crystal-growth-indomethacin-polymorphs](../../../cards/2017-tian-polymers-melt-crystal-growth-indomethacin-polymorphs/paper.html) · Solid state stability / Physical stability · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C22 | claim, mechanism, authors: asserted | Growth requires molecules to cross the solid-liquid interface and attach to growth sites; the kinetic factor is molecular mobility (viscosity or self-diffusion) and the thermodynamic driving force is the free energy difference, proportional to the undercooling; near the melting point growth is slow for lack of driving force, at lower temperatures mobility falls, giving the bell-shaped curves, with thermodynamic control above and kinetic control below the maximum [rests on: R7; cited: refs 17, 34, 39, 40] | p.16 |
| C28 | claim, conclusion, authors: asserted ("correlates") | The highest viscosity of IDM-PVP correlates with the generally more pronounced effect of PVP in the mobility-controlled region: at 80-100 °C PVP reduced growth rates 5-25-fold against 2-12 for HPMC and 2-3 for HPMCAS [rests on: R13, R12] | p.17 |
| C39 | claim, mechanism, authors: "it appears" | Because the three polymers inhibit IDM polymorphs growing from the same liquid to different extents, the effect cannot be rationalized by the polymer's action on the liquid phase per se (for example on mobility); it appears that the polymers act on the crystal-melt interface of each polymorph differently [rests on: R12, R15] | p.19 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C44 | claim, mechanism, authors: "perhaps, at least intuitively, consistent"; "may restrict" | The stronger CEX hydrogen bonds with PVP and PVP/VA may restrict diffusive motion and hence self-association of drug molecules, in line with literature examples linking interactions to physical stability [rests on: R3, R4, R5, R6, R29; cited: refs 7, 44] | p.8 |
| C46 | claim, conclusion, authors: discussion: asserted ("It is clear"); conclusions: asserted ("was not predictive") | Tg, taken as a measure of molecular mobility, cannot alone explain the differences in stability at 94% RH: the binaries except PVP-K12 have similar Tg but very different crystallization kinetics; Tg was not predictive of crystallization tendency under high RH [rests on: R17, R23] | p.8, p.10 |

## 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: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C38 | claim, mechanism, authors: "may arise, in part" | The susceptibility of INDester to crystallization may arise in part from its low Tg [rests on: M2] | p.28 |
| C51 | claim, generalisation, authors: "suggests that there may be"; "may" | The LoC drop from 10 to 5% DL at 17 °C, below the wet Tg of IND, suggests some impact of drug Tg on the LoC: drugs in the glassy state may achieve lower LoC than those in the supercooled liquid state [rests on: R29, M1] | p.32 |
| C55 | claim, mechanism, authors: "is expected to depend"; "may explain" | For ASDs, polymer dissolution rate is expected to depend on the water absorbed to form the gel layer, which falls with DL and may explain polymer-controlled dissolution at low DL, and on the Tg of the hydrated matrix or gel layer relative to the temperature; lowering the temperature impedes chain mobility and disentanglement, which may explain the lower IND LoC at lower temperatures [rests on: R29; cited: ref 37] | p.33 |

## 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: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C11 | claim, assumption, authors: asserted ("A previous study showed") | Lower HPMC-AS 1H NMR peak intensity in the presence of drug-rich droplets reflects polymer distributed into the droplets, whose mobility is suppressed, so the NMR-detected concentration measures polymer left in the bulk solution [rests on: cited: refs 28, 42] | p.11 |

## 2020 Ueda — Polymer type impacts amorphous solubility and drug-rich phase colloidal stability: A mechanistic study using nuclear magnetic resonance spectroscopy · Dissolution / C. Amorphous solubility and LLPS

[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 · measured · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | ¹H NMR aromatic region above S_a,IBP, HPMC and PVP-VA — as R9, polymer 300 µg/mL — IBP-rich peaks broadened and moved down-field relative to buffer: HPMC ≈7.06 and ≈6.87 (+ 100), ≈7.05 and ≈6.86 (+ 200), ≈7.04 and ≈6.85 ppm (+ 300); PVP-VA ≈7.10 and ≈6.91 (+ 100), ≈7.10 and ≈6.90 (+ 200), ≈7.09 and ≈6.90 ppm (+ 300) (read from Fig. 5); IBP-rich peak area increased with IBP concentration; aqueous-phase IBP peaks broader than in buffer at all three concentrations, at unchanged positions | Fig. 5, p.26; text p.23-24 |
| C21 | claim, mechanism, authors: "indicates"; asserted ("strongly suppressed"); "consistent with"; "unsurprising" | NMR peak broadening indicates mobility suppression, so in HPMC and PVP-VA the IBP mobility in the IBP-rich phase was strongly suppressed, together with changes in its chemical environment, consistent with the earlier finding that HPMC distributes into the IBP-rich phase; given this mixing, the shifts of the IBP-rich peaks are unsurprising [rests on: R10; cited: refs 22, 41, 42] | p.23-24 |

## 2021 Moseson — Amorphous Solid Dispersions Containing Residual Crystallinity: Competition Between Dissolution and Matrix Crystallization · ASD process / ASD process

[2021-moseson-residual-crystallinity-dissolution-matrix-crystallization](../../../cards/2021-moseson-residual-crystallinity-dissolution-matrix-crystallization/paper.html) · ASD process / ASD process · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C54 | claim, mechanism, authors: asserted; "as would be expected" | On hydration the amorphous BCL/PVPVA solid gains significant molecular mobility that lets it crystallize; preferential PVPVA dissolution is expected at such a high drug loading [rests on: R25, R26; cited: refs 10, 11, 26] | p.14 |
| C56 | claim, mechanism, authors: asserted ("therefore"); "may have" | This mobility lets drug molecules reorganize into crystals or join nearby crystals, and rapid polymer depletion disrupts drug-polymer interactions that may have stabilized the ASD under ambient conditions [rests on: argument only] | p.14 |

## 2021 Saboo — Exploring the Role of Surfactants in Enhancing Drug Release from Amorphous Solid Dispersions at Higher Drug Loadings · Dissolution / A. Release mechanism and LoC

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C43 | claim, mechanism, authors: "could be related"; "should theoretically"; "may compete"; conclusions: "may also play a role" | TPGS acts as a plasticizer that lowers Tg and raises molecular mobility; a lower Tg should let polymer disentanglement start with less water, favour polymer dissolution, and so compete with phase separation and prevent the drug-rich surface layer; conclusions: higher mobility may also play a role in the higher LoC [rests on: R5; cited: refs 47, 49] | p.17, p.19 |
| C44 | claim, generalisation, authors: "could help" | Enhanced mobility and/or the favourable morphology of the drug-rich domains could help drive the higher LoC of ternary ASDs [rests on: R5, R21, R23] | p.17 |
| C45 | claim, prior hypothesis, authors: asserted ("highlighting") | Tg relative to the dissolution temperature affects ASD release, as the indomethacin-PVPVA LoC fell below the Tg, so molecular mobility plays an important role [rests on: R27] | p.17 |

## 2021 Ueda — Effect of Polymer Species on Maximum Aqueous Phase Supersaturation Revealed by Quantitative Nuclear Magnetic Resonance Spectroscopy · Dissolution / C. Amorphous solubility and LLPS

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C6 | claim, mechanism, authors: asserted ("arise from") | The broadening and downfield shift of IBP-rich-phase peaks arise from suppressed IBP mobility in the drug-rich phase together with a changed chemical environment, both from polymer distributing into the drug-rich phase [rests on: R3; cited: refs 29, 30, 35, 36] | p.1347 |
| C17 | claim, mechanism, authors: "indicating"; mobility contribution "also appears to contribute" | The chemical environment of IBP in the bulk aqueous phase does not change with polymer concentration; the dissolved peaks broaden with polymer concentration, with contributions from exchange and from mobility suppression in the IBP-rich phase, which depends on the amount of polymer there [rests on: R7] | p.1348 |
| C49 | claim, conclusion, authors: asserted ("demonstrated") | NMR showed that polymer mixing changed both the chemical environment and the molecular mobility of IBP in the drug-rich phase, while the polymer had minimal impact on IBP dissolved in the bulk aqueous phase [rests on: R1, R3, R7] | p.1353 |

## 2022 Jr — Impact of Polymer Type on Thermal Degradation of Amorphous Solid Dispersions Containing Ritonavir · ASD process / ASD process

[2022-alvarenga-polymer-type-thermal-degradation-ritonavir-asd](../../../cards/2022-alvarenga-polymer-type-thermal-degradation-ritonavir-asd/paper.html) · ASD process / ASD process · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C17 | claim, conclusion, authors: "we infer" | PVP grades showed no statistically significant difference in degradation; because the grades differ in molecular weight, which is closely linked to viscosity, polymer global mobility differences are not a major factor in RTV-PVP degradation [rests on: R15, R17] | p.337 |
| C20 | claim, conclusion, authors: "generally"; "appears"; asserted | Tg and degradation show conflicting trends: across RTV-PVP K-30, RTV-PVP/VA 64, RTV-HPMCAS and RTV-HPMC stability generally increases with Tg, but HPMCAS MF (Tg 72.6 °C) appears more stable than HPMCAS LF (75.0 °C); PVP and PVP/VA grades and DLs span a wide Tg range without a significant difference in degradation; no clear correlation between Tg and RTV degradation [rests on: R3, R4, R10, R13, R15, R16, R18] | p.337-338 |
| C21 | claim, caveat, authors: asserted ("It is worth noting") | Tg is only a crude indicator of molecular mobility; specific interactions such as hydrogen bonding and a high API weight fraction can make Tg and mobility deviate [rests on: argument only] | p.338 |
| C34 | claim, conclusion, authors: asserted ("was not found") | The molecular mobility hypothesis had no direct relationship to degradation extent: no correlation across polymer types ranked by Tg or T/Tg, and no change in degradation across PVP grades (Tg of the formulated systems stated as 80 to 170 °C), PVP/VA VP:VA ratios or DL [rests on: R14, R17, R18] | p.341-342 |

## 2022 Soto — Impact of Surfactants on the Performance of Clopidogrel-Copovidone Amorphous Solid Dispersions: Increased Drug Loading and Stabilization of Nanodroplets · Dissolution / A. Release mechanism and LoC

[2022-correa-soto-surfactants-clopidogrel-copovidone-asd-nanodroplets](../../../cards/2022-correa-soto-surfactants-clopidogrel-copovidone-asd-nanodroplets/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C15 | claim, mechanism, authors: asserted; "clearly" | The droplet peaks appear at 50 °C but not at 37 °C because the higher temperature makes CPD in the droplets mobile enough (short enough reorientation correlation time) for solution NMR; with a Tg of −9 °C, mobility at 37 °C is insufficient [rests on: R8, R31; M1] | p.174-175 |
| C51 | claim, generalisation, authors: "is emerging"; "potentially" | A low formulation Tg is emerging as favourable for release, but the higher mobility also allows crystallization and AAPS [rests on: argument only] | p.184 |

## 2022 Correasoto — Role of surfactants in improving release from higher drug loading amorphous solid dispersions · Dissolution / A. Release mechanism and LoC

[2022-correa-soto-surfactants-higher-drug-loading-atazanavir-pvpva-asds](../../../cards/2022-correa-soto-surfactants-higher-drug-loading-atazanavir-pvpva-asds/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C13 | claim, prior hypothesis, authors: "if"; "is expected" | With dry and wet Tg of 105 and 55 °C, ATZ has limited molecular mobility below its Tg; if mobility restricts dissolution, faster and higher release is expected when the temperature is closer to or above Tg [rests on: cited: Saboo 2020; M1] | p.3 |
| C22 | claim, mechanism, authors: "suggest"; "In support of this supposition" | The film images suggest that surfactants increase mobility and facilitate phase separation; binary films phase separating within 10 min at 50 °C and 100% RH, closer to the ATZ Tg, support this [rests on: R9, R10, R11, R12] | p.6 |
| C37 | claim, generalisation, authors: "likely underpin" | The critical role of mobility is highlighted by release of both components at 55 °C and by water-induced phase separation at the higher temperature but not at 37 °C; mobility-dependent polymer release likely underpins the poorer release of ASDs of high-Tg compounds compared with lower-Tg drugs [rests on: R5, R6, R9, R12, R25] | p.8-9 |
| C41 | claim, mechanism, authors: "is supported by" | Enhanced mobility with each surfactant is supported by water-induced phase separation in these systems and its absence in the surfactant-free system, since mobility is required for phase separation [rests on: R9, R10, R11; cited: Barnes 1999] | p.9 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C5 | claim, prior hypothesis, authors: "may"; "likely" | Salt formation may alter the crystallization tendency of a drug; strong drug-counterion electrostatic interactions likely stabilize the amorphous form through a higher Tg and lower molecular mobility, and bulky counterions may hinder crystallization sterically [rests on: cited: refs 8, 16-19] | p.132 |
| C7 | claim, prior hypothesis, authors: "It was hypothesized" | Hypothesis: DLM sulfonic acid salts resist solid-state crystallization better than the amorphous free base because of their higher Tg, and keeping the salt amorphous in ASDs improves release [rests on: argument only] | p.132 |

## 2022 Hiew — Combining drug salt formation with amorphous solid dispersions – a double edged sword · Dissolution / A. Release mechanism and LoC

[2022-hiew-combining-drug-salt-formation-asd-double-edged-sword](../../../cards/2022-hiew-combining-drug-salt-formation-asd-double-edged-sword/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C1 | claim, prior hypothesis, authors: abstract: asserted; introduction: "probably one of the most important" | Tg is a key property of amorphous compounds: physical and chemical stability depend on storage temperature relative to Tg, and recrystallization speeds up markedly above Tg [rests on: cited: refs 19-21] | p.47 |
| C47 | claim, mechanism, authors: "potential explanation" | Separating drug from polymer needs molecular mobility; for high-Tg salts the hydrated salt is plasticized far less than the hydrated polymer, as the neat salts absorb much less water, so the Tg asymmetry can arrest a thermodynamically favoured phase separation, a concept established for polymer-solvent blends and other systems [rests on: R4, R5; cited: refs 49, 50] | p.58 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C24 | claim, conclusion, authors: results: "can be linked", "generally"; discussion: asserted ("on trend") | Crystallization onset can be linked to thermal properties: the least stable arms (EH60 at 75% RH; ERL/PVPVA, stated as 75% RH) had negative Tg − T, longer-stable arms (LP40, NH10) generally positive; samples crystallized more readily when stored above their Tg [rests on: R11, R12] | p. 40704; p. 40706 |
| C25 | claim, mechanism, authors: asserted ("This confirms") | Sample mobility, rather than system chemistry or particle attributes, was the primary mechanism by which some coated systems still crystallized [rests on: R11, R12] | p. 40704 |
| C41 | claim, mechanism, authors: asserted ("This effect was demonstrated herein") | Water mechanism: nucleation and growth rates rise with RH through moisture-enhanced mobility; shown here by shorter onset at higher RH for EH60 (43 vs 75%) and LP40 (31 vs 43%) through lower wet Tg [rests on: R11, R12; cited: refs 67, 68] | 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: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C3 | claim, prior hypothesis, authors: "We hypothesized"; "indicated" | In the earlier BCL/PVPVA study, matrix crystallization dominated the achievable supersaturation through competition between dissolution and crystallization of the hydrated amorphous solid, appeared to be surface-driven, and was hypothesized to arise because incongruent release left the hydrated amorphous drug highly mobile and unprotected by interactions with the polymer [rests on: cited: ref 11; R21] | p.4-5, p.29 |
| C46 | claim, mechanism, authors: asserted ("can") | The highly mobile hydrated drug can crystallize within the boundary layer, lowering dissolved concentrations and the driving force for further release; crystallization kinetics depend on the thickness and extent of the amorphous drug-rich phase and crystalline network in the shell [rests on: R14, R15] | p.31-32 |
| C58 | claim, mechanism, authors: "may provide"; "suggests a potential" | Surface enrichment of surfactant, documented for several ternary ASDs, may give high local mobility at the particle surface, a potential mechanism for the greater susceptibility after mechanical activation [rests on: cited: ref 60] | p.34 |
| C60 | claim, mechanism, authors: "We hypothesize" | Keeping the ASD matrix homogeneous until drug release is hypothesized to protect the amorphous drug from preferential polymer dissolution and from hydration-induced mobility and Tg reduction [rests on: argument only] | p.34 |

## 2022 Ueda — Variable-Temperature NMR Analysis of the Thermodynamics of Polymer Partitioning between Aqueous and Drug-Rich Phases and Its Significance for Amorphous Formulations · Dissolution / C. Amorphous solubility and LLPS

[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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C10 | claim, mechanism, authors: asserted ("Indeed") | Mixing of polymer with the IBP-rich phase causes the down-field shift and broadening of IBP-rich-phase peaks and suppresses IBP mobility there; polymer inside the IBP-rich phase is invisible in solution NMR because of its long re-orientational correlation time; the lower aqueous polymer signal with IBP present supports the mixing [rests on: R4, R7, R8; cited: refs 33, 36] | p.103 |
| C13 | claim, mechanism, authors: sharpening: asserted; HPMC: "it can be assumed" | IBP-rich-phase peaks sharpen with temperature in PVP and PVP−VA solutions because IBP mobility rises; for HPMC the mobility gain is assumed to be partly cancelled by additional HPMC mixing at higher temperature [rests on: R5] | p.104 |
| C20 | claim, mechanism, authors: asserted | Crystalline IBP gives broad 1H peaks because strong homonuclear dipolar couplings are incompletely averaged at 10 kHz MAS; amorphous IBP (Tg −45 °C) gives solution-like sharp peaks at 40 °C because rapid isotropic motion averages the couplings [rests on: R11, M1; cited: refs 52, 58, 59] | p.105 |
| C22 | claim, mechanism, authors: "would be expected"; "consistent with" | The broader IBP peaks in ASDs come from mobility suppression by higher viscosity and/or IBP-polymer interactions; the slight down-field shift of aliphatic and aromatic peaks fits a more polar environment [rests on: R11] | p.105 |
| C27 | claim, conclusion, authors: asserted ("reflecting") | IBP peaks dominate the PST spectra because IBP molecules are more mobile than polymer molecules in the ASDs [rests on: R12; cited: ref 70] | p.106 |

## 2023 Correasoto — Release Enhancement by Plasticizer Inclusion for Amorphous Solid Dispersions Containing High Tg Drugs · Dissolution / A. Release mechanism and LoC

[2023-correa-soto-plasticizer-release-enhancement-high-tg-pvpva-asds](../../../cards/2023-correa-soto-plasticizer-release-enhancement-high-tg-pvpva-asds/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C14 | claim, prior hypothesis, authors: "it is expected" | If low mobility, reflected in a high Tg, limits drug release, a plasticizer is expected to increase the LoC of LED (dry Tg 160 °C, binary LoC 5% DL) [rests on: argument only; cited: ref 16] | p.783 |
| C19 | claim, prior hypothesis, authors: "A possible reason"; "it is expected" | A possible reason for the LoC increase of the two high Tg drugs is plasticization raising mobility, so little improvement is expected for a lower Tg drug such as RTV (Tg 50 °C, binary LoC 25% DL), whose molecular mobility is expected to be less limiting [rests on: argument only; R15] | p.783 |
| C31 | claim, mechanism, authors: "can be broadly rationalized"; "at a simplistic level"; "may" | The release gains can be broadly rationalized by trends between poor release and API Tg and by the Tg reduction from the plasticizer: at a simplistic level a plasticizer may increase mobility of the ASD components, promoting polymer dissolution, and may affect formation of the drug-rich barrier postulated above the LoC [rests on: R16, R17, R18; cited: refs 12, 16, 17] | p.787 |
| C39 | claim, mechanism, authors: "it is reasonable to suggest"; conclusion: "The suggested mechanism" | It is reasonable to suggest that one mechanism by which plasticizers enhance drug dissolution rate and the LoC of high Tg API ASDs is increased polymer chain mobility, i.e. a faster disentanglement rate; conclusion: the suggested mechanism is enhanced polymer disentanglement [rests on: R13, R6, R12, R23] | p.788 |

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Role of Drug Load and Molecular Interactions · Dissolution / A. Release mechanism and LoC

[2023-deac-asd-drug-load-molecular-interactions-loc](../../../cards/2023-deac-asd-drug-load-molecular-interactions-loc/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C40 | claim, mechanism, authors: "can occur"; "can kinetically trap" | Long equilibration can occur when the hydrophobic phase has a high Tg, where low molecular mobility can kinetically trap the polymer [rests on: argument only] | p.732 |
| C17 | claim, conclusion, authors: asserted | TIPP and MeTIPP suspensions equilibrated very slowly at 37 °C; at 60 °C TIPP equilibrated within 3 h, whereas MeTIPP did not reach equilibrium because the drug crystallized after 1 h [rests on: R9, R10.b] | p.727 |

## 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: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| 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 |
| C33 | claim, prior hypothesis, authors: asserted | Earlier coatings: an enteric coating gave colonic delivery of a tacrolimus-HPMC ASD; enteric coating avoided crystallization of niclosamide-copovidone ASD by delaying release to intestinal pH, where crystallization is less favourable owing to drug ionization; non-enteric coatings (polymer nanocoatings, ethyl cellulose, atomic layer coating) reduce surface molecular mobility and delay solid-state crystallization [rests on: cited: refs 7, 19, 20, 21, 27, 32, 37, 38, 65, 71; R21] | p.8 |

## 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 · used · as: molecular mobility

| id | kind | content | locator |
|---|---|---|---|
| C46 | claim, mechanism, authors: asserted ("serves to"; "will reduce") | The high polymer content of the nanodroplets, particularly with H, lowers molecular mobility and lowers the drug chemical potential by dilution, and both reduce the crystallization tendency [rests on: R17; argument only] | p.231 |

## Mentioned only

- 1997 Taylor — [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 (ref C4)
- 2006 Marsac — [2006-marsac-drug-polymer-miscibility-solubility](../../../cards/2006-marsac-drug-polymer-miscibility-solubility/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref C59)
- 2008 Konno — [2008-konno-polymer-type-felodipine-asd-dissolution](../../../cards/2008-konno-polymer-type-felodipine-asd-dissolution/paper.html) · Dissolution / B. Supersaturation from ASD dissolution (ref 14)
- 2008 Konno — [2008-konno-polymers-inhibit-amorphous-felodipine-moisture-crystallization](../../../cards/2008-konno-polymers-inhibit-amorphous-felodipine-moisture-crystallization/paper.html) · Solid state stability / Physical stability (ref C2 C4)
- 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 12)
- 2011 Kestur — [2011-kestur-polymer-chemistry-crystal-growth-bifonazole-nimesulide](../../../cards/2011-kestur-polymer-chemistry-crystal-growth-bifonazole-nimesulide/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref C1)
- 2012 Hsieh — [2012-hsieh-ph-induced-precipitation-weak-bases-supersaturation-solid-state](../../../cards/2012-hsieh-ph-induced-precipitation-weak-bases-supersaturation-solid-state/paper.html) · Dissolution / D. Crystallization from solution (ref C43)
- 2013 Ilevbare — [2013-ilevbare-polymers-supersaturation-induction-times](../../../cards/2013-ilevbare-polymers-supersaturation-induction-times/paper.html) · Dissolution / D. Crystallization from solution (ref E4)
- 2014 Trasi — [2014-trasi-taylor-amorphous-nilutamide-low-temperature-nucleation](../../../cards/2014-trasi-taylor-amorphous-nilutamide-low-temperature-nucleation/paper.html) · Solid state stability / Crystallization tendency (ref 6)
- 2015 Purohit — [2015-purohit-phase-separation-kinetics-asd-water](../../../cards/2015-purohit-phase-separation-kinetics-asd-water/paper.html) · Characterization methods / Solid-state methods (ref C23 C24)
- 2015 Sato — [2015-sato-cellulose-polymer-chiral-crystallization-inhibition-enantiomers](../../../cards/2015-sato-cellulose-polymer-chiral-crystallization-inhibition-enantiomers/paper.html) · Solid state stability / Physical stability (ref 10)
- 2016 Sousa — [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 (ref C5)
- 2016 Mosqueragiraldo — [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 (ref 27)
- 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 C42)
- 2017 Trasi — [2017-trasi-commercial-amorphous-tacrolimus-crystallization-stress](../../../cards/2017-trasi-commercial-amorphous-tacrolimus-crystallization-stress/paper.html) · Solid state stability / Physical stability (ref C3 C5)
- 2019 Elkhabaz — [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 (ref 22)
- 2019 Trasi — [2019-trasi-solvent-granulation-ritonavir-lopinavir-asd](../../../cards/2019-trasi-solvent-granulation-ritonavir-lopinavir-asd/paper.html) · ASD process / ASD process (ref C2)
- 2020 Trasi — [2020-trasi-lumefantrine-asd-granules-solvent-evaporation](../../../cards/2020-trasi-lumefantrine-asd-granules-solvent-evaporation/paper.html) · Solid state stability / Physical stability (ref C2)
- 2021 Bhujbal — [2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation](../../../cards/2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation/paper.html) · Solid state stability / Physical stability (ref 11)
- 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 15)
- 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 11)