# Evidence: hydrogen bonding

Parent: — · class: molecular interaction · names merged here: hydrogen bonding

59 papers measured or used it, 5 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | IR acid carbonyl bands of solid dispersions — P3 dispersions, 5-70 wt% PVP (P8) — cyclic dimer carbonyl peak decreases in intensity while the non-hydrogen bonded carbonyl peak increases between 5 and 20% PVP; at 20% PVP and above a single broad peak at 1726 cm−1, which becomes a shoulder as indomethacin content decreases further and the PVP carbonyl absorption dominates | Fig. 5, p.1695; text p.1696 |
| R12 | record, measured | IR band at 1636 cm−1 — P3 dispersions versus P4 physical mixes — absent in physical mixes; present in dispersions with 5-50% PVP; at 60-70% PVP merged with the non-hydrogen bonded carbonyl peak and apparent only as a shoulder; overall band considerably broader than in the physical mix | Fig. 5, p.1695; text p.1696 |
| R15 | record, measured | IR carbonyl region of acetic acid-methylpyrrolidone mixtures — P5, 0-100 wt% methylpyrrolidone (P8, NaCl windows) — two intense carbonyl peaks: acid 1716 cm−1, methylpyrrolidone amide 1688 cm−1; with increasing methylpyrrolidone the 1759 cm−1 shoulder grows relative to the 1716 cm−1 dimer peak; methylpyrrolidone carbonyl first seen at 1652 cm−1, 36 cm−1 below pure methylpyrrolidone; at higher methylpyrrolidone a second peak at 1688 cm−1; text: free methylpyrrolidone carbonyl from between 30 and 40% methylpyrrolidone; figure: a separate band between the 1716 and 1652 cm−1 peaks visible from ≈50% (read from Fig. 6a) | Fig. 6a, p.1696; text p.1695-1696 |
| R16 | record, measured | IR carbonyl region of indomethacin dissolved in methylpyrrolidone — P5, 30-70 wt% methylpyrrolidone (P8) — indomethacin 1710 cm−1 peak disappears and the 1735 cm−1 shoulder develops into a single peak at 1723 cm−1; at low methylpyrrolidone a hydrogen-bonded methylpyrrolidone carbonyl peak at 1649 cm−1; the peak at the free methylpyrrolidone position, coincident with the benzoyl carbonyl, grows relative to the 1649 cm−1 peak with increasing methylpyrrolidone | Fig. 6b, p.1696 |
| C33 | claim, conclusion, authors: asserted ("is assigned") | The 1726 cm−1 band is the non-hydrogen-bonded acid C=O of an indomethacin molecule hydrogen-bonded through its OH to PVP; the 1636 cm−1 band, absent in physical mixes, is hydrogen-bonded PVP carbonyl [rests on: R10, R11, R12] | p.1696 |
| C35 | claim, conclusion, authors: discussion: "Spectral data support the fact"; abstract results: "indicating hydrogen bonding"; abstract conclusions and summary: asserted | Indomethacin forms hydrogen bonds with PVP, between the drug hydroxyl and the polymer carbonyl, at the expense of dimer formation [rests on: R11, R12, R14, R15, R16] | p.1691, p.1696, p.1697 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | felodipine reference IR bands — crystalline and amorphous felodipine films (P7) — crystalline: NH stretch 3373 cm⁻¹, single C=O stretch 1696 cm⁻¹; amorphous: NH stretch 3341 cm⁻¹ (Table 2: 3340), C=O split into 1701 and 1682 cm⁻¹ | text p.2698-2699; Figs. 7-9; Table 2, p.2701 |
| R11 | record, measured | felodipine NH stretching region versus PVP content — felodipine/PVP films 0-70% PVP (P7) — text: NH peak broadens and develops a low-wavenumber shoulder as PVP rises; at 30% PVP a broad peak with two poorly resolved maxima at approximately 3345 and 3290 cm⁻¹; with more PVP the low-wavenumber component grows at the expense of the high-wavenumber peak; at 70% PVP a shoulder at 3345 cm⁻¹ remains. Figure: main maximum ≈3300 cm⁻¹ at 40% shifting to ≈3290 cm⁻¹ at 60-70%; a second band at ≈3225-3230 cm⁻¹ in the 40-70% spectra, present as a weak shoulder near ≈3240 cm⁻¹ in amorphous felodipine and the 10-30% spectra (read from Fig. 7a); PVP alone flat in this region | Fig. 7a, p.2699; text p.2699-2700 |
| R13 | record, measured | NH and carbonyl regions versus HPMCAS content — felodipine/HPMCAS films 0-70% (P7) — text: slight increase of the NH peak to higher wavenumber; height of the 1701 cm⁻¹ peak increases relative to the 1682 cm⁻¹ peak. Figure: NH maximum ≈3341 cm⁻¹ at 10% to ≈3355 cm⁻¹ at 70%; HPMCAS alone carbonyl band ≈1742 cm⁻¹ (read from Fig. 8) | Fig. 8, p.2699; text p.2700 |
| R14 | record, measured | NH and carbonyl regions versus HPMC content — felodipine/HPMC films 0-70% (P7) — text: NH peak stays in essentially the same position as in amorphous felodipine and broadens slightly; height of the 1701 cm⁻¹ peak increases relative to the 1682 cm⁻¹ peak. Figure: NH maximum ≈3341 cm⁻¹ at 10% to ≈3345 cm⁻¹ at 60%; background rising toward 3450 cm⁻¹ at 50-70%, as in HPMC alone (read from Fig. 9) | Fig. 9, p.2700; text p.2700 |
| R15 | record, measured | peak height ratio of 1701 cm⁻¹ (non-hydrogen-bonded C=O) to 1682 cm⁻¹ (hydrogen-bonded C=O) — felodipine/HPMCAS and felodipine/HPMC films (P7) — sub-table below; text: ratio increases with polymer concentration | Fig. 10, p.2700 |
| R16 | record, measured | NH peak position by hydrogen-bond pattern (cm⁻¹) — amorphous felodipine; dispersions at 70% w/w polymer (table footnote) — sub-table below (Table 2 transcribed in full) | Table 2, p.2701 |
| C29 | claim, conclusion, authors: asserted ("was found to be") | Felodipine-polymer hydrogen-bond strength ranks PVP > HPMC > HPMCAS: stronger than in amorphous felodipine with PVP, similar with HPMC, slightly weaker with HPMCAS; abstract: hydrogen bonds formed with each polymer, stronger with PVP than with the others [rests on: R16, R11, R13, R14] | p.2692, p.2702 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, cited (ref 28) | hydrogen bonding between nifedipine and PVP — ref 28 — extensive specific hydrogen bonding interactions demonstrated | p.2421 |
| C24 | claim, mechanism, authors: "most likely" | The discrepancy most likely arises from applying solubility parameters to systems with specific interactions: Eq. 2 assumes the unlike interaction equals the geometric mean of the like interactions, reasonable for van der Waals interactions but not for specific directional interactions such as the nifedipine–PVP hydrogen bonds [rests on: R4, R14; cited: refs 17, 21] | p.2420-2421 |
| C25 | claim, generalisation, authors: "are likely to be inaccurate" | Since many APIs and pharmaceutical polymers form specific interactions, solubility-parameter estimates of χ are likely to be inaccurate for such systems [rests on: cited: refs 2, 7, 8, 29] | p.2421 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, measured | NH-stretch band positions (cm⁻¹) and band shape — amorphous, crystalline, and amorphous dispersion at 4:1 PVP acceptor:drug donor (P6) — values ≈, read from Fig. 8: nifedipine amorphous ≈3345 (broad), crystalline ≈3318, dispersion ≈3287 and ≈3220; felodipine amorphous ≈3345, crystalline ≈3363, dispersion ≈3288 and ≈3223; text: amorphous peak positions of the two drugs very similar; amorphous nifedipine NH band broader than amorphous felodipine; crystal NH frequency lower than amorphous for nifedipine and higher than amorphous for felodipine | Fig. 8, p.2311; text p.2310 |
| R13 | record, measured | NH-stretch features of felodipine with PVP — felodipine films with increasing PVP (P6) — shoulder at 3,420 cm⁻¹; peak at 3,345 cm⁻¹; with increasing PVP a shoulder, then a peak, appears at 3,288 cm⁻¹; the same development is reported for nifedipine | p.2311-2312 |
| R14 | record, measured | NH-region spectra versus PVP acceptor:drug donor ratio 0, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 (bottom to top) — nifedipine-PVP (a) and felodipine-PVP (b) dispersions (P6) — read from Fig. 11: at ratio 0 one band near ≈3340 cm⁻¹; with rising ratio bands near ≈3290 and ≈3225 cm⁻¹ grow and the ≈3340 band becomes a shoulder, in both systems; amplitudes not quantified | Fig. 11, p.2313 |
| R15 | record, measured | NH peak height ratio, drug-drug band (3,345 cm⁻¹) over drug-PVP band (3,288 cm⁻¹), versus PVP acceptor:drug donor ratio (error bars one SD) — nifedipine-PVP and felodipine-PVP dispersions (P6) — sub-table below; text: peak positions and breadths of the drug-PVP bands very similar for the two drugs | Fig. 12, p.2313; text p.2312 |
| C16 | claim, conclusion, authors: position: "as indicated by"; breadth: "there appears to be" | Average hydrogen-bond strength in the two pure amorphous forms is very similar (NH peak position), with a slightly broader distribution of strengths in nifedipine (NH peak breadth) [rests on: R12] | p.2310 |
| C17 | claim, conclusion, authors: asserted; "may provide some insight" | Hydrogen bonding in crystalline nifedipine is on average stronger than in its amorphous form (lower NH frequency in the crystal), whereas amorphous felodipine has stronger average hydrogen bonding than its crystal; this agrees with Tang et al. and may give insight into the molecular-level difference between the drugs [rests on: R12, R20; cited: refs 30-33] | p.2310 |
| C27 | claim, conclusion, authors: "is associated with"; "can be assigned" | The 3,420 cm⁻¹ shoulder is free NH, the 3,345 cm⁻¹ peak is drug-drug hydrogen bonding, and the 3,288 cm⁻¹ band that grows with PVP is drug-polymer hydrogen bonding of the NH to the PVP carbonyl; the same holds for nifedipine [rests on: R13, R14; cited: ref 33] | p.2311-2312 |
| C28 | claim, conclusion, authors: "indicates" | The low-wavenumber NH band of the dispersions shows that drug-polymer hydrogen bonds are stronger than the hydrogen bonds in the pure amorphous drugs [rests on: R12, R13] | p.2312 |

## 2007 Towler — Spectroscopic Characterization of Intermolecular Interactions in Solution and Their Influence on Crystallization Outcome · Solid state stability / Crystallization tendency

[2007-towler-solution-interactions-crystallization-outcome](../../../cards/2007-towler-solution-interactions-crystallization-outcome/paper.html) · Solid state stability / Crystallization tendency · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | IR band positions and assignments in indomethacin solutions — EtOH and MeNO2 — sub-table below | Table 2, p.636 |
| R12 | record, measured | carbonyl band of dilute indomethacin in ethanol, IR and Raman — EtOH, lower concentrations — broad peak around 1660 cm-1 at the same position in IR and Raman; breadth similar to that of the solid-state spectrum of amorphous indomethacin | p.636 |
| R18 | record, measured | carbonyl-region Raman of solutions at supersaturations where α crystallizes, against solid α — indomethacin in EtOH and in MeNO2 (supersaturations not printed); solid α — solid α: ≈1688, ≈1679 and ≈1648; EtOH solution: one broad maximum ≈1681 tailing to lower wavenumber; MeNO2 solution: maximum ≈1682 and a local minimum near ≈1647 (read from Fig. 10 against the tick marks). Text: the α band at 1650 cm-1 is absent from both solution spectra | Fig. 10, p.637; text p.637 |
| C19 | claim, conclusion, authors: "can be assigned" | The broad band near 1660 cm-1 of dilute indomethacin in ethanol arises from both carbonyl groups hydrogen bonded to solvent molecules [rests on: R11.c, R12] | p.636 |
| C29 | claim, conclusion, authors: "The inference is"; conclusions: "No evidence was observed" | The 1650 cm-1 Raman band of α, from the amide carbonyl–carboxylic acid hydrogen bond, is absent from both solutions at α-producing supersaturations, so an interaction present in the solid crystallized is not present in solution before crystallization [rests on: R18, R3.e] | p.637 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | FTIR NH and carbonyl bands after exposure and drying — 25% PVP films (P1), 75% RH at 25 °C for 0 (initial), 1, 3, 4, 5, 6, 7 weeks, dried before measurement (P5) — NH region: band maximum ≈3333 cm⁻¹ (initial) to ≈3339 cm⁻¹ (7 weeks), second band ≈3231-3234 cm⁻¹ (read from Fig. 7a); the lower-wavenumber shoulder (text: 3,291 cm⁻¹, arrow in Fig. 7a) loses intensity relative to the higher-wavenumber component (text: around 3345 cm⁻¹) as exposure time increases; carbonyl region: the shoulder at around 1,655 cm⁻¹ decreases in intensity after exposure and drying; no peak at 3,373 cm⁻¹ | Fig. 7, p.974; text p.974-975 |
| R17 | record, cited | FTIR band assignments used — felodipine dispersions — NH stretch: ≈3345 cm⁻¹ felodipine-felodipine and 3,291 cm⁻¹ felodipine-PVP hydrogen bonding (ref 11); C=O shoulder at around 1,655 cm⁻¹: PVP carbonyl hydrogen bonded with the drug (ref 19); 3,373 cm⁻¹: NH stretch of crystalline felodipine (no reference given) | p.974-975 |
| C21 | claim, mechanism, authors: results: "These results suggest"; "consistent with"; discussion: "appears to undergo"; abstract: "appeared to undergo" | In 25% PVP dispersions absorbed moisture disrupts felodipine-PVP hydrogen bonds, giving more drug-drug interactions, and the disruption persists after the water is removed (NH shoulder at 3,291 cm⁻¹ and C=O shoulder at 1,655 cm⁻¹ decrease); the dispersion appears to undergo molecular-level changes [rests on: R10, R17] | p.969, p.974-975, p.977 |

## 2009 Marsac — Estimation of Drug–Polymer Miscibility and Solubility in Amorphous Solid Dispersions Using Experimentally Determined Interaction Parameters · Solid state stability / Miscibility and drug-polymer interactions

[2009-marsac-drug-polymer-miscibility-solubility-asd-interaction-parameters](../../../cards/2009-marsac-drug-polymer-miscibility-solubility-asd-interaction-parameters/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, simulated and measured per column | dipole moment (P5) and shift of the PVP C=O band in a dispersion with one donor group per carbonyl acceptor (P4) — single molecules (dipole); amorphous dispersions with PVP (shift) — sub-table below; text: shifts are to lower wavenumber | Table IV, p.148 |
| C39 | claim, mechanism, authors: asserted; "providing evidence" | Felodipine, nifedipine and sucrose self-associate by hydrogen bonds in the amorphous state (refs 61, 49), but this is compensated by hydrogen bonds to PVP that are stronger than the drug–drug bonds because PVP carries the better acceptor; the shift of the PVP carbonyl peak to lower wavenumber provides evidence for these drug–polymer hydrogen bonds [rests on: R12; cited: refs 49, 51, 61, 62] | p.148 |
| C42 | claim, mechanism, authors: "most likely"; "is expected"; "appears" | Indomethacin's larger-magnitude χ (−0.82) and lower γ in EP (0.146) can most likely be rationalized by the higher acidity of its carboxyl donor, expected to form stronger hydrogen bonds with PVP than the NH groups of felodipine and nifedipine or the OH groups of sucrose, with the greater carbonyl shift as evidence; indomethacin appears to form the most energetically favourable mixture with PVP [rests on: R7.e, R9.e, R12.c] | p.149 |

## 2009 Rumondor — Evaluation of Drug-Polymer Miscibility in Amorphous Solid Dispersion Systems · Solid state stability / Miscibility and drug-polymer interactions

[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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C18 | claim, prior hypothesis, authors: "Studies have demonstrated"; "These results indicate" | Earlier IR work on felodipine-PVP and nifedipine-PVP showed drug-polymer specific interactions: NH shifts from drug-polymer hydrogen bonds and a rise of the free carbonyl peak with polymer, read as disrupted drug-drug interactions in favour of drug-polymer ones [rests on: R23; cited: refs 9, 10, 23, 26, 27] | p.2526 |
| C20 | claim, mechanism, authors: "is thought to"; "presumably" | The PC1 loading reflects composition; the PC2 loading is thought to arise from specific drug-polymer interactions, its largest NH and carbonyl features presumably reflecting drug-polymer hydrogen bonding [rests on: R7] | p.2527 |
| C39 | claim, mechanism, authors: asserted ("will be favorable") | In felodipine-PVP and nifedipine-PVP the established drug-polymer hydrogen bonds add to the entropic drive and favour mixing, giving one-phase dispersions [rests on: R23; cited: refs 23, 24, 27, 32] | pp.2532-2533 |
| R23 | record, cited (refs 9, 10, 23, 26, 27; refs 23, 24, 27, 32) | IR evidence of drug-polymer specific interactions in earlier work — felodipine-PVP and nifedipine-PVP solid dispersions — peak shifts or shoulders not explained by composition; shifts of the drug NH stretching peak assigned to drug-polymer hydrogen bonding; relative intensity of the free drug carbonyl peak rising with polymer content (refs 9, 10, 23, 26, 27); drug-polymer hydrogen bonding in these systems established (refs 23, 24, 27, 32) | p.2526, p.2532 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | felodipine NH stretching peak position (cm⁻¹) — amorphous felodipine and spin-coated dispersions with 50% w/w polymer (P6, P7) — sub-table below | Table 2, p.2394 |
| R11 | record, measured | IR of felodipine/PVAc films — 0, 20, 30, 40, 50% w/w PVAc (P6, P7) — NH peak 3345 cm⁻¹ at 20% (text), ≈3348 at 30% and ≈3352 at 40% (read from Fig. 7a), 3354 at 50% (R9.b); PVAc carbonyl band at ≈1740 cm⁻¹ (read from Fig. 7b) grows with PVAc content; ratio of the felodipine free carbonyl peak (1701) to the hydrogen-bonded carbonyl peak (1682) increases with PVAc content (text) | Fig. 7, p.2394; text p.2395 |
| R12 | record, measured | IR of felodipine/HPMCAS films — 0, 20, 30, 40, 50% w/w HPMCAS (P6, P7) — NH peak 3343 cm⁻¹ at 20% (text), ≈3345 at 30% and ≈3347 at 40% (read from Fig. 8a), 3348 at 50% (R9.c); HPMCAS carbonyl band at ≈1740 cm⁻¹ (read from Fig. 8b); ratio of free to hydrogen-bonded felodipine carbonyl peak increases with HPMCAS content (text) | Fig. 8, p.2394; text p.2395 |
| R13 | record, measured | IR of felodipine/PVP/VA films — 0, 20, 30, 40, 50% w/w PVP/VA (P6, P7) — NH peak stays at 3341 cm⁻¹ at 20% w/w but broadens on the low-wavenumber side; NH peak shifts down with increasing polymer content, to 3298 at 50% (R9.d); a distinct shoulder at 3290 cm⁻¹ develops and grows in intensity with polymer content (text); a second band near ≈3230 cm⁻¹ grows with polymer content (read from Fig. 9a); polymer carbonyl bands at ≈1738 and ≈1685 cm⁻¹ overlap the felodipine carbonyl region (read from Fig. 9b); reference trace labelled "PVA/VA alone" | Fig. 9, p.2394; text p.2395 |
| R14 | record, measured | IR of felodipine/PVP films — 0, 20, 30, 40, 50% w/w PVP (P6, P7) — largest NH change of the four polymers: downward shift and broadening, more pronounced with increasing PVP content, to 3294 cm⁻¹ at 50% (R9.e); a band near ≈3225 cm⁻¹ grows with PVP content (read from Fig. 10a); strong PVP carbonyl band at ≈1680 cm⁻¹ overlaps the felodipine carbonyl region (read from Fig. 10b) | Fig. 10, p.2395; text p.2395 |
| C26 | claim, conclusion, authors: asserted | The strength/extent of drug–polymer hydrogen bonding ranks PVP > PVP/VA > HPMCAS ≥ PVAc [rests on: R9, R11-R14] | p.2390, p.2396 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | IR NH stretching band of amorphous felodipine — pure felodipine and 20 wt% PVP K-12, K-29/32, K-90 films, 25 °C (P7) — pure felodipine 3341 cm⁻¹; with PVP shifted to 3337 cm⁻¹ and broadened; extent of shift and broadening the same for the three PVP grades | p.3589; Fig. S3, SI p.3 |
| C13 | claim, conclusion, authors: "indicate"; "indicating"; abstract: "indicate" | The NH shift and broadening with PVP mean stronger and/or more numerous drug-polymer than drug-drug interactions, and the felodipine-PVP interaction does not depend on PVP molecular weight in the range studied [rests on: R9] | p.3585, p.3589; SI p.3 |
| C30 | claim, conclusion, authors: asserted | Hydrogen bonding between felodipine and PVP is independent of PVP molecular weight, so differences in intermolecular interactions cannot explain the molecular-weight effect [rests on: R9] | p.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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | NH-stretch band positions in dry dispersions — felodipine–PVP films, 25 °C (P1, P5) — drug–drug hydrogen-bonded NH band centred at 3341 cm−1; drug–polymer hydrogen-bonded NH band at 3290 cm−1; no significant PVP absorption in the NH region (text; Fig. 7 caption). Bands named elsewhere in the paper as 3345 and 3290 cm−1 (pp.176-178) | p.172, p.176 |
| R2 | record, measured | NH-region spectra from 0 °C (bottom) to as high as 180 °C (top) — dispersions with (a) 0, (b) 30, (c) 37, (d) 46, (e) 74 wt% PVP; 5–15 °C steps (P6) — (a) one main band, maximum ≈3340 cm−1 in the lowest and ≈3350 cm−1 in the highest spectrum, shoulder ≈3420 cm−1; (b) maximum ≈3345 cm−1 with shoulder ≈3300 and band ≈3230 cm−1; (c) broad maximum ≈3300–3340 cm−1 and band ≈3230 cm−1; (d) and (e) maximum ≈3297 cm−1, band ≈3225 cm−1 and the ≈3340 cm−1 band as a shoulder; in (b)–(e) the band near 3290–3300 cm−1 is present in every spectrum up to the highest temperature (read from Fig. 1); text: at high PVP content the drug–polymer band dominates and the drug–drug band appears as a shoulder | Fig. 1, p.173 |
| R3 | record, measured | drug–drug NH peak position vs temperature (cm−1, n = 3 trials) — 0, 30, 54 wt% PVP films (P6) — sub-table below; text: pure amorphous felodipine 3337 cm−1 at 5 °C to 3350 cm−1 at 160 °C (see X1) | Fig. 2a, p.174; text p.172 |
| R4 | record, measured | drug–polymer NH peak position vs temperature (cm−1, n = 3 trials) — 30 and 54 wt% PVP films (P6) — sub-table below; text: 30 wt% PVP 3288 cm−1 at 5 °C to 3296 cm−1 at 160 °C | Fig. 2b, p.174; text p.172 |
| R6 | record, measured | NH peak positions on heating (▲) and cooling (●) — 37 wt% PVP film, 0–160 °C (P6) — heating and cooling points superimpose (text: no hysteresis); drug–drug ≈3344 cm−1 at 0 °C to ≈3351–3353 cm−1 at 160 °C; drug–polymer ≈3291.5 cm−1 at 0 °C to ≈3298 cm−1 at 160 °C (read from Fig. 3) | Fig. 3, p.174; text p.173 |
| R16 | record, measured | NH spectra during isothermal hold at 125 °C — 50% PVP film after about 4 h at 94% RH and 1 h dry-air purge; 0 to 1500 min (P13) — initial spectrum: main band ≈3340 cm−1, shoulder ≈3300 cm−1, weak band ≈3230 cm−1; with time the band near 3290–3297 cm−1 grows relative to the band near 3340–3345 cm−1, and the late spectra approach the never-exposed reference (maximum ≈3297 cm−1, band ≈3228 cm−1) (read from Fig. 11) | Fig. 11, p.178; text p.177 |
| R17 | record, measured | peak-height ratio h(3290)/h(3345) (E2) vs ln time at 125 °C — the R16 sample; reference line = never-exposed film of the same ratio — sub-table below | Fig. 12, p.178 |
| C5 | claim, assumption, authors: asserted | The NH region reports felodipine's cohesive and adhesive hydrogen bonds: the ≈3341–3345 cm−1 band is drug NH bonded to the carbonyl of another drug molecule, the 3290 cm−1 band drug NH bonded to the PVP carbonyl [rests on: cited: ref 10; R1] | p.172, p.178 |
| C6 | claim, conclusion, authors: "indicating"; "indicative of" | The upward shift of the NH peak positions with temperature reflects a gradual weakening of intermolecular hydrogen bonding, for pure felodipine in agreement with ref 11 [rests on: R3, R4; cited: refs 11-17] | p.172, p.173 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C37 | claim, mechanism, authors: "may" | Specific felodipine-HPMCAS interactions may couple the motions of drug and polymer side chains, and water may barely affect this coupling because HPMCAS has multiple hydrogen-bond donors and acceptors per repeat unit that can bind water and keep the drug-polymer interaction intact [rests on: R14; cited: refs 12, 30, 31] | p.752 |

## 2010 Rumondor — Analysis of the Moisture Sorption Behavior of Amorphous Drug–Polymer Blends · Solid state stability / Physical stability

[2010-rumondor-moisture-sorption-amorphous-drug-polymer-blends](../../../cards/2010-rumondor-moisture-sorption-amorphous-drug-polymer-blends/paper.html) · Solid state stability / Physical stability · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C11 | claim, prior hypothesis, authors: "suggested"; "hypothesized" | Crowley and Zografi suggested the size of the discrepancy relates to specific drug–polymer interactions and hypothesized the largest difference at about a 1:1 molar ratio of drug hydrogen bond donors to the PVP repeat-unit acceptor [rests on: cited: ref 10] | p.1057-1058 |
| C14 | claim, mechanism, authors: "it has been suggested"; "If ... indeed"; "it is intuitive" | HPMC and HPMCAS, unlike PVP, have multiple hydrogen bond donors and acceptors per repeat unit and have been suggested to interact more weakly with felodipine (ref 17); if specific drug–polymer interaction causes the reduction in uptake, blends with these cellulose polymers would be less affected [rests on: R7, R8, R9; cited: ref 17] | p.1058-1059 |
| R10 | record, derived (relation named, not printed) | drug:PVP weight ratio at a 1:1 molar ratio of drug hydrogen bond donors to the PVP repeat-unit hydrogen bond acceptor — indomethacin–PVP; felodipine–PVP — 76:24 (indomethacin–PVP); 78:22 (felodipine–PVP) | p.1058 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | IR band positions (cm⁻¹) with the authors' assignments — spin-coated films (P1, P2), dry: polymers, amorphous drugs, 50 wt% polymer dispersions — sub-table below (sh = shoulder, w = weak); assignments copied as printed | Table 1, p.481 |
| R4 | record, measured | IR NH region after humid storage — felodipine-50% PVPVA films, as prepared and after 1 day at 54% and at 84% RH, dried (P4) — spectra: main band ≈3300 cm⁻¹ with a shoulder at ≈3340 cm⁻¹ that is highest after 84% RH (read from Fig. 2a); text: relative intensity of the 3341 cm⁻¹ band increased with storage RH; at 84% RH a 17% reduction in intensity of the drug-polymer H-bond band relative to the drug-drug H-bond band | Fig. 2a, p.483; text p.481, p.489 |
| R6 | record, measured | IR carbonyl region after humid storage — quinidine-50% PVP films, as prepared and after 1 day at 54% and at 84% RH, dried — 1681 cm⁻¹ band with 1662 cm⁻¹ shoulder in dispersions (absent in PVP alone); shoulder decreased after 54% RH and was virtually eliminated after 84% RH; at 84% RH a 47% reduction in intensity of the drug-polymer H-bond band relative to the free vinylpyrrolidone carbonyl band | Fig. 3a, p.484; text p.482, p.489 |
| R7 | record, measured | IR carbonyl region after humid storage — quinidine-50% PVPVA films, as prepared and after 1 day at 84% and at 94% RH, dried — three bands between 1650 and 1800 cm⁻¹; 1665 cm⁻¹ band (absent in pure polymer and pure drug) decreased slightly in relative intensity after storage, less than the 1662 cm⁻¹ shoulder of quinidine-PVP (R6); at 84% RH an 11% reduction | Fig. 4a, p.484; text p.482-483, p.489-490 |
| R20 | record, derived (relation named, not printed) | red shift of the vinylpyrrolidone carbonyl band of PVPVA on H-bonding to the drug — dry 50 wt% PVPVA dispersions (R1) — indomethacin-PVPVA: 42-44 cm⁻¹; other PVPVA dispersions studied: 19-22 cm⁻¹ | text p.489 |
| C28 | claim, mechanism, authors: "This supposition is supported"; "would result" | Indomethacin forms stronger interactions with PVPVA than felodipine, quinidine and pimozide do, judged by the larger carbonyl red shift; its COOH group is a better hydrogen-bond donor than NH or OH; stronger interactions give a lower χDP and a more favourable ΔHmix, consistent with the absence of demixing in indomethacin-PVPVA, as reported with PVP [rests on: R20, R13, R3.h; cited: ref 10] | p.489 |
| C34 | claim, mechanism, authors: "approximately equal"; "most likely explained" | For felodipine and quinidine the drug-polymer hydrogen bond with PVPVA is about as strong as with PVP (similar red shifts), so the smaller demixing with PVPVA is most likely explained by less water sorbed rather than by interaction strength [rests on: R1, R18, R4-R7] | p.490 |

## 2011 Baird — Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions · Solid state stability / PEG dispersions

[2011-baird-drug-peg-eutectic-composition-modeling-solid-dispersions](../../../cards/2011-baird-drug-peg-eutectic-composition-modeling-solid-dispersions/paper.html) · Solid state stability / PEG dispersions · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | IR band positions, measured versus calculated (additive) spectrum — 25:75 drug-PEG 3350 melts (P4) — sub-table below | Fig. 5, p.209; text p.209-210 |
| C29 | claim, mechanism, authors: "indicative" | The large carbonyl shifts of chlorpropamide and aceclofenac (R10.a, R10.c) indicate a change in drug-drug hydrogen bonding because the drug hydrogen bonds with the hydroxyl or ether groups of PEG [rests on: R10.a, R10.c] | p.209 |
| C30 | claim, mechanism, authors: "likely"; "thus" | Because PEG 3350 carries far more ether than hydroxyl groups, the drug likely donates a hydrogen bond to the PEG ether oxygen; this leaves fewer drug donors for the drug carbonyls, hence their shift to higher wavenumber [rests on: R12, R10.a, R10.c] | p.209 |
| C33 | claim, conclusion, authors: "suggesting" | The nominal shift of the haloperidol aromatic C-N band and the OH stretching region resembling the calculated spectrum suggest minimal haloperidol-PEG hydrogen bonding and no specific interactions [rests on: R10.h, R11] | p.210 |
| C34 | claim, conclusion, authors: asserted | Loratadine, which has only acceptor groups, shows no evidence of hydrogen bonding of its carbonyl or tertiary nitrogen with PEG, and its aromatic C-N band does not shift [rests on: R10.e, R10.f] | p.210 |

## 2011 Kestur — Influence of polymer chemistry on crystal growth inhibition of two chemically diverse organic molecules · Solid state stability / Miscibility and drug-polymer interactions

[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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | NH stretching position of nimesulide in solution — dichloromethane, 1-100 mg ml−1 (P9) — text: 3345 cm−1 at every concentration; figure: maximum ≈3345 cm−1 for all seven spectra | p.6716; Fig. S1, SI pdf p.1 |
| R12 | record, measured | NH region of crystalline and amorphous nimesulide — KBr pellet (P7) and spin-coated film (P8) — text: NH position of the undercooled melt similar to the crystal; figure: maximum ≈3288 cm−1 (crystalline, narrow band) and ≈3276 cm−1 (amorphous, broader band) | Fig. 6, p.6717; text p.6717 |
| R13 | record, measured | NH region of nimesulide with 30 wt% polymer (Fig. 7 caption; data in the image printed above the Fig. 8 caption) — solvent-cast films (P10): no polymer (solid), PVP K12 (dashed), PVP/VA (dotted), PVAc (dash-dotted) — text: small changes in the NH region with polymer; figure: maximum ≈3281 cm−1 without polymer and ≈3258-3265 cm−1 with each polymer (≈16-23 cm−1 lower); intensity at 3150-3200 cm−1 highest for PVP, then PVP/VA, then PVAc, lowest without polymer | Fig. 7, p.6717 (image above Fig. 8 caption); text p.6717 |
| R14 | record, measured | PVP carbonyl region (Fig. 8 caption; data in the image printed above the Fig. 7 caption) — pure PVP K12 (dash-dotted) and nimesulide-PVP films with 20, 30, 40 and 50 wt% PVP (solid lines) (P10); nimesulide alone (dashed) — text: changes observed; a shoulder (arrow) associated with drug-polymer interactions; figure: pure PVP maximum ≈1684 cm−1, dispersions ≈1680 cm−1 (≈4 cm−1 lower) with a shoulder at ≈1657 cm−1 whose height differs among the four compositions; nimesulide alone shows no band in 1720-1630 cm−1 | Fig. 8, p.6717 (image above Fig. 7 caption); text p.6717 |
| R17 | record, measured | NH stretching position with added hydrogen bonding partner — 50 mg ml−1 nimesulide in dichloromethane alone, with acetic acid, and with 1-ethyl-2-pyrrolidinone (1:1 molar) (P9) — text: minimal changes to the NH region; figure: maximum ≈3345 cm−1 in all three spectra | Fig. S4, SI pdf p.4; text p.6717 |
| C15 | claim, mechanism, authors: discussion: "should be capable"; "should be preferred"; abstract: "This may be related to" | Any polymer with a donor stronger than the bifonazole C-H should form more favourable hydrogen bonds with the imidazole nitrogen than the drug-drug C-H···N contacts, disrupting drug-drug interactions and delaying crystallization; this is the case for PAA, whose COOH O-H is a much stronger donor [rests on: R18, R7; cited: ref 16] | p.6712, p.6716 |
| C23 | claim, conclusion, authors: "suggesting some extent"; "confirming"; abstract: "did occur" | Small NH-region changes with polymer suggest some drug-polymer interaction, and changes in the PVP carbonyl region confirm drug-polymer interactions in nimesulide-PVP dispersions [rests on: R13, R14] | p.6712, p.6717 |
| C30 | claim, generalisation, authors: "appears to depend" | Polymer effectiveness appears to depend not only on drug chemistry but also on the availability of hydrogen bonding groups [rests on: R7, R9, R13, R14, R17] | p.6712 |

## 2011 Rumondor — Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture · Solid state stability / Physical stability

[2011-rumondor-asd-moisture-aaps-pvp-opls](../../../cards/2011-rumondor-asd-moisture-aaps-pvp-opls/paper.html) · Solid state stability / Physical stability · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | IR carbonyl region and OH band, dry clofoctol–PVP — films at 100, 90, 70, 50, 30, 10% PVP (P1, P2) — PVP carbonyl peak at 1,682 cm⁻¹ in pure PVP; a new peak at 1,663 cm⁻¹ grows as PVP content falls (Fig. 2, arrow): maximum ≈1,684 with shoulder ≈1,663 at 50% PVP, maximum ≈1,663 with shoulder ≈1,684 at 30% PVP, single maximum ≈1,663 at 10% PVP (read from Fig. 2); clofoctol free OH peak at 3,365 cm⁻¹ moves to 3,263 cm⁻¹ and broadens in the binary films (not shown); pure clofoctol has no significant absorption in the carbonyl region | Fig. 2, p.1211 |
| R3 | record, measured | IR carbonyl region, dry probucol–PVP — films (P1, P2) — PVP carbonyl peak 1,682 → 1,663 cm⁻¹ (data not shown); peaks at the same locations as clofoctol–PVP (Fig. 2 caption) | p.1211 |
| R4 | record, measured and calculated | IR carbonyl region, dry indoprofen–PVP — films at 100, 90, 70, 50, 30, 0% PVP (P1, P2); calculated 50% physical mixture (P5) — from 100 to 70% PVP the free PVP carbonyl peak at 1,682 cm⁻¹ loses relative intensity and a shoulder develops at 1,641 cm⁻¹ (Fig. 3, arrow); the 50% PVP film spectrum differs from the calculated 50% physical-mixture spectrum, which has no band near 1,641 cm⁻¹; pure amorphous indoprofen: shoulder ≈1,734, maxima ≈1,699 and ≈1,611 cm⁻¹ (read from Fig. 3) | Fig. 3, p.1211-1212 |
| R5 | record, measured | IR carbonyl region, dry nilutamide–PVP — films at 100, 90, 70, 50, 30, 10, 0% PVP (P1, P2) — amorphous nilutamide carbonyl peaks at 1,787 and 1,729 cm⁻¹, positions unchanged in the dispersions; a shoulder develops at 1,663 cm⁻¹ (Fig. 4, arrow), about as high as the ≈1,680 band at 30% PVP (read from Fig. 4) | Fig. 4, p.1212 |
| C11 | claim, conclusion, authors: asserted ("evidence") | The clofoctol–PVP red shift 1,682 → 1,663 cm⁻¹ is evidence of API–polymer specific interactions, the new peak being PVP carbonyl hydrogen bonded to the drug; the OH shift and broadening are further evidence of hydrogen bonding [rests on: R2] | p.1211 |
| C13 | claim, conclusion, authors: asserted ("clearly show") | Indoprofen–PVP dispersion spectra cannot be constructed from the spectra of the pure amorphous components; 1,682 cm⁻¹ is non-hydrogen-bonded PVP carbonyl and 1,641 cm⁻¹ PVP carbonyl hydrogen bonded to the indoprofen COOH, as reported for indomethacin–PVP and ketoprofen–PVP [rests on: R4; cited: refs 7, 13] | p.1211-1212 |
| C14 | claim, conclusion, authors: asserted | The 1,663 cm⁻¹ shoulder in nilutamide–PVP is PVP carbonyl hydrogen bonded to the nilutamide NH [rests on: R5] | p.1212 |

## 2011 Zhu — Time-Resolved SAXS/WAXS Study of the Phase Behavior and Microstructural Evolution of Drug/PEG Solid Dispersions · Solid state stability / PEG dispersions

[2011-zhu-time-resolved-saxs-waxs-drug-peg-solid-dispersions](../../../cards/2011-zhu-time-resolved-saxs-waxs-drug-peg-solid-dispersions/paper.html) · Solid state stability / PEG dispersions · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C9 | claim, conclusion, authors: "consistent with"; "reveals" | BZC, CPM and IBP have estimated solubility above 20% in PEG at 25 °C, consistent with their negative interaction parameters; their structures carry hydrogen bond donors that can interact with the PEG ether oxygen, and they have moderate melting points [rests on: R5.b-d] | p.934 |
| C11 | claim, mechanism, authors: asserted | Drug-polymer interactions change drug-drug hydrogen bonding, which shifts the carbonyl band (around 1700 cm⁻¹); similar results were reported for other drug-polymer systems [rests on: R20; cited: SI ref 1] | SI pdf p.2 |
| R20 | record, measured | ATR-FTIR spectra, 1800-1000 cm⁻¹, measured (solid line) versus calculated physical mixture (dashed) — drug/PEG 20/80, molten (P8) — KET/PEG: measured and calculated nearly superimposed, carbonyl band ≈1650 cm⁻¹ in both; BZC/PEG: carbonyl band ≈1700 cm⁻¹ (measured, split) versus ≈1686 cm⁻¹ (calculated), further differences near 1600, 1270 and 1170 cm⁻¹; IBP/PEG: carbonyl band ≈1735 (measured) versus ≈1703 cm⁻¹ (calculated); NLU/PEG: carbonyl band ≈1733 versus ≈1721 cm⁻¹, differences at 1350-1280 cm⁻¹ (all read from Fig. S2); CPM/PEG and HLP/PEG spectra not shown | Fig. S2, SI pdf p.3; text SI pdf p.2 |

## 2012 Ilevbare — Effect of Binary Additive Combinations on Solution Crystal Growth of the Poorly Water-Soluble Drug, Ritonavir · Dissolution / D. Crystallization from solution

[2012-ilevbare-ritonavir-binary-additive-crystal-growth](../../../cards/2012-ilevbare-ritonavir-binary-additive-crystal-growth/paper.html) · Dissolution / D. Crystallization from solution · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C13 | claim, prior hypothesis, authors: "It has been proposed"; "can potentially interact" | The strong growth inhibition by Pn-IPAAmd has been proposed to come from its moderate hydrophobicity plus hydrogen bonding of its amide group to the fast-growing faces, which expose carbonyl oxygen and thiazole nitrogen atoms [rests on: cited: ref 31; R5] | p.6053-6054 |
| C35 | claim, mechanism, authors: "may be partly attributed" | The strong inhibition by CAP Adp 0.85/Pn-IPAAmd may be partly due to hydrogen bonding of Pn-IPAAmd to the fast-growing faces [rests on: cited: refs 31, 46] | p.6057 |
| C41 | claim, mechanism, authors: "considered unlikely" | Electrostatic and hydrogen-bonding forces are unlikely to dominate complex formation between the polymers: water competes with hydrogen bonds, and the adipate (pKa ≈4.43) is nearly fully ionized at pH 6.8, removing it as a hydrogen-bonding group and causing charge repulsion [rests on: argument only; cited: refs 4, 49-51] | p.6057-6058 |

## 2012 Ilevbare — Understanding Polymer Properties Important for Crystal Growth Inhibition—Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir · Dissolution / D. Crystallization from solution

[2012-ilevbare-ritonavir-polymer-properties-crystal-growth-inhibition](../../../cards/2012-ilevbare-ritonavir-polymer-properties-crystal-growth-inhibition/paper.html) · Dissolution / D. Crystallization from solution · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C4 | claim, prior hypothesis, authors: asserted | Adsorption can be physical (usually reversible; van der Waals and electrostatic forces) or chemical (covalent; strong, usually irreversible); hydrophobicity, electrostatic interaction and hydrogen bonding contribute to it; understanding adsorption is essential to understanding inhibition by polymers [rests on: cited: refs 16, 19-24] | p.3134 |
| C45 | claim, mechanism, authors: "can potentially"; "assuming" | The four fastest-growing BFDH faces, roughly perpendicular to a, expose carbonyl oxygens and thiazole nitrogens that, assuming they are also the fast faces in the experiment, can potentially interact with the amide group of Pn-IPAAmd [rests on: R5] | p.3142 |
| C47 | claim, mechanism, authors: "can likely be attributed" | The strong inhibition by Pn-IPAAmd can likely be attributed to its moderate hydrophobicity combined with fortuitous hydrogen bonding to the fast-growing faces [rests on: R4, R6, R9] | p.3142 |
| C48 | claim, mechanism, authors: "probably" | The other amide polymers, Pnn-DMAAmd and PAcAmd, were probably ineffective because they are too hydrophilic or have no hydrogen bond donor groups (Fig. 3) [rests on: R9] | p.3142 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R13 | record, measured | FTIR NH and C=O stretch, crystal versus supercooled liquid — flutamide (P4) — crystal: NH sharp at 3360 cm−1, C=O sharp at 1716 cm−1; amorphous: NH broadened and shifted to 3315 cm−1, C=O split into a more intense peak at 1681 cm−1 and a shoulder with maximum at 1710 cm−1 | Fig. 7, p.3225; text p.3225 |
| R14 | record, measured | NH stretch peak position (cm−1; unit not printed in the table) — flutamide and 1:1 molar mixtures (P4) — sub-table below; text: largest shift 28 cm−1, with PVP | Table 3, p.3226 |
| R15 | record, measured | FTIR C=O region with PVP — flutamide-PVP 1:1 (P4) — PVP carbonyl band moves from 1679 cm−1 (neat PVP) to 1658 cm−1 in the mixture; figure: mixture peaks at ≈1683 and ≈1658 cm−1 with a shoulder near ≈1710 cm−1 | Fig. 8, p.3226; text p.3226 |
| R16 | record, measured | FTIR C=O region with PDMA — flutamide-PDMA 1:1 (P4) — PDMA carbonyl band moves from 1641 to 1620 cm−1; relative intensity of the higher-wavenumber flutamide C=O shoulder (≈1710 cm−1) increases | Fig. 9, p.3226; text p.3226 |
| C21 | claim, conclusion, authors: "suggests" | Hydrogen bonding is on average stronger in amorphous than in crystalline flutamide, somewhat unexpected but not unprecedented [rests on: R13] | p.3225 |
| C39 | claim, conclusion, authors: asserted ("clearly showed") | FTIR clearly showed interactions of flutamide with the polymer acceptor groups (downward NH and polymer C=O shifts); for the carbonyl polymers, larger NH decreases go with greater growth inhibition; the computed carbonyl oxygen charges also match the extent of growth reduction [rests on: R14, R15, R16, R25, R3] | p.3228 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, measured | FTIR band positions of crystalline and amorphous APAP — form II crystallized from an amorphous film; amorphous APAP (P8) — form II: NH stretch sharp at 3331 cm−1, OH stretch broad at 3162 cm−1, C=O stretch 1650 cm−1; amorphous: bands broadened, NH and OH merged into one broad peak centred around 3301 cm−1, C=O at 1655 cm−1 with a distinct low-wavenumber shoulder at 1636 cm−1 | Fig. 9, p.5193; text p.5193-5194 |
| R15 | record, cited | hydrogen-bond distances in APAP form II — single crystal structure, CSD code HXACAN21 — NH to phenolic O 2.939 Å; OH to carbonyl O 2.712 Å | p.5193 |
| R16 | record, measured | FTIR of APAP with PAA — 30% w/w PAA film (P8) — combined NH/OH peak 3301 → 3320 cm−1; PAA acid C=O 1705 → 1714 cm−1; increased intensity of the 1636 cm−1 shoulder | Fig. 10, p.5194; text p.5194 |
| R17 | record, measured | FTIR of APAP with PVP — 30% w/w PVP film (P8) — NH/OH peak 3301 → 3283 cm−1; pyrrolidone C=O 1679 → 1657 cm−1 | Fig. 11, p.5194; text p.5194 |
| R18 | record, measured | FTIR of APAP with PVPVA — 30% w/w PVPVA film (P8); data not shown — NH/OH peak 3301 → 3294 cm−1; pyrrolidone C=O 1682 → 1657 cm−1 | p.5194 |
| C24 | claim, assumption, authors: "usually indicates"; "is expected" | For a hydrogen-bonded group, a shift to lower wavenumber usually means a stronger bond and a shift to higher wavenumber a bond weaker than in the pure condensed phase; APAP, with donors and acceptors, is expected to interact with polymers carrying either [rests on: cited: refs 26, 27] | p.5193 |
| C31 | claim, conclusion, authors: results: "found to correlate well"; discussion: asserted; conclusions: "could be correlated" | More favourable drug-polymer hydrogen bonding correlates well with growth inhibition: the polymers with the greatest inhibitory effect (PAA, PVP, PVPVA) show the greatest FTIR changes, with the vinylpyrrolidone carbonyl bonding the APAP phenol and the PAA acidic OH bonding the APAP amide carbonyl (abstract: PAA and PVP observed to hydrogen-bond with APAP; conclusions: growth inhibition "could be correlated" to hydrogen bonding) [rests on: R6, R16, R17, R18, R19, R20] | p.5188, p.5194, p.5195, p.5196 |
| C34 | claim, generalisation, authors: "seem to correlate well"; "further suggests" | Drug-polymer hydrogen bonding seems to correlate well with the decrease in growth rates of supercooled APAP, and the study further suggests that hydrogen bonding should be considered a major contributor to the stabilisation of amorphous dispersions [rests on: R6, R8, R16, R17, R18, R20; cited: ref 7] | p.5195 |

## 2012 Eerdenbrugh — Molecular Weight Effects on the Miscibility Behavior of Dextran and Maltodextrin with Poly(vinylpyrrolidone) · Solid state stability / Miscibility and drug-polymer interactions

[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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, measured | PVP carbonyl stretching band (normalized, offset) versus DEX1 weight fraction — DEX1-PVP12 films (P4), 0-0.9 DEX1 — pure PVP band maximum at 1680 cm−1 (non-hydrogen-bonded); a lower-wavenumber band with maximum at 1661 cm−1 grows as DEX1 is added; carbonyl band virtually unchanged between 0.8 and 0.9 DEX1; an additional weak band with maximum at 1597 cm−1 at 0.9 DEX1; the pure DEX1 band lies at 1601 cm−1 (data not shown) | Fig. 2b, p.2758 |
| R5 | record, measured | PVP carbonyl band at 0.5 DEX for DEX6 with each PVP grade; references pure PVP12 and 0.5 DEX1-PVP12 — films (P4) — text: DEX6-PVP12 shows less of the hydrogen-bonded band than DEX1-PVP12; DEX6-PVP17 band similar to DEX6-PVP12; large further reductions for PVP25, PVP30 and PVP90; a similar reduction with PVP MW at 0.2 and 0.8 DEX (Fig. S4), clearest at 0.8. Figure: the 0.5 DEX1-PVP12 reference peaks at the shifted position; the DEX6-PVP12 and DEX6-PVP17 bands are broadened toward lower wavenumber; the PVP25, PVP30 and PVP90 bands peak near the pure-PVP position with a low-wavenumber shoulder | Fig. 3b, p.2759; text p.2759 |
| R14 | record, derived (E1) | fraction of hydrogen-bonded PVP carbonyls fHB versus DEX weight fraction (pure PVP plotted at 0) — films (P4), fitting (P5); quadratic DEX1-PVP12 curve (E2) drawn in every panel — sub-table below; text: DEX1-PVP12 fHB rises rapidly at 0.1-0.4 DEX, more moderately at 0.5-0.7, then plateaus at 0.8-0.9 where both values are 1.00; DEX6 at 0.2: PVP12 and PVP17 points overlap, PVP25, PVP30 and PVP90 points overlap; DEX6-PVP25 has the largest fitting error of all systems (Table S1, SI not supplied) | Fig. 6, p.2762; text p.2761-2762 |
| C12 | claim, mechanism, authors: asserted | The 1661 cm−1 band is the hydrogen-bonded carbonyl, red-shifted because hydrogen bonding weakens the carbonyl vibration [rests on: R2; cited: refs 31-33] | p.2758 |
| C23 | claim, generalisation, authors: abstract and results: asserted; discussion: asserted ("it is clear") | Both blend miscibility and DEX-PVP hydrogen bonding vary widely with the MW of both polymers, from completely miscible with extensive hydrogen bonding, through partially miscible with intermediate bonding, to virtually immiscible with little or no bonding; the miscibility behaviour depends strongly on the MW of both polymers [rests on: R13, R14] | p.2754, p.2760, p.2762 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C10 | claim, mechanism, authors: "the most plausible explanation" | The redshift of the PVP carbonyl band from bulk (1680-1682 cm−1) to AFM-IR (1660 cm−1) is most plausibly explained by hydrogen bonding with absorbed gas-phase moisture, given dry air in the bulk measurement and no humidity control in the AFM-IR measurement [rests on: R5.a; P3, P6] | p.1462 |

## 2012 Zhu — Modification of Crystallization Behavior in Drug/Polyethylene Glycol Solid Dispersions · Solid state stability / PEG dispersions

[2012-zhu-api-peg-solid-dispersion-crystallization-behavior](../../../cards/2012-zhu-api-peg-solid-dispersion-crystallization-behavior/paper.html) · Solid state stability / PEG dispersions · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R25 | record, measured | ATR-FTIR spectrum of molten FNB/PEG compared with a calculated physical-mixture spectrum — FNB/PEG 20/80 w/w, molten state (P11); 1800-1000 cm⁻¹ shown — measured and calculated spectra have the same peak positions and similar shape; the calculated trace lies slightly below the measured trace between ≈1560 and ≈1200 cm⁻¹ and below ≈1060 cm⁻¹ (read from Fig. S2); SI text: calculated spectrum very similar to the experimental one | Fig. S2, SI p.2-3 |
| C44 | claim, mechanism, authors: "probably due to" | The different behaviour of PEG with IBP and FNB comes from their different ability to hydrogen-bond with PEG: IBP hydrogen-bonds with PEG, while FNB lacks donor groups and PEG has mainly acceptor groups [rests on: R16, R20, R25; cited: refs 12, 13] | p.552 |
| C45 | claim, conclusion, authors: asserted ("further confirmed") | The spherulite growth rates confirm this: PEG spherulites grew more slowly with BZC and IBP (both hydrogen-bond with PEG) than with the non-interacting APIs [rests on: R22; cited: refs 12, 23] | p.552 |
| C49 | claim, conclusion, authors: asserted | The measured spectrum of molten FNB/PEG is very similar to the calculated physical-mixture spectrum, so there are no FNB-PEG interactions [rests on: R25] | SI p.3 |

## 2013 Ilevbare — Impact of Polymers on Crystal Growth Rate of Structurally Diverse Compounds from Aqueous Solution · Dissolution / D. Crystallization from solution

[2013-ilevbare-polymers-crystal-growth-structurally-diverse-compounds](../../../cards/2013-ilevbare-polymers-crystal-growth-structurally-diverse-compounds/paper.html) · Dissolution / D. Crystallization from solution · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, measured | N−H stretching peak positions (cm⁻¹) of seed crystals conditioned without and with PVPVA, spectra shown 3600−2800 cm⁻¹ — celecoxib (CLB, CLB-PVPVA) and efavirenz (EFZ, EFZ-PVPVA) seeds after overnight exposure to 100 µg/mL PVPVA (P14) — celecoxib: 3331 → 3321 and 3225 → 3217; other peaks essentially unchanged; efavirenz: 3316 → 3308 | Fig. 9, pdf p.8; text pdf p.8 |
| C31 | claim, assumption, authors: asserted ("In general") | Hydrogen bonds lower the wavenumber of the X−H stretching peak (red-shift by bond lengthening); the X−H stretching region (N−H at 3500−3200 cm⁻¹) is used to classify hydrogen bonds [rests on: cited: refs 45, 46] | pdf p.8 |
| C32 | claim, mechanism, authors: "suggest"; "appear to contribute" | The N−H shifts to lower wavenumbers point to specific intermolecular interactions between celecoxib or efavirenz and PVPVA, and these interactions contribute to PVPVA's effectiveness as a growth inhibitor [rests on: R12] | pdf p.8 |
| C51 | claim, mechanism, authors: "we surmise"; "are likely" | For PVPVA, electrostatic interactions are unlikely because polymer and drugs are un-ionized at pH 6.8; the main force driving PVPVA adsorption is specific intermolecular interaction, hydrogen bonds from the efavirenz amide and celecoxib sulfonamide groups to the PVPVA carbonyl oxygen [rests on: R10, R12] | pdf 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | OH stretching region of naringenin-HPMC films versus naringenin content — spin-coated films (P4), 0 (HPMC), 10, 30, 50% (w/w) naringenin — text: the OH stretching region broadened and moved to lower wavenumber as naringenin increased. Figure: band maximum ≈3470 cm-1 for HPMC and 10% naringenin; broad maximum ≈3400-3410 cm-1 for 30% naringenin; ≈3335 cm-1 for 50% naringenin (read from Fig. 3) | Fig. 3, p.4; text p.4 |
| R2 | record, measured | polyphenol OH stretching peak position (cm-1) at 30% (w/w) polyphenol — P4; 30% (w/w) was the highest polyphenol content that gave a thin amorphous film with every polymer; PAA not listed (R11) — sub-table below | Table 1, p.5; text p.4 |
| R3 | record, measured | polymer C=O stretching region of naringenin-PVP films versus naringenin content — P4; 0 (100% PVP), 10, 30, 50, 70% (w/w) naringenin and amorphous naringenin — text: a shoulder at 1661 cm-1 appears and grows with naringenin content, 21 cm-1 below the non-hydrogen-bonded C=O peak of pure PVP at 1682 cm-1. Figure: PVP band maximum ≈1683 cm-1 in 100% PVP, 10% and 30% naringenin; at 30% naringenin an added broad plateau ≈1665-1637 cm-1; at 50% naringenin a shoulder ≈1677 cm-1 and a maximum ≈1638 cm-1; at 70% naringenin a maximum ≈1639 cm-1; amorphous naringenin absorbs from ≈1665 to ≈1580 cm-1 with maxima ≈1641, ≈1614 and ≈1599 cm-1 (all read from Fig. 4) | Fig. 4, p.5; text p.5 |
| R4 | record, measured; shift derived (polymer peak minus dispersion peak, relation not printed) | C=O stretching peak positions of the pure polymers and of dispersions with 30% (w/w) flavonoid, and the shifts (cm-1) — P4; HPMC not listed (no carbonyl, R11) — sub-table below | Table 2, p.6; text p.5 |
| R5 | record, derived (from R2, R4) | OH peak position versus carbonyl shift — dispersions with 30% (w/w) polyphenol; naringenin circles, quercetin squares — PVP points at ≈21-24 cm-1 shift and ≈3135-3138 cm-1; HPMCAS, E100 and CMCAB points at 0-3 cm-1 shift and ≈3329-3396 cm-1; HPMC drawn only by its OH values on the left axis and PAA only by its −2 cm-1 shift at the lower axis end (≈3450 cm-1), each joined to a straight trend line by dotted lines; the line runs from ≈3435 cm-1 at −2 cm-1 to ≈3110 cm-1 at 24 cm-1; fit method, equation and statistics not printed (read from Fig. 5) | Fig. 5, p.6; text p.5 |
| C10 | claim, conclusion, authors: asserted | In the OH region the polymers rank from strongest to weakest hydrogen bonder PVP > HPMCAS > E100 ≥ HPMC ≥ CMCAB; PAA cannot be ranked there (R11) [rests on: R2] | p.4 |
| C14 | claim, conclusion, authors: "was inferred"; "reasonably good agreement" | From the carbonyl shifts, hydrogen-bond strength ranks PVP > HPMCAS > CMCAB > E100 > PAA, in reasonably good agreement with the OH-region ranking given that HPMC and PAA can each be evaluated in one region only [rests on: R4, R2, R11] | p.5 |
| C15 | claim, conclusion, authors: "indicates a good correlation"; "propose" | The plot of OH peak position against carbonyl shift indicates a good correlation between the hydrogen-bond strengths from the two regions; placing PAA and HPMC on the trend line from their single value, all data give the order PVP > HPMCAS > HPMC ≥ CMCAB ≥ E100 > PAA (repeated on p.9) [rests on: R5, R2, R4] | p.5, 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | IR bands of resveratrol-PVP K29/32 films (0, 10, 30% resveratrol) — P5 — OH region: resveratrol OH maximum at around 3193 cm−1 at 30%, against 3238 cm−1 for crystalline resveratrol (text); lowest OH position of all resveratrol-polymer systems; broadening more pronounced than with E100. C=O region: pure PVP 1682 cm−1; at 30% bands at 1680 cm−1 and a new shoulder at 1656 cm−1 (26 cm−1 below 1682); shoulder weaker at 10% than at 30%; crystalline resveratrol trace flat in this region | Fig. 3, p.176; text p.175 |
| R6 | record, measured | IR bands of resveratrol-E100 films — P5 — sub-table below; text: OH at 3391 cm−1 with 60% polymer; slight broadening, less than with PVP K29/32; new C=O band at 1701 cm−1 (Table 1 value at 30%); ratio of the 1730 cm−1 band to the new band higher at higher polymer content | Fig. 4, p.177; text p.175 |
| R10 | record, measured | C=O stretching positions, pure polymer and with 30% resveratrol — P5 — sub-table below | Table 1, p.178 |
| R11 | record, measured | resveratrol OH peak position at 40% (w/w) resveratrol — P5 — sub-table below | Table 2, p.178 |
| C12 | claim, conclusion, authors: "consistent with"; "suggesting" | The PVP K29/32 dispersion OH band below that of crystalline resveratrol is consistent with stronger resveratrol-polymer interactions than those in the crystal, and its being the lowest of all systems suggests the strongest hydrogen bonds of all polymers [rests on: R5, R11] | p.175 |
| C19 | claim, conclusion, authors: asserted; "good agreement" | Hydrogen-bond strength by OH position ranks PVP K29/32 > HPMC > HPMCAS > E100 > CMCAB (PAA not rankable); for all polymers except HPMC the carbonyl region agrees with the OH inferences [rests on: R11, R10] | p.176 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | FTIR NH stretching peak positions — crystalline and amorphous celecoxib (P5) — crystalline: 3335 and 3223 cm−1; amorphous: 3364 and 3269 cm−1 | Fig. 5, p.254; text p.254 |
| R7 | record, measured | FTIR of celecoxib–PVP — composition not printed (P5) — NH stretching peaks at lower wavenumber, the lower one at 3192 cm−1 (Fig. 5d); PVP C=O stretch 1681 → 1668 cm−1 (data not shown) | Fig. 5, p.254; text p.254 |
| R9 | record, measured | FTIR NH region of celecoxib–TPGS — 50% TPGS, spin-coated film (P5) — text: considerable shift of the celecoxib NH peak relative to amorphous celecoxib; figure: one broad NH band with maximum ≈3230 cm−1, against bands at ≈3360 and ≈3270 cm−1 for amorphous celecoxib; TPGS alone shows no band in this region (read from Fig. 6) | Fig. 6, p.254; text p.254 |
| R10 | record, measured | FTIR PVP C=O stretch in the ternary — celecoxib–TPGS–PVP, composition not printed (P5) — C=O at 1661 cm−1, against 1668 cm−1 in celecoxib–PVP (R7); spectra not shown | text p.254 |
| C20 | claim, conclusion, authors: "indicating" | The higher NH wavenumbers of amorphous celecoxib indicate weaker hydrogen bonding between celecoxib molecules than in the crystal [rests on: R6] | p.254 |
| C21 | claim, conclusion, authors: results: "indicating"; discussion: "consistent with" | The NH shift and the PVP C=O shift indicate hydrogen bond formation between celecoxib and PVP [rests on: R7] | p.254, p.255 |
| C23 | claim, conclusion, authors: asserted | TPGS produced a considerable shift of the celecoxib NH peak relative to amorphous celecoxib, and in the ternary the PVP C=O shift to lower wavenumber is slightly greater [rests on: R9, R10] | p.254 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | FTIR NH and C=O positions, crystalline (stable) versus amorphous nilutamide (cm−1) — ATR spectra (P4) — crystal: NH 3266, C=O 1777 and 1718 (text p.7191); amorphous: NH ≈3313, C=O ≈1789 and ≈1728 (read from Fig. 6); text: the amine and carbonyl stretching peaks both shifted to higher wavenumbers in the amorphous form | Fig. 6, p.7190; text p.7190-7191 |
| R12 | record, measured | FTIR NH and C=O positions with PVP — 1:1 molar nilutamide-PVP spin-coated film (P4) — text: drug NH and polymer C=O shifted to lower wavenumbers. Figure: NH band maximum ≈3313 (nilutamide) versus a broad band ≈3300–3230 with maximum ≈3130 (mixture); PVP C=O ≈1678 (PVP alone) versus ≈1662 (mixture); nilutamide C=O ≈1788 and ≈1728 in both (read from Fig. 7) | Fig. 7, p.7190; text p.7190 |
| R20 | record, measured | FTIR of the three crystal forms (cm−1) — ATR (P4) — sub-table below | Fig. 11, p.7192; text p.7191-7192 |
| C16 | claim, conclusion, authors: "suggested" | The higher NH and C=O wavenumbers of the amorphous form mean weaker hydrogen bonds between nilutamide molecules in the amorphous state than in the crystal [rests on: R10] | p.7190 |
| C18 | claim, mechanism, authors: "indicating"; "this is possible because" | The NH and PVP C=O shifts mean nilutamide-PVP hydrogen bonds stronger than those in nilutamide alone, possible because PVP has a better acceptor group than nilutamide [rests on: R12] | p.7190 |
| C28 | claim, mechanism, authors: "could indicate"; "suggests"; "potentially"; "most likely" | The broad, low-shifted NH band of form I could mean stronger or more extensive hydrogen bonding; since its carbonyl peaks shift slightly upward, the NH is potentially hydrogen bonded to another electron-rich group, most likely the nitro group (NO symmetric stretch 1368 to 1350 cm−1) [rests on: R20.a–b] | p.7191 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | OH peak position (cm-1) — spin-coated films at 80% w/w curcumin (P1, P4) — sub-table below | Table 1, p.979 |
| R4 | record, measured | polymer C=O stretching peak position (cm-1) — neat polymer and spin-coated film with 80% w/w curcumin (P1, P4) — sub-table below | Table 2, p.979 |
| R6 | record, measured | IR spectra of PVP dispersions versus curcumin content — PVP films, 20, 40, 60, 80 wt% curcumin (P1, P4) — OH region, text: curcumin OH peak maximum around 3187 cm-1 at 80% curcumin (R3.f), the lowest of all dispersions; figure: broad band without a sharp maximum at 80% (plateau ≈3380 to ≈3190) and maximum ≈3185 at 60% (read from Fig. 7a). Carbonyl region, text: new shoulder at 1655 cm-1 at 80% curcumin, 27 cm-1 below the non-hydrogen-bonded PVP carbonyl at 1682 cm-1 (R4.a); ratio of free to hydrogen-bonded carbonyl rises with polymer content; figure: maximum ≈1681 at 20 and 40 wt% curcumin (40%: shoulder ≈1660), broad maximum ≈1662 at 60%, shoulder ≈1655 beside the curcumin bands at 80% (read from Fig. 7b) | Fig. 7, p.980-981 |
| R8 | record, measured | PVP carbonyl band shape, 1710-1630 cm-1 — curcumin-PVP films at 20, 40, 60 wt% curcumin and neat PVP (P1, P4) — sub-table below | Fig. 14a, p.983 |
| C14 | claim, conclusion, authors: "suggests"; "confirms"; "provides further evidence" | PVP, whose amide carbonyl is a strong acceptor, formed the strongest and most extensive hydrogen bonds with curcumin: the lowest OH maximum (3187 cm-1), and a new hydrogen-bonded carbonyl shoulder at 1655 cm-1 (27 cm-1 shift) that confirms curcumin-PVP hydrogen bonding [rests on: R3.f, R4.a, R6] | p.980-981 |
| C32 | claim, conclusion, authors: asserted ("in direct contrast"; "Indeed") | The curcumin-PVP result contrasts directly with resveratrol-PVP, where PVP was an extremely effective inhibitor, and the IR spectra show much less hydrogen bonding between PVP and curcumin than between PVP and resveratrol [rests on: R8, R9] | p.984 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C42 | claim, mechanism, authors: "likely" | HPMC substitution reduces the hydroxyl donors available to ITZ's carbonyl acceptor and ITZ has no donor groups, so any ITZ-HPMC miscibility is likely entropy-driven with little contribution from favourable interactions [rests on: argument only (Fig. 1 structures); M1, M2; cited: ref 20] | p.16 |
| M1 | material | itraconazole (ITZ) Attix Pharmaceuticals (Ontario, Canada); structure Fig. 1d | p.5; p.20 |
| M2 | material | hydroxypropylmethylcellulose (HPMC) 606 grade, gift from Shin-Etsu Chemical Co. (Tokyo, Japan); structure Fig. 1c with R = H or CH3 or CH2CH(OH)CH3 | p.5; p.20 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | hydrogen-bonding motif in the crystal — ATP(S), high melting point polymorph (P8) — hydrogen-bonded dimers: OH group of one molecule (donor) to the N of the NH2 group of another molecule (acceptor); the NH2 protons are not hydrogen bonded | Fig. 11, p.5051; text p.5049-5050 |
| R11 | record, measured | IR NH/OH stretching region, crystalline versus amorphous — ATP(S) (P5) — crystal: sharp asymmetric and symmetric NH stretches at 3365 and 3307 cm−1 on a broad OH band; amorphous: similar pattern, peaks broadened and at higher wavenumbers (asymmetric NH2 stretch at 3390 cm−1; symmetric ≈3325 cm−1, read from Fig. 10) | p.5050; Fig. 10 |
| R12 | record, measured | IR of dispersions with HPMCP — ATP(S) and ATP(R) with 30% HPMCP (P5) — NH/OH region: OH peak at slightly higher wavenumber; larger change in the NH peaks with a new peak at 3253 cm−1 (Fig. 12); carbonyl region: pure HPMCP carbonyl at 1727 cm−1, a new peak at 1699 cm−1 in the dispersions (Fig. S1); spectra with ATP(R) and ATP(S) identical | p.5050; Fig. 12, p.5051; Fig. S1, SI p.1 |
| R13 | record, measured | IR NH/OH region of dispersions with HPMCAS LF — ATP(S) and ATP(R) with 30% HPMCAS LF (P5) — new NH peak at 3290 cm−1; OH peak slightly higher in wavenumber; changes larger for ATP(S); the 3390 cm−1 asymmetric NH2 band drastically reduced in the ATP(S) dispersion and present to a greater extent in the ATP(R) dispersion | p.5050-5051; Fig. 13, p.5051 |
| R14 | record, measured | IR NH/OH region of dispersions with HPMCAS HF — ATP(S) and ATP(R) with 20% HPMCAS HF (P5) — new peak at 3290 cm−1 in both; the 3390 cm−1 band more intense in the ATP(S) dispersion than in the ATP(R) dispersion | p.5051; Fig. 14 |
| C16 | claim, conclusion, authors: "consistent with" | In HPMCP dispersions the ATP NH2 group acts as a hydrogen-bond donor to polymer acceptor groups, in particular carbonyls, which lowers the NH stretching frequency (new 3253 cm−1 band) and gives a new carbonyl band (1699 cm−1) [rests on: R12] | p.5050 |
| C29 | claim, mechanism, authors: "most likely due to" | The different inhibition of the enantiomers by HPMCAS is most likely due to differences in the ability of each enantiomer to hydrogen bond with the polymer, which in turn affects crystallization [rests on: R13, R14, R7, R8] | abstract p.5046; conclusions p.5052 |

## 2015 Trasi — Evaluating the influence of polymers on nucleation and growth in supersaturated solutions of acetaminophen · Dissolution / D. Crystallization from solution

[2015-trasi-polymers-nucleation-growth-supersaturated-acetaminophen](../../../cards/2015-trasi-polymers-nucleation-growth-supersaturated-acetaminophen/paper.html) · Dissolution / D. Crystallization from solution · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C27 | claim, mechanism, authors: "could be" | The failure of PAA in solution could be caused by its ionization at pH 6.8 and its consequent inability to form hydrogen bonds, which are important for growth inhibition in the solid state [rests on: cited: refs 12, 16] | p.1247 |
| C33 | claim, mechanism, authors: "indicates"; "most certainly"; "can result in" | The polymer-induced change of APAP crystal morphology shows that the polymers are adsorbed preferentially on specific faces depending on the direction of the strongest H-bonds; attachment to the faster-growing faces can lower desupersaturation rates [rests on: R12; cited: ref 22] | p.1247 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R18 | record, simulated | total count of NVP-bile salt hydrogen bonds over the trajectory — P9, P10; dimers; cut-offs 3.0 Å, 20° — NVP-SHDC 192; NVP-SC 10 (text; Fig. 7B ≈192 and ≈10) | Fig. 7B, p.38; text p.19 |
| R21 | record, simulated | contact pattern and representative conformations of NVP-SHDC and NVP-SC dimers — P9, P10 — hydrogen bonds formed between bile salt hydroxyl groups on the polar face, or carboxyl groups, and the nitrogen or carbonyl of NVP; NVP-SHDC in contact for the majority of the trajectory, via van der Waals and hydrogen-bonded interactions; NVP-SC interactions sporadic and mainly van der Waals; on the polar face NVP sits closer to SHDC (Fig. 8B) than to SC (Fig. 8D); panels A and C show contact via the non-polar face | Fig. 8, p.39; text p.19-20 |
| C32 | claim, generalisation, authors: asserted ("drastic") | Bile salt chemistry, the number and position of hydroxyl groups, has a drastic impact on the number of NVP-bile salt hydrogen bonds [rests on: R18] | p.19 |
| C57 | claim, mechanism, authors: "may indicate" | The opposite trend for glycine conjugates may indicate an important role of drug-bile salt hydrogen bonding with the glycine head group [rests on: R16] | p.27 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C29 | claim, mechanism, authors: "suggesting" | The significantly different C=O stretching peaks point to different C=O to N-H intermolecular interactions in the different crystal structures [rests on: R18] | p.17 |

## 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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C35 | claim, mechanism, authors: "potential" | The carboxylate termination in the Adp and Sub monomers bends the side chain toward the cellulose ring through potential intramolecular hydrogen bonds [rests on: R14] | p.3665 |
| C45 | claim, conclusion, authors: "there appears evidence"; A6: "clear evidence" | Terminus-to-terminus RDFs give evidence of hydrogen bonding between side-chain termini in A1a, A5a and A5b, of repulsion between same-charge termini with close opposite-charge contacts in A6, and of repulsion between same-sign termini in Adp, A5b and A6 but not A5a; among unbranched oligomers only Adp shows repulsion [rests on: R21] | p.3667 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | IR carbonyl region, normalized — IDM-HPMC films 5-95% DL and amorphous IDM (100%) (P1, P5) — amorphous IDM peaks at 1733, 1709 and 1683 cm-1; 5% DL: relative intensity of 1733 cm-1 increased and 1709 cm-1 peak absent; spectra did not change significantly until 50% DL; at 60% DL the 1709 cm-1 peak becomes apparent and its relative intensity increases with DL. Figure: 5-30% traces deepest minimum at ≈1705 cm-1; 40% and 50% traces intermediate there; 60-95% traces with a band at ≈1709 cm-1 growing with DL; 100% trace strongest at ≈1709 cm-1 with the ≈1733 cm-1 band reduced to a shoulder | Fig. 9, p.14; text p.13-14 |
| R12 | record, measured | IR of IDM-PVP films — P1, P5; data not shown (spectra reported in ref 32) — 5-80% DL: peaks at 1733 and 1709 cm-1 absent, new peaks at 1724 and 1640 cm-1; higher DL: spectra similar to pure amorphous IDM | p.14 |
| C24 | claim, assumption, authors: asserted ("can") | IDM carbonyl groups and HPMC hydroxyl groups can interact by hydrogen bonding [rests on: argument only (Fig. 1)] | p.13 |
| C26 | claim, conclusion, authors: "indicate" | In the 5% DL HPMC film, HPMC disrupts IDM self-association, notably the dimeric hydrogen bonding, which accounts for the loss of the 1709 cm-1 band [rests on: R10] | p.13 |
| C28 | claim, conclusion, authors: "indicating"; "was estimated to be at least" | In IDM-PVP films at 5-80% DL the new 1724 and 1640 cm-1 bands show strong IDM-PVP interaction; at higher DL drug-drug interactions dominate; the IR miscibility limit is at least 80% DL [rests on: R12] | p.14 |

## 2016 Xie — Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives · Dissolution / B. Supersaturation from ASD dissolution

[2016-xie-celecoxib-high-drug-loading-asd-paa-cellulose-derivatives](../../../cards/2016-xie-celecoxib-high-drug-loading-asd-paa-cellulose-derivatives/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C63 | claim, mechanism, authors: "indicates"; "may disrupt"; "might occur"; "suggests" | The 1735 cm-1 shoulder growing at the expense of the 1710 cm-1 band as PAA:HPMC decreases shows that HPMC may disrupt PAA acid dimers, possibly by hydrogen bonds between HPMC OH and PAA C=O or between PAA OH and HPMC acceptor groups; PAA and HPMC therefore show some degree of miscibility [rests on: R21] | p.32 |

## 2017 Purohit — Phase Behavior of Ritonavir Amorphous Solid Dispersions during Hydration and Dissolution · Dissolution / A. Release mechanism and LoC

[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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C46 | claim, mechanism, authors: "can be expected"; "are expected" | PVP and PVPVA have hydrogen-bond acceptors but no donors, HPMCAS has both; RTV-HPMCAS interactions can be expected to be more numerous and diverse; with water, these interactions and the higher hydrophilicity of PVP and PVPVA are expected to give a higher Δχ for RTV-PVP and RTV-PVPVA [rests on: argument only; E4] | pdf p.15 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R1 | record, measured | N-H stretching bands of neat CEX (ATR) — crystalline CEX as received; amorphous CEX by melt quench (P3) — crystalline: doublet at 3322 and 3225 cm−1 (asymmetric and symmetric NH2 stretch of the sulfonamide); amorphous: 3351 and 3268 cm−1 | text p.3; Fig. S1 (not supplied) |
| R3 | record, measured | IR of CEX:PVP films versus ratio — 9:1, 7:3, 5:5, 3:7, 1:9 with neat amorphous CEX and neat PVP (P2); PVP grade not named in the caption — new N-H band at 3196 cm−1 grows at the expense of the 3268 cm−1 band as polymer loading increases; PVP C=O at 1682 cm−1 develops a shoulder at 1661 cm−1 (CEX has no absorbance there) that grows as the drug:polymer ratio increases; figure: 1661 cm−1 arrow on the 9:1 trace, 3196 cm−1 arrow on the 1:9 trace | Fig. 2a, p.4; text p.3 |
| R4 | record, measured | IR of CEX:PVP/VA films — P2; ratios not printed — pyrrolidone C=O at 1684 cm−1 develops a shoulder at 1662 cm−1; acetate C=O shows minimal change except at the highest drug loadings; CEX N-H shifts from 3268 to approximately 3198 cm−1 | text p.3; Fig. S2 (not supplied) |
| R5 | record, measured | IR of CEX:HPMCAS films versus ratio — 9:1 to 1:9 (P2) — CEX N-H band at 3268 cm−1 shifts gradually toward 3237 cm−1 as polymer loading increases; HPMCAS ester carbonyl shifts from 1743 to 1734 cm−1 as drug loading increases | Fig. 2b, p.4; text p.3 |
| R7 | record, measured | IR of PVP:HPMCAS films — 10-90% w/w HPMCAS with the neat polymers (P2) — PVP C=O at 1682 cm−1 develops a shoulder at 1643 cm−1 (arrow on the 90% HPMCAS trace); the 1682 cm−1 band persists and stays dominant in the blend spectra even at high HPMCAS weight fractions | Fig. 3, p.5; text p.3 |
| C11 | claim, conclusion, authors: asserted ("clearly indicates") | The CEX:PVP spectral changes reflect hydrogen bonding between the NH2 group of CEX and the C=O of PVP [rests on: R3] | p.3 |
| C16 | claim, conclusion, authors: "clear signs of miscibility"; "indicating" | PVP and HPMCAS are miscible through hydrogen bonding of the PVP C=O to the carboxylic acid OH of HPMCAS, a stronger hydrogen bond than CEX-PVP [rests on: R7, R3; cited: ref 37] | p.3 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | IR OH-stretch region (3380-3540 cm−1) and other systems — LPV-EC films (P11); LPV-CA and LPV-EUD films — amorphous EC peak at 3481 cm−1, amorphous LPV no peak in 3440-3540 cm−1; with LPV the EC peak at 3470 cm−1; no IR peak shifts for LPV-CA and LPV-EUD (data not shown) | Fig. 6B, p.121; text p.119 |
| C32 | claim, conclusion, authors: "consistent with" | The shift of the EC OH band from 3481 to 3470 cm−1 with LPV reflects a change in hydrogen bonding in the presence of the drug [rests on: R11] | p.119 |
| C53 | claim, conclusion, authors: discussion: "revealed"; results: "may be assigned", "consistent with" | IR revealed drug-polymer hydrogen bonding in CAP, EC, HPMCAS and HPMCP ASDs [rests on: R10, R11] | p.123; p.119 |
| C55 | claim, mechanism, authors: "can be rationalized"; "may also" | The order follows functional groups: HPMCP has about 31% carboxylic acid-containing phthalyl groups that can hydrogen-bond strongly with LPV, and LPV phenyl rings may π-π stack with the phthalates; HPMCAS-HF has only about 7% succinoyl groups; EC has about 50% unreacted hydroxyls that can hydrogen-bond [rests on: M2, M3, M5; cited: refs 50, 51] | p.123 |

## 2019 Que — Insights into the Dissolution Behavior of Ledipasvir-Copovidone Amorphous Solid Dispersions: Role of Drug Loading and Intermolecular Interactions · Dissolution / A. Release mechanism and LoC

[2019-que-ledipasvir-copovidone-asd-loc-interactions](../../../cards/2019-que-ledipasvir-copovidone-asd-loc-interactions/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R24 | record, measured | 1H NMR NH peaks with VP monomer — P8; as R23 — four NH peaks above 10 ppm (text); at 0 mg/mL VP ≈11.18 and ≈10.99 ppm (larger) and ≈10.74 and ≈10.56 ppm (smaller); at 80 mg/mL ≈11.27, ≈11.16, ≈11.03, ≈10.97 ppm; across 0 to 80 mg/mL the two smaller peaks move downfield by ≈0.4 ppm, the two larger by ≤ ≈0.1 ppm (read from Fig. 14; peaks tracked across traces by the extractor) | Fig. 14, p.31; text p.26, p.35 |
| R16 | record, measured | F 1s components by XPS — P7; neat amorphous ledipasvir and ASDs 5, 10, 20, 50% DL before dissolution — neat amorphous ledipasvir: one peak at 687.1 ± 0.1 eV; ASDs: an additional peak at 684.0 ± 0.2 eV (about 3 eV lower); share of F 1s at 684.0 eV 77, 73, 42, 18% at 5, 10, 20, 50% DL (text); Fig. 8: ≈77.5, ≈73.5, ≈41.5, ≈17.5%, neat ledipasvir 0%; Fig. 3S: neat drug single peak ≈687 eV, 20% DL ASD two fitted components ≈684 and ≈687 eV | text p.22; Fig. 8, p.24; Fig. 3S, SI p.4 |
| C26 | claim, mechanism, authors: "potentially can"; asserted | Ledipasvir F can accept a hydrogen bond from the NH of a neighbouring molecule; of the four NH groups, the two imidazole NH form stronger intramolecular hydrogen bonds to a carbonyl (seven-member ring), giving larger, higher-shift peaks little affected by VP, while the other two NH can bond intermolecularly to F [rests on: R24] | p.26 |
| C27 | claim, mechanism, authors: "more likely"; "as indicated by" | VP disrupts the intermolecular bonds by hydrogen bonding to NH (more likely, given the larger NH shift and peak area with VP) rather than by a halogen bond or dipolar interaction with F [rests on: R24] | p.26-27 |
| C39 | claim, mechanism, authors: asserted; "indicating" | The VP carbonyl group hydrogen-bonds to ledipasvir amine groups and so disrupts the drug-drug hydrogen bonds; two NH protons become deshielded with VP [rests on: R23, R24] | p.35 |
| C40 | claim, mechanism, authors: asserted ("explaining"; "therefore provides evidence") | In neat ledipasvir F accepts a hydrogen bond from an amine proton; when PVPVA's carbonyl takes over that NH, F gains electrons, which explains the lower-BE F 1s peak, so the XPS data are evidence of a drug-PVPVA interaction [rests on: R16] | p.35 |

## 2020 Hate — Influence of Drug-Silica Electrostatic Interactions on Drug Release from Mesoporous Silica-Based Oral Delivery Systems · Mesoporous silica / Mesoporous silica

[2020-hate-drug-silica-electrostatic-interactions-mesoporous-release](../../../cards/2020-hate-drug-silica-electrostatic-interactions-mesoporous-release/paper.html) · Mesoporous silica / Mesoporous silica · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, measured | amount of drug adsorbed on SBA-15 at pH 6.8 with competing adsorbates (mg/g, bars with error bars) — P3; KET and CLZ; 0.5 M urea or 50 mM TEA — sub-table below; text: KET and CLZ adsorption reduced drastically with TEA; with urea a small reduction for KET and no difference for CLZ | Fig. 6, p.17; text p.17 |
| C6 | claim, prior hypothesis, authors: "typically" | Drugs interact with silica by electrostatic interaction or hydrogen bonding depending on drug chemistry and pH; strong interactions give higher loading and sustained release, poor interactions lower loading and burst release; silanol-drug hydrogen bonds are relatively weak [rests on: cited: refs 16-18] | p.5 |
| C29 | claim, mechanism, authors: "suggested" | The small effect of urea on KET adsorption points to some hydrogen bonding between uncharged KET and silanol groups in addition to electrostatic interaction [rests on: R14] | p.20 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | carbonyl band positions (cm⁻¹), text values and readings from Fig. 2 (≈, about ±3 cm⁻¹) — amorphous drugs versus drug-loaded SBA-15, ATR-FTIR (P4); blank SBA-15 — sub-table below; blank SBA-15 shows no absorption between 1600 and 1800 cm⁻¹ | text p.16; Fig. 2, p.17 |
| R4 | record, measured | XPS Si 2p binding energy (eV) — SBA-15, IND/SBA, INDME/SBA (P6) — text, Si 2p3/2: 103.8 (SBA-15), 103.4 (IND/SBA), 103.3 (INDME/SBA); figure, maximum of the Si 2p envelope: ≈104.0, ≈103.5, ≈103.4 (read from Fig. 3); presence of the drugs verified by N 1s and Cl 2p spectra (data not shown) | text p.18; Fig. 3, p.18 |
| R5 | record, measured | XPS O 1s spectra — SBA-15, IND, INDME, IND/SBA, INDME/SBA (P6) — text: O 1s of IND/SBA and INDME/SBA at lower BE than SBA-15; the pure drugs show a low-BE shoulder (assigned to carbonyl) and a high-BE component (assigned to ether and OH oxygen); INDME/SBA O 1s symmetric, without the low-BE component; IND/SBA O 1s with a weak low-BE shoulder; no O 1s values printed. Figure (read from Fig. 3): maxima ≈533.2 (SBA-15), ≈533.0 (IND/SBA), ≈532.8 eV (INDME/SBA); fitted components of the pure drugs C=O ≈531.6, C-O-C ≈532.7 and OH (IND) ≈533.5 eV; fitted INDME component in INDME/SBA close to zero intensity; fitted IND component in IND/SBA small, centred ≈532.5 eV | text p.18-19; Fig. 3, p.18 |
| R14 | record, measured | Qa without and with urea (mg/g, mean ± SD, n = 3) — P9, equal initial activity ~0.2 — IND 12.4 ± 1.9 → 6.1 ± 1.7; INDME 14.2 ± 0.3 → 5.8 ± 1.0; p < 0.05 for both; Fig. 7 bars ≈12.3, ≈6.0, ≈14.0 and ≈6.1 | p.24; Fig. 7, p.25 |
| C41 | claim, mechanism, authors: discussion: "suggest"; abstract: "The results demonstrate"; conclusion: "were found" | The predominant interaction of both drugs with silica is hydrogen bonding between the drug carbonyl acceptor groups and the silanol donors, consistent with published work on other molecules [rests on: R3, R4, R5, R14; cited: refs 55-58] | p.2, p.35, p.40 |
| C42 | claim, mechanism, authors: "It is apparent"; "appear to be key"; "may explain"; abstract: asserted | Removing the hydrogen-bond donor by esterification does not affect the interaction with SBA-15, because the acceptor groups appear key; this may explain the similar adsorption on the normalized scale; the abstract states that a drug donor group did not enhance adsorption [rests on: R3, R12] | p.2, p.35 |

## 2020 Que — Evidence for Halogen Bonding in Amorphous Solid Dispersions · Solid state stability / Miscibility and drug-polymer interactions

[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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R17 | record, cited | literature values and findings the authors rely on — see sub-table — sub-table R17 | pp. 2-5, 22, 27-29 |
| C23 | claim, mechanism, authors: "lends support"; "providing further support" | The 2-4 eV halogen BE shift is significant and comparable to shifts from H-bonding, which supports a specific intermolecular interaction as its origin; smaller shifts reported for I...N halogen bonds add support [rests on: R7; cited: refs 56, 57, 58] | pp. 27-28 |
| C24 | claim, generalisation, authors: "can be" | Halogen and hydrogen bonds share directionality and can have comparable interaction strengths [rests on: cited: refs 61, 62] | p. 29 |
| C25 | claim, conclusion, authors: "appears" | In these systems the XB strength appears similar to weak H-bonding: KF 0.6-1.1 M-1 vs 0.7 M-1 for weak H-bonds to F, and IR shifts of 2-6 cm-1 vs 20-30 cm-1 for PVP-drug H-bonds [rests on: R11, R12, R17] | p. 29 |

## 2020 Saboo — Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers. · Dissolution / A. Release mechanism and LoC

[2020-saboo-asd-drug-loading-polymer-hydrophobicity-release](../../../cards/2020-saboo-asd-drug-loading-polymer-hydrophobicity-release/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R24 | record, measured | NH stretch peak position (cm⁻¹) — amorphous felodipine and 30% DL ASD films (P11) — sub-table below (Table 3); figure: maxima at ≈3342 (felodipine), ≈3292 (PVP and PVPVA, which also show a second band near ≈3225), ≈3362 (EUDS, magenta) and ≈3355 (HPMCAS, orange); HPMC shows no distinct maximum, only a shoulder near ≈3350 (read from Fig. 13); polymers show no significant peaks in this region (data not shown); a shoulder or second peak at 3342 cm⁻¹ remains for most ASDs | Table 3, p.12; Fig. 13, p.12; text p.8, p.10 |
| R25 | record, measured | IR carbonyl stretching region — amorphous felodipine and Fel:HPMC 30:70 film (P11) — amorphous felodipine: doublet at 1701 and 1682 cm⁻¹; Fel-HPMC: 1682 cm⁻¹ peak not discernible, single slightly broader peak at 1699 cm⁻¹ | Fig. S8, SI p.10 |
| C24 | claim, assumption, authors: asserted | In neat amorphous felodipine the NH group hydrogen-bonds to the carbonyl of another drug molecule, and its peak position varies with interaction strength, so NH shifts reflect disruption of drug-drug bonds and possible drug-polymer bonds [rests on: cited: refs 17, 18, 41] | p.8 |
| C25 | claim, conclusion, authors: "consistent with"; "suggesting"; "appears to be the case" | The NH downshift with PVP and PVPVA is consistent with stronger drug-polymer hydrogen bonds than in amorphous felodipine; the upshift with EUDS and HPMCAS suggests weaker interactions; with HPMC there is no NH shift and carbonyl changes indicate an interaction of similar strength to neat drug; the hydrogen-bonding order is PVP ≅ PVPVA > HPMC > HPMCAS > EUDS; residual drug-drug bonding means the extent of drug-polymer bonding cannot be quantified [rests on: R24, R25] | p.8, p.10 |

## 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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | ATR-FTIR carbonyl band position, neat polymer versus 4:6 dispersion (cm−1) — P6 — sub-table below; new band at around 1560 cm−1 in the CAP, HPMCP and L100 dispersions; acid donor region: broad peaks; lumefantrine has no carbonyl group, amorphous lumefantrine bands at ≈1635, ≈1590 and ≈1565 cm−1 (read from Fig. 5a) | Fig. 5, p.7; text p.5-6 |
| C11 | claim, mechanism, authors: "anticipated"; "suggests"; "indicating" | The polymer carbonyls, anticipated to self-hydrogen-bond with the polymer carboxylic acid donors, shift to higher wavenumbers with lumefantrine, which reflects a change in hydrogen bonding; the small HPMCP shift reflects some drug-polymer interaction [rests on: R9] | p.5-6 |
| C26 | claim, mechanism, authors: "presumably"; "suggests"; "would likely" | Artemether could not be made amorphous at a reasonable loading, presumably because of its rigid structure and lack of hydrogen-bonding groups; its low melting point means an artemether dispersion would likely have a low Tg and poor stability [rests on: R6, R7] | p.8 |

## 2021 Que — Impact of Drug−Polymer Intermolecular Interactions on Dissolution Performance of Copovidone-Based Amorphous Solid Dispersions · Dissolution / A. Release mechanism and LoC

[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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured (rows a, c, d, e); cited ref 17 (row b) | VP carbonyl band of PVPVA vs DL — ASD films at 10−90% DL (P2) — see sub-table R7 | Section 4.2.1, p.3500−3501; Section 5, p.3503; Fig. 2, p.3500 |
| C5 | claim, conclusion, authors: results: "indicating"; discussion: "confirms" | TIPP and PHPH form hydrogen bonds between their hydroxyl groups and the VP carbonyl of PVPVA. [rests on: R7] | Section 4.2.1, p.3501; Section 5, p.3503 |
| C33 | claim, conclusion, authors: abstract: asserted; discussion: "appears to trend" | On a per-mole basis the LoC ranks TIPP < PHPH < Me-TIPP < Me-PHPH, and what appears to trend with it is interaction ability: PHPH and TIPP (phenolic hydrogen-bond donors, strong specific interactions) have much lower LoCs than Me-TIPP (halogen bonding only) and Me-PHPH (nonspecific); abstract: hydrogen-bonding ASDs had lower LoCs and halogen-only or nonspecific compounds considerably higher LoCs. [rests on: R19, R20, R7, R12] | Abstract, p.3496; Section 5, p.3505 |
| C35 | claim, generalisation, authors: discussion: "it appears", "may lead to"; conclusions: "indicating", "may be detrimental", "perhaps counterintuitively" | Although hydrogen bonding is known to improve solid-state physical stability, compound−polymer hydrogen bonding may lower the LoC, with no drug-rich colloids above the LoC and worse release at moderate DLs; weaker or absent specific interactions give markedly better release up to 30−40% DL with colloid formation, in line with an indomethacin vs methyl-ester analogue study. [rests on: R15, R19, R20, R7; cited: refs 11, 12, 42] | Section 5, p.3505; Conclusions, p.3506 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C37 | claim, assumption, authors: asserted ("should be considered") | Eq 4 also assumes ideal mixing without specific interactions, whereas the IBP carboxylic acid is a strong hydrogen bond donor that can interact with the polymer; adding the interaction parameter χ gives eq 5 [rests on: argument only] | p.1352 |
| C40 | claim, mechanism, authors: abstract: asserted ("as a result of more extensive drug−polymer interactions"); discussion: "consistent with"; "would, in turn, be consistent with" | IBP interacts more strongly with PVP-VA (pyrrolidone carbonyl acceptor) than with HPMC 603 (weak OH and ether acceptors): the larger downfield shift with PVP-VA despite less polymer in the drug-rich phase fits stronger interaction, which would in turn fit the larger drop in dissolved IBP with PVP-VA [rests on: R3, R5, R14, R19; cited: refs 50-53] | p.1344, p.1353 |
| R14 | record, cited | Flory-Huggins χ between IBP and PVP-VA — 1/1 IBP/PVP-VA blend in an ASD (ref 50) — ca. −1; IBP-PVP-VA hydrogen bonding reported, giving a negative χ; pyrrolidone carbonyl of vinylpyrrolidone as hydrogen bond acceptor for the carboxylic acid (refs 51, 52) | p.1352 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C35 | claim, mechanism, authors: "may offer some support"; "may"; "perhaps"; "possibly"; "further suggesting" | Intermolecular interactions may help explain the protection by PVP and PVP/VA: most degradants form by intramolecular attack during hydrolysis, so interactions may protect RTV; FT-IR shifts, perhaps from hydrogen bonding, lie in regions of the more reactive groups; the PVP over PVP/VA order is possibly from more interactions with the vinyl pyrrole carbonyl; the absence of interaction evidence with HPMCAS or HPMC further supports this [rests on: R20, R10] | p.342 |
| C29 | claim, conclusion, authors: "might indicate"; "may suggest" | The 1720 cm⁻¹ shoulder of RTV-PVP K-30 might reflect changed hydrogen bonding from ASD formation or a simple overlap of RTV and PVP bands; the shifted and broadened 1681 cm⁻¹ band of RTV-PVP/VA 64, seen before (ref 27), may mean that RTV interacts preferentially with the C=O of vinyl pyrrole [rests on: R20; cited: ref 27] | p.340-341 |
| C5 | claim, prior hypothesis, authors: "indicating"; "may be more protective"; "suggested" | Earlier studies: polymers lowered the TGA degradation onset of posaconazole, with PVP/VA possibly more protective than HPMCAS, and PVP/VA delayed the onset of indomethacin (ref 3); PVP was protective or destabilizing for indomethacin depending on interactions and drug-polymer ratio (refs 14, 15); cellulose acetate protected ibuprofen and naproxen, suggested to be from hydrogen bonding (ref 16); the stabilization mechanism is complex [rests on: cited: refs 3, 14-16] | p.333 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R18 | record, measured | carbonyl-region FTIR (1800-1550 cm−1) of ASD films — spin-coated films (P10): free base 10, 25%; PEG 250 diacid (1:1) 25, 30%; benzoate 20, 25, 30%; PEG 250 diacid (2:1) 25, 30%; besylate, tosylate, camsylate 10, 15, 30%; HCl 10, 20, 30%; sulfate 5, 30% DL; with neat PVPVA, amorphous lumefantrine and each neat salt — PVPVA vinyl acetate C=O at 1736 cm−1 and vinylpyrrolidone C=O at 1684 cm−1; no shift of either peak at any DL except in the tosylate ASDs; peak height ratios changed with DL for several ASDs (Fig. S4, SI not supplied), most visibly for the PEG 250 diacid (1:1) salt with excess acid groups (Fig. 12b) | Fig. 12, p.56; text p.55-56 |
| C24 | claim, conclusion, authors: "suggests"; "there might be" | Changes in FTIR peak height ratios with DL point to a minor extent of interaction between some lumefantrine salts and PVPVA carbonyls, most visible for the non-stoichiometric salt with excess acid groups [rests on: R18] | p.55-56 |
| C30 | claim, conclusion, authors: "indicated"; "appear" | FTIR shows that the lumefantrine salts generally have a very low tendency to interact with PVPVA; only the PEG 250 diacid/sulfate salts with an unreacted acid group showed some sign of hydrogen bonding, and specific interactions of the stoichiometric salts with PVPVA appear less extensive than in systems studied before [rests on: R18] | p.57 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R16 | record, measured | ATR-FTIR carbonyl region of ASDs — P13; ASD powders, all DLs; neat polymers and amorphous lumefantrine — neat polymer peaks (dashed lines, Fig. 5): PVPVA 1730 (vinyl acetate) and 1670 cm−1 (vinylpyrrolidone), HPMCAS 1733, HPMCP 1719, CAP 1719, Eudragit L 100 1702 cm−1; single well-resolved carbonyl peak for HPMCAS, HPMCP, CAP; broad band spanning ≈20 cm−1 for Eudragit L 100. Shifts to higher wavenumber with DL: PVPVA vinyl acetate +2 cm−1 at 25% DL with no further shift, vinylpyrrolidone gradual, +6 cm−1 at 50% DL; HPMCAS and HPMCP +2−6 cm−1, with 2 cm−1 already at 5% DL; CAP +8 and +21 cm−1 at 25 and 50% DL; Eudragit L 100 +13 and +21 cm−1 at 25 and 50% DL; CAP and Eudragit L 100 no shift at 5 and 10% DL | p.404; Fig. 5, p.402 |
| R17 | record, measured | transmission FTIR of dried spin-coated films — P14; PVPVA and lumefantrine−PVPVA films (Fig. S1 labels 10, 25, 50% DL) — carbonyl peaks at 1736 and 1684 cm−1 did not shift as DL increased | p.404; Fig. S1, SI p.2 |
| C20 | claim, conclusion, authors: asserted ("This shows") | Lumefantrine does not hydrogen bond with the PVPVA carbonyl groups; there was little evidence of drug−polymer hydrogen bonding from the IR spectra [rests on: R17] | p.404, p.411; SI p.2 |
| C22 | claim, mechanism, authors: "are likely able"; "is therefore suggestive" | Enteric polymers likely self-associate through hydrogen bonds of their carboxylic acids, so the blue shift on adding lumefantrine reflects a change in hydrogen bonding within the polymer [rests on: R16] | p.404 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R19 | record, measured | 13C CP-MAS spectra — P8; PVPVA, amorphous BCL, crystalline BCL form 1, 30-SE/MP, 30-HME/CM30s, 30-SE/CM5m — most peak positions of the three ASDs unchanged vs amorphous BCL; text: the peak at 144.4 ppm shifted by approximately 1.5 ppm in the ASDs; figure: ASD peak at ≈144 ppm vs amorphous BCL ≈142 ppm (read from Fig. 12B), same in all three ASDs; peak tentatively assigned to the aromatic carbon adjacent to N-H (ChemDraw prediction, Fig. S8, and ref 44) | Fig. 12, p.28; text p.27 |
| R25 | record, cited | BCL-polymer hydrogen bonding — BCL with PVP and the PVP family of polymers, refs 45, 61 (Andrews et al.) — intermolecular interactions (hydrogen bonding) observed by FTIR and Raman spectroscopy | text p.27, p.35 (refs 45, 61) |
| C34 | claim, mechanism, authors: "tentatively assigned"; "suggest a possible" | The ~1.5 ppm shift of the 144.4 ppm peak, tentatively assigned to the aromatic carbon next to N-H, suggests possible N-H…O=C hydrogen bonding between BCL and PVPVA, in agreement with earlier FTIR/Raman of BCL-PVP [rests on: R19, R25] | p.27 |
| C63 | claim, mechanism, authors: "can be speculated upon"; "may also play a role" | Not all ASDs are susceptible to matrix crystallization; speculated reasons from BCL: BCL-PVP-family hydrogen bonds, found here with PVPVA, are rapidly disrupted on hydration leaving the drug unprotected; drugs above their wet Tg are more mobile; amorphous BCL crystallizes rapidly above Tg despite high glass forming ability; amorphous BCL can be mechanically activated [rests on: R19, R25, R26; cited: refs 14, 62] | p.35 |

## 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 · measured · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | solid-state 1H MAS spectra — P5, P6; crystalline IBP, amorphous IBP, ASDs with polymer weight ratio 40%; 40 °C — sub-table below; text: crystalline IBP broad peaks around 1, 7 and 12.5 ppm (aliphatic, aromatic, carboxylic); amorphous IBP highly resolved sharp peaks; IBP peaks broader in ASDs than in amorphous IBP; polymer peaks at higher field overlap aliphatic IBP peaks; aliphatic and aromatic IBP peaks of ASDs slightly down-field of amorphous IBP; carboxylic proton a single peak at 9−10 ppm in every ASD, at the highest field for IBP/HPMC | Fig. 6, p.105; text p.105-106 |
| R13 | record, measured | carboxylic proton peak versus temperature — P6; ASDs with polymer weight ratio 40%; 25, 40, 55 °C — up-field shift with increasing temperature in all three ASDs; printed 25 → 55 °C differences: IBP/HPMC 0.717 ppm, IBP/PVP−VA 0.271 ppm, IBP/PVP 0.279 ppm; peak positions at 25, 40, 55 °C ≈9.7, ≈9.3, ≈9.0 (HPMC), ≈9.9, ≈9.8, ≈9.6 (PVP−VA), ≈9.7 (broad), ≈9.6, ≈9.5 ppm (PVP) (read from Fig. 8) | Fig. 8, p.107 |
| R15 | record, derived (E9) | chemical shift temperature coefficient TC of IBP carboxylic acid proton — R13 — around −9 × 10−3 ppm/K for IBP/PVP and IBP/PVP−VA ASDs; −24 × 10−3 ppm/K for IBP/HPMC ASD | p.107 |
| C23 | claim, mechanism, authors: "suggesting"; "likely" | The large up-field shift of the carboxylic proton in ASDs suggests weakened hydrogen bonding: all three polymers likely disrupt IBP dimers [rests on: R11; cited: refs 65-67] | p.105 |
| C24 | claim, mechanism, authors: "it can be assumed"; "likely contributed" | Remaining IBP dimers can be assumed minimal in the PVP and PVP−VA ASDs at 40% polymer; the carboxylic proton at 9−10 ppm, down-field of a free carboxylic proton (~8 ppm), likely reflects drug-polymer hydrogen bonding [rests on: R11, R28; cited: refs 63-65, 68, 69] | p.105 |
| C32 | claim, conclusion, authors: "indicates"; "implying"; "reflecting" | The TC of about −9 × 10−3 ppm/K indicates intermolecular hydrogen bonding of the IBP carboxylic proton with PVP and PVP−VA; the larger TC for IBP/HPMC implies that this bond with HPMC is disrupted more easily on heating, and the up-field carbonyl shift reflects reduced C=O hydrogen bonding, so the IBP-HPMC interaction is highly temperature-dependent while that with PVP or PVP−VA is less so [rests on: R13, R14, R15; cited: refs 73-79] | p.107 |

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: A Close Look at the Dissolution Interface · Dissolution / A. Release mechanism and LoC

[2023-deac-asd-dissolution-interface](../../../cards/2023-deac-asd-dissolution-interface/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C64 | claim, prior hypothesis, authors: asserted | Strong drug-polymer interactions, especially hydrogen bonding, improve physical stability but can harm release, especially in PVPVA ASDs; the low LoC of PHPH-PVPVA was attributed to adhesive hydrogen bonding, and similar effects were noted for other compounds [rests on: cited: refs 13, 23, 47-49] | p.2231 |
| C65 | claim, mechanism, authors: abstract: "This was due to"; discussion: asserted (cited ref 22); conclusions: "was due to" | Hydrogen bonding increases PVPVA distribution into the hydrophobic phase, making it volumetrically larger (associative separation; segregative when the polymer prefers the hydrophilic phase); this incorporation of polymer is why the continuous hydrophobic phase formed at lower DL for PHPH, a high polymer content giving a low LoC [rests on: R6, R7, R12; cited: refs 22, 50] | p.2217, p.2231-2232, p.2233 |

## 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: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: asserted ("As demonstrated by spectroscopic methods") | The LoC correlates with drug-polymer interaction strength, lower for stronger interactions: for the four analogues (PHPH hydrogen bonds, TIPP hydrogen and halogen bonds, MeTIPP halogen bonds, MePHPH none) hydrogen-bonding systems had significantly lower LoCs, the LoC falling with the cumulative strength/extent of specific interactions; indomethacin versus its ester showed the same in PVPVA [rests on: cited: refs 14, 31, 34; R8, R17] | p.722, p.724, p.729 |
| C46 | claim, mechanism, authors: "it is reasonable to infer" | It is reasonable to infer that the phenol-containing compounds take up much PVPVA into the insoluble phase because of favourable drug-polymer interactions, whereas for the methoxy derivatives the lack of hydrogen bonds makes extensive polymer distribution into that phase energetically less favourable [rests on: R3, R8; cited: ref 69] | p.732 |

## 2024 Bapat — Interplay of Drug−Polymer Interactions and Release Performance for HPMCAS-Based Amorphous Solid Dispersions · Dissolution / A. Release mechanism and LoC

[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 · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C41 | claim, mechanism, authors: "can be rationalized"; "this conjecture" | Neutral PHPH complexes HPMCAS efficiently and lowers release on the same trendline as the cations; this is rationalized by hydrophobic hydrogen bonding: the HPMCAS carboxylate offers a hydrogen-bonding site for the phenolic groups of PHPH, supported by phenol-carboxylate (including succinate) complexes in water and by PHPH forming an insoluble complex with copovidone [rests on: R12.l, R14.p; cited: refs 18, 74, 75] | p.1475 |
| C22 | claim, prior hypothesis, authors: "suggest" | Recent studies suggest a correlation between drug-polymer hydrogen bonding and poor release at modest DL for copovidone ASDs of lipophilic drugs; for HPMCAS and other enteric polymers the impact of interactions, including ionic ones, is largely unknown [rests on: cited: refs 17, 18, 23] | p.1472-1473 |
| C3 | claim, prior hypothesis, authors: "have been implicated"; "it has been noted for some systems" | Specific drug-polymer interactions such as hydrogen bonding have been implicated in reduced release at relatively low DL; for HPMCAS ASDs fewer mechanistic studies exist, and some systems show a gradual rather than drastic decrease of release with DL [rests on: cited: refs 14, 17-29] | p.1466 |

## 2024 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior · Dissolution / A. Release mechanism and LoC

[2024-deac-asd-ternary-phase-diagrams-release](../../../cards/2024-deac-asd-ternary-phase-diagrams-release/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: hydrogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C22 | claim, mechanism, authors: "A potential explanation" | A potential explanation for this association is that PHPH, unlike MePHPH, can form strong hydrogen bonds with PVPVA [rests on: cited: ref 18] | p.1909 |
| C35 | claim, mechanism, authors: asserted; hydrogen bonds "suggested to persist" | PVPVA partitioning to the hydrophilic phase makes MePHPH tie lines negative and places the critical point near the right side of the triangle, while partitioning to the hydrophobic phase makes PHPH tie lines positive with the critical point near the left side; the difference arises from weak van der Waals MePHPH-PVPVA interaction versus PHPH-PVPVA hydrogen bonds suggested to persist in water [rests on: R22, R23, R15; cited: ref 31] | p.1911 |
| C38 | claim, mechanism, authors: "likely" | The larger miscibility region of PHPH-PVPVA-water likely arises from PHPH hydrogen bonding with PVPVA and water [rests on: R23, R28] | p.1911 |
| C56 | claim, mechanism, authors: "likely" | PHPH-PVPVA hydrogen bonding likely produced the high polymer content of the PHPH hydrophobic phase, which led to phase inversion at low DL; the weak MePHPH-PVPVA interaction gave negligible polymer in the hydrophobic phase and a higher inversion DL [rests on: R10, R17, R35] | p.1915 |

## Mentioned only

- 2015 Raina — [2015-raina-precipitation-crystallization-supersaturated-dihydropyridines-synchrotron](../../../cards/2015-raina-precipitation-crystallization-supersaturated-dihydropyridines-synchrotron/paper.html) · Dissolution / D. Crystallization from solution (ref C45)
- 2015 Xie — [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 (ref 6)
- 2016 Sato — [2016-sato-phb-crystal-growth-supercooled-organic-compounds](../../../cards/2016-sato-phb-crystal-growth-supercooled-organic-compounds/paper.html) · Solid state stability / Physical stability (ref C11)
- 2018 Mosqueragiraldo — [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 (ref C3)
- 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 23)