# Evidence: polymer salt formation

Parent: — · class: formulation design · names merged here: polymer salt formation

3 papers measured or used it, 0 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.

## 2022 Qi — Improved dissolution of an enteric polymer and its amorphous solid dispersions by polymer salt formation · Dissolution / A. Release mechanism and LoC

[2022-qi-enteric-polymer-salt-hp50-miconazole-asd-dissolution](../../../cards/2022-qi-enteric-polymer-salt-hp50-miconazole-asd-dissolution/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: polymer salt formation

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured (wt%); derived, relation not printed (molar %) | sodium content of HP-50-Na — elemental analysis by ICP-OES (P8) and 1H NMR (Figure S2, SI) — 3.38%-3.52% by weight; molar sodium content 91 to 95% | p.4 |
| R9 | record, measured | polymer release (%) versus time, neat compacts (mean, n = 3) — HP-50-Na and HP-50 (P10), 50 mM phosphate, pH 6.8, 37 °C — sub-table below. Text: close to 100% of HP-50-Na dissolved at 80 min against about 40% of HP-50 | Fig. 5, p.6; text p.4 |
| R10 | record, derived (P10) | normalized dissolution rate (mg·min⁻¹·cm⁻²), mean with SD bar, n = 3 — neat compacts, 50 mM phosphate, pH 6.8, 37 °C — sub-table below. Text: the amine salts showed nearly complete dissolution after 80 min (profiles not shown in the main text) | Fig. 6, p.6; text p.4 |
| R12 | record, derived (P10) | normalized dissolution rate (mg·min⁻¹·cm⁻²) at two buffer capacities, mean with SD bar, n = 3 — HP-50-Na and HP-50 compacts in 50 mM (M16) and 5 mM (M17) phosphate — sub-table below. Text: HP-50-Na rate the same in both media; HP-50 6-fold lower in 5 mM than in 50 mM phosphate | Fig. 8, p.6; text p.6, p.8 |
| R15 | record, derived (P10) | normalized drug release rate (mg·min⁻¹·cm⁻²), mean with SD bar, n = 3 — 20% DL miconazole ASDs, 50 mM phosphate, pH 6.8 — HP-50 ≈0.22 (SD bar within ≈0.01); PTEA ≈2.70 (SD bar to ≈3.00); HP-50-Na ≈3.15 (SD bar to ≈3.17) (read from Fig. 11). Text: drug release from the HP-50-Na ASD 14 times faster than from the HP-50 ASD | Fig. 11, p.7; text p.7 |
| C3 | claim, conclusion, authors: abstract and results: asserted ("~ 3-fold"); discussion: "more than twice as fast" | Polymer salts dissolve about 3-fold faster than HP-50 at pH 6.8 in 50 mM sodium phosphate; HP-50-Na about 3-fold faster than HP-50 [rests on: R9, R10] | p.1, p.4, p.8 |
| C6 | claim, generalisation, authors: asserted | Polymer ionization and buffer capacity are critical for the dissolution of HP-50-based systems, and pre-ionization via polymer salt formation is a successful strategy for designing polymers for improved ASD performance [rests on: R9-R15] | p.1 |
| C31 | claim, mechanism, authors: asserted ("confirms"; "Clearly") | Pre-ionization by salt formation removes the generation and transport of protons; the HP-50 versus HP-50-Na comparisons (faster in 50 mM phosphate, independent of buffer capacity, soluble in water) confirm that proton generation and removal by carriers hinder dissolution of the protonated polymer, and salt formation overcomes the dependence on proton-carrier concentration [rests on: R9, R10, R12, R16] | p.8 |

## 2023 Bapat — Does Media Choice Matter When Evaluating the Performance of Hydroxypropyl Methylcellulose Acetate Succinate-Based Amorphous Solid Dispersions? · Dissolution / A. Release mechanism and LoC

[2023-bapat-hpmcas-asd-media-choice-buffer-capacity-release](../../../cards/2023-bapat-hpmcas-asd-media-choice-buffer-capacity-release/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: polymer salt formation

| id | kind | content | locator |
|---|---|---|---|
| M4 | material | HPMCAS-TEA triethylamine salt prepared in-house from M3 (P4); cryomilled, sieved 106-250 µm | p.5716 |
| P4 | method | polymer salt formation (acid-base reaction) | p.5716 |
| R15 | record, measured | gel layer apparent pH (mean ± SD) — gel removed from compacts after exposure in the IDR apparatus (P10) — sub-table below | p.5720; methods p.5717-5718 |
| R16 | record, measured | normalized release rate plotted against gel layer apparent pH — HPMCAS in 25, 50, 100 mM pH 6.8 and 50 mM pH 7.5 phosphate; HPMCAS-TEA in 50 mM pH 6.8 phosphate (labels in figure) — HPMCAS: gel pH 5.6, 6.0, 6.2, 6.3 (R15.b-e) against rates ≈0.60, ≈0.90, ≈1.01, ≈1.09 (the R5.c-e and R5.l media); HPMCAS-TEA: gel pH 6.7 against ≈1.62; x error bars ≈±0.10-0.15 pH, y error bars ≤≈0.04 (read from Fig. 10); the glycine point (R15.f) is not plotted | Fig. 10, p.5723 |
| R18 | record, measured | normalized release rate versus rotation speed — neat HPMCAS and HPMCAS-TEA compacts (P7); media as labelled in the figure legend — sub-table below | Fig. 7a, p.5722; text p.5720 |
| C41 | claim, conclusion, authors: "further supported"; "extremely close" | The pre-ionized polymer salt, which releases no protons, has a gel pH extremely close to bulk pH and releases faster than protonated HPMCAS, further supporting the relationship [rests on: R15.h, R16, R18.e] | p.5724 |

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

[2023-nguyen-pretomanid-hpmcas-asd-fed-fasted-performance](../../../cards/2023-nguyen-pretomanid-hpmcas-asd-fed-fasted-performance/paper.html) · Bioperformance / Bioperformance · used · as: polymer salt formation

| id | kind | content | locator |
|---|---|---|---|
| C26 | claim, prior hypothesis, authors: "is expected" | HPMCAS-HF dissolves only when a critical fraction of its carboxylic acid groups is ionized, i.e. above a threshold pH; adding a base is expected to speed polymer dissolution, and hence drug release, by raising the microenvironmental pH [rests on: cited: refs 29, 42] | p.3176 |
| C67 | claim, mechanism, authors: "likely" | Adding a base likely forms a polymer salt, which earlier enhanced HPMCP dissolution [rests on: cited: ref 29] | p.3182 |
| E7 | equation | counterion stoichiometry, base to polymer acid groups: moles of base = moles of carboxylic acid groups of HPMCAS-HF, a 1:1 molar ratio (in words) | p.3172, p.3176 |