# Evidence: critical ionization for polymer dissolution

Parent: — · class: solution behaviour · names merged here: critical ionization; critical ionization extent; critical ionization for polymer dissolution; critical ionization fraction; polymer ionization threshold

5 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 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 · used · as: critical ionization fraction

| id | kind | content | locator |
|---|---|---|---|
| E2 | equation | critical ionization model of polymer dissolution (Willson): DR ∝ [A−]/[HA] | p.409 |
| R27 | record, derived (extrapolation of R24; relation not printed) | critical ionization fraction for dissolution of neat CAP and HPMCP — literature data of R24 — CAP: dissolution rate approaching zero at an ionized fraction of ≈0.94; HPMCP: minimum pH for dissolution ∼5 by extrapolation of Fig. S4, a critical ionization fraction of slightly less than 0.83 | p.410 |
| C57 | claim, mechanism, authors: "can be accounted for"; asserted | CAP needs ≈0.94 of its groups ionized to dissolve, more than the 0.88 left free, so the 25% DL CAP ASD does not release; HPMCP needs slightly less than 0.83, about what is left free, so its 25% DL ASD still releases slowly; CAP, needing a larger ionized fraction, is more susceptible to an additive that forms a hydrophobic ion pair with its −COOH groups [rests on: R27, R25, R13.w, R13.ac] | p.410 |

## 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 · used · as: critical ionization

| id | kind | content | locator |
|---|---|---|---|
| R19 | record, cited | critical ionization percent of HP-50 — Hiew and Taylor 2022, ref 9 — approximately 83% ionization | p.9 |
| C36 | claim, mechanism, authors: "confirmed"; "perhaps explained"; "may explain" | The BIS-TRIS series confirms the importance of the ionized form; the almost 2-fold drop from 100 to 80% ionization is perhaps explained by a minimum ionization needed for hydrophobic ionizable polymers to dissolve, and the critical ionization of about 83% estimated for HP-50 may explain it; partially ionized polymers can ionize further but still need proton removal, though less than HP-50 [rests on: R13, R19; cited: refs 9, 35] | p.8-9 |

## 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 · used · as: polymer ionization threshold

| id | kind | content | locator |
|---|---|---|---|
| C12 | claim, conclusion, authors: asserted | Solution pH becomes important as it approaches the threshold pH for polymer dissolution, so HPMCAS dissolves more slowly in FeSSIF-V2 (pH 5.8) than in pH 6.8 phosphate of corresponding buffer capacity [rests on: R5.h, R5.d] | p.5718 |
| C14 | claim, mechanism, authors: "presumably" | No HPMCAS dissolved in FeSSIF V1 because pH 5.0 is too low to reach the threshold ionization needed for the chains to become solubilized [rests on: R8] | p.5718-5719 |

## 2025 Bapat — Impact of HPMCAS Grade on the Release of Weakly Basic Drugs from Amorphous Solid Dispersions · Dissolution / A. Release mechanism and LoC

[2025-bapat-hpmcas-grade-weak-base-asd-release-complexation](../../../cards/2025-bapat-hpmcas-grade-weak-base-asd-release-complexation/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: critical ionization extent

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: asserted | Critical ionization fraction model: an acidic polymer starts to dissolve only after a critical fraction of its ionizable groups is ionized, and its rate then rises with further ionization; ionization to carboxylate enhances hydration, plasticization and dilution of the chains [rests on: cited: refs 45, 46] | p.397 |
| C22 | claim, generalisation, authors: "may be related"; "likely to be detrimental" | The opposite lumefantrine release results with poly(acrylic acid) and with enteric polymers may relate to polymer hydrophilicity: poly(acrylic acid) is soluble even un-ionized, enteric polymers only above a critical ionization extent, so molecularly mixed components that impede hydration of a critical number of ionizable groups are likely detrimental for release [rests on: R16; cited: refs 3, 45, 76] | p.402-403 |
| C25 | claim, mechanism, authors: "A similar explanation can be applied" | By analogy with Heller's maleic anhydride copolymers (larger hydrophobic moiety needs a larger critical ionization extent, pKa unchanged), LF, with a larger ratio of hydrophilic succinoyl to hydrophobic acetyl groups and pKa similar to the other grades, needs a lower degree of ionization to dissolve and has a lower dissolution pH threshold [rests on: R14, M3-M5; cited: refs 78] | p.403 |

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

[2025-kaur-bdq-hpmcas-complexation-media-asd-release](../../../cards/2025-kaur-bdq-hpmcas-complexation-media-asd-release/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: critical ionization for polymer dissolution

| id | kind | content | locator |
|---|---|---|---|
| C28 | claim, assumption, authors: "It is apparent"; "estimated" | About 77% ionization of HPMCAS is needed for dissolution to start, estimated from the ionization at a threshold pH of 5.5 with a pKa of 5.0 [rests on: R21; cited: refs 22, 27] | p.9-10 |
| C33 | claim, mechanism, authors: "suggest"; "may explain" | At pH 6.0 and 5.8, with HPMCAS 91.5 and 88.1% ionized and BDQ >99% ionized, BDQ cations are in slight excess over carboxylates, so only a low extent of interaction is needed to bring ionized groups below the 77% solubility threshold; the excess BDQ may explain why complexation is highest at these pH values [rests on: R21, R5, R7; C28] | p.9-10 |
| C46 | claim, mechanism, authors: "may play a role"; "is expected to impede" | This traces back to the critical ionization of about 77% estimated for HPMCAS-MF; hydration resulting from ionization, rather than ionization itself, solubilizes the chains (charge repulsion may play a role); complex formation does not interfere with ionization but is expected to impede hydration and hence plasticization, chain dilution and release [rests on: C28; argument only] | p.10 |