# Evidence: pH-dependent polymer solubility

Parent: — · class: solution behaviour · names merged here: pH-dependent polymer solubility

9 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.

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

[2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions](../../../cards/2015-chen-surfactants-crystallization-celecoxib-hpmcas-asd-suspensions/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| P1 | method | acidified aqueous medium preparation | Materials, p. 6 |
| C17 | claim, conclusion, authors: asserted | HPMCAS leaching is considerable in SDS, more than 3 orders of magnitude above the HCl medium where it is only a few µg/mL; STC raises it less than SDS; Triton X100 gives a profile similar to HCl. [rests on: R18] | Results p. 18 |

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

[2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior](../../../cards/2015-wegiel-resveratrol-solid-dispersions-aqueous-phase-behavior/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| C14 | claim, conclusion, authors: asserted ("It is clear") | For 25% resveratrol HPMCAS dispersions, crystallization rate and extent did not differ significantly between pH 6.8 and pH 1.2, although HPMCAS dissolves at pH 6.8 and not at pH 1.2. [rests on: R17, R18] | Results, pdf p.7 |
| C16 | claim, mechanism, authors: appeared | Resveratrol crystallization appeared to occur in or at the surface of the dispersion matrix, from microscopy and from rapid crystallization even when release was blocked by polymer insolubility (CMCAB; HPMCAS at pH 1.2). [rests on: R9, R17, R18] | Discussion, pdf p.10 |
| C28 | claim, mechanism, authors: can be rationalized | The absence of enhanced concentration from E100 dispersions can be rationalized by E100 not dissolving at pH 6.8, restricting drug release. [rests on: R11] | Discussion, pdf p.10 |

## 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 · used · as: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| C6 | claim, prior hypothesis, authors: asserted; "are expected" | Polymers inhibit crystallization from the solid matrix and the supersaturated solution; enteric polymers such as Eudragit and HPMCAS are used for processability and solution crystallization inhibition, and their ASDs are expected to exist as suspensions under gastric conditions [rests on: cited: refs 12-16] | p.114-115 |
| C12 | claim, assumption, authors: asserted | CA, EC and EUD are water insoluble and CAP, HPMCAS and HPMCP practically insoluble at low pH within the test conditions, so they serve as model insoluble polymers; HPMC is water soluble and serves as positive control [rests on: argument only; R5] | p.115, p.117 |
| C64 | claim, generalisation, authors: "should remain"; "are still anticipated" | In those ASDs there is no driving force for crystallization, so they should remain physically stable for long periods, dry and as suspensions, the ideal scenario for an ASD; release and supersaturation are still expected once the polymer meets higher pH in the small intestine [rests on: R3.e, R3.g; argument only] | p.124 |

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

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

| id | kind | content | locator |
|---|---|---|---|
| M3 | material | hydroxypropyl methylcellulose phthalate (HPMCP), P-50 grade Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) | p.2 |
| M11 | material | Eudragit® L 100-55 (methacrylic acid - ethyl acrylate copolymer 1:1) Evonik (Darmstadt, Germany) | p.2, p.3 |
| C9 | claim, prior hypothesis, authors: asserted | The dissolution pH threshold of an enteric polymer varies with polymer chemistry and depends on the number of carboxylic and other functional groups [rests on: cited: ref 33] | p.2 |
| C23 | claim, conclusion, authors: "consistent with expectations" | Dissolution of the coating within 10-15 min in acetate pH 6.0 is consistent with expectations, as this pH exceeds the dissolution threshold of Eudragit L 100-55; pH 6.0 represents gastric pH 30 min after a meal (6-6.5) [rests on: R7.h, R22; cited: ref 9] | p.4 |

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

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

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | polymer solubility versus pH (µg/mL, HPLC-ELSD) — P3; 37 °C, 48 h — sub-table below; text: all five polymers insoluble below pH 4.5; colorimetric and HPLC-ELSD values similar (data not shown); order at pH 6.5 HPMCP-50 ≈ HPMCAS-LF > HPMCAS-MF > HPMCP-55 > HPMCAS-HF; HPMCAS-HF dissolved only at about pH 6.0 or higher; at pH 5.0 above 100 µg/mL for all except HPMCAS-HF (p.1691) | Fig. 1, p.1684; text p.1684, p.1691 |
| M4 | material | HPMCP P-50 (HPMCP-50) Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) | p.1682 |
| C13 | claim, conclusion, authors: asserted ("consistent with expectations") | The enteric polymers were insoluble below pH 4.5, in line with expectations and their chemical properties (Table 3); the two polymer assays gave similar solubilities [rests on: R4; M4-M8] | p.1684 |
| C14 | claim, mechanism, authors: asserted ("consistent with"; "due to"; "Owing to") | The low HPMCAS solubility below pH 5.0 matches the succinoyl pKa of about 5.0; HPMCAS-LF is more soluble than -MF at pH 5.5 owing to its higher succinoyl content, and HPMCAS-HF dissolves only from about pH 6.0 owing to its higher acetyl:succinoyl ratio; HPMCP-55 is less soluble than HPMCP-50 at pH 5.0, in line with its higher reported pKa [rests on: R4; M4-M8] | p.1684 |

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

[2024-polyzois-praziquantel-racemic-enantiopure-asd-release](../../../cards/2024-polyzois-praziquantel-racemic-enantiopure-asd-release/paper.html) · Dissolution / B. Supersaturation from ASD dissolution · used · as: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| C23 | claim, mechanism, authors: asserted ("an expected outcome") | Poor HPMCAS-MF ASD release under gastric conditions (not above 25%) is an expected outcome, since HPMCAS-MF is an enteric polymer of rather hydrophobic nature with limited solubility below pH 6 [rests on: R15.a-b; cited: refs 53-55] | p.5291, p.5292 |
| C36 | claim, mechanism, authors: "significantly"; "not surprising" | HPMC-based ASDs released significantly better in acid (peak 81% within 50 min), which is not surprising because HPMC is readily soluble at gastric pH [rests on: R15.c; cited: ref 76] | p.5292 |
| M6 | material | HPMCAS-MF AQOAT AS-MF, Shin-Etsu (Tokyo, Japan) | p.5287 |
| M8 | material | HPMC E5 LV Methocel E5 Premium LV, The Dow Chemical Company (Midland, MI) | p.5287 |

## 2025 Hiew — The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations · Dissolution / A. Release mechanism and LoC

[2025-hiew-surface-composition-wettability-high-drug-loading-asd](../../../cards/2025-hiew-surface-composition-wettability-high-drug-loading-asd/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| C6 | claim, prior hypothesis, authors: asserted; "have been reported" | The pH-dependent solubility of enteric polymers allows anti-solvent precipitation in acidified water, more environmentally friendly than processes using large volumes of organic solvent; co-precipitated particles have been reported to have larger specific surface areas than spray-dried and hot-melt-extruded ASDs [rests on: cited: refs 27-31] | p.290 |
| C32 | claim, mechanism, authors: "can be rationalized" | Exposed surface area mattered only in the FaSSIF stage because HPMCAS is insoluble at gastric pH; breaking agglomerates by sonication increased the area exposed and so aided wetting [rests on: R13] | p.298 |
| M2 | material | HPMCAS AQOAT AS-LG, Shin-Etsu (Tokyo) | p.290 |

## 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: pH-dependent polymer solubility

| id | kind | content | locator |
|---|---|---|---|
| R3 | record, measured | appearance of polymer-only control in buffer — HPMCAS LF or MF THF stock added to buffer at 0.5 mg/mL (P7) — transparent, clear solution in pH 5.8 buffer and in the higher-pH buffers | p.3, p.4 |
| R4 | record, cited | HPMCAS solubility at pH 5.0 — blank FeSSIF-V1 pH (ref 13) — ~250 µg/mL (LF) and ~110 µg/mL (MF) | p.4 |
| C11 | claim, conclusion, authors: asserted | HPMCAS alone is soluble at pH 5.8 and above; complexation was studied only where the polymer is soluble without drug, so blank FeSSIF-V1 (pH 5.0) was not used [rests on: R3, R4] | p.4 |
| C27 | claim, prior hypothesis, authors: asserted | HPMCAS is a weak acid (pKa ~5), insoluble when unionized and soluble when sufficiently ionized; its dissolution starts with water uptake and ionization at the interface, hydration, swelling and a thin gel layer, with H+ release lowering the surface pH below bulk (values in R22) [rests on: cited: refs 9, 14, 15, 16, 27] | p.8-9 |
| C51 | claim, conclusion, authors: "in line with" | Poor release in FeSSIF-V1 is in line with polymer-controlled release because the polymer is poorly soluble at this pH [rests on: R16, R4; C40] | p.10 |

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

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

| id | kind | content | locator |
|---|---|---|---|
| R5 | record, measured | HPMCAS concentration in the supernatant vs time during ASD dissolution (µg/mL; right axis full scale 900 µg/mL at 10 wt% DL and 300 µg/mL at 25 wt% DL) — as R4; HPLC-ELSD (P6) — sub-table below for H and for M at pH 5.5 (all values ≈, read from Fig. 4); other series (L and M at pH 6.5 and 7.5, L at pH 5.5): ≈75-99% of full scale at 5 min and ≈93-100% by 10-15 min; at 25 wt% DL they fall to ≈86-91% of full scale by 180 min (≈258-273 µg/mL), at 10 wt% DL they stay at ≈95-98% | Fig. 4, p.227 |
| C16 | claim, mechanism, authors: results: "could be attributed"; discussion: asserted ("because") | Incomplete release reflects the different pH-dependent solubilities of the grades, L being more soluble at lower pH; H releases completely only at the highest pH because the polymer is less soluble at lower pH [rests on: R5; cited: ref 38] | p.227, p.231 |