# Evidence: drug-polymer ionic interactions

Parent: drug-polymer interactions · class: molecular interaction · names merged here: drug-polymer ionic interaction; drug-polymer ionic interactions; drug–polymer acid–base interaction; drug–polymer ionic interaction; electrostatic drug-polymer interaction

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.

## 2021 Bhujbal — Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation · Solid state stability / Physical stability

[2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation](../../../cards/2021-bhujbal-lumefantrine-asd-spray-antisolvent-precipitation/paper.html) · Solid state stability / Physical stability · measured · as: drug–polymer ionic interaction

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, measured | % protonation of lumefantrine tertiary nitrogen (XPS N1s, mean ± SD, n = 3) — ASDs and amorphous lumefantrine (P6) — sub-table below | Table 1, p.2427 |
| C21 | claim, prior hypothesis, authors: asserted ("As observed previously") | Protonation of the lumefantrine nitrogen by acidic polymers gives a second N1s peak at 402 eV next to the neutral 399 eV peak, the higher binding energy fitting a positive charge [rests on: cited: refs 38, 39] | p.2427 |
| C22 | claim, conclusion, authors: asserted ("significant") | All ASDs show significant protonation relative to amorphous lumefantrine; most in HPMCP and EL100, then CAP, least in HPMCAS [rests on: R8] | p.2427 |
| C23 | claim, generalisation, authors: "There also appears to be some correlation" | Protonation increases with polymer loading [rests on: R8.a−f] | p.2427 |
| C50 | claim, conclusion, authors: asserted ("a correlation is not observed") | At 4:6, protonation ranks HPMCP > EL100 > CAP > HPMCAS > amorphous lumefantrine, stability ranks HPMCP > HPMCAS > CAP > EL100 > amorphous lumefantrine, so protonation does not correlate with stability here [rests on: R8, R1, R4] | p.2429−2430 |
| C52 | claim, generalisation, authors: "may confer" | A higher degree of tertiary-nitrogen protonation may confer greater stability to the ASD [rests on: R8, R4, R20] | p.2430 |

## 2022 Moseson — Atomic Layer Coating to Inhibit Surface Crystallization of Amorphous Pharmaceutical Powders · ASD process / ASD process

[2022-moseson-atomic-layer-coating-surface-crystallization-asd-powders](../../../cards/2022-moseson-atomic-layer-coating-surface-crystallization-asd-powders/paper.html) · ASD process / ASD process · used · as: drug–polymer acid–base interaction

| id | kind | content | locator |
|---|---|---|---|
| C33 | claim, mechanism, authors: "are likely" | Acid−base interactions are the likely reason for the better physical stability of ERL/HPMCAS [rests on: cited: ref 24 (R21)] | p. 40706 |
| R21 | record, cited | ERL–polymer stabilization — ref 27 (Mudie et al.); ref 24 — ERL formulated with HPMCAS and other enteric polymers (ref 27); acid–base interactions between ERL and HPMCAS (ref 24) | p. 40706 |

## 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: electrostatic drug-polymer interaction

| id | kind | content | locator |
|---|---|---|---|
| C38 | claim, conclusion, authors: "it is clear"; "It can be concluded" | Ionization of LOR is necessary for insoluble complexation with HPMCAS: at pH well above pKa no complexation, rising as pH approaches pKa; LOR, which lacks hydrogen bond donors, interacts with ionized HPMCAS mainly electrostatically [rests on: R13; M5] | p.1475 |
| C46 | claim, recommendation, authors: asserted ("should be considered") | When formulating HPMCAS ASDs of lipophilic drugs, the drug's ability to form interactions with the polymer that persist in water should be considered; these matter most for lipophilic weak bases that form electrostatic interactions when drug and polymer are both ionized [rests on: R12, R14] | p.1475 |
| C5 | claim, prior hypothesis, authors: "it was suggested" | HPMCAS can form hydrogen bonds and ionic interactions with drugs; a previous group study suggested that poor performance of lumefantrine ASDs with enteric polymers came from drug-polymer ionic interactions that reduced polymer hydration and dissolution [rests on: cited: refs 14, 42, 43] | p.1467 |

## 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 · measured · as: drug-polymer ionic interactions

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured; DL column derived (relation not printed) | % polymer complexed with drug (mean ± SD, n = 3) and corresponding ASD drug loading — drug and polymer from THF into pH 6.0 phosphate buffer (P9), polymer 0.5 mg/mL — sub-table below; rows a-l are also plotted in Fig. 6 | Table 4, p.402 |
| R11 | record, measured; MF column cited (ref 3) | % HPMCAS complexation with LOR versus pH (error bars SD, n = 3) — 1:1 LOR/COOH molar ratio, phosphate buffers (P9) — sub-table below; the same points are replotted in Fig. S1 | Fig. 7, p.403; Fig. S1, SI p.2 |
| R12 | record, measured | % HPMCAS complexation with CNZ at pH 5.8 (error bars SD, n = 3); the pH 6.0 series in the same figure plot R9.a-d (LF) and R10 (MF, cited) — phosphate buffer pH 5.8 (P1 row c, P9) — sub-table below | Fig. 8, p.403 |
| C34 | claim, mechanism, authors: asserted; "consequently" | Release was compromised by drug-polymer electrostatic interactions forming an insoluble complex that reduced drug and polymer release; the extent of complex formation, and so the release rate, depends on drug ionization and hence on medium pH (abstract: a higher pH, with less ionized drug, improved release) [rests on: R2, R3, R9, R11, R13] | p.397, p.404 |

## 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 · measured · as: drug-polymer ionic interaction

| id | kind | content | locator |
|---|---|---|---|
| R19 | record, measured | N 1s XPS spectra — BDQ free base, BDQ maleate, 40% DL BDQ-MF ASD, MF complex at 1:1 BDQ:COOH, 40% DL ASD after 1 h in pH 6.5 buffer (P15) — free base: single N 1s peak at about 399.5 eV; maleate salt: peaks at 399 and 402 eV; complex and 40% DL ASD: two N 1s peaks with BEs similar to the maleate salt; ASD after 1 h in pH 6.5 buffer: text reports reduced intensity of the N 1s "at 399 eV"; figure: ionized component at ≈402 eV small in the top spectrum (DR 40/60); dashed lines at ≈402 eV (ionized) and ≈399 eV (unionized) (read from Fig. 9) | Fig. 9, p.9; text p.7-8 |
| R20 | record, measured | XPS percent N protonation (relative to the ionizable N group) and surface drug concentration (from N 1s and C 1s fitting, P15) — samples of A8 — sub-table below | Table 4, p.9 |
| C25 | claim, conclusion, authors: "indicating" | The similar ionized-N fractions of the insoluble complex and the dry 40% DL ASD indicate that drug-polymer ionic interactions form not only during precipitation but also during ASD manufacture from organic solvents [rests on: R20.c, R20.d] | p.8 |
| C35 | claim, conclusion, authors: "confirmed"; "indicating" | Although BDQ is poorly soluble at pH 5.0 and above, XPS confirmed that BDQ in the precipitate is substantially ionized, indicating drug-polymer ionic interactions rather than free base; the ASD also contains drug-polymer ionic interactions, as seen before for basic drugs with HPMCAS (abstract: ionic complexation confirmed by XPS) [rests on: R20.c, R20.d, R2; cited: refs 16, 35, 36] | p.1, p.10 |