# Evidence: hydrophobic ion pairing

Parent: — · class: molecular interaction · names merged here: hydrophobic ion pair; hydrophobic ion pairing

3 papers measured or used it, 3 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: hydrophobic ion pair

| id | kind | content | locator |
|---|---|---|---|
| C53 | claim, mechanism, authors: discussion: "We believe"; "is expected"; conclusions: "are postulated"; "is thought" | The lumefantrine−polymer ion pair reduces the number of carboxylate groups available for hydration, which lowers polymer dissolution and, by slowing chain disentanglement in the gel layer, polymer and drug release; ionic interactions are responsible for the diminished release as DL rises [rests on: R20, R19, R13] | p.410, p.411 |
| 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 |

## 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: hydrophobic ion pairing

| id | kind | content | locator |
|---|---|---|---|
| C33 | claim, prior hypothesis, authors: asserted ("It is well known"; "widely observed") | The solubility of a molecule can be reduced by complexation with an oppositely charged amphiphile (hydrophobic ion pairs); ionic polymers form insoluble complexes with oppositely charged amphiphiles (SDS with a cationic cellulose; dextran sulfate or alginate with ciprofloxacin, chlorpromazine, amitriptyline, doxepin); oppositely charged polyelectrolytes form complex coacervates [rests on: cited: refs 57-70] | p.1474 |
| C32 | claim, mechanism, authors: discussion: "partially rationalize"; "likely largely accounts"; abstract: asserted ("led to"; "resulted in") | Because complexation lowers HPMCAS solubility, it is expected to slow polymer dissolution; eq 3 partially rationalizes the lower release with complexation, with reduced hydration from lipophilicity likely also contributing; reduced solubility from complexation likely largely accounts for the right-hand trendline and lipophilicity is likely dominant for the left-hand one. Abstract: electrostatic interactions between HPMCAS and lipophilic cationic drugs led to insoluble complexes, which resulted in poor release [rests on: R14, R12, E3] | p.1466, p.1474 |

## 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: hydrophobic ion pairing

| id | kind | content | locator |
|---|---|---|---|
| C5 | claim, prior hypothesis, authors: asserted ("attributed") | In earlier work with HPMCAS-MF, weakly basic drugs cationic at the dissolution pH released poorly, attributed to hydrophobic ion pairs formed by drug-polymer electrostatic interaction that reduce polymer hydration [rests on: cited: ref 3] | p.398 |
| 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 |

## Mentioned only

- 2023 Deac — [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 (ref 58)
- 2023 Hiew — [2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release](../../../cards/2023-hiew-grazoprevir-hierarchical-cpad-surface-drug-release/paper.html) · Dissolution / A. Release mechanism and LoC (ref C36)
- 2025 Fagan — [2025-fagan-permeation-enhancers-insulin-minitablet-biorelevant-media](../../../cards/2025-fagan-permeation-enhancers-insulin-minitablet-biorelevant-media/paper.html) · Peptide permeability / Peptide permeability (ref C41)