# Evidence: Higuchi two-component dissolution model

Parent: — · class: transport and absorption · names merged here: Higuchi critical mixture ratio; Higuchi two-component dissolution model

2 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.

## 2019 Indulkar — Insights into the dissolution mechanism of ritonavir-copovidone amorphous solid dispersions: importance of congruent release for enhanced performance · Dissolution / A. Release mechanism and LoC

[2019-indulkar-ritonavir-copovidone-asd-congruent-release-loc](../../../cards/2019-indulkar-ritonavir-copovidone-asd-congruent-release-loc/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: Higuchi two-component dissolution model

| id | kind | content | locator |
|---|---|---|---|
| E4 | equation | Higuchi two-component diffusion-controlled dissolution model (critical mixture ratio):  | p.12-13 |
| C23 | claim, prior hypothesis, authors: asserted | In the Higuchi two-component model (non-interacting, non-disintegrating, diffusion-controlled) the interface composition stays constant only at the critical mixture ratio; otherwise the surface enriches in one component that then controls dissolution; for components of very different solubility the drug fraction giving polymer control is very low and no component can release faster than its pure form, unless soluble complexes form [rests on: cited: refs 26, 38; E4] | p.12-13 |
| C24 | claim, prior hypothesis, authors: "appear to" | Corrigan notes that the Higuchi models appear to describe high-DL ASDs controlled by a drug-rich surface layer but not low-DL ASDs; simultaneous release of drug and polymer over a range of compositions at high polymer fraction contradicts the single-composition prediction [rests on: cited: refs 25, 26, 39-42] | p.13 |

## 2020 Saboo — Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers. · Dissolution / A. Release mechanism and LoC

[2020-saboo-asd-drug-loading-polymer-hydrophobicity-release](../../../cards/2020-saboo-asd-drug-loading-polymer-hydrophobicity-release/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: Higuchi critical mixture ratio

| id | kind | content | locator |
|---|---|---|---|
| E4 | equation | Higuchi critical mixture ratio for two-component dissolution: N_drug/N_polymer = (D_drug · C_s(drug))/(D_polymer · C_s(polymer)) | p.11; SI p.11 |
| R27 | record, derived (E4) | Higuchi critical mixture ratio N_drug/N_polymer for Fel-PVPVA — inputs: C_s(drug) = amorphous solubility 8 µg/mL; C_s(polymer) = PVPVA solubility 46 mg/mL (cited, SI ref 1); D_drug/D_polymer = 10 (Stokes-Einstein, drug about 1 nm, polymer hydrodynamic radius about 10 nm, similar viscosity) — printed 1.7 x 10⁻⁶ (SI); main text: the DL of an ASD is always above this ratio (≥1% DL) | SI Section S4, SI p.11; text p.11 |
| C35 | claim, prior hypothesis, authors: asserted; "It has been argued" | Higuchi's diffusion models allow congruent release only at the critical mixture ratio of Eq. 4; at other ratios release is initially diffusion-controlled (Eq. 1) and forms a drug-rich porous layer; at low DL there may be too little drug to form and support an intact porous drug-rich layer (Corrigan) [rests on: cited: refs 38, 11, 5] | p.11 |
| C36 | claim, conclusion, authors: asserted ("for all practical purposes") | Because the solubilities of drug and polymer differ so much, the DL of an ASD is for all practical purposes always above the critical mixture ratio (≥1% DL, SI Section S4) [rests on: R27] | p.11; SI p.11 |
| C37 | claim, conclusion, authors: "may adequately describe" | Higuchi's model may describe high-DL ASDs but fails for low-DL ASDs that release congruently over a range of DLs, here up to 10% DL for PVP and HPMC and 15% DL for PVPVA [rests on: R14, R15; cited: refs 13, 36, 31, 4] | p.11 |