# Evidence: associative phase separation

Parent: — · class: phase behaviour · names merged here: associative phase separation

3 papers measured or used it, 1 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.

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: A Close Look at the Dissolution Interface · Dissolution / A. Release mechanism and LoC

[2023-deac-asd-dissolution-interface](../../../cards/2023-deac-asd-dissolution-interface/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: associative phase separation

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | in situ morphology of dissolving PHPH-PVPVA compacts — P7 — sub-table below; text: both dyes partitioned into the hydrophobic phase after phase separation, which stayed magenta, while the hydrophilic phase was depleted of both dyes and appeared black; the distance between onset and glass/gel boundary visually decreased with DL | Figs. 8-10, p.2226-2228; text p.2222-2223 |
| R12 | record, measured | onset Tg and drug concentration of the released hydrophobic phase (neat-component Tg columns in B1) — hydrophobic phase (nanoparticle pellet) from 30% DL MePHPH-PVPVA and 5% DL PHPH-PVPVA compacts (P10, P11); DSC triplicate — sub-table below; text: the 5% DL PHPH hydrophobic phase contained approximately 75% PVPVA on a dry basis; the Tg of each hydrophobic phase was below 37 °C | Table 3, p.2228; text p.2226 |
| C28 | claim, conclusion, authors: "This indicates"; "consistent with" | In PHPH ASDs both dyes partition into the hydrophobic phase, indicating it is considerably less hydrophobic than in MePHPH ASDs, consistent with associative phase separation with substantial polymer in that phase (Table 3, ref 22) [rests on: R7, R12; cited: ref 22] | p.2222 |
| C65 | claim, mechanism, authors: abstract: "This was due to"; discussion: asserted (cited ref 22); conclusions: "was due to" | Hydrogen bonding increases PVPVA distribution into the hydrophobic phase, making it volumetrically larger (associative separation; segregative when the polymer prefers the hydrophilic phase); this incorporation of polymer is why the continuous hydrophobic phase formed at lower DL for PHPH, a high polymer content giving a low LoC [rests on: R6, R7, R12; cited: refs 22, 50] | p.2217, p.2231-2232, p.2233 |

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Role of Drug Load and Molecular Interactions · Dissolution / A. Release mechanism and LoC

[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 · measured · as: associative phase separation

| id | kind | content | locator |
|---|---|---|---|
| R2 | record, derived (E1) | PVPVA concentration in the nanoparticle phase (wt% dry basis, n = 3) — PHPH and MePHPH nanoparticles, methods A and B (P1, P2), 5 min equilibration at 37 °C, aqueous-phase concentrations by 1H NMR or HPLC — sub-table below | Table 2, p.727 |
| R3 | record, derived (E1) | equilibrium PVPVA amount in nanoparticles (%w/w dry basis), from aqueous-phase NMR concentrations — (a) four drugs at 60 °C; (b) PHPH and MePHPH at 37 and 60 °C; P1, P2, P8; TIPP in pH 2.5 buffer, others pH 6.8 — sub-table below; text: PHPH "nearly 75%" polymer, TIPP "relatively high", MeTIPP and MePHPH "less than 10%" | Fig. 2, p.727; text p.727 |
| C47 | claim, conclusion, authors: asserted | MePHPH-PVPVA separates segregatively (insoluble phase rich in drug and poor in polymer, PVPVA in the aqueous phase) and PHPH-PVPVA associatively (insoluble phase enriched in both, a complex coacervate); in the conclusions TIPP is grouped with PHPH as associative and MeTIPP with MePHPH as segregative [rests on: R2, R3, R8; cited: refs 70, 71] | p.732-733, p.734 |
| C48 | claim, generalisation, authors: asserted | Associative separation gives positively sloped tie lines with the plait point on the left (low drug) side of the diagram; segregative separation gives negatively sloped tie lines with the plait point on the right [rests on: argument only (Fig. 9)] | p.733 |

## 2024 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior · Dissolution / A. Release mechanism and LoC

[2024-deac-asd-ternary-phase-diagrams-release](../../../cards/2024-deac-asd-ternary-phase-diagrams-release/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: associative phase separation

| id | kind | content | locator |
|---|---|---|---|
| R15 | record, measured | total composition and equilibrium binode compositions (wt%, SD from n = 4 "except where noted"; no row is marked) — all equilibrated nondilute (P4) and dilute (P5) mixtures, 37 °C — sub-table below (rows are not labelled with the mixture in the source; see X12) | Table S1, SI p.6 |
| R17 | record, measured | PVPVA in hydrophobic phase versus total water (replot of R15 hydrophobic PVPVA) — (a) MePHPH-PVPVA-water; (b) PHPH-PVPVA-water; 37 °C — (a) ≈13.7, ≈6.9, ≈4.2, ≈2.5 wt% at 25, 50, 80, 99 wt% total water (R15.d, a, c, e); (b) ≈42, ≈47.5, ≈52 wt% at 60, 80, 99 wt% total water (R15.f, h, i); R15.g (69.0 wt% water) not plotted; text at 80 wt% total water: ~47% (PHPH) versus ~5% (MePHPH) (values read from Fig. 6) | Fig. 6, p.1908 |
| C18 | claim, conclusion, authors: "consistent with"; "indicate" | The low PVPVA content of the MePHPH-rich phase and the negatively sloped MePHPH tie lines are consistent with segregative phase separation; the positively sloped PHPH tie lines indicate associative phase separation [rests on: R6, R15, R22, R23; cited: ref 31] | p.1907, p.1910 |
| C21 | claim, mechanism, authors: "the data suggest"; "surprising" | The data suggest that water causes PVPVA to leave the hydrophilic phase and partition into the PHPH-rich phase because PVPVA prefers to interact with PHPH over water [rests on: R17, R15.f-i] | p.1908-1909 |

## Mentioned only

- 2024 Deac — [2024-deac-asd-polymer-molecular-weight-failure-mode-loc](../../../cards/2024-deac-asd-polymer-molecular-weight-failure-mode-loc/paper.html) · Dissolution / A. Release mechanism and LoC (ref 37)