# Evidence: segregative phase separation

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

4 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.

## 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: segregative phase separation

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | in situ morphology of dissolving MePHPH-PVPVA compacts (blue = prodan, red = R6G, magenta = both) — P7; 37 °C pH 6.8 buffer, manual pipette mixing — sub-table below; text: all compacts formed a gel layer; all MePHPH-PVPVA ASDs showed separation of blue and red colours somewhere in the gel layer; the onset distance from the glass/gel boundary decreased with DL; light-signal loss in the gel in Figs. 5b, 6b-g and 7b,d | Figs. S2, S3 (SI p.3-4), Figs. 5-7 (p.2223-2225); text p.2222, p.2223, p.2231 |
| 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 |
| C25 | claim, conclusion, authors: "This indicates" | The separation of blue and red colours in all MePHPH-PVPVA gels indicates segregative phase separation into a hydrophobic and a hydrophilic phase [rests on: R6; 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: segregative 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: Role of polymer molecular weight and identification of a new failure mode · Dissolution / A. Release mechanism and LoC

[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 · measured · as: segregative phase separation

| id | kind | content | locator |
|---|---|---|---|
| R11 | record, measured | composition of the hydrophilic (solution) and hydrophobic (nanodroplet) phases, wt%, mean ± SD, n = 4 — 10% DL K12 and 10% DL K29/32 ASDs mixed with buffer at ASD:water 40:60, heated to about 90 °C and cooled, centrifuged at 37 °C (P9); x-axis of Fig. 6 labels the polymer "PVPVA" (X2) — sub-table below; text: compositions statistically similar for the two grades; hydrophobic phase about ~80 wt% clotrimazole; hydrophilic phase ~40 wt% PVP, ~60 wt% water and trace clotrimazole | Fig. 6, p.8; text p.8 |
| C28 | claim, conclusion, authors: asserted | PVP segregates from clotrimazole during water-induced phase separation (segregative phase separation): a drug-rich hydrophobic phase and a PVP- and water-rich hydrophilic phase with trace drug [rests on: R11] | p.8 |
| C29 | claim, generalisation, authors: asserted | Segregative separation occurs in weakly interacting drug-polymer systems; strongly interacting systems separate associatively, with the polymer distributing more into the hydrophobic phase [rests on: cited: refs 37-39] | p.8 |

## 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: segregative 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 |
| C19 | claim, mechanism, authors: "This suggests"; "may be intuitive" | The data suggest that adding water drives PVPVA out of the MePHPH-rich phase into the water-rich phase because PVPVA prefers to interact with water rather than MePHPH [rests on: R17, R15.a-e] | p.1908 |