# Evidence: phase inversion

Parent: — · class: phase behaviour · names merged here: phase inversion

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.

## 2012 Eerdenbrugh — Nanoscale Mid-Infrared Evaluation of the Miscibility Behavior of Blends of Dextran or Maltodextrin with Poly(vinylpyrrolidone) · Characterization methods / Solid-state methods

[2012-van-eerdenbrugh-nanoscale-mid-ir-dextran-maltodextrin-pvp-miscibility](../../../cards/2012-van-eerdenbrugh-nanoscale-mid-ir-dextran-maltodextrin-pvp-miscibility/paper.html) · Characterization methods / Solid-state methods · measured · as: phase inversion

| id | kind | content | locator |
|---|---|---|---|
| R15 | record, measured | local AFM-IR spectra — DEX450-PVP12 (P6); one marked position each in a discrete domain (green), the continuous phase (red) and near a phase boundary (yellow) (Fig. 5B); n not stated — intensity of the DEX band near 1350 cm−1 highest in the continuous-phase spectrum, intermediate at the boundary position, lowest in the discrete domain; all three dominated by the PVP carbonyl band ≈1660 cm−1 (read from Fig. 5C); spectral differences subtle (text); other measurements close to phase boundaries gave similar intermediate spectra (data not shown) | Fig. 5C, p.1464; text p.1464 |
| R17 | record, measured | average AFM-IR spectra of each phase — DEX40-PVP90 (P6) — continuous phase (n = 6): PVP band pattern; thicker discrete domains (n = 4): DEX bands at ≈1440, ≈1360 and ≈1290 cm−1 present, carbonyl ≈1660 cm−1 of similar height (read from Fig. 6D) | Fig. 6D, p.1465 |
| C43 | claim, conclusion, authors: asserted | Among the blends with distinct continuous and discrete phases, DEX450-PVP12 and DEX40-PVP12 have a DEX-rich continuous phase with PVP-rich discrete domains, whereas phase inversion occurs in DEX40-PVP90 and DEX6-PVP90 [rests on: R15, R17, R23; C37] | p.1467 |

## 2022 Yang — Release mechanisms of amorphous solid dispersions: Role of drug-polymer phase separation and morphology · Dissolution / A. Release mechanism and LoC

[2022-yang-release-mechanisms-rtv-pvpva-asd-phase-separation-morphology](../../../cards/2022-yang-release-mechanisms-rtv-pvpva-asd-phase-separation-morphology/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: phase inversion

| id | kind | content | locator |
|---|---|---|---|
| C46 | claim, mechanism, authors: "are anticipated"; "is anticipated"; "can also contribute" | Morphology depends on the relative amounts of the soluble polymer-rich and insoluble drug-rich phases: the lower-volume phase forms the discrete phase and the higher-volume phase the continuous one, so phase inversion from discrete to continuous drug-rich phase is expected as DL increases; coalescence of low-Tg phase-separated regions, driven by surface area minimization, can also make the drug-rich phase continuous [rests on: argument only] | pdf p.23 |
| C59 | claim, generalisation, authors: "more likely"; "is expected" | Phase separation morphology depends strongly on the initial composition and the pathway into the two-phase region, and the low-composition component tends to form the discrete phase; a discrete drug-rich phase is therefore expected at low DL, giving rapid congruent release [rests on: cited: refs 53-61] | pdf p.25 |

## 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: phase inversion

| 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 |
| R9 | record, measured | morphology of the compact surface after partial dissolution — MePHPH-PVPVA compacts 30, 40, 50% DL; P8 — sub-table below | Fig. 11, p.2229; text p.2223-2224, p.2231 |
| C26 | claim, conclusion, authors: asserted; "visually apparent" | The morphology of the MePHPH hydrophobic phase depends on DL: discrete particles below 1 μm at 5, 20 and 30% DL; networks at 40 and 50% DL, the interconnected proportion increasing with DL; at 50% DL the morphology inverts (hydrophobic continuous, hydrophilic discrete), persists and coarsens [rests on: R6] | p.2222 |
| C35 | claim, conclusion, authors: asserted ("reveals") | Surface phase separation at 40% DL MePHPH is heterogeneous, and the 50% DL surface shows the inverse of the 30% DL morphology [rests on: R9] | p.2224 |

## 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: phase inversion

| id | kind | content | locator |
|---|---|---|---|
| R8 | record, measured | film morphology after 1 h at 100% RH, 37 °C, versus DL — K12 films 20, 30, 40% DL; K29/32 films 30, 40% DL (P10) — sub-table below; text: the drug-rich phase formed droplet domains up to 30% DL; at 40% DL it was a continuous phase and the hydrophilic phase formed dispersed droplets within it; phase inversion between 30 and 40% DL for both K12 and K29/32 (p.9) | Fig. 4, p.7; text p.6, p.9 |
| C23 | claim, conclusion, authors: asserted ("widely known") | The 40% DL film morphology (continuous drug-rich phase with dispersed hydrophilic droplets) is phase inversion, widely known and shown to be a release failure mode in other systems; here named Failure Mode II [rests on: R8; cited: refs 21, 26-27] | p.6 |
| C40 | claim, conclusion, authors: "suggesting"; "does not appear" | Phase inversion would occur at a different DL if the hydrophobic-phase composition differed, which it did not for the two grades; direct observation places inversion between 30 and 40% DL for both K12 and K29/32, so polymer molecular weight does not appear to influence phase inversion in this system [rests on: R11, R8] | p.9 |
| C41 | claim, conclusion, authors: "possibly" (K60, K90) | The LoC of K29/32, and possibly of K60 and K90, is limited by phase inversion (Failure Mode II), as in other systems; the LoCs of K12, K17 and K25 lie significantly below the DL needed for phase inversion [rests on: R12, R8] | p.9 |

## 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: phase inversion

| id | kind | content | locator |
|---|---|---|---|
| R18 | record, measured | morphology evolution by confocal fluorescence (red hydrophilic, blue hydrophobic) — MePHPH-PVPVA films 10-60% DL (P3), 100% RH, 37 °C (P11) — sub-table below; text: all films initially homogeneous; onset morphology co-continuous at every DL including the lowest; morphology after 1 h persisted at least 6 h for DLs below and above 40% | Fig. 7, p.1908; text p.1909 |
| R19 | record, measured | morphology evolution by confocal fluorescence — PHPH-PVPVA films 5-20% DL (P3), 100% RH, 37 °C (P11) — sub-table below; text: earliest detected morphology already had one phase dispersed and persisted | Fig. 8, p.1909 |
| R35 | record, derived (E12, P20) | Wα at onset of water-induced phase separation versus DL — PC-SAFT diagrams, hydration path to spinodal, local equilibrium; (a) MePHPH-PVPVA, (b) PHPH-PVPVA — (a) Wα ≈0.02 at ≈5% DL rising to ≈0.15 at ≈27% DL; dry critical point (Wα 0.5) at ≈33% DL; ≈0.82 at ≈39.5% DL rising to ≈0.85 at ≈67% DL; no computed point between ≈27 and ≈39.5% DL other than the critical point. (b) ≈0.02 at ≈0.9% DL to ≈0.16 at ≈3.0% DL; critical point ≈3.7% DL; ≈0.82 at ≈4.5% DL, ≈0.80-0.86 up to ≈29% DL (all read from Fig. 16); overlaid micrographs: the persistent-morphology images of R18 (10-60% DL) and R19 (5-20% DL) | Fig. 16, p.1915 |
| C24 | claim, conclusion, authors: p.1909: asserted; inversion near 40%: "likely"; p.1913: asserted | After PDT the persistent morphology of MePHPH-PVPVA depends on DL: hydrophobic phase dispersed for DL up to 30% and continuous for DL above 40%; the co-continuous range (after 1 h) lies somewhere between 30 and 50% DL with the phase inversion point likely near 40% DL; in the discussion, hydrophobic domains are interconnected for DL of 40% or higher [rests on: R18] | p.1909, p.1913 |
| C25 | claim, prior hypothesis, authors: asserted; "can occur" | In two-phase amorphous systems the minority phase is dispersed in the continuous majority phase; increasing it gives a co-continuous range whose centre is the phase inversion point, then inversion; phase inversion can occur near a phase fraction of 0.5 in immiscible liquids and polymer blends once the persistent morphology forms [rests on: cited: refs 48-51] | p.1909, p.1914 |
| C27 | claim, conclusion, authors: asserted | PHPH-PVPVA films show a DL dependence of morphology similar to MePHPH, with phase inversion between 10 and 15% DL and no transitory co-continuous morphology [rests on: R19] | p.1909 |
| C57 | claim, conclusion, authors: asserted ("good correlation") | Both systems have a narrow co-continuity range, so the phase inversion point marks where the hydrophobic phase becomes continuous; with the critical point correlating with inversion, PHPH-PVPVA forms a continuous hydrophobic phase at lower DL (~5 to 12.5%) than MePHPH-PVPVA (35-40%), and the dispersed-to-continuous change correlates well with the release decline at the LoC (R37) [rests on: R18, R19, R35, R37] | p.1915 |