# Evidence: drug-rich phase coarsening

Parent: — · class: phase behaviour · names merged here: coarsening; coarsening of the drug-rich phase; droplet coarsening; drug-rich phase coarsening; nanodroplet coarsening

4 papers measured or used it, 2 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.

## 2020 Ueda — Impact of hypromellose acetate succinate grade on drug amorphous solubility and in vitro membrane transport · Bioperformance / Bioperformance

[2020-ueda-hpmcas-grade-amorphous-solubility-membrane-transport](../../../cards/2020-ueda-hpmcas-grade-amorphous-solubility-membrane-transport/paper.html) · Bioperformance / Bioperformance · measured · as: coarsening of the drug-rich phase

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | drug-rich droplets without polymer — P4 conditions without polymer — droplets rapidly coarsened and crystallized (data not shown) | p.10 |
| R6 | record, measured | Z-average of drug-rich droplets during agitation (nm, n = 3, mean ± SD; all values ≈, read from Fig. 4) — P5: ATZ 300 µg/mL with 2700 µg/mL polymer; CLZ 600 µg/mL with 1000 µg/mL polymer; 300 rpm, 37 °C — sub-table below; text: AS-LF droplets grew slightly at an early stage but stayed below 300 nm over 3 h; AS-HF droplets kept their initial size; Z-average 100~300 nm (p.13); CLZ about 100 nm (AS-HF) versus 250 nm (AS-LF) (p.17) | Fig. 4, pdf p.29; text p.11, p.13, p.17 |
| C18 | claim, conclusion, authors: asserted ("effectively"; "regardless of the drug") | Pre-dissolved HPMC-AS effectively inhibited coarsening of the drug-rich phase and stabilized the nanodroplets; droplet size fell with HPMC-AS concentration and was smaller with AS-HF than with AS-LF regardless of the drug [rests on: R4, R5] | p.10 |
| C19 | claim, conclusion, authors: asserted ("effectively maintained") | Under 3 h agitation AS-LF droplets grew slightly at an early stage but stayed below 300 nm, whereas AS-HF effectively maintained the initial size of ATZ- and CLZ-rich droplets [rests on: R6] | p.11 |

## 2021 Saboo — Exploring the Role of Surfactants in Enhancing Drug Release from Amorphous Solid Dispersions at Higher Drug Loadings · Dissolution / A. Release mechanism and LoC

[2021-saboo-tpgs-felodipine-pvpva-asd-release-high-loading](../../../cards/2021-saboo-tpgs-felodipine-pvpva-asd-release-high-loading/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: coarsening

| id | kind | content | locator |
|---|---|---|---|
| C40 | claim, mechanism, authors: "can be rationalized"; "can release" | At 5% and 10% TPGS persistent discrete drug-rich domains sit in a continuous polymer-rich phase; this can be rationalised by TPGS lowering the interfacial energy between the phases, which reduces coarsening so the domains persist and can be released intact as the gel layer recedes [rests on: R21, R23] | p.17 |
| C50 | claim, mechanism, authors: "supportive"; "clearly a feasible explanation" | Micro-CT supports continuous drug-rich domains without surfactant, in agreement with AFM; rapid coarsening of the drug-rich domains is a feasible explanation for the loss of release, so both phase separation and the resulting morphology matter [rests on: R19, R21] | p.19 |
| C51 | claim, mechanism, authors: "clearly effective"; "suggesting" | Surfactant is effective at keeping the drug-rich phase as discrete domains, which suggests it reduces coarsening kinetics [rests on: R21, R23] | p.19 |

## 2022 Soto — Impact of Surfactants on the Performance of Clopidogrel-Copovidone Amorphous Solid Dispersions: Increased Drug Loading and Stabilization of Nanodroplets · Dissolution / A. Release mechanism and LoC

[2022-correa-soto-surfactants-clopidogrel-copovidone-asd-nanodroplets](../../../cards/2022-correa-soto-surfactants-clopidogrel-copovidone-asd-nanodroplets/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: nanodroplet coarsening

| id | kind | content | locator |
|---|---|---|---|
| R6 | record, measured | Z-average ratio and PDI ratio (value at time t divided by value at t = 0; mean ± SD, n = 3; values read from Fig. 2) — CPD nanodroplets at 37 °C in PB alone or with CTAB 50, SDS 50, TPGS 4, TWN 5 μg/ml (P6) — sub-table below; text: droplets in buffer grew in size and PDI; CTAB produced large agglomerates floating on the solution surface (SI section S2); size stability also checked by NTA | Fig. 2, p.174; text p.173 |
| R19 | record, measured | droplet Z-average (d.nm) and PDI at 90 min of ASD dissolution (mean ± SD, n = 3; values read from Fig. 10) — 40 and 50 DL ASDs (P11, P16) — sub-table below | Fig. 10, p.180; text p.177 |
| C12 | claim, conclusion, authors: asserted | CPD nanodroplets are unstable in buffer; the surfactant level needed to stop growth depends on the surfactant (50 μg/ml SDS, ≤5 μg/ml TPGS or TWN), and CTAB destabilizes them into floating agglomerates [rests on: R6, R24] | p.173 |
| C37 | claim, mechanism, authors: "consistent with" | The rapid coarsening without surfactant reflects the high interfacial energy of the lipophilic CPD-rich phase [rests on: R6] | p.182 |
| C38 | claim, generalisation, authors: discussion: "in general"; "by an unknown mechanism"; abstract: "did show some benefits" | Surfactants in general slow the coarsening of drug-rich nanodroplets formed by LLPS, CTAB excepted (unknown mechanism), and work at very low concentrations, which suits formulation limits on surfactant [rests on: R6, R24] | p.167, p.182 |

## 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: coarsening

| 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 |
| C34 | claim, mechanism, authors: "may have been due to" | A few larger hydrophobic domains on the 30% DL MePHPH surface may have formed by coalescence or aggregation [rests on: R9.a] | p.2224 |
| C38 | claim, mechanism, authors: "likely" | The 40% DL gel changed from heterogeneous at 2 min to homogeneous at 20 min likely because hydrophobic and hydrophilic domains moved and coalesced into large domains, as on the surface (Fig. 11h) [rests on: R11.b, R9.b] | p.2225 |

## Mentioned only

- 2021 Ueda — [2021-ueda-polymer-species-maximum-aqueous-supersaturation-nmr](../../../cards/2021-ueda-polymer-species-maximum-aqueous-supersaturation-nmr/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref C43)
- 2022 Ueda — [2022-ueda-polymer-partitioning-ibuprofen-drug-rich-phase-nmr](../../../cards/2022-ueda-polymer-partitioning-ibuprofen-drug-rich-phase-nmr/paper.html) · Dissolution / C. Amorphous solubility and LLPS (ref 33)