# Evidence: nanodroplet agglomeration

Parent: — · class: phase behaviour · names merged here: droplet agglomeration; nanodroplet agglomeration

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.

## 2018 Hate — Insight into Amorphous Solid Dispersion Performance by Coupled Dissolution and Membrane Mass Transfer Measurements · Bioperformance / Bioperformance

[2018-hate-asd-coupled-dissolution-membrane-mass-transfer](../../../cards/2018-hate-asd-coupled-dissolution-membrane-mass-transfer/paper.html) · Bioperformance / Bioperformance · measured · as: nanodroplet agglomeration

| id | kind | content | locator |
|---|---|---|---|
| R20 | record, measured | DLS mean size and PDI over time — solvent-shift solution of 200 µg/mL ATZ with 1 mg/mL PVPVA in pH 6.8 buffer, during a dissolution-absorption run — mean size ≈245, ≈260, ≈275, ≈290, ≈270, ≈700, ≈455 and ≈10000 nm and PDI ≈0.09, ≈0.16, ≈0.27, ≈0.33, ≈0.25, ≈0.57, ≈0.34 and ≈0.51 at 0, 15, 30, 45, 60, 75, 90 and 105 min (read from Fig. S4); text: size and PDI increased and derived count rate decreased with time (count rate not shown) | Fig. S4, SI p.3; p.14 |
| C27 | claim, conclusion, authors: asserted | In PVPVA-containing solutions the nanodroplets agglomerated: size and PDI rose and derived count rate fell with time [rests on: R20] | p.14 |
| C34 | claim, mechanism, authors: "indicating"; "Most likely" | For the 10% DL PVPVA ASD no nanospecies were detected in filtered samples, yet the unfiltered ratio of 0.89 indicates a drug-rich hydrophobic environment; most likely nanodroplets formed in the boundary layer agglomerated rapidly and escaped detection [rests on: R11, R12.f] | p.15 |
| C41 | claim, mechanism, authors: "Most likely"; "depicting" | The 10% DL PVPVA receiver Cmax was somewhat lower than for the 10% DL cellulose ASDs but slightly above that of a solution at the amorphous solubility; most likely colloids agglomerated into micron-sized species retained by the filter; the constant receiver concentration depicts a reservoir effect of the agglomerates [rests on: R13.g, R12.f] | p.17-18 |

## 2023 Yang — Drug Release from Surfactant-Containing Amorphous Solid Dispersions: Mechanism and Role of Surfactant in Release Enhancement · Dissolution / A. Release mechanism and LoC

[2023-yang-surfactant-containing-asd-release-enhancement](../../../cards/2023-yang-surfactant-containing-asd-release-enhancement/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: droplet agglomeration

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | phase morphology, Tween 80 30–70–10 — P7 at 5, 10, 20 min; P8 at 0, 0.5, 1, 2, 5 min — surfaces: discrete red domains with extensive agglomeration/coalescence at all times; cross sections: agglomerated red droplets in the gel layer; in situ: discrete droplets formed in the hydrated gel and agglomerated at the gel–solution interface; diffuse green moving into the bulk; chunks of agglomerated droplets entering the bulk at 2 and 5 min | Fig. 7a–k, p.2831–2832; text p.2827 |
| C20 | claim, mechanism, authors: could potentially explain; can be accounted for | Agglomeration of drug-rich droplets in Tween 80 ASDs makes them harder to remove from the gel and reduces the contact area between the polymer/water-rich phase and the bulk, which could explain the slower release. [rests on: R10, R2.e, R5.d] | Results, p.2827; Discussion, p.2842 |

## 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: nanodroplet agglomeration

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | film morphology after 3 and 11 h at 100% RH, 37 °C (blue = prodan, drug-rich hydrophobic phase; red = Alexa Fluor 488, water/polymer-rich hydrophilic phase) — 10% DL K12 and 10% DL K29/32 films (P10) — sub-table below; text: phase separation seen after 3 h; in both films the drug-rich phase appeared as droplets and the hydrophilic phase was continuous; in the K12 film the drug-rich domains appeared to agglomerate extensively into strands, especially after 11 h; in the K29/32 film the droplets stayed separate (no agglomeration into strands) | Fig. 3, p.6; text p.6 |
| R10 | record, measured | morphology at the dissolution front by in situ confocal microscopy (green-circled regions: 1 dry ASD, 2 gel layer, 3 solution; water entering from right to left; scale bar 25 µm) — 10% DL K12 compact after 2 min; 10% DL K29/32 compact after more than 7 min; pH 8.0 buffer, 37 °C (P8) — sub-table below | Fig. 5, p.7; text p.6-9 |
| C22 | claim, mechanism, authors: "likely" | The agglomeration of drug-rich domains into strands in the K12 film is the likely mechanism behind the poor release of this system; it is named Failure Mode I [rests on: R7, R1] | p.6 |
| C26 | claim, mechanism, authors: asserted | In the K12 compact the droplets, initially dispersed, agglomerated near the gel/solution boundary into an interconnected network of strings anchored in the gel layer and strong enough to withstand the hydrodynamic forces; as the surrounding hydrophilic phase was diluted and the polymer diffused out the network collapsed into denser agglomerates near the solution, so the droplets accumulated at the gel-solution interface instead of releasing; this Failure Mode I leads to a low LoC [rests on: R10] | p.7-8, p.9 |
| C38 | claim, mechanism, authors: "appears" | The lower LoCs below Mc (K12, K17, K25) appear to be caused by nanodroplet agglomeration in the gel layer, a newly discovered mechanism distinct from phase inversion; it is named Failure Mode I, phase inversion Failure Mode II [rests on: R7, R10, R12] | p.9 |

## Mentioned only

- 2019 Elkhabaz — [2019-elkhabaz-posaconazole-asd-phase-transformations-biorelevant-media](../../../cards/2019-elkhabaz-posaconazole-asd-phase-transformations-biorelevant-media/paper.html) · Dissolution / B. Supersaturation from ASD dissolution (ref C28)