# Evidence: phase separation morphology

Parent: — · class: phase behaviour · names merged here: phase morphology; phase separation morphology; phase-separated morphology; phase-separation morphology

6 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 morphology

| id | kind | content | locator |
|---|---|---|---|
| R14 | record, measured | topography — DEX450-PVP12 film; Fig. 5A 50 × 30 µm area, colour scale 0-200 nm; Fig. 5B 5 × 3 µm area, 0-100 nm — submicrometer-sized discrete domains, lower (thinner), dispersed in a thicker continuous phase; domain diameters in Fig. 5B ≈0.2-0.7 µm (read against the 1 µm scale bar) | Fig. 5A-B, p.1464; text p.1464 |
| R16 | record, measured | topography — DEX40-PVP90 film, colour scales 0-250 nm, scale bars 10, 5 and 1 µm — discrete domains of about 5 to 10 µm diameter, higher (thicker), in a thinner continuous phase (Fig. 6A-B); smaller discrete domains of about a few hundred nanometers to a few micrometers in the continuous phase (Fig. 6B-C); 10 marked positions about 2.5 µm apart: 6 in the continuous phase, 4 on discrete domains (counted on Fig. 6B) | Fig. 6A-C, p.1465; text p.1465 |
| R19 | record, measured | topography — DEX6-PVP90 film, colour scales 0-75 nm, scale bars 10 and 1 µm — discrete domains (higher) distributed in a thinner continuous phase; domain diameters ≈0.3-0.6 µm (read from Fig. 8B); features in the centre and lower right-hand corner of Fig. 8B are artifacts from sample damage by the cantilever (caption) | Fig. 8A-B, p.1466; text p.1465, p.1467 |
| R22 | record, measured | topography — DEX40-PVP12 film; Fig. 9A colour scale 0-750 nm, scale bar 10 µm; Fig. 9B 0-500 nm, 1 µm — discrete domains (lower, thinner) dispersed in a thicker continuous phase; the domain in Fig. 9B ≈1.5-2 µm across, dark domains in Fig. 9A ≈0.4-1.8 µm (read against the scale bars); 10 marked positions about 0.5 µm apart: 4 in the domain, 6 in the continuous phase (counted on Fig. 9B) | Fig. 9A-B, p.1467; text p.1467 |
| C27 | claim, generalisation, authors: p.1465: "domains tend to become smaller"; p.1467: "Again, the effect of lowering the MW of DEX or PVP leads to" | Domain size decreases as the MW of either polymer decreases: as the MW of PVP decreases (DEX450 series), when the MW of DEX is lowered (DEX40-PVP90 versus DEX450 blends), and for DEX40-PVP12 compared with DEX450-PVP12 and DEX40-PVP90 [rests on: R8, R9, R11, R12, R14, R16, R19, R22] | p.1465, p.1467 |
| C48 | claim, conclusion, authors: abstract: asserted; conclusions: "could be gained" | AFM gave structural insight into the two-phase systems: size, shape and distribution of the domains and their dependence on polymer MW [rests on: R9, R12, R14, R16, R19, R22] | p.1459, p.1468 |

## 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 · measured · as: phase separation morphology

| id | kind | content | locator |
|---|---|---|---|
| R21 | record, measured | AFM topography and deflection after 12 h at ≈100% RH — 30% DL films at 0, 2, 5, 10% TPGS (P12-P14); 10 µm × 10 µm — sub-table below | Fig. 11, p.13; text p.13 |
| R23 | record, measured | AFM-nanoIR images after 12 h at ≈100% RH — 30% DL films at 0 and 10% TPGS (P16); 10 µm × 10 µm — 0% TPGS: height scale −90 to 90 nm; ratio image shows contiguous, elongated drug-rich (red) regions interleaved with drug-lean (blue) regions. 10% TPGS: height scale −35 to 35 nm; round, separated drug-rich domains in a continuous drug-lean phase. Text: elevated height features are drug-rich; surrounding continuous phase polymer-rich or drug-lean. IR image scale −0.1 to 0.1 V; ratio scale −1.5 to 1.5 | Fig. 13, p.14; text p.14 |
| R19 | record, measured | micro-CT cross-sections of 30% DL tablets after 10 min of dissolution — P11; 0, 2, 5, 10% TPGS; scale bar 2 mm — 0% and 2% TPGS: porous surface layer with dark voids at the dissolution front, marked by a double arrow; 5% TPGS: homogeneous section throughout the thickness; 10% TPGS: homogeneous section with small surface features at the front | Fig. 10, p.12; text p.12 |
| C37 | claim, mechanism, authors: "We propose" | Proposed release model (Fig. 14), extending the group's binary model (ref 17): a transient gel layer forms where water plasticizes polymer chains, which disentangle before release; at high DL whether release is drug- or polymer-controlled depends largely on the architecture of the drug-rich phase formed by phase separation in the hydrated matrix [rests on: R19, R21, R23; cited: refs 17, 47] | p.16-17 |
| C53 | claim, mechanism, authors: conclusions: "is thought to"; abstract: "appeared to be linked" | TPGS improves release by preventing a continuous drug-rich layer at the compact-water interface; abstract: discrete spherical drug-rich domains with surfactant appeared linked to congruent, rapid release, and a contiguous drug-rich phase formed without surfactant at higher DLs [rests on: R21, R23, R19, R9] | p.1, 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: phase-separation morphology

| id | kind | content | locator |
|---|---|---|---|
| R20 | record, measured | film morphology, binary CPD-PVPVA ASDs — 40, 50, 60 DL films before and after 5 min at 100% RH (P17); red = Nile red (561 nm), green = Alexa 488 (488 nm) — before exposure all three films uniform; after exposure: 40 DL unchanged and uniform; 50 DL bicontinuous structure of Nile red-rich and Alexa 488-rich domains; 60 DL continuous Nile red-rich (drug) phase with discrete Alexa 488-rich (polymer) domains | Fig. 11, p.180; text p.177 |
| R21 | record, measured | film morphology with SDS — as R20 with 5 g SDS per 100 g (P17) — 40 DL uniform after exposure; 50 DL after exposure: results text "a small extent of heterogeneity in fluorescence intensity", discussion text "remains homogeneous (within the detection limit of the measurement which is ~500 nm)"; 60 DL after exposure: continuous CPD-rich phase with polymer-rich discrete domains smaller than in the binary 60 DL film | Fig. 12, p.181; text p.180, p.185 |
| R22 | record, measured | film morphology with TPGS — as R20 with 5 g TPGS per 100 g (P17) — 40 DL uniform after exposure; 50 DL bicontinuous after exposure; 60 DL large irregular structures after exposure | Fig. 13, p.181; text p.180 |
| R23 | record, measured | film morphology with TWN — as R20 with 5 g TWN per 100 g (P17) — 40 DL uniform after exposure; 50 and 60 DL fine-scale heterogeneous pattern after exposure; text: bicontinuous morphology "for DLs above 50%" | Fig. 14, p.182; text p.180 |
| C32 | claim, conclusion, authors: "appears"; "consistent with"; "in line with" | In binary films exposed to 100% RH, 50 DL forms a bicontinuous structure, 40 DL stays unchanged and at 60 DL the drug forms the continuous phase; this matches the release profiles and earlier reports that continuous drug-rich phases go with poor release [rests on: R20, R17; cited: ref 68] | p.177, p.180 |
| C33 | claim, conclusion, authors: "indicating"; "suggesting" | Ternary films at 50 and 60 DL phase separate after humidity exposure: with SDS only slightly at 50 DL and more at 60 DL (drug continuous, smaller polymer domains); with TPGS bicontinuous at 50 DL and more coarsened at 60 DL; with TWN bicontinuous above 50 DL [rests on: R21, R22, R23] | p.180 |

## 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 · measured · as: phase separation morphology

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | surface morphology of partially dissolved compacts, Nile red channel (scale bar 50 µm) — dye-containing compacts, P2, P5, P6 — sub-table below; text: black areas present in several images | Fig. 3, pdf p.9-10; text pdf p.8-9 |
| R6 | record, measured | cross-section morphology, Nile red plus Alexa Fluor 488 (scale bars 50 µm) — dye-containing compacts, P2, P5, P6 — sub-table below | Fig. 5, pdf p.12-13; text pdf p.11-12, p.24 |
| C4 | claim, generalisation, authors: "appear to be" | The domain size and interconnectivity of phase-separated drug-rich domains are critical factors for drug release from RTV-PVPVA ASDs [rests on: R4, R6] | pdf p.3 |
| C58 | claim, conclusion, authors: "indicates"; "is likely dependent" | Correlating morphology with release shows that a continuous drug-rich phase is catastrophic for drug release, and the transition from congruent to incongruent release above a certain DL depends on the phase morphology after AAPS, in agreement with Han et al. [rests on: R2, R4, R6, R10-R13; cited: ref 52] | pdf p.25 |

## 2022 Yang — Phase separation in surfactant-containing amorphous solid dispersions: Orthogonal analytical methods to probe the effects of surfactants on morphology and phase composition · Solid state stability / Physical stability

[2022-yang-surfactant-containing-rtv-pvpva-asd-phase-separation](../../../cards/2022-yang-surfactant-containing-rtv-pvpva-asd-phase-separation/paper.html) · Solid state stability / Physical stability · measured · as: phase-separated morphology

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | AAPS time-lapse, binary 30% DL — RTV-PVPVA 30-70 film; same conditions; scale bar 50 µm — homogeneous at 0 min; bicontinuous red/green structure at 5 min; coarser red drug-rich network at 10 and 30 min | Fig. 3b, p.6; §4.1, p.5 |
| R5 | record, measured | AAPS time-lapse, SDS film — RTV-PVPVA-SDS 30-70-5; same conditions; scale bar 10 µm — homogeneous at 0 and 5 min; fine texture at 10 min; discrete circular red drug-rich domains at 30 min, larger than those with Tween 80 | Fig. 3c, p.6; §4.1, p.5 |
| R6 | record, measured | AAPS time-lapse, Tween 80 film — RTV-PVPVA-Tween 80 30-70-5; same conditions; scale bar 10 µm — homogeneous at 0 and 5 min; dense, very small discrete red domains at 10 and 30 min | Fig. 3d, p.6; §4.1, p.5 |
| R7 | record, measured | AAPS time-lapse, Span 20 film — RTV-PVPVA-Span 20 30-70-5; same conditions; scale bar 50 µm — homogeneous at 0 min; irregular red drug-rich domains with bicontinuous regions at 5 min; at 10 and 30 min large green polymer-rich areas next to regions of discrete and continuous red drug-rich domains | Fig. 3e, p.6; §4.1, p.5 |
| R8 | record, measured | AAPS time-lapse, Span 85 film — RTV-PVPVA-Span 85 30-70-5; same conditions; scale bar 50 µm — homogeneous at 0 min; bicontinuous structure at 5 min; coarsened continuous red drug-rich regions beside large green areas at 10 and 30 min | Fig. 3f, p.6; §4.1, p.5 |
| R22 | record, measured | phase assignment and cross-contamination of spectra, all five films — Fig. 9 films — drug-rich phase continuous with Span 85 and discrete with SDS, Tween 80 and Span 20; binary film bicontinuous; in all systems no drug bands in polymer-rich spectra and no polymer bands in drug-rich spectra | §4.6, p.8 |
| R23 | record, measured | O-PTIR ratio map 1530/1680 cm⁻¹, binary film — RTV-PVPVA 30-70; 50 × 40 µm; colour scale 0–2 — high-ratio (drug-rich, red) region forms a connected network enclosing low-ratio (blue) polygonal domains; text calls the structure bicontinuous | Fig. 10a, p.12; §4.6, p.8 |
| C9 | claim, conclusion, authors: asserted | Morphology: surfactant-free films lacey or bicontinuous; Tween 80 and SDS films discrete circular drug-rich domains; Span 20 films both continuous and discrete drug-rich domains; Span 85 films a continuous drug-rich phase only (initially bicontinuous plus interconnected drug-rich domains, §5.4). [rests on: R4, R5, R6, R7, R8, R17, R18, R19, R20, R21] | §6, p.15; §5.4, p.14 |

## 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 morphology

| 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 |
| 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 |
| 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 |
| C46 | claim, conclusion, authors: "appears" | The morphology of the two phases after amorphous phase separation appears to differentiate congruent from incongruent release [rests on: R1, R2, R6, R7] | p.2230 |