# Evidence: surfactant partitioning into the drug-rich phase

Parent: — · class: phase behaviour · names merged here: surfactant partitioning into the drug-rich phase

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.

## 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: surfactant partitioning into the drug-rich phase

| id | kind | content | locator |
|---|---|---|---|
| R12 | record, measured; derived | TPGS concentration in the aqueous phase and nanodroplet composition — TPGS 50 μg/ml with CPD 70 μg/ml (nanodroplets present), single-pulse quantitative NMR (P9); temperature of this measurement not stated — aqueous TPGS fell from 50 μg/ml to 33 ± 5.4 μg/ml; TPGS inside the nanodroplets gave no detectable NMR signal; composition derived as 50:17 w/w CPD:TPGS; HPLC of supernatant after pelleting of nanodroplets showed TPGS incorporation (SI section S3) | p.176 |
| R13 | record, measured | CPD and TPGS peaks at 50 °C with TPGS — CPD 70 + TPGS 50 μg/ml versus CPD 70 μg/ml alone, 50 °C (P8) — CPD solution-phase peaks broadened and shifted up-field; nanodroplet peaks shifted down-field and more intense than without TPGS | Fig. 6, p.176 |
| C18 | claim, mechanism, authors: "suggests" | The down-field shift and sharpening of the nanodroplet peaks with TPGS at 50 °C mean that TPGS partitions into the nanodroplets, making the drug environment more polar and more mobile [rests on: R13] | p.176 |
| C19 | claim, conclusion, authors: "indicated"; "suggested"; "confirmed" | TPGS is depleted from the aqueous phase by CPD nanodroplets, its signal inside the viscous droplets is not detected, and the droplets hold about 50:17 w/w CPD:TPGS; HPLC after pelleting confirms TPGS incorporation [rests on: R12] | p.176 |
| C60 | claim, generalisation, authors: conclusions: "tended to"; abstract: "were observed to interact differently" | Surfactants interact differently with CPD: non-ionic ones partition into the drug-rich phase, ionic ones act at the nanodroplet-water interface [rests on: R7, R12, R13, R14, R25] | p.167, p.185 |

## 2022 Correasoto — Role of surfactants in improving release from higher drug loading amorphous solid dispersions · Dissolution / A. Release mechanism and LoC

[2022-correa-soto-surfactants-higher-drug-loading-atazanavir-pvpva-asds](../../../cards/2022-correa-soto-surfactants-higher-drug-loading-atazanavir-pvpva-asds/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: surfactant partitioning into the drug-rich phase

| id | kind | content | locator |
|---|---|---|---|
| R17 | record, measured | ATZ in solution and nanodroplets and additive in solution by 1H NMR (µg/ml, mean ± SD) — 200 µg/ml total ATZ with additive, 37 °C (P10) — sub-table below; text: within detection limits no evidence of PVPVA or VP partitioning; SDS solution concentration reduced by less than 10%; Span®20, Span®80, Span®85 solution concentrations depleted by as much as 65%, 68% and 25% | Table 2, p.9; text p.7 |
| R19 | record, derived (relation not printed) | approximate ATZ:Span weight ratio in nanodroplets — Span®20, Span®80, Span®85 at 20 µg/ml with 200 µg/ml ATZ (R17) — 29:3 (Span®20), 62:5 (Span®80), 60:4 (Span®85) | text p.7 |
| C26 | claim, conclusion, authors: PVPVA, VP, TPGS: asserted; Spans: "seemed" | Within detection limits PVPVA and VP do not partition into ATZ nanodroplets; TPGS solution concentration was only minimally affected; Span®20, Span®80 and Span®85 seemed to partition into the nanodroplets [rests on: R17] | p.7 |
| C45 | claim, conclusion, authors: asserted | There is little correlation between release enhancement and surfactant affinity for the drug in water: SDS shows little affinity for the drug, Span®80 partitions into the drug-rich nanodroplets, and both enhance release [rests on: R17, R2] | p.9 |

## 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: surfactant partitioning into the drug-rich phase

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | RTV LLPS (onset of scattering) concentration — phosphate buffer 50 mM pH 6.8, 37 °C; additive levels per row; error bars SD, n = 3 — rows in the sub-table below | Fig. 5, p.7; §4.3, p.5 |
| R13 | record, measured | observed ¹H NMR spectral changes per surfactant (Table 1 observation column) — RTV 200 µg/ml nanodroplet suspensions, 37 °C; surfactant level per row — rows in the sub-table below; quantification of peak areas in SI (not supplied) | Table 1, p.8; §4.4, p.7 |
| R18 | record, measured | O-PTIR spectra, SDS film — RTV-PVPVA-SDS 30-70-5; field 166.14 × 124.8 µm — discrete-phase spectrum matches amorphous RTV; continuous-phase spectrum matches PVPVA and carries a 2852 cm⁻¹ band; text: only spectra from the continuous domain showed the 2852 cm⁻¹ peak | Fig. 9b, p.10; §4.6, pp.8–9 |
| R19 | record, measured | O-PTIR spectra, Tween 80 film — RTV-PVPVA-Tween 80 30-70-5; field 55.38 × 41.6 µm; discrete circular domains — discrete-domain spectrum: RTV bands, a 1352 cm⁻¹ band and C–H intensity 2924 > 2963 cm⁻¹; continuous-phase spectrum: PVPVA bands without new features at 1352 cm⁻¹ or in the C–H region | Fig. 9c, p.10; §4.6, p.9 |
| R20 | record, measured | O-PTIR spectra, Span 20 film — RTV-PVPVA-Span 20 30-70-5; field 55.38 × 41.6 µm; points in discrete domain, at interface, in continuous phase — discrete-domain spectrum: RTV bands plus 2855 cm⁻¹; interface spectrum: both RTV and PVPVA bands plus 2855 cm⁻¹ (text: an appreciable number of interface spectra showed both); continuous-phase spectrum: PVPVA bands | Fig. 9d, p.11; §4.6, pp.8–9 |
| R21 | record, measured | O-PTIR spectra, Span 85 film — RTV-PVPVA-Span 85 30-70-5; field 166.14 × 124.8 µm — continuous-phase spectrum: RTV bands plus the Span 85 C–H band; discrete-phase spectrum: PVPVA bands without the Span 85 band; continuous-phase trace runs off the 25 mV axis near 1460 cm⁻¹ | Fig. 9e, p.11; §4.6, pp.8–9 |
| C19 | claim, mechanism, authors: "suggests" | The LLPS data point to little or no distribution of PVPVA or SDS into RTV nanodroplets and to partitioning of Tween 80 and the Spans into the drug-rich phase. [rests on: R10] | §4.3, p.5 |
| C46 | claim, conclusion, authors: asserted ("good agreement"; "compelling evidence") | Phase preferences from O-PTIR agree with aqueous partitioning: PVPVA hardly enters RTV nanodroplets and is absent from drug-rich spectra; Tween 80 and the Spans partition into nanodroplets and are found in the RTV-rich phase; SDS does neither and is found only in the PVPVA-rich phase. [rests on: R10, R13, R15, R18, R19, R20, R21, R22] | §5.2, p.13 |
| C61 | claim, generalisation, authors: asserted | Across the four surfactants, the most hydrophilic (SDS) resides mainly in the polymer-rich phase and the more hydrophobic ones preferentially in drug-rich domains. [rests on: R18, R19, R20, R21] | §6, p.15 |

## 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 · used · as: surfactant partitioning into the drug-rich phase

| id | kind | content | locator |
|---|---|---|---|
| R24 | record, cited (ref 39) | earlier results on the same surfactant-containing RTV–PVPVA ASDs — water sorption from the vapour phase — all four surfactants lowered the Tg of the ternary ASDs relative to the binary ASD; surfactants altered AAPS kinetics and morphology; Span 20 and Span 85 partition into the RTV-rich phase after AAPS; Tween 80 adsorbs on RTV-rich nanodroplets; SDS has no IR peaks in the 1522/1369 cm⁻¹ region | text p.2819, p.2833, p.2834, p.2841 |
| C18 | claim, mechanism, authors: results: can be attributed; discussion: is expected to be | The continuous drug-rich layer of the Span 85 30% DL ASD has a very low Tg from Span 85 partitioning, hence low mechanical strength and low persistence; IDR shear removes it as fast as or faster than it forms, so only discrete domains are seen in IDR compacts. [rests on: R8, R22; cited: R24] | Results, p.2826; Discussion, p.2842 |
| C35 | claim, mechanism, authors: results: would be expected; discussion: can lead | Spans partition into the drug-rich phase and lower its Tg, so drug-rich domains from Span ASDs should have lower Tg than in the binary system; the higher mobility can speed ripening and change morphology. [rests on: R22; cited: R24, ref 23] | Results, p.2834; Discussion, p.2841 |