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• W4220996890 endingPage "121708" @default.
• W4220996890 startingPage "121708" @default.
• W4220996890 abstract "Amorphous-amorphous phase separation (AAPS) is an important phase transition process for amorphous solid dispersion (ASD) performance both in terms of drug release as well as physical and chemical stability during storage. Addition of surfactants to ASD systems can impact both of these processes. One possible mechanism through which surfactants affect ASD performance is via their impact on AAPS. Unfortunately, despite their increasing usage in ASD formulations, the effect of surfactant on AAPS is still poorly understood, and there are limited analytical techniques that provide microstructural and composition information about phase separated ASDs. In this study, the impact of four surfactants (sodium dodecyl sulfate, Tween 80, Span 20 and Span 85) on water-induced phase separation in ASDs formulated with ritonavir and polyvinylpyrrolidone/vinyl acetate (PVPVA) was investigated using a variety of orthogonal analytical methods. Transparent films of ASDs with different compositions were prepared by spin coating. Fluorescence confocal microscopy in combination with an in situ humidity chamber was used to monitor the kinetics and morphology of phase separation following exposure to high relative humidity. Optical photothermal IR analysis of phase separated films enabled characterization of domain composition and surfactant distribution. Liquid-liquid phase separation concentration, zeta potential and solution nuclear magnetic resonance spectroscopy measurements enabled interpretation of interaction with and partition of surfactants into the drug-rich phase. It was found that phase separation kinetics and morphology were notably changed by the surfactants. Further, the surfactants showed different affinities for the drug-rich versus the aqueous/polymer-rich phases. The employed analytical techniques were found to be complementary in providing insight into surfactant location in phase separated systems. This study highlights the complexity of phase separation, especially in the presence of surfactants, and provides a foundation to understand the impact of AAPS on ASD performance." @default.
• W4220996890 created "2022-04-03" @default.
• W4220996890 creator A5019910492 @default.
• W4220996890 creator A5036297131 @default.
• W4220996890 creator A5041679814 @default.
• W4220996890 creator A5046954964 @default.
• W4220996890 creator A5065235454 @default.
• W4220996890 creator A5090835640 @default.
• W4220996890 date "2022-05-01" @default.
• W4220996890 modified "2023-10-16" @default.
• W4220996890 title "Phase separation in surfactant-containing amorphous solid dispersions: Orthogonal analytical methods to probe the effects of surfactants on morphology and phase composition" @default.
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