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• W4226454041 endingPage "134928" @default.
• W4226454041 startingPage "134928" @default.
• W4226454041 abstract "Cocrystal engineering has become increasingly prevalent as an efficient and versatile route to overcome solubility limitations and improve the oral bioavailability of poorly soluble drugs. However, the unwanted solution-mediated phase transformation of cocrystals to less soluble parent drugs in the gastrointestinal tract may fail to deliver the drug in the body in a sufficient quantity. This study explores how bile salt sodium taurocholate (STC) affects the dissolution performance of indomethacin-saccharin (IMC-SAC) cocrystals. Fluorescence microscopy was used for in situ monitoring of the phase transformation of IMC-SAC cocrystals in the presence and absence of STC during dissolution. Intrinsic dissolution tests, atomic force microscopy and energy dispersive X-ray spectroscopy revealed that there was a significant relationship between the coformer release rate and the kinetics of the phase transformation of cocrystals. The addition of low-concentration STC in the buffer significantly inhibited the phase transformation of IMC-SAC cocrystals by retarding the release of SAC from cocrystals, leading to enhanced release rates of IMC. A molecular dynamics simulation revealed that preferential adsorption of STC molecules on the cocrystal surface may be responsible for the suppression of drastic release of SAC from the cocrystal lattice, thus preventing a rapid crystallization of IMC at the solid–liquid interface. The presence of STC in the buffer could also prolong the supersaturation of IMC, accounting for the overall improved in vitro and in vivo performance of IMC-SAC cocrystals. This study provides a deeper insight into the mechanisms of solution-mediated phase transformation of cocrystals in the presence of endogenous surfactant, which could also be used as an effective strategy to improve the absorption performance of pharmaceutical cocrystals by minimizing the risk of phase transformation during dissolution." @default.
• W4226454041 created "2022-05-05" @default.
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• W4226454041 date "2022-05-01" @default.
• W4226454041 modified "2023-10-11" @default.
• W4226454041 title "Impact of bile salt on solution-mediated phase transformation of pharmaceutical cocrystals: The importance of coformer release kinetics" @default.
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• W4226454041 doi "https://doi.org/10.1016/j.cej.2022.134928" @default.
• W4226454041 hasPublicationYear "2022" @default.
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