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- W2613862808 abstract "Supersaturating formulations have become a popular approach to address the issue of inadequate aqueous solubility for small molecules. Given that prevention of nucleation may not be always possible, it is of particular interest to control crystal growth from supersaturated solutions in order to maximize the extent of oral absorption of therapeutic agents. Bile salts are endogenous surfactants that are present in biorelevant dissolution media and can have direct impact on the in vivo performance of therapeutic agents due to their presence in the gastrointestinal tract. In this study, an in situ common history seeding method was implemented to provide seeds that better mimic crystals formed from aqueous supersaturated solutions. By forming seeds in situ and then regenerating supersaturation, we were able to probe the influence of biorelevant bile salts on telaprevir crystal growth rates and secondary nucleation. The extent of growth inhibition was found to vary with bile salt chemistry and aggregation level. It was also noted that sodium taurocholate and sodium taurochenodeoxycholate inhibited secondary nucleation of telaprevir from highly supersaturated solutions. The impact of bile salts on crystal growth and secondary nucleation is of relevance for improved understanding of precipitation kinetics of supersaturating dosage forms." @default.
- W2613862808 created "2017-05-19" @default.
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- W2613862808 date "2017-05-18" @default.
- W2613862808 modified "2023-10-14" @default.
- W2613862808 title "Impact of Bile Salts on Solution Crystal Growth Rate and Residual Supersaturation of an Active Pharmaceutical Ingredient" @default.
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- W2613862808 doi "https://doi.org/10.1021/acs.cgd.7b00464" @default.
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