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• W2072080551 abstract "The present study pursued to profile the intestinal solubility of nine HIV protease inhibitors (PIs) in fasted- and fed-state human intestinal fluids (FaHIF, FeHIF) aspirated from four volunteers. In addition, the ability of fasted- and fed-state simulated intestinal fluids (FaSSIF, FeSSIF) to predict the intestinal solubility was evaluated. All PIs were poorly soluble in FaHIF (from 7-μM for ritonavir to 327-μM for darunavir) and FeHIF (from 15-μM for atazanavir to 409μM for darunavir). For four of nine PIs, food intake significantly enhanced the solubilizing capacity of intestinal fluids (up to 18.4-fold increase for ritonavir). The intersubject variability (average coefficient of variance CVfed=60.6%, CVfasted=40.4%) was higher as compared with the intrasubject variability (CVfed=41.3%, CVfasted=20.5%). PI solubilities correlated reasonably well between FaSSIF and FaHIF (R=0.817), but not between FeSSIF and FeHIF (R=0.617). To conclude, postprandial conditions increased the inter- and intrasubject variability of the PIs. The inability of FeSSIF to accurately predict the FeHIF solubility emphasizes the need for a multivariate approach to determine solubility profiles, taking into account solid-state characteristics, pH, mixed bile acid/phospholipid micelles, and digestive products. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3800–3807, 2013" @default.
• W2072080551 created "2016-06-24" @default.
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• W2072080551 date "2013-10-01" @default.
• W2072080551 modified "2023-09-27" @default.
• W2072080551 title "Solubility Profiling of HIV Protease Inhibitors in Human Intestinal Fluids" @default.
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• W2072080551 doi "https://doi.org/10.1002/jps.23698" @default.
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