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• W2033305262 abstract "Lipid-based formulations of danazol with varying quantities of included surfactant have been examined in vitro and in vivo. Formulations comprising fatty acid ester surfactants were readily hydrolysed during in vitro digestion, although Cremophor RH40 (CrRH) was less effectively hydrolysed than Cremophor EL (CrEL). Formulations comprising high quantities of digestible surfactant also appeared to less effectively prevent danazol precipitation during in vitro evaluation. These trends were replicated in vivo where danazol bioavailability in beagle dogs was higher after oral administration of self-emulsifying formulations employing 55% (w/w) CrRH when compared with CrEL. The oral bioavailability of danazol after administration of drug formulated in surfactant alone, however, was poor. Studies using predispersed and encapsulated formulations of CrRH subsequently suggested that the low bioavailability of the single surfactant formulations reflected poor dispersion. Mixtures of surfactants, improved dispersion and good oral bioavailability of danazol was evident after administration of formulations comprising CrRH and either Pluronic L121 or Gelucire 44-14, in spite of evidence of danazol precipitation during in vitro digestion of the Gelucire formulation. These data suggest that effective dispersion and resistance to precipitation during both dispersion and digestion are key design parameters for lipid-based formulations comprising high proportions of surfactant. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:995–1012, 2008" @default.
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• W2033305262 date "2008-02-01" @default.
• W2033305262 modified "2023-10-16" @default.
• W2033305262 title "Evaluation of the Impact of Surfactant Digestion on the Bioavailability of Danazol after Oral Administration of Lipidic Self-Emulsifying Formulations to Dogs" @default.
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• W2033305262 doi "https://doi.org/10.1002/jps.21246" @default.
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