Pharmacokinetics of Saquinavir After Intravenous and Oral Dosing of Saquinavir: Hydroxybutenyl-β-Cyclodextrin Formulations
Document Type
Article
Publication Date
1-1-2008
Description
The current research evaluated the ability of hydroxybutenyl-β-cyclodextrin (HBenBCD) to enhance saquinavir in vitro solubility and in vivo oral bioavailability; both the base and mesylate salt forms of saquinavir were investigated. HBenBCD was effective and significantly improved saquinavir solubility in aqueous media. In the presence of 10 wt % HBenBCD, saquinavir base solubility in water was increased to ca. 5.5 ± 0.4 mg/mL and represents a 27-fold increase from that observed in water (207 ± 5 mg/mL) in the absence of HBenBCD. Saquinavir-HBenBCD formulations were found to have rapid dissolution over a wide pH range (1.2-6.8), and saquinavir solubility in these media was maintained throughout the experiments. When saquinavir-HBenBCD formulations were administered to Wistar-Hannover rats, saquinavir was rapidly absorbed and rapidly eliminated. Rapid saquinavir elimination was particularly pronounced when saquinavir-HBenBCD formulations were given as an oral aqueous gavage. Saquinavir oral bioavailability in rats obtained from saquinavir mesylate capsules (2.0% ± 0.7%) was increased (9 ± 4)-fold (18.6% ± 7.3%) when dosed with saquinavir base-HBenBCD capsules. Clearly, HBenBCD can significantly improve the solubility and oral bioavailability of saquinavir; however, further formulation studies are required to optimize saquinavir oral delivery using this technology.
Citation Information
Buchanan, Charles; Buchanan, Norma L.; Edgar, Kevin J.; Little, James L.; Ramsey, Michael G.; Ruble, Karen M.; Wacher, Vincent J.; and Wempe, Michael F.. 2008. Pharmacokinetics of Saquinavir After Intravenous and Oral Dosing of Saquinavir: Hydroxybutenyl-β-Cyclodextrin Formulations. Biomacromolecules. Vol.9(1). 305-313. https://doi.org/10.1021/bm700827h PMID: 18072746 ISSN: 1525-7797