期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 93, 期 5, 页码 1110-1121出版社
JOHN WILEY & SONS INC
DOI: 10.1002/jps.20039
关键词
lipid-based drug delivery; lipid digestion; poorly water-soluble drugs; absorption bioavailability
The relative oral bioavailability (BA) of halofantrine base (Hf) was assessed in male beagle dogs after administration of a medium chain triglyceride (MCT), a long chain triglyceride (LIST), and a blended LCT/MCT lipid solution formulation of Hf (Study 1) and after, administration of suspensions of Hf base and Hf . HCl in LCT (Study 2). A series of in vitro lipid digestion experiments were also performed in an attempt to clarify the data obtained. In vitro drug solubilization profiles were markedly dependent on the mass of lipid employed in lipid digestion experiments. At high lipid masses (similar to25 mg triglyceride/mL), MCT formulations gave maximal benefit, whereas at low lipid concentrations (similar to5 mg triglyceride/mL), LCT formulations provided improved solubilization capacity. The in vitro digestion and solubilization data at lower lipid masses were consistent with the in vivo data where the BA of Hf after oral administration of the LCT solution > LCT/MCT blend > MCT solution. The second BA study showed similar, albeit variable, exposure after oral administration of a suspension of Hf base or Hf . HCl in LCT and this trend was broadly consistent with in vitro results. This study demonstrates the potential utility of in vitro digestion models to assess and rank order the in vivo performance of lipid solution and suspension formulations of poorly water-soluble drugs such as Hf. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
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