期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 63, 期 6, 页码 817-824出版社
WILEY
DOI: 10.1111/j.2042-7158.2011.01286.x
关键词
bile; intestinal absorption; polyethylene glycol 400; polysorbate 80; poorly water-soluble drugs
资金
- Drug Research Academy, Faculty of Pharmaceutical Sciences, University of Copenhagen
Objectives The aim of this study was to examine the effects of bile on the oral absorption of the poorly water-soluble compound, halofantrine, when administered to rats in vehicles consisting of the co-solvent polyethylene glycol 400 (PEG 400) alone or in mixtures with the surfactant polysorbate 80 (PS 80) (95 : 5; 85 : 15; 75 : 25 PEG 400 : PS 80). Methods Halofantrine (17.5 mg/kg) was administered to bile duct cannulated (BDC) and sham-operated rats in a fixed vehicle volume of 5 ml/kg. Key findings The bioavailability of halofantrine was significantly lower in BDC rats when dosed with 0-5% PS 80 in PEG 400 compared with BDC rats dosed with > 15% PS 80. Increasing the concentration of PS 80 to 15-100% eliminated this difference. A possible explanation for the lower bioavailability of halofantrine in BDC rats when dosed in pure PEG 400 could be the dilution of the vehicle by intestinal fluids, decreased transit time and precipitation in the gastrointestinal tract upon dilution of PEG 400. Conclusions The addition of PS 80 to the formulation increased its solubilising power upon dilution and may have inhibited precipitation and substituted the absence of bile above a certain level. Adjusting the level of surfactant in drug formulations could therefore be used to minimise variability in the bioavailability from co-solvent systems based upon differences in bile concentration between individuals.
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