生物等效性和生物利用度杂志

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Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

TK Indira, PK Lakshmi, J Balasubramaniam and YV Rajesh

The purpose of this study was to investigate the effect of different solubilizers namely alpha tocopherol, soyphosphatidylcholine 70, Phospholipon 80H, and Phospholipon 90H on the bioavailability of sustained release fenofi-brate pellets using fluid bed coating by applying Taguchi design to optimize the type and concentration of solubilizer at four levels namely 0.5%, 1%, 1.5%, and 2%. The pellets were prepared by loading the fenofibrate blended with other excipients onto the core sugar pellets with the aid of the binder solution. Taguchi experimental runs with alphatocopherol 1% and Phospholipon 90H 2% (test) showed significant differences in in vitro dissolution behavior of drug compared to the pure drug. The pharmacokinetics of pure drug and test was evaluated in healthy male Wistar rats and found that t1/2 was reduced significantly (4.36 and 4.02 hours) while AUC0-t (32.14 ± 6.38 μg h/ml, 36.94 ± 6.2 μgh/ml), Cmax (8.7 ± 2.31 μg/ml, 9.8 ± 2.2 μg/ml) were improved markedly compared to the pure drug with t1/2 (7.339314± 3.1 hours), AUC0-t (11.89 ± 8.13 μg h/ml), and Cmax (5.137 ± 3.37 μg/ml). The extent of the mean plasma exposure of fenofibrate was 2.7 and 3.1 fold higher in animals treated with test. The ANOVA results revealed that type and concentration of solubilizer are crucial for enhancement of in vitro dissolution profile. Hence use of solubilizers may be the promising way to improve the oral bioavailability of fenofibrate.