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Sep 28, 2018

Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach

Abstract

For performance assessment of the lipid-based drug delivery systems (LBDDS), in vitrolipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilisation processes. Much of previous research on in vitro lipolysis have mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values (Foral,predicted) of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, while the in vivo oral bioavailability (Foral) of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The Foral,predicted corresponded well with the Foral for both formulations, demonstrating that the combination of in vitrolipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivointestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.

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