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

Lee, Jong Bong; Kim, Tae Hwan; Feng, Wanshan; Choi, Hyeon Gwan; Zgair, Atheer; Shin, Soyoung; Yoo, Sun Dong; Gershkovich, Pavel; Shin, Beom Soo

Abstract

For performance assessment of the lipid-based drug delivery systems (LBDDS), in vitro lipolysis 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 vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in [less than] 1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.

Citation

Lee, J. B., Kim, T. H., Feng, W., Choi, H. G., Zgair, A., Shin, S., …Shin, B. S. (2019). Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach. Pharmaceutical Sciences, 108(2), 1047-1052. https://doi.org/10.1016/j.xphs.2018.09.025

• Journal Article Type: Article
• Acceptance Date: Sep 10, 2018
• Online Publication Date: Sep 28, 2018
• Publication Date: Feb 1, 2019
• Deposit Date: Sep 12, 2018
• Publicly Available Date: Sep 12, 2018
• Journal: Pharmaceutical Sciences
• Print ISSN: 1735-403X
• Electronic ISSN: 2383-2886
• Publisher: Tabriz University of Medical Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 108
• Issue: 2
• Pages: 1047-1052
• DOI: https://doi.org/10.1016/j.xphs.2018.09.025
• Public URL: https://nottingham-repository.worktribe.com/output/1071349
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0022354918305537?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined InVitro Lipolysis/Microsomal Metabolism Approach; Journal Title: Journal of Pharmaceutical Sciences; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.xphs.2018.09.025; Content Type: article; Copyright: © 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.
• Contract Date: Sep 12, 2018