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Abstract
Purpose
Fenofibrate and statin combination therapy is highly recommended by the current clinical guidelines for treatment of mixed dyslipidemia. In this study, an innovative delayed-release preparation of fenofibrate was designed to reduce the risk of muscle toxicity, caused by simultaneous administration of this combination therapy, by altering the pharmacokinetic profile of fenofibrate, as well as to improve the oral bioavailability of the modified-release formulation.
Methods
Micronized fenofibrate was used to prepare drug-loaded cores via a powder layering process before multiparticulate pellet coating. Different coating formulations (Eudragit® RS PO/E100, Eudragit® RS PO/RL PO, Eudragit® NE30D/HPMC, and EC/HPMC) were screened, and their in vitro release was compared with the commercial sustained-release pellets Lipilfen®. Two optimized formulations were evaluated in beagle dogs using two commercial preparations of fenofibrate (the immediate-release preparation Lipanthyl® and the sustained-release pellets Lipilfen®) as references.
Results
The in vivo release of fenofibrate from R1 and R2 selected from in vitro tests exhibited a lag phase, and then rapid and complete drug release. The relative bioavailabilities of R1 and R2 were 100.4% and 201.1%, respectively, which were higher than that of Lipilfen® (67.2%).
Conclusion
The modified fenofibrate pellets developed showed enhanced bioavailability and delayed-release properties. They have the potential to improve safety and compliance when co-administrated with statins. This is the first report of a delayed-release fenofibrate preparation.
Acknowledgments
This work was supported by the National Key Technologies R&D Program of China during the 13th Five-Year Plan Period (grant No. 2016YFC1000902) and the Scientific Research Project of Shanghai Municipal Health and Family Planning Commission (grant number: 20144Y0049 and 201540357). The authors thank Sarah Dodds, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
Disclosure
The authors report no conflicts of interest in this work.