藥學研究－非諾貝特聯合他汀類藥物(Pharmaceutical Research)

Purpose: Fenofibrate and statin combination therapy is highly recommended by the current clinical guidelines for treatment of combined 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 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 greater than that of Lipilfen® (67.2%).

Conclusion: The modified fenofibrate pellets developed 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.

Purpose: Combination therapy of Ffenofibrate and statins combination therapy is highly recommended by the current clinical guidelines for the 1treatment of combinedmixed2 dyslipidemia. In this study, we formulated 3an innovative delayed-release preparation of fenofibrate was designed to achieve the following: 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 fFenofibrate was usedmicronized to prepare drug-loaded cores via a powder layering process before multiparticulate pellet coating. Different coating formulations were screened, and their in vitro release profiles was compared with the commercial sustained-release pellets Lipilfen®. Two optimized formulations were evaluated in Beagle dogs using and compared with 4two 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 thenfollowed by 5rapid and complete drug release. The relative bioavailabilities of R1 and R2 were 100.4% and 201.1%, respectively, which were greater 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-administratedadministered 6with statins. This is the first report of a delayed-release fenofibrate preparation.

Purpose: Combination1According to current guidelines.combination therapy of Ffenofibrate and statins combination therapy is highly recommended by the current clinical guidelines for the 2treatment oftreating combinedmixed3 dyslipidemia. In this study, we formulated 4an innovative delayed-release preparation of fenofibrate was designed to achieve the following: to reduce the risk of muscle toxicity, caused by simultaneous administration of this combination therapy, by altering the pharmacokinetic profile of fenofibrate, as well asand to improve the oral bioavailability of the modified-release formulation.

Methods: Micronized fFenofibrate was usedmicronized and used to prepare drug-loaded cores via a powder-5layering process before performing 6multiparticulate pellet coating. Different coating formulations were screened, and their in vitro release profiles waswere compared with those of the commercial sustained-release pellets Lipilfen®. Two optimized formulations were evaluated in Beagle dogs using7 models and compared with two reference commercial preparations of fenofibrate (, Lipanthyl®(the immediate-release preparation Lipanthyl®) and Lipilfen®(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 thenwhich was followed by 8rapid and complete drug release. The relative bioavailabilities of R1 and R2 were 100.4% and 201.1%, respectively, which were greater9were higher than that of Lipilfen® (67.2%).

Conclusion: The modifiedModified fenofibrate pellets developed showed enhanced bioavailability and delayed-release properties. They have the potential toproperties and can improve safety and compliance when co-administratedadministered10 with statins. This To the best of our knowledge, this is the first report of a delayed-release preparation of fenofibrate preparation11.