목적: 복합 이상지혈증을 치료하는 현행 임상 지침에서는 페노피브레이트와 스타틴의 복합 치료법을 적극적으로 권장하고 있다. 본 연구에서는 페노피브레이트의 약동학적 프로파일을 변경함으로써 이 복합요법의 동시 투여로 발생할 수 있는 근육 독성 위험을 줄이고, 변경된 방출 포뮬레이션에서 경구 투여 시 생체 이용률을 개선하기 위하여 페노피브레이트의 혁기적인 지연 방출 제제 포뮬레이션을 만들었다.
방법: 다분자 펠릿 코팅을 하기 전, 분말 층화 과정을 통해 약물 적재 코어를 준비하기 위하여 페노피브레이트를 미립자화 시켰다. 연구진은 다양한 코팅 포뮬레이션을 검토하였고, 시험관 내(in vitro) 방출 프로파일은 상업용 지속 방출 제제 펠릿 Lipilfen(리필펜)과 비교하였다. 그중 가장 최적화된 두 가지 포뮬레이션을 비글을 대상으로 평가하였고, 페노피브레이트 레퍼런스 시판 제제인 즉시 방출 제제인 Lipanthyl®과 지속 방출 펠릿인 Lipilfen®을 비교하였다.
결과: 시험관 내 시험에서 선택한 R1 및 R2의 체내 페노피브레이트 방출은 유도기를 보인 후 신속하고 완전한 약물 방출을 나타냈다. R1과 R2의 상대 생체 이용률은 Lipilfen® (67.2%)보다 높은 100.4%와 201.1%로 각각 나타났다.
결론: 변경된 페노피브레이트는 향상된 생체 이용률과 지연 방출 제제의 특성을 보였으며, 스타틴과 함께 복합 투여될 때 안전성과 순응도를 잠재적으로 개선할 수 있다. 이는 우리가 아는 바로는, 페노피브레이트에 대한 지연 방출 제제에 대한 최초의 연구 결과이다.
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.
Purpose: According to current guidelines.combination therapy of fenofibrate and statins is highly recommended for treating mixed dyslipidemia. In this study, we formulated an innovative delayed-release preparation of fenofibrate to reduce the risk of muscle toxicity, by altering the pharmacokinetic profile of fenofibrate and to improve the oral bioavailability of the modified-release formulation.
Methods: Fenofibrate was micronized and used to prepare drug-loaded cores via a powder-layering process before performing multiparticulate pellet coating. Different coating formulations were screened, and their in vitro release profiles were compared with those of the commercial sustained-release pellets Lipilfen®. Two optimized formulations were evaluated in Beagle dogs models and compared with two reference commercial preparations of fenofibrate, Lipanthyl®(the immediate-release preparation) and Lipilfen®(the sustained- release pellets) .
Results: The in vivo release of fenofibrate from R1 and R2 (selected from in vitro tests) exhibited a lag phase, which was followed by rapid and complete drug release. The relative bioavailabilities of R1 and R2 were 100.4% and 201.1%, respectively, which werehigher than that of Lipilfen® (67.2%).
Conclusion: Modified fenofibrate pellets showed enhanced bioavailability and delayed-release propertiesand can improve safety and compliance when co-administered with statins. To the best of our knowledge, this is the first report of a delayed-release preparation of fenofibrate.
