FORMULASI MATRIKS PATCH TRANSDERMAL DOMPERIDON SERTA UJI IN VITRO DAN IN VIVO

SEKAR AYU PAWESTRI, Prof. Dr. apt. Akhmad Kharis Nugroho, M.Si.; Dr. apt. Rr. Endang Lukitaningsih, M.Si.; Dr. apt. Purwantiningsih, M.Si.

2021 | Disertasi | DOKTOR ILMU FARMASI

Domperidon adalah antagonis dopamin dengan efek antiemetik yang memiliki bioavailabilitas oral hanya sekitar 15%. Terapi domperidon yang ditujukan pada pasien khususnya pasien anak berupa sediaan patch diharapkan dapat meningkatkan kenyamanan pasien. Penggunaan asam oleat dan isopropil alkohol sebagai enhancer dalam sediaan transdermal dilaporkan mampu meningkatkan permeasi obat. Penelitian ini bertujuan untuk mengoptimasi sediaan matriks patch transdermal domperidon serta mengevaluasi permeasi formula optimum matriks patch secara in vitro dan in vivo. Optimasi formula matriks patch domperidon dengan variasi konsentrasi asam oleat dan isopropil alkohol menggunakan metode simplex lattice design. Perangkat lunak WinsAAM version 3.3.0 digunakan untuk menganalisis mekanisme permeasi obat secara in vitro. Analisis dengan PK-Solver 2.0 digunakan untuk memperoleh parameter farmakokinetik secara in vivo pada hewan uji kelinci yang meliputi Tmaks, Cmaks, dan AUC. Formula optimum matriks patch domperidon diperoleh dengan komposisi asam oleat 0,87 % dan isopropil alkohol 12,17% dalam matriks patch. Permeasi formula optimum matriks patch domperidon secara in vitro mengikuti model empat kompartemen dengan satu kompartemen lag. Profil farmakokinetik formula optimum matriks patch domperidon memiliki nilai bioavailabilitas absolut 2,05 % pada hewan uji kelinci secara in vivo.

Domperidone is a dopamine antagonist with antiemetic effects that has an oral bioavailability of only about 15%. Domperidone therapy in patch dosage form for patients, especially pediatric patients, are expected to increase patient convenience. Oleic acid and isopropyl alcohol as enhancers in transdermal preparations have been reported to increase drug permeation. This study aims to optimize the preparation of the domperidone transdermal patch matrix and evaluate the permeation of optimum formula in vitro and in vivo. Optimization of the domperidone matrix patch formula with variations of the concentration of oleic acid and isopropyl alcohol was using the simplex lattice design method. The optimum formula composition for the domperidone matrix patch was tested for permeation in vitro and in vivo. WinsAAM version 3.3.0 software was used to analyze in vitro permeation. PK-Solver 2.0 was used to obtain in vivo pharmacokinetic parameters in rabbit, including Tmax, Cmax, and AUC. The optimum formula of the domperidone patch matrix obtained was a composition of 0,87% oleic acid and 12,17% isopropyl alcohol in the patch matrix. Permeation of optimum formula of domperidone patch matrix in vitro followed a four-compartment model with one lag compartment. The pharmacokinetic profile of the optimum formula of the domperidone patch matrix has an absolute bioavailability value of 2,05% in rabbits in vivo.

Kata Kunci : domperidon, matriks patch, transdermal, farmakokinetik