OPTIMASI FORMULA MATRIKS TRANSDERMAL PENTAGAMAVUNON-0 DENGAN KOMBINASI POLIMER POLYVINYLPYROLLIDONE DAN POLIVINIL ALKOHOL MENGGUNAKAN SIMPLEX LATTICE DESIGN

Nirwati Rusli, Dr. Akhmad Kharis Nugroho,M.Si., Apt.

2014 | Tesis | S2 Ilmu Farmasi

Tingkat metabolisme lintas pertama yang tinggi menyebabkan penghantaran oral pentagamavunon-0 (PGV-0) tidak efektif sehingga penghantaran transdermal dalam bentuk sediaan matriks menjadi alternatif penghantaran PGV-0. Penelitian ini bertujuan untuk mengetahui pengaruh kombinasi polimer PVP dan PVA terhadap sifat fisikokimia dan laju pelepasan PGV-0 dari matriks serta mengetahui profil transpor transdermal PGV-0 melewati kulit secara in vitro pada formula optimum. Rancangan formula berdasarkan simplex lattice design menggunakan software Design Expert versi 7.1.5. Evaluasi fisikokimia matriks meliputi kesan visual, bobot, ketebalan, moisture content, moisture uptake, folding endurance dan kandungan obat dar matriks serta uji pelepasan PGV-0 dari matriks. Data jumlah kumulatif obat yang terlepas dari uji pelepasan formula optimum dianalisis menggunakan software WinSAAM. Uji transport PGV-0 secara in vitro melalui membran kulit tikus menggunakan sel difusi vertikal. Hasil penelitian memberikan informasi bahwa kombinasi polimer PVP dan PVA memberikan pengaruh positif terhadap sifat fisikokimia matriks dengan moisture uptake antara 0,56 hingga 4,02%, drug content 100,51 hingga 107,58%, jumlah persen PGV-0 terdisolusi berkisar antara 6,13 hingga 10,87%. Hasil pengujian jumlah obat yang terlepas terhadap formula optimum dengan komposisi PVP dan PVA (5,5:3) menunjukkan bahwa pelepasan PGV-0 dari matriks transdermal mengikuti model tiga kompartemen dengan kinetika orde pertama. Transpor PGV-0 menunjukkan bahwa formula optimum belum dapat menghantarkan obat melalui kulit secara in vitro

PGV-0 delivery in oral route is difficult due to the high intensity of first-pass metabolism. Delivery of PGV-0 in transdermal matrix formulation can be attractive. This research aimed to determine effect of combination PVP and PVA polymers on the was physicochemical properties and the release rate of PGV-0 matrix, and the in vitro transdermal transport profile of the optimum formula across the skin. The design of matrix formulation was based on simplex lattice design by using Design Expert software version 7.1.5. Physicochemical properties such as visual observasion, weight, thickness, moisture content, moisture uptake, folding endurance, drug content of the matrix, and release rate of PGV-0 from the matrix was evaluated. The cumulative amount of drug released from optimum formula release study were analyzed by using WinSAAM software. In vitro transdermal transport study of PGV-0 through rat skin membrane was performed using vertical diffusion cell. The results provided an information that a combination PVP and PVA polymers had a positive influence on physicochemical properties of the matrix with the moisture uptake between 0.56 to 4.02%, the drug content of 100,51 to 107.58%, and the percent amount of PGV-0 released ranged from 6.13 to 10.87%. The results of the amount of drug released from optimum formula with ratio composition of PVP and PVA (5,5:3) showed that release of PGV-0 from transdermal matrix described by a three-compartment models with first-order kinetic. The in vitro transport of PGV-0 indicated that optimum formula has not been able to deliver sufficient drugs across the skin.

Kata Kunci : Pentagamavunon-0, PVP, PVA, matriks transdermal