OPTIMASI FORMULA MATRIKS TRANSDERMAL PENTAGAMAVUNON-0 DENGAN KOMBINASI POLIMER PVP K30 DAN HIDROKSIPROPIL METILSELULOSA MENGGUNAKAN SIMPLEX LATTICE DESIGN

Beti Pudyastuti, Dr. Akhmad Kharis Nugroho,M.Si., Apt.

2014 | Tesis | S2 Ilmu Farmasi

Sistem penghantaran pentagamavunon-0 (PGV-0) secara transdermal dapat menjadi alternatif untuk mengatasi metabolisme lintas pertama yang intensif pada rute peroral. Penelitian ini bertujuan untuk mengoptimasi formula matriks transdermal PGV-0 dengan kombinasi polimer PVP K30 dan HPMC serta mengetahui profil transpor transdermal PGV-0 secara in vitro pada formula matriks optimum. Komposisi PVP K30 dan HPMC dalam formula ditentukan dengan bantuan piranti lunak Design Expert 7.1.5. Kesan visual, bobot, ketebalan, moisture content, daya serap kelembaban, ketahanan pelipatan, kandungan zat aktif, dan dissolution efficiency dari pelepasan PGV-0 selama 6 jam dievaluasi sebagai respon untuk menentukan formula optimum matriks. Pengujian transpor transdermal secara in vitro dilakukan terhadap matriks formula optimum selama 24 jam menggunakan sel difusi tipe vertikal dan membran kulit tikus. Hasil penelitian menunjukkan kombinasi polimer PVP K30 dan HPMC berpengaruh signifikan terhadap respon nilai visual, persen moisture content, dan nilai DE360. Kombinasi 1,98% PVP K30 dan 4,52% HPMC sebagai formula optimum dapat menghasilkan matriks yang homogen dan lentur dengan moisture content sebesar 3,21%. Nilai DE360 formula optimum sebesar 9,11% mengindikasikan 101,93 μg PGV-0 dapat dilepaskan dari matriks selama 6 jam. Analisis profil pelepasan dengan WinSAAM versi 3.0.7 menunjukkan pelepasan PGV-0 mengikuti model 4 kompartemen dengan 2 kompartemen lag. Meskipun demikian, PGV-0 hasil transpor transdermal secara in vitro melewati membran kulit pada formula optimum matriks transdermal PGV-0 selama 24 jam tidak terdeteksi. Pengembangan lebih lanjut diperlukan untuk mengoptimalkan transpor transdermal PGV-0.

Transdermal delivery is one of the alternative delivery system to avoid the high intensity of first pass metabolism of pentagamavunon-0 (PGV-0) in peroral route. The purposes of this research were (1) to optimize the formula of PGV-0 transdermal matrix with a combination of PVP K30 and HPMC polymers; (2) to observe the in vitro transport profile of PGV-0 from optimum formula. The simplex lattice optimization approach of the transdermal matrix formulas was performed by using Design Expert 7.1.5 software. The visual appearance, weight, thickness, moisture content, moisture uptake, folding endurance, drug content, and dissolution efficiency of the release profil of PGV-0 from the matrices for 6 hours were evaluated as responses to determine optimum formula of matrix. Transdermal transport study was carried out on the optimum formula using vertical diffusion cells and full-thickness rat skin for 24 hours. The results showed that a combination of PVP K30 and HPMC polymers had a significant influence on the visual appearance, moisture content, and dissolution efficiency of PGV-0. Combination of 1,98% of PVP K30 and 4,52% of HPMC as the optimum formula could produce homogeneous and flexible matrix with moisture content of 3,21%. The dissolution efficiency was 9,11%, indicating that 101,93 μg of PGV-0 released from the optimum formula during 6 hours. Analysis of the release results by using WinSAAM 3.0.7 software shows that the optimum formula of matrix follows 4 compartments model with 2 lag compartments. The results of transdermal transport study showed that PGV-0 were not detected during 24 hours. It needs further development to optimize the transdermal transport of PGV-0.

Kata Kunci : Pentagamavunon-0, Matriks transdermal, PVP K30, HPMC