PENGARUH KADAR ASAM OLEAT, ISOPROPIL ALKOHOL, DAN PROPILEN GLIKOL TERHADAP KARAKTERISTIK FISIKOKIMIA PATCH KALIUM LOSARTAN DENGAN POLIMER MATRIKS HYDROXYPROPYL METHYLCELLULOSE DAN POLYVYNIL ALCOHOL BESERTA PROFIL TRANSPOR TRANSDERMAL IN VITRO

RINA WIDIASTUTI, Dr. Akhmad Kharis Nugroho, M.Si., Apt

2012 | Tesis | S2 Ilmu Farmasi

Losartan merupakan antagonis reseptor angiotensin II yang poten, namun memiliki bioavailabilitas yang rendah (33%). Senyawa ini mengalami metabolisme lintas pertama di hati. Oleh karena itu, sistem penghantaran transdermal menjadi salah satu upaya alternatif untuk meningkatkan bioavailabilitas obat. Tujuan dilakukan penelitian ini adalah untuk mengetahui pengaruh asam oleat, isopropil alkohol, dan propilen glikol terhadap karakteristik fisikokimia patch dengan polimer matriks HPMC dan PVA serta profil transpor transdermal in vitro. Asam oleat, isopropil alkohol, dan propilen glikol sebagai enhancer ditentukan komposisinya dengan pendekatan simplex lattice design. Pada patch masing-masing formula dilakukan pengujian karakteristik fisikokimia meliputi ketebalan, bobot, susut pengeringan (LOD), daya serap kelembaban (moisture uptake), folding endurance, drug content, serta evaluasi kesan visual patch. Pengujian transpor transdermal in vitro menggunakan sel difusi tipe vertikal yang dimodifikasi. Kadar losartan hasil transpor ditetapkan dengan metode HPLC. Selanjutnya digunakan bantuan software WinSAAM untuk memperoleh informasi profil dan prediksi parameter transpor losartan. Hasil penelitian menunjukkan patch kalium losartan dapat dibuat dengan kombinasi asam oleat, isopropil alkohol, dan propilen glikol dalam polimer matriks HPMC dan PVA dan ketiga enhancer mempunyai pengaruh terhadap karakteristik fisikokimia sediaan. Patch kalium losartan formula optimum yang diperoleh dengan proporsi asam oleat 2,3%, isopropil alkohol 4,2%, dan propilen glikol 9,5% memberikan karakteristik ketebalan (0,628 ± 0,00) mm, bobot patch (131,37 ± 0,84) mg, loss on drying (16,8 ± 1,31)%, moisture uptake (10,91 ± 0,41)%, drug content (100,0 ± 0,78)%, dan folding endurance > 300 lipatan. Patch kalium losartan mampu memberikan transpor transdermal in vitro dengan model 4 kompartemen mengikuti kinetika orde pertama. Prediksi kadar obat dalam plasma maksimum sebesar 0,6 ng/mL untuk luas area patch 2,01 cm2.

Losartan, one of the potent angiotensin II receptor antagonist has a low bioavailability (33%) due to intensive metabolism in the liver. Therefore, the transdermal delivery system could be one alternative efforts to improve the bioavailability of the drug. The aimed of this study was to determine the effect of oleic acid, isopropyl alcohol, and propylene glycol on the physicochemical characteristics of the patch with hydroxypropyl methylcellulose (HPMC) and polyvynil alcohol (PVA) polymer matrix as well as to characterize the profile of transdermal transport in vitro. Oleic acid, isopropyl alcohol, propylene glycol and its composition is determined by the simplex lattice design approach. Physicochemical characteristics including thickness, weight, loss on drying, moisture uptake, folding endurance, drug content, as well as the evaluation of the visual impression of the patch were evaluated. Transdermal transport was`evaluated in vitro using vertical diffusion cell. Concentrations of losartan transport were determined using HPLC method. WinSAAM software was used to analyze the transport data based on compartemental method. The results showed a combination of oleic acid, isopropyl alcohol, and propylene glycol in the matrix polymer of HPMC and PVA can be made adequate patch and enhancers have an influence on the physicochemical characteristics of losartan kalium patch. Optimum condition of patches had 2.3% of oleic acid, 4.2% isopropyl alcohol, and 9.5% of propylene glycol with the characteristic thickness (0.628 ± 0.00) mm, weights patch (131.37 ± 0.84) mg, loss on drying (16,8 ± 1.31)%, moisture uptake (10.91 ± 0.41)%, drug content (100.0 ± 0.78)%, and folding endurance > 300. Transport of losartan was adequately described by a four-compartement model. Losartan have transported at the 11th hours since the patch was applied. Predicted plasma drug could reach a level of 0.6 ng / mL when a 2.01 cm2 patch was used after 56 hours.

Kata Kunci : losartan, patch, transdermal, enhancer