PENGARUH PROPILEN GLIKOL, ASAM OLEAT DAN ISOPROPIL ALKOHOL PADA SIFAT FISIKOKIMIA DAN TRANSPOR IN VITRO FORMULA PATCH TRANSDERMAL KALIUM LOSARTAN DENGAN POLIMER HIDROKSIPROPIL METIL SELULOSA DAN EUDRAGIT RL100

Nuryanti, Dr. Akmad Kharis Nugroho, M.Si., Apt

2012 | Tesis | S2 Ilmu Farmasi

Losartan merupakan suatu antihipertensi yang poten yang memiliki level bioavailabilitas rendah dan waktu paruh eliminasi yang cepat. Tujuan penelitian ini adalah untuk mengetahui pengaruh propilen glikol, asam oleat dan isopropil alkohol dalam formula patch transdermal kalium losartan dengan polimer hidroksipropil metil selulosa dan Eudragit RL100 terhadap karakteristik fisikokimia patch. Selain itu pada penelitian ini juga ingin diketahui permeasi losartan melalui membran kulit tikus. Rancangan formula berdasarkan simplex lattice design menggunakan software Design Expert versi 7. Evaluasi karakteristik meliputi visual, ketebalan, bobot, daya serap kelembaban, susut pengeringan, ketahanan terhadap pelipatan dan kandungan obat dalam sediaan patch transdermal. Uji transport losartan secara in vitro melalui membran kulit tikus menggunakan sel difusi vertikal yang dimodifikasi. Penetapan kadar transpor losartan menggunakan instrumen HPLC dan dianalisis menggunakan software WinSAAM versi 3.0.7. Proporsi formula optimum yaitu propilen glikol 44,4%, asam oleat 29,3%, dan isopropil alkohol 26,3% dengan karakteristik tebal 0,6 mm, bobot 82,2 mg, susut pengeringan 12,8%, daya serap kelembaban 6,4%, ketahanan terhadap pelipatan lebih dari 300 lipatan dan kandungan obat dalam sediaan patch transdermal 98,9%. Transpor in vitro losartan menghasilkan model lima kompartemen dengan kinetika orde pertama.

Losartan is one of the potent antihypertension which has low oral bioavailability level and short elimination half-life. This research was aimed to determine the effect of propylene glycol, oleic acid and isopropyl alcohol in the formula losartan potassium transdermal patch with hydroxypropyl methyl cellulose and Eudragit RL100 polimers, to the physicochemical characteristics of the patch. In addition, this study also wanted to know the permeation losartan via rat skin membrane. Design of the level formulation was based on simplex lattice design method using Design Expert version 7. The evaluations included visual appearance patch, weight and thickness, moisture uptake, loss on drying, folding endurance and drug content. In vitro transport studies of losartan via rat skin membrane was evaluated in a modified vertical diffusion cells system. The assay of losartan was performed using HPLC method. Transport data were then analyzed by WinSAAM 3.0.7. Optimum formula consisted of 44.4% of propylene glycol, 29.3% of oleic acid, and 26.3% of isopropyl alcohol with the thickness of 0.6 mm, weighs of 82.2 mg, loss on drying at 12.8%, moisture uptake at 6,4%, more than 300 of folding endurance and, 98.9% of drug contents . The in vitro transport of losartan data could be adequately described by a five-compartment model with first-order mass transfer kinetics.

Kata Kunci : propilen glikol, asam oleat, isopropil alkohol, kalium losartan, patch transdermal