PENGARUH ASAM OLEAT, PROPILEN GLIKOL DAN ISOPROPIL ALKOHOL PADA FORMULA PATCH TRANSDERMAL KALIUM LOSARTAN DENGAN MATRIKS HIDROKSIPROPIL METILSELULOSA DAN ETIL SELULOSA
OKTAVIA INDRATI, Dr. Akhmad Nugroho, M.Si, Apt
2012 | Tesis | S2 Ilmu FarmasiPada suatu formula patch transdermal, banyak faktor yang dapat berpengaruh terhadap sifat fisikokimianya. Penelitian ini bertujuan untuk mengkaji pengaruh asam oleat, propilen glikol dan isopropil alkohol dalam formulasi patch transdermal kalium losartan dengan matriks hidroksipropil metilselulosa dan etil selulosa. Selain itu, pada penelitian ini juga ingin diketahui apakah konsentrasi plasma maksimum losartan dalam bentuk sediaan patch transdermal hasil prediksi dapat mencapai level konsentrasi terapetik. Komposisi menggunakan bantuan software Design Expert versi 7. Patch transdermal dibuat sebanyak 7 formula dengan metode pencetakan. Patch yang dibuat selanjutnya diuji sifat fisikokimanya yang meliputi kesan visual, pengukuran bobot, ketebalan, susut pengeringan, nilai moisture uptake, kandungan zat aktif serta ketahanan terhadap pelipatan. Formula terbaik dipilih berdasarkan hasil uji sifat fisikokimia patch transdermal. Patch formula terbaik kemudian diuji transpor zat aktifnya secara in vitro dengan alat sel difusi tipe vertikal menggunakan membran kulit tikus. Data hasil pengujian secara in vitro dianalisis menggunakan bantuan software WinSAAM versi 3.0.7. Hasil uji menunjukkan bahwa peningkatan jumlah asam oleat sebanding dengan peningkatan ketebalan, bobot dan kandungan obat dalam patch tetapi berbanding terbalik dengan susut pengeringan dan moisture uptake. Peningkatan jumlah propilen glikol sebanding peningkatan dengan ketebalan, bobot, susut pengeringan dan kandungan obat tetapi berbanding terbalik dengan moisture uptake. Peningkatan jumlah isopropil alkohol sebanding dengan bobot, moisture uptake dan kandungan obat tetapi berbanding terbalik dengan ketebalan dan susut pengeringan. Formula terbaik adalah yang mengandung asam oleat sebanyak 5,3% v/v, propilen glikol sebanyak 1,0% v/v dan isopropil alkohol sebanyak 7,8% v/v. Selain itu, konsentrasi plasma losartan in vivo hasil prediksi dalam bentuk sediaan patch transdermal masih jauh di bawah konsentrasi plasma pemberian secara oral dosis tunggal 40 mg pada manusia.
There are many factors that affect the physicochemical properties of the transdermal patch. This study aimed to assess the effects of oleic acid, propylene glycol and isopropyl alcohol on potassium losartan transdermal patch formulas with ethyl cellulose and hydroxypropyl methylcelullose as matrix. In addition, this study also wanted to know whether the prediction of the plasma concentrations of the losartan on a transdermal patch could reach or not the therapeutic concentration level in human. Proportions of oleic acid, propylene glycol and isopropyl alcohol on transdermal patches were determined by using software program of Design Expert 7. Transdermal patches were made by using moulding method and their physicochemical properties including the visual impression, weight, thickness, loss on drying, the moisture uptake, the drug content and folding endurance were evaluated. The best formula was determined based on its appropriate physicochemical properties. The in vitro permeation study of the patch was conducted by using a vertical type diffusion cell and the data obtained were analyzed by using software program of WinSAAM 3.0.7. The results showed that increasing the amount of oleic acid was proportional to the increasing of thickness, weight and drug content of the patch but inversely proportional to the increasing of loss on drying and moisture uptake. Increasing the amount of propylene glycol was also proportional to the increasing of thickness, weight, loss on drying and drug content but inversely proportional to the increasing of moisture uptake. Meanwhile, increasing the amount of isopropyl alcohol was proportional to the increasing of weight, moisture uptake and drug content but inversely proportional to the increasing of thickness and loss on drying. The best formula obtained consisted of 5.3% v/v oleic acid, 1.0% v/v propylene glycol and 7.8% v/v isopropyl alcohol. In addition, the predicted in vivo plasma concentration of the losartan transdermal patch was still far below the plasma concentration of oral delivery in human with the single dose of 40 mg.
Kata Kunci : kalium losartan, asam oleat, propilen glikol, isopropil alkohol, patch transdermal
