Abstrak

Losartan, senyawa antagonis reseptor angiotensin II, mempunyai bioavailabilitas oral 0.25-0.35.  Bioavailabilitas yang rendah ini dapat diatasi dengan penghantaran obat secara transdermal. Enhancer sering ditambahkan ke dalam formula sediaan transdermal, misalnya propilen glikol (PG).  Penelitian ini bertujuan mempelajari pengaruh kadar propilen glikol terhadap permeasi transdermal losartan pada kadar obat yang berbeda. Penelitian dilakukan secara in vitro dengan sel difusi tipe vertikal dilakukan terhadap empat formula yaitu 2% potasium losartan (k-los) :15% PG (F1), 10% k-los :15% PG (F2), 2% k-los :20% PG (F3), dan 10% k-los: 20% PG (F4) dengan dapar sitrat pH 5 sebagai mediumnya.  Kulit punggung tikus jantan galur wistar digunakan sebagai membran, PBS pH 7,4 sebagai medium kompartemen reseptor, dan HPLC untuk pengukuran kadar k-los dalam kompartemen reseptor dengan detektor UV. Hasil penelitian menunjukkan bahwa peningkatan kadar k-los dari 2% ke 10% pada kadar PG 15% meningkatkan fluks, sedangkan pada kadar 20% tidak berpengaruh terhadap fluks.  Peningkatan kadar PG dari 15% ke 20% justru menurunkan fluks pada kadar k-los 2%, dan tidak berpengaruh pada kadar k-los 10%.  Nilai lag time tidak berbeda diantara semua fomula. Hal ini berarti penggunaan enhancer PG lebih dari 15% justru merugikan permeasi transdermal.

Kata Kunci : transdermal, losartan, propilen glikol, enhancer

Abstract

Losartan is an angiotensin receptor antagonis which has low oral bioavailability (0.25-0.35).  Transdermal drug delivery system is needed as one solution for this low oral bioavailability drug.  Propilen glikol (PG), as enhancer, is frequently added in transdermal dosage form.  This research was purposed to explore the effect of PG as losartan permeation enhancer in various concentration of potasium losartan (k-los). The research was carried out in vitro using vertical tipe difusion cel for 4 formulas, i.e. 2% potasium losartan (k-los) :15% PG (F1), 10% k-los :15% PG (F2), 2% k-los :20% PG (F3), and 10% k-los: 20% PG (F4) using citric buffer pH 5 as donor medium, while PBS pH 7,4 was used as receptor medium.  The dorsal skin of white wistar male rat was used as membrane.  HPLC with UV detector was used to determine the concentration of k-los appear in receptor compartment. The results show that increasing of k-los concentration from 2% to 10% can increase the flux if PG concentration is 20%, but it does not have any significant effect to the flux if the PG concentration is 15%.  Increasing PG concentration from 15% to 20% decrease the flux permeation in k-los concentration of 2%, and does not have any significant effect in concentration of k-los of 10%.  The lag time permeation does not has any significant differencess.  It means that PG as enhancer in the concentration above 15% doesn’t have any adventages.

Keywords : transdermal, losartan, propilen glycol, enhancer