FORMULASI DAN UJI TRANSPOR SECARA IN VITRO MIKROEMULSI TRANSDERMAL KETOPROFEN MENGGUNAKAN VIRGIN COCONUT OIL SEBAGAI FASE MINYAK

INDRI MAHARINI, Dr. Akhmad Kharis Nugroho, M.Si., Apt.

2013 | Tesis | S2 Ilmu Farmasi

Mikroemulsi telah banyak dipelajari untuk meningkatkan bioavailabilitas obat yang sukar larut. Tujuan dari penelitian ini adalah : 1) formulasi mikroemulsi transdermal ketoprofen yang stabil dan 2) mengevaluasi kemampuan mikroemulsi dalam mencapai konsentrasi efektif ketoprofen . Komposisi mikroemulsi terdiri dari Virgin Coconut Oil (VCO) sebagai fase minyak, akuades, tween 80/propilen glikol (3:1) sebagai surfaktan dan kosurfaktan yang diformulasi dan dioptimalkan menggunakan Simplex Lattice Design. Formulasi mikroemulsi menggunakan water titration method. Evaluasi karakteristik fisik meliputi viskositas, stabilitas fisik, keseragaman kandungan zat aktif, dan difusi ketoprofen. Penilaian stabilitas fisik ditentukan dengan pengamatan fraksi pemisahan mikroemulsi selama 45 hari. Pada penelitian ini dilakukan juga uji stabilitas dipercepat (yaitu uji sentrifugasi dan uji freeze-thaw) dan uji turbiditas. Membran selofan digunakan sebagai pembatas antara kompartemen donor dan kompartemen akseptor. Jumlah obat yang terdifusi dari mikroemulsi ditentukan selama 4,5 jam. Pengamatan ukuran partikel formula optimum menggunakan transmission electron microscopy. Uji Permeasi ketoprofen formula optimum menggunakan sel difusi vertikal selama 10 jam . Komposisi formula optimum yang terdiri dari VCO 3 % , air 54,5% , dan 10 % tween 80/propilen glikol (3:1) dengan konsentrasi ketoprofen 2,5 % b/b. Karakteristik mikroemulsi yang dihasilkan yaitu : 1) warna kuning jernih dengan bau spesifik, 2) nilai pH sekitar 4, 3) tipe sediaan mikroemulsi minyak dalam air. Tidak ada pemisahan fase pada pengamatan selama 45 hari, uji sentrifugasi dan uji freeze thaw. Hasil uji Viskositas, persen turbiditas, ukuran partikel, dan difusi obat masing-masing adalah 119,3 cps, 0,02 %, 34-61 nm dan 1 ± 0,14 %. Nilai prediksi rata-rata konsentrasi plasma yang diperoleh adalah 6,3 ng/mL. Hal ini menunjukkan formulasi yang diperoleh mampu mencapai konsentrasi efektif ketoprofen.

Microemulsions have been widely studied to enhance the bioavailability of the poorly soluble water drug. The aims of this study were: 1) to prepare stable ketoprofen microemulsion for transdermal therapy and 2) to evaluate the feasibility of microemulsion to reach effective concentration of ketoprofen. Microemulsion composed of Virgin Coconut Oil (VCO) as oil phase, water, tween 80/propilen glikol (3:1) as surfactant and co-surfactant were formulated and optimized using Simplex Lattice Design. The formulations were prepared by water titration method. The physical characteristics, i.e. viscosity, physical stability, drug content uniformity, and the diffusion of ketoprofen were evaluated. The physical stability assessment was determined by observation of the separation fraction of microemulsions in 45 days. The accelerated stability tests (i.e. centrifugation test and freeze-thaw study) and turbidity test were also carried out in this study. The cellophane membrane was used in diffusion studies as a separator between donor and acceptor compartments. The amount of the diffused drug from microemulsions was determined within 4.5 hours. The particle size measurement was carried out on optimum formula using transmission electron microscopy. Transdermal permeation of ketoprofen was evaluated with the optimum formula using vertical diffusion cells for 10 hours. The optimum formula composed of 3% VCO, 54.5% water, and 10% tween 80/propilen glikol (3:1) were selected to be loaded with 2.5 % w/w of ketoprofen. The characteristics of microemulsion were: 1) clear yellow microemulsion with specific odor, 2) pH values of about 4, 3) oil in water microemulsion type. There was no separation phase during of 45 days, centrifugation test and freeze thaw study. The viscosity, % turbidity, particle size, and diffusion of drug were 119.3 cps, 0.02%, 34-61 nm, and 1 ± 0.14%, respectively. Average predictive value of plasma concentrations obtained was 6.3 ng/mL. Indicating the feasibility of the formulation to reach effective concentration therapy.

Kata Kunci : ketoprofen, mikroemulsi, VCO, tween 80, propilen glikol, Simplex Lattice Design.