PEMBENTUKAN DAN KARAKTERISASI KOMPLEKS INKLUSI FENILBUTAZON DAN Î’-SIKLODEKSTRIN DENGAN METODA CO-GRINDING
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ABSTRAK
Fenilbutazon merupakan obat Anti Inflamasi Non Steroid (NSAID) dan diklasifikasikan dalam kelas II dari biopharmaceutic classification systems (BSC) yang memiliki kelarutan rendah permeabilitas tinggi. Pembentukan kompleks inklusi merupakan salah satu metoda untuk meningkatkan kelarutan dan disolusi suatu zat dalam air. Penelitian ini bertujuan untuk meningkatkan kelarutan dan laju disolusi fenilbutazon dengan cara pembentukan kompleks inklusi fenilbutazon dengan β-siklodekstrin. Pembuatan kompleks inklusi dilakukan dengan metoda co-grinding dengan variasi rasio molar 1:1, 2:1 dan 1:2. Interaksi padatan komplek inklusi dan campuran fisik dikarakterisasi dengan difraksi sinar X serbuk, spektrofotometri inframerah, Scanning Microscopy electron (SEM) dan Differential Thermal Analyzer (DTA). Uji disolusi dilakukan dengan mengacu pada uji disolusi USP apparatus II. Hasil karakterisasi kompleks inklusi menggunakan spektrofotometri inframerah, Scanning Microscopy electron (SEM) dan Differential Thermal Analyzer (DTA) memperlihatkan adanya interaksi antara fenilbutazon dan β-siklodekstrin dan terbentuk komplek inklusi fenilbutazon-β-siklodekstrin. Hasil difraksi sinar-x menunjukkan bahwa pembentukan komplek inklusi fenilbutazon-β-siklodekstrin menurunkan derjat kristalinitas obat. Uji disolusi secara in vitro menunjukkan terjadinya peningkatan laju disolusi komplek inklsi dibandingkan dengan fenilbutazon murni.
Kata kunci : Fenilbutazon, β-siklodekstrin, Co-grinding, dan kompleks inklusi.
ABSTRACT
Phenylbutazone is a Non-Steroid Anti-Inflammatory drugs (NSAID and classified in class II of biopharmaceutic classification system (BSC) which has low solubility, high permeability. Formation of inclusion complexes is one method to increase the solubility and dissolution of a substance in the water. This study investigated improving of inclusion complex with B-cyclodextrin to solubility and dissolution rate of phenylbutazone. Inclusion complexes was made by co-grinding method in molar ratio 1: 1, 2: 1 and 1: 2. The solid state interaction inclusion complexes and physical mixture was evaluated by using X-raypowder diffraction, thermal DTA, and SEM. The dissolution studies were conducted in USP type II apparatus. The results characterization of inclusion complexes using infrared spectrophotometry, Scanning Electron Microscopy (SEM) and Differential Thermal Analyzer (DTA) showed that there was interaction between phenylbutazone and β-cyclodextrin, and inclusion complexes was formed. The results of x-ray diffraction showed that inclusion complex of β-cyclodextrin-phenylbutazon reduced the degrees of crystallinity of the drug. In vitro dissolution test showed inclusion complex in dissolution rate was higher than pure phenylbutazone.
Key words : Phenylbutazone, β- cyclodextrin, Co-grinding, and inclusion complex
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