PEMBENTUKAN DAN KARAKTERISASI KOMPLEKS INKLUSI FENILBUTAZON DAN Î’-SIKLODEKSTRIN DENGAN METODA CO-GRINDING

Rini Agustin; Fathya Intan Lestari; Auzal Halim

doi:10.26874/kjif.v3i1.92

Penulis

Rini Agustin Universitas Andalas Padang
Fathya Intan Lestari Universitas Andalas Padang
Auzal Halim Universitas Andalas Padang

DOI:

https://doi.org/10.26874/kjif.v3i1.92

Abstrak

ABSTRAK

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FenilbutazonÂ 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 Î²-siklodekstrin. Pembuatan kompleks inklusi dilakukan denganÂ 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) Â memperlihatkan adanya interaksi antara fenilbutazon dan Î²-siklodekstrin dan terbentuk komplek inklusi fenilbutazon-Î²-siklodekstrin. Hasil difraksi sinar-x menunjukkan bahwa pembentukan komplek inklusi fenilbutazon-Î²-siklodekstrin menurunkan derjat kristalinitas obat. Uji disolusi secara in vitroÂ menunjukkan terjadinya peningkatan laju disolusi komplek inklsi dibandingkan dengan fenilbutazon murni.

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Kata kunci : Fenilbutazon, Î²-siklodekstrin, Co-grinding, danÂ kompleks inklusi.

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ABSTRACT

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Phenylbutazone is a Non-Steroid Anti-Inflammatory drugs (NSAID and classified Â 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 Î²-cyclodextrin, and inclusion complexes was formed. The results of x-ray diffraction showed that inclusion complex of Î²-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.

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Key wordsÂ Â : Phenylbutazone, Î²- cyclodextrin, Co-grinding, and inclusion complex

Referensi

Anonim., 2003. United states pharmacopoeia XXVI (revision). Rockville : United State Pharmacopoeia Conventing Inc.

Bazegar-Jalali, M., Valizadeh, H., Adibkia, K., 2007, Enhancing Dissolution Rate of Carbamazepine via Cogrinding with crosspovidone and Hydroxypropylmethylcellulose, Iranian Journal of Pharmaceutical Research, 6(3), 159-165.

Bekers, O., Uijtendaal, E.V., Beijnen, J.H., Bult, A., and Undenberg, W.J.M.,(1991), Cyclodextrin in Pharmaceutical Field, Drug Dev. Ind. Pharm, 17 (11), 1503 â€“1549.

Depkes RI., 1995. Farmakope Indonesia Edisi IV. Departemen Kesehatan RI. Jakarta.

Friedrich, H., Nada, A., dan Bodmeir, R., (2005), Solid State and Dissolution Rate characterization of co-ground mixture of Nifedipine and hydrophilic Carriers, Drug Development Industrial Pharmacy, 31, 719-728.

Garg, A, dan Singh, S., (2009), Solid State Interaction of Raloxifene HCL with Diffeent Hydrophilic Carriers During Co-grinding and its Effect on Dissolution Rate, Drug Development Industrial Pharmacy, 35, 455-470.

Loftsson T, Brewster ME. (1996). Pharmaceutical applications of b- siklodekstrin I, drug solubilization and stabilization. J Pharm Sci, 85(10), 1017- 1024.

Neha, Preeti, C., Atin, K., Rajan, P., Kumar, M. R., Santanu, M., Pardeep, K., Munsab, A., & Shamim, A. (2012). Approaches to improve the solubility and bioavailability of poorly soluble drugs and different parameter to screen them, Novel Science International Journal of Pharmaceutical Science, 1(4), 171-182.

Silverstein, R.M., Bassler, G.C., Morrill, T.C., (1981). Spectrometric Identification of Organic Compounds, 4th ed., New York: John Wiley & Sons, hal. 108-120, 166-170.

Vogt M, Kunath K, Dressman JB. (2008). Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug in dogs. Eur J Pharm Biopharm, 68, 338â€“45.

Zaini E, Agnesia S W, Rini A. Enhancement of Dissolution Rate of Meloxicam by co-grinding Technique Using Hydroxypropylmethylcellulose, Journal of Chem. And Pharm. Res, 2014 6 (11) : 263-2.