시플로덱으트린류를 이용한 새로운 플루코나졸 수성 주사제의 설계

Design of New Ptrenteral Aqueous Formulations of Fluconazole by the Use of Modified Cyclodextrins

The purpose of this study is to investigate the inf1uence of cyclodextrins (CDs): and different acids on the solubility of fluconazole, and to formulate its more concentrated parenteral aqueous solution. Solubility studies of fluconazole with β- CD, 2-hydroxypropyl-β-CD (HPCD), sulfobutyl ether β-CD (SBCD) and dimethyl-β-CD (DMCD) were performed. The aqueous solubility of fluconazole was measured in different concentrations of different acids with or without addition of CDs. Solubility of fluconazole increased in the rank order of β-CD 1H-NMR studies confined the formation of an inclusion complex of fluconazole with HPCD. It was also shown by the NMR studies that the complex formed was a 1:1 complex. Among the different acids used, maleic acid and phosphoric acid increased solubility of fluconazole. The lower the pH of solution is, the more fluconazole dissolved, regardless of acids. Addition of HPCD (50 mM) to acid solutions increased the solubility about two times. New fluconazole injections at a dose of 10 mg/ml could be prepared in aqueous solutions containing 10% HPCD or 15% SBCD. These parenteral solutions did not form any precipitates at 4oC and was very stable at elevated temperatures. These results demonstrate that it is possible to develop a parenteral aqueous solution of fluconaEole with a smaller injection volume using HPCD or SBCD.