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  • Design of New Parenteral Aqueous Formulations of Fluconazole by the Use of Modified Cyclodextrins
저자명
이소윤,전인구
간행물명
약학회지
권/호정보
2001년|45권 4호|pp.357-365 (9 pages)
발행정보
대한약학회
파일정보
정기간행물|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

The purpose of this study is to investigate the influence of cyclodextrins (CDs) and different acids on the solubility of fluconazole, and o formulate its more concentrated parenteral aqueous solution. Solubility studies of fluconazole with 7-CD, 2-hydroxypropyl-$eta$-CD (HPCD), sulfobutyl ether $eta$-CD (SBCD) and dimethyl-$eta$-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 $eta$-CD<SBCD<HPCD<DMCD. HPCD and SBCD were chosen as solubilizers owing to their high solubilizing property and their low systemic toxicity. $^1$H-NMR studies confirmed 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 4$^{circ}C$ and was very stable at elevated temperatures. These results demonstrate that it is possible to develop a parenteral aqueous solution of fluconazole with a smaller injection volume using HPCD or SBCD.