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羟丙基-β-环糊精对环丙沙星用于眼部给药的溶解度、稳定性及体外释放的影响

Effect of hydroxypropyl-beta-cyclodextrin on the solubility, stability and in-vitro release of ciprofloxacin for ocular drug delivery.

作者信息

Bozkir Asuman, Denli Zeynep Fusun, Basaran Berrin

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, 06100 Tandogan, Ankara, Turkey.

出版信息

Acta Pol Pharm. 2012 Jul-Aug;69(4):719-24.

Abstract

Eye drops in the form of an aqueous solution with a lower viscosity are preferred for local administrations in ophthalmology. In ophthalmic formulations, cyclodextrins (CDs) are frequently used in recent years in order to increase water solubility, stability and bioavailability of an active substance and decrease an irritation to the eye. The scope of the present study was to investigate the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the solubility, stability and in vitro release of ciprofloxacin (CIP). According to the phase solubility studies, A(L) type solubility curve was obtained. HPCD improved the solubility of CIP 3 times at pH 5.5 and 2 times at pH 7.4. The two month stability studies indicated that CIP was more stable at pH 5.5 than at pH 7.4 and the stability of CIP was significantly increased by HPCD. The stability constant of the HPCD:CIP complex was increased further by a-ddition of 0.1% (w/v) polymer (HPMC and PVP) to the aqueous medium including HPCD. Stability constant of solutions prepared in an ultrasonic water bath was higher than solutions prepared by heating in an autoclave. The results indicated that the CIP:HPCD complex increased in vitro release of CIP and the addition of polymer promoted this increase even more.

摘要

粘度较低的水溶液形式的眼药水更适合眼科局部给药。在眼科制剂中,近年来经常使用环糊精(CDs)来提高活性物质的水溶性、稳定性和生物利用度,并减少对眼睛的刺激。本研究的范围是研究羟丙基-β-环糊精(HPCD)对环丙沙星(CIP)的溶解度、稳定性和体外释放的影响。根据相溶解度研究,获得了A(L)型溶解度曲线。HPCD在pH 5.5时将CIP的溶解度提高了3倍,在pH 7.4时提高了2倍。为期两个月的稳定性研究表明,CIP在pH 5.5时比在pH 7.4时更稳定,并且HPCD显著提高了CIP的稳定性。通过向包含HPCD的水性介质中添加0.1%(w/v)的聚合物(HPMC和PVP),HPCD:CIP复合物的稳定性常数进一步提高。在超声水浴中制备的溶液的稳定性常数高于在高压釜中加热制备的溶液。结果表明,CIP:HPCD复合物增加了CIP的体外释放,并且聚合物的添加进一步促进了这种增加。

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