Kulkarni Madhur, Nagarsenker Mangal
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Mumbai-400 098, India.
Indian J Pharm Sci. 2008 Jul-Aug;70(4):466-71. doi: 10.4103/0250-474X.44595.
Rofecoxib, a practically insoluble cox-2 selective nonsteroidal antiinflammatory agent was subjected to improvement in solubility by preparing its binary mixtures with beta cyclodextrin using various methods such as physical mixing, co-grinding, kneading with aqueous methanol and co-evaporation from methanol-water mixture. Characterization of the resulting binary mixtures by differential scanning calorimetry and X-ray diffraction studies indicated partial amorphization of the drug in its binary mixtures. In vitro dissolution studies exhibited remarkable increase in rate and extent of dissolution of the drug from its complexes with beta -cyclodextrin. Pure rofecoxib as well as its co-ground binary mixture were formulated as aqueous gels for topical application. In vitro skin permeation of rofecoxib from formulation containing rofecoxib-cyclodextrin complex was significantly higher (p<0.05) at 1, 2, 12, 18 and 24 hr as compared to formulation containing pure rofecoxib. This could be attributed to better solubility of binary mixture in the aqueous gel vehicle leading to greater concentration gradient between the vehicle and skin and hence higher flux of the drug.
罗非昔布是一种几乎不溶的环氧化酶-2（COX-2）选择性非甾体抗炎药，通过与β-环糊精制备二元混合物来改善其溶解度，采用了多种方法，如物理混合、共研磨、用甲醇水溶液捏合以及从甲醇-水混合物中共蒸发。通过差示扫描量热法和X射线衍射研究对所得二元混合物进行表征，结果表明药物在其二元混合物中部分非晶化。体外溶出度研究显示，药物从其与β-环糊精的复合物中的溶出速率和溶出程度显著增加。将纯罗非昔布及其共研磨二元混合物制成用于局部应用的水性凝胶。与含有纯罗非昔布的制剂相比，含罗非昔布-环糊精复合物的制剂在1、2、12、18和24小时时罗非昔布的体外皮肤渗透显著更高（p<0.05）。这可能归因于二元混合物在水性凝胶载体中的更好溶解性，导致载体与皮肤之间更大的浓度梯度，从而使药物通量更高。
