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格列本脲与羟丙基-β-环糊精和其他增溶剂的三元配合物的形成及其对不同搅拌速度下格列本脲在水相和缓冲介质中释放行为的影响。

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds.

机构信息

Department of Pharmacy, Karpagam University, Coimbatore, Tamilnadu, India.

出版信息

Drug Dev Ind Pharm. 2012 Nov;38(11):1328-36. doi: 10.3109/03639045.2011.650645. Epub 2012 Jan 28.

Abstract

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and L-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:L-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50 rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.

摘要

格列吡嗪,磺酰脲类衍生物,广泛用作降血糖药。本研究试图寻找最有效的第三种成分,与羟丙基-β-环糊精(HPβCd)形成三元复合物,以提高其溶解速率,并减少用于与格列吡嗪形成二元复合物的 HPβCd 的用量。此外,本研究的目的还在于开发一种有区别的溶解介质,以区分用于形成三元复合物系统的不同增溶剂的效果。十二烷基硫酸钠、泊洛沙姆 188、聚乙烯吡咯烷酮 K-30、乳糖和精氨酸与 HPβCd 和格列吡嗪一起用于配制三元体系。与其他增溶剂相比,以 1:1:0.5 的比例配制的格列吡嗪:HPβCd:精氨酸三元体系显示出最快的溶解速率。在搅拌速度为 50rpm 的无缓冲水性介质中产生了最具区别性的溶解曲线。DSC 热图谱和粉末 X 射线分析显示药物的结晶度降低。这表明药物形成无定形固体分散体或分子包封到环糊精腔中。

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