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尼美舒利改性刺梧桐树胶固体混合物:制备、表征及处方开发

Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and formulation development.

作者信息

Babu G V Murali Mohan, Kumar N Ravi, Himasankar K, Seshasayana A, Murthy K V Ramana

机构信息

Division of Industrial Pharmacy, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India.

出版信息

Drug Dev Ind Pharm. 2003 Sep;29(8):855-64. doi: 10.1081/ddc-120024181.

Abstract

Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization.

摘要

制备了尼美舒利(NS)与改性刺梧桐树胶(MGK)的固体混合物,以提高NS的溶出速率。通过共研磨法制备不同比例的固体混合物,研究药物-载体比例对NS溶出速率的影响。还通过物理混合、捏合和固体分散技术制备固体混合物,以研究制备方法的影响。进行差示扫描量热法(DSC)、X射线衍射(XRD)和平衡溶解度研究,以解释体外溶出速率研究的结果。结果清楚地表明,NS的溶出速率取决于固体混合物中MGK的浓度,最佳重量比为1:4(NS:MGK)。尽管通过不同方法制备的所有固体混合物中NS的溶出速率均显著提高,但固体分散体的溶出速率提高最大。基于它们对溶出效率的影响,方法的顺序为固体分散体>捏合>共研磨>物理混合>纯NS。制备了纯药物和固体混合物(1:4 w/w,NS:MGK)的片剂。尽管含固体分散体的片剂溶出试验结果最佳,但从实际角度来看,含共研磨混合物的片剂适合商业化。

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