Ammar H O, Salama H A, Ghorab M, Mahmoud A A
Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt.
Int J Pharm. 2006 Aug 31;320(1-2):53-7. doi: 10.1016/j.ijpharm.2006.04.002. Epub 2006 Apr 18.
The effect of complexation of glimepiride, a poorly water-soluble antidiabetic drug, with beta-cyclodextrin and its derivatives (HP-beta-CyD and SBE-beta-CyD) in presence of different concentrations of water-soluble polymers (HPMC, PVP, PEG 4000 and PEG 6000) on the dissolution rate of the drug has been investigated. The results revealed that the dissolution rate of the drug from these ternary systems is highly dependent on polymer type and concentration. The dissolution rate of the drug from ternary systems containing PEG 4000 or PEG 6000 seems to be generally higher than from systems containing HPMC or PVP. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% for PEG 4000 or PEG 6000 and at 20% concentration of HPMC or PVP. The dissolution rate of the drug from the ternary system glimepiride-HP-beta-CyD-5% PEG 4000 was high compared to the other systems. Tablets containing the drug or its equivalent amount of this ternary system were prepared and subjected to accelerated stability testing at 40 degrees C/75% R.H. to investigate the effect of storage on the chemical stability as well as therapeutic efficacy of the tablets. The results revealed stability of the tablets and consistent therapeutic efficacy on storage.
研究了在不同浓度水溶性聚合物（羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚乙二醇4000和聚乙二醇6000）存在下，难溶性抗糖尿病药物格列美脲与β-环糊精及其衍生物（羟丙基-β-环糊精和磺丁基醚-β-环糊精）的络合对药物溶出速率的影响。结果表明，药物从这些三元体系中的溶出速率高度依赖于聚合物的类型和浓度。含有聚乙二醇4000或聚乙二醇6000的三元体系中药物的溶出速率似乎通常高于含有羟丙基甲基纤维素或聚乙烯吡咯烷酮的体系。当聚乙二醇4000或聚乙二醇6000的聚合物浓度为5%，羟丙基甲基纤维素或聚乙烯吡咯烷酮的浓度为20%时，观察到药物溶出速率有最佳增加。与其他体系相比，格列美脲-羟丙基-β-环糊精-5%聚乙二醇4000三元体系中药物的溶出速率较高。制备了含有该药物或其等量该三元体系的片剂，并在40℃/75%相对湿度下进行加速稳定性试验，以研究储存对片剂化学稳定性以及治疗效果的影响。结果表明片剂具有稳定性，储存时治疗效果一致。
