通过与β-环糊精络合改善呋塞米的溶解性能。

Improvement of dissolution properties of furosemide by complexation with beta-cyclodextrin.

作者信息

Ozdemir N, Ordu S

机构信息

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

出版信息

Drug Dev Ind Pharm. 1998 Jan;24(1):19-25. doi: 10.3109/03639049809082348.

Abstract

The purpose of this study was to increase the solubility of furosemide (FR) with inclusion compound of beta-cyclodextrin (beta-CD). The interaction between FR and beta-CD in solution was studied by the solubility method. The phase solubility studies reveal a Bs-type diagram with an inclusion complex of 1:1 molar ratio and a stability constant of 823.5 M(-1). The solid complexes of FR with beta-CD were prepared by using freeze-drying, kneading, and co-precipitation methods. In addition, the physical mixture was prepared for comparison. Inclusion complexation was confirmed by the results from the studies of x-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. The rates of release of the active material from the resulting complexes were determined from dissolution studies using the flow-through cell method. The dissolution rate of FR was significantly enhanced by inclusion of the beta-CD in the formulations. The rate of release of the active material was found to be dependent on the preparation method of the complexes, and the drug prepared by the kneading method was shown to have the fastest dissolution profile compared to the other methods used in this study.

摘要

本研究的目的是通过与β-环糊精(β-CD)形成包合物来提高呋塞米(FR)的溶解度。采用溶解度法研究了FR与β-CD在溶液中的相互作用。相溶解度研究揭示了一种Bs型相图,其包合物的摩尔比为1:1,稳定常数为823.5 M⁻¹。采用冷冻干燥法、捏合法和共沉淀法制备了FR与β-CD的固体复合物。此外,还制备了物理混合物用于比较。通过X射线衍射、差示扫描量热法和红外光谱研究结果证实了包合络合作用。使用流通池法通过溶出度研究测定了所得复合物中活性物质的释放速率。在制剂中加入β-CD可显著提高FR的溶出速率。发现活性物质的释放速率取决于复合物的制备方法,与本研究中使用的其他方法相比,捏合法制备的药物显示出最快的溶出曲线。

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