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采用固体分散技术提高别嘌醇的溶出度曲线

Enhancement of the dissolution profile of allopurinol by a solid dispersion technique.

作者信息

Samy A M, Marzouk M A, Ammar A A, Ahmed M K

机构信息

Department of Pharmaceutics, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

出版信息

Drug Discov Ther. 2010 Apr;4(2):77-84.

Abstract

The aim of the present study was to improve the solubility, and therefore the dissolution of poorly water-soluble allopurinol. Solid dispersions of allopurinol were prepared with different polymers or carriers such as polyvinylpyrrolidone (PVP K30 and PVP K90), polyethylene glycol (PEG 4000 and PEG 6000), urea and mannitol at two drug : carrier ratios (1:1) and (1:2). Different methods such as melting and solvent evaporation methods were used to improve dissolution characteristics and solubility of allopurinol. The solid dispersions were characterized using a differential scanning calorimeter (DSC) and X-ray diffraction (XRD) while the interactions which took place were identified with fourier transform infrared (FTIR) spectroscopy. Due to formation of hydrogen bonds between allopurinol and urea and mannitol, a transition of allopurinol from the crystalline to amorphous state was achieved. The DSC thermograms of the solid dispersions indicated the potential of heat induced interactions between allopurinol and the carriers used could influence dissolution rate of the drug. The dissolution amount (%) of pure allopurinol was 80% at 45 min. F5, F3, F6, F7, and F1 showed better dissolution percentages of 100, 93, 92.4, 90.6, and 89%, respectively, at 45 min.

摘要

本研究的目的是提高难溶性药物别嘌醇的溶解度,进而提高其溶出度。以不同的聚合物或载体,如聚乙烯吡咯烷酮(PVP K30和PVP K90)、聚乙二醇(PEG 4000和PEG 6000)、尿素和甘露醇,按两种药物与载体比例(1:1)和(1:2)制备别嘌醇固体分散体。采用不同方法如熔融法和溶剂蒸发法来改善别嘌醇的溶出特性和溶解度。使用差示扫描量热仪(DSC)和X射线衍射仪(XRD)对固体分散体进行表征,同时用傅里叶变换红外光谱(FTIR)确定发生的相互作用。由于别嘌醇与尿素和甘露醇之间形成了氢键,实现了别嘌醇从晶态到非晶态的转变。固体分散体的DSC热谱图表明,别嘌醇与所用载体之间热诱导相互作用的可能性可能会影响药物的溶出速率。纯别嘌醇在45分钟时的溶出量为80%。F5、F3、F6、F7和F1在45分钟时分别显示出更好的溶出百分比,分别为100%、93%、92.4%、90.6%和89%。

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