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介孔碳酸镁诱导难溶性药物的过饱和

Supersaturation of poorly soluble drugs induced by mesoporous magnesium carbonate.

作者信息

Zhang Peng, Zardán Gómez de la Torre Teresa, Welch Ken, Bergström Christel, Strømme Maria

机构信息

Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-751 21, Sweden.

Department of Pharmacy, Uppsala Biomedical Centre, Uppsala University, Uppsala SE-751 23, Sweden.

出版信息

Eur J Pharm Sci. 2016 Oct 10;93:468-74. doi: 10.1016/j.ejps.2016.08.059. Epub 2016 Aug 31.

Abstract

This work investigates whether the solubility of poorly soluble compounds can be improved by using mesoporous magnesium carbonate (MMC) as the drug delivery system. A solvent evaporation method was used to load structurally diverse model drugs (celecoxib, cinnarizine and griseofulvin) into the pores of MMC. The drug-loaded carrier system was then characterized in terms of porosity, crystallinity, and release profiles by a variety of experimental techniques, including X-ray diffraction, nitrogen adsorption analysis, differential scanning calorimetry, infrared spectroscopy, UV absorption spectroscopy, and thermogravimetric analysis. All three drugs were in a non-crystalline state after loading into the pores of MMC. The concentrations of the drugs in solution over time (a measure of the release rates from loaded MMC) were higher than the corresponding concentrations (dissolution rates) of equal amounts of the crystalline drugs. The release rates were five (celecoxib), three (cinnarizine) and two times (griseofulvin) higher than the dissolution rates of their crystalline counterparts. Supersaturation release profiles were also observed; the areas under the concentration-time curves (0-240min) were 25- (celecoxib), 5- (cinnarizine) and 2-fold (griseofulvin) greater than those of the crystalline drugs. Hence, MMC shows promise as a general drug delivery vehicle for increasing the bioavailability of compounds with dissolution rate- or solubility-limited absorption.

摘要

本研究探讨了使用介孔碳酸镁(MMC)作为药物递送系统是否可以提高难溶性化合物的溶解度。采用溶剂蒸发法将结构多样的模型药物(塞来昔布、桂利嗪和灰黄霉素)载入MMC的孔隙中。然后通过多种实验技术,包括X射线衍射、氮吸附分析、差示扫描量热法、红外光谱、紫外吸收光谱和热重分析,对载药载体系统的孔隙率、结晶度和释放曲线进行了表征。三种药物载入MMC孔隙后均处于非晶态。随着时间推移,溶液中药物的浓度(衡量载药MMC释放速率的指标)高于等量结晶药物的相应浓度(溶解速率)。释放速率分别比其结晶对应物的溶解速率高五倍(塞来昔布)、三倍(桂利嗪)和两倍(灰黄霉素)。还观察到了过饱和释放曲线;浓度-时间曲线下的面积(0-240分钟)分别比结晶药物大25倍(塞来昔布)、5倍(桂利嗪)和2倍(灰黄霉素)。因此,MMC有望作为一种通用的药物递送载体,用于提高吸收受溶解速率或溶解度限制的化合物的生物利用度。

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