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采用糖类载体通过固体分散技术提高依托考昔的溶解度和溶出度

Solubility and dissolution enhancement of etoricoxib by solid dispersion technique using sugar carriers.

作者信息

Das Abhisekh, Nayak Amit Kumar, Mohanty Biswaranjan, Panda Satyabrata

机构信息

Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Orissa, Mayurbhanj 757086, India.

出版信息

ISRN Pharm. 2011;2011:819765. doi: 10.5402/2011/819765. Epub 2011 Sep 5.

Abstract

The aim of the present study was to improve solubility and dissolution of the poorly aqueous soluble drug, etoricoxib by solvent evaporation technique using various sugar carriers, such as lactose, sucrose, and mannitol. Etoricoxib solid dispersions and their respective physical mixtures using lactose, sucrose, and mannitol were prepared in different ratios by solvent evaporation technique. The percent yield, drug content, saturation solubility, and in vitro dissolution of etoricoxib solid dispersions and physical mixtures were analyzed. Etoricoxib solid dispersions were characterized by FTIR spectroscopy, XRD, and DSC analysis. The FTIR spectroscopic analysis revealed the possibility of intermolecular hydrogen bonding in various solid dispersions. The XRD and DSC studies indicated the transformation of crystalline etoricoxib (in pure drug) to amorphous etoricoxib (in solid dispersions) by the solid dispersion technology. Both the aqueous solubility and dissolution of etoricoxib were observed in all etoricoxib solid dispersions as compared with pure etoricoxib and their physical mixtures. The in vitro dissolution studies exhibited improved dissolution in case of solid dispersion using lactose than the solid dispersions using both sucrose and mannitol. The in vitro dissolution of etoricoxib from these solid dispersions followed Hixson-Crowell model.

摘要

本研究的目的是通过溶剂蒸发技术,使用乳糖、蔗糖和甘露醇等各种糖类载体,提高难溶性药物依托考昔的溶解度和溶出度。采用溶剂蒸发技术,以不同比例制备了依托考昔与乳糖、蔗糖和甘露醇的固体分散体及其相应的物理混合物。分析了依托考昔固体分散体和物理混合物的产率、药物含量、饱和溶解度和体外溶出度。通过傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)和差示扫描量热法(DSC)对依托考昔固体分散体进行了表征。FTIR光谱分析揭示了各种固体分散体中分子间氢键形成的可能性。XRD和DSC研究表明,通过固体分散技术,结晶型依托考昔(纯药物中)转变为无定形依托考昔(固体分散体中)。与纯依托考昔及其物理混合物相比,所有依托考昔固体分散体的水溶性和溶出度均有所提高。体外溶出度研究表明,使用乳糖的固体分散体的溶出度比使用蔗糖和甘露醇的固体分散体有所提高。依托考昔从这些固体分散体中的体外溶出符合希克森-克劳威尔模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e59e/3263729/2c20e4df5840/PHARMACEUTICS2011-819765.001.jpg

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