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由壳聚糖和黄原胶组成的层状基质系统的缓释。

Sustained-release from layered matrix system comprising chitosan and xanthan gum.

作者信息

Phaechamud Thawatchai, Ritthidej Garnpimol C

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand.

出版信息

Drug Dev Ind Pharm. 2007 Jun;33(6):595-605. doi: 10.1080/03639040601015521.

Abstract

Sustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH3+ of chitosan molecule and COO- of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.

摘要

以壳聚糖和黄原胶为基质材料,采用直接压片法制备盐酸普萘洛尔缓释片。含壳聚糖和黄原胶的基质在酸性环境中能有效延长药物释放,其延长药物释放的效果比含单一聚合物的基质更显著。向基质中增加乳糖可通过增强药物释放来调节药物释放特性。选择壳聚糖与黄原胶比例为1:1且乳糖含量为75%(w/w)的组分通过压片制备层状基质。增加屏障层或中间层的基质用量会导致药物释放延长。从药物从一个平面表面释放的研究来看,随着屏障层用量增加,药物通过屏障层释放的滞后时间明显变长。将实验溶出数据用数学表达式(幂律、一级、Higuchi方程和零级)进行最小二乘法拟合,以研究药物释放机制。用聚合物基质分层可延长药物释放,并使释放模式向零级转变。壳聚糖 - 黄原胶三层片的药物释放因不同环境pH下电荷密度的差异而具有pH依赖性。傅里叶变换红外光谱(FT - IR)和差示扫描量热法(DSC)研究表明壳聚糖分子的NH₃⁺与黄原胶分子的醋酸根或丙酮酸根的COO⁻之间存在电荷相互作用。扫描电子显微镜(SEM)图像显示形成了疏松的膜状但多孔的薄膜,这是由于聚合物在吸收溶出介质后松弛形成凝胶层所致。溶剂渗透速率降低导致聚合物溶解速率降低,同时由于壳聚糖和黄原胶之间的离子相互作用,药物扩散也随之降低。这表明壳聚糖和黄原胶的应用可产生具有持续药物释放的层状基质片剂。

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