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两性离子共聚物作为酒石酸美托洛尔缓释载体的合成与表征

Synthesis and characterization of Zwitterionic co-polymers as matrices for sustained metoprolol tartrate delivery.

作者信息

Kamenska Elena, Kostova Bistra, Ivanov Ivo, Rachev Dimitar, Georgiev George

机构信息

Faculty of Chemistry, Department of Applied Organic Chemistry, Sofia University, 1 James Bourchier Avenue, Sofia 1164, Bulgaria.

出版信息

J Biomater Sci Polym Ed. 2009;20(2):181-97. doi: 10.1163/156856209X404488.

Abstract

Very stable co-polymer (vinyl acetate (VA)-co-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) (p(VA-co-DMAPS)) latexes with different compositions have been synthesized by emulsifier-free emulsion co-polymerization. The dry p(VA-co-DMAPS)s have been used in the preparation of drug tablets for sustained Metoprolol tartrate release. It has been shown that the tablet swelling depends on the mol fraction of DMAPS monomer units (m(DMAPS)), pH and ionic strength (I). An original explanation, based on the swelling behavior of p(VA-co-DMAPS), has been proposed for the "overshooting" phenomenon observed. It assumes the formation of hydrophilic domains with a higher m(DMAPS) in the co-polymer tablets. The formation of dipole-dipole clusters between the DMAPS units at different m(DMAPS) and I are the main cause for the established differences in both the swelling kinetics of the p(VA-co-DMAPS) matrices and Metoprolol tartrate release. The obtained results show that for p(VA-co-DMAPS) matrices-based tablets controlled sustained Metoprolol tartrate release can be realized just by varying two parameters, co-polymer composition and I.

摘要

通过无皂乳液共聚合成了具有不同组成的非常稳定的共聚物(醋酸乙烯酯(VA)-co-3-二甲基(甲基丙烯酰氧基乙基)丙烷磺酸铵(DMAPS)(p(VA-co-DMAPS))乳胶。干燥的p(VA-co-DMAPS)已用于制备用于酒石酸美托洛尔缓释的药物片剂。结果表明,片剂溶胀取决于DMAPS单体单元的摩尔分数(m(DMAPS))、pH值和离子强度(I)。基于p(VA-co-DMAPS)的溶胀行为,对观察到的“过冲”现象提出了一种原理解释。它假定在共聚物片剂中形成了具有较高m(DMAPS)的亲水域。在不同的m(DMAPS)和I下,DMAPS单元之间形成偶极-偶极簇是p(VA-co-DMAPS)基质溶胀动力学和酒石酸美托洛尔释放存在既定差异的主要原因。所得结果表明,对于基于p(VA-co-DMAPS)基质的片剂,仅通过改变共聚物组成和I这两个参数就可以实现酒石酸美托洛尔的可控缓释。

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