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热固化条件对醋酸乙烯酯-聚乙烯吡咯烷酮基质中药物释放的影响。

Effects of thermal curing conditions on drug release from polyvinyl acetate-polyvinyl pyrrolidone matrices.

机构信息

Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan.

出版信息

AAPS PharmSciTech. 2010 Mar;11(1):253-66. doi: 10.1208/s12249-010-9378-z. Epub 2010 Feb 20.

Abstract

This study aimed to investigate the effects of dry and humid heat curing on the physical and drug release properties of polyvinyl acetate-polyvinyl pyrrolidone matrices. Both conditions resulted in increased tablet hardness; tablets stored under humid conditions showed high plasticity and deformed during hardness testing. Release from the matrices was dependent on the filler's type and level. Release profiles showed significant changes, as a result of exposure to thermal stress, none of the fillers used stabilized matrices against these changes. Density of neat polymeric compacts increased upon exposure to heat; the effect of humid heat was more evident than dry heat. Thermograms of samples cured under dry heat did not show changes, while those of samples stored under high humidity showed significant enlargement of the dehydration endotherm masking the glass transition of polyvinyl acetate. The change of the physical and release properties of matrices could be explained by the hygroscopic nature of polyvinyl pyrrolidone causing water uptake; absorbed water then acts as a plasticizer of polyvinyl acetate promoting plastic flow, deformation, and coalescence of particles, and altering the matrices internal structure. Results suggest that humid heat is more effective as a curing environment than dry heat for polyvinyl acetate-polyvinyl pyrrolidone matrices.

摘要

本研究旨在探讨干热和湿热固化对聚醋酸乙烯-聚乙烯吡咯烷酮基质的物理性能和药物释放性能的影响。两种条件都导致片剂硬度增加;在潮湿条件下储存的片剂表现出高塑性,并在硬度测试中变形。从基质中的释放取决于填充剂的类型和水平。由于热应力的影响,释放曲线发生了显著变化,所使用的填充剂都没有稳定基质对抗这些变化。暴露于热时,纯聚合物压块的密度增加;干热的影响比湿热更明显。在干热下固化的样品的热图谱没有显示变化,而在高湿度下储存的样品的热图谱显示出脱水性吸热的明显放大,掩盖了聚醋酸乙烯的玻璃化转变。基质的物理和释放性能的变化可以用聚乙烯吡咯烷酮的吸湿性来解释,导致水分吸收;吸收的水然后作为聚醋酸乙烯的增塑剂,促进塑性流动、变形和颗粒聚结,并改变基质的内部结构。结果表明,湿热作为聚醋酸乙烯-聚乙烯吡咯烷酮基质的固化环境比干热更有效。

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