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粉末混合物和片剂结构对疏水性醋酸淀粉基质片剂药物释放机制的影响。

The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets.

作者信息

van Veen B, Pajander J, Zuurman K, Lappalainen R, Poso A, Frijlink H W, Ketolainen J

机构信息

Department of Pharmaceutics, University of Kuopio, Kuopio, Finland.

出版信息

Eur J Pharm Biopharm. 2005 Oct;61(3):149-57. doi: 10.1016/j.ejpb.2005.04.007. Epub 2005 Jul 7.

Abstract

This study investigates the release mechanism of a hydrophilic drug (caffeine) from hydrophobic matrix tablets composed of starch acetate. Different particle size fractions of starch acetate were mixed with caffeine (22% V/V) to obtain various mixture organisations in the powder, as well as in the final tablet. The organisation of powder mixtures was calculated by the carrier payload of starch acetate particles, while the pore size distributions in tablets were measured by mercury intrusion porosimetry. A carrier payload below 1 indicated the existence of a free starch acetate particle surface, while numbers greater than 1 pointed to a complete occupation of the starch acetate particle surface area by caffeine particles. The carrier payload calculations gave a good prediction for the existence of a starch acetate matrix in the tablet structures. Caffeine matrices in tablets compressed from the mixtures could be detected by mercury intrusion porosimetry measurements. The existence of different matrices, as well as different pore networks, determined the physical changes of the tablets and the release mechanism of caffeine during dissolution tests. When a tablet contained only a caffeine matrix, rapid tablet disintegration and immediate release of the total amount of caffeine occurred. A single matrix of starch acetate resulted in tablets that remained intact, although cracks were formed. The co-existence of matrices of both materials created surface erosion of the tablet. The caffeine release profiles of tablets that remained intact or showed erosion were fitted by an equation containing both diffusional and relaxational factors to describe the effect of tablet porosity on drug release.

摘要

本研究考察了亲水性药物(咖啡因)从由醋酸淀粉组成的疏水性基质片剂中的释放机制。将不同粒径级分的醋酸淀粉与咖啡因(22% V/V)混合,以在粉末以及最终片剂中获得各种混合物结构。通过醋酸淀粉颗粒的载体负载量计算粉末混合物的结构,而通过压汞法测量片剂中的孔径分布。载体负载量低于1表明存在游离的醋酸淀粉颗粒表面,而大于1的数值则表明醋酸淀粉颗粒表面积被咖啡因颗粒完全占据。载体负载量计算对片剂结构中醋酸淀粉基质的存在给出了良好的预测。通过压汞法测量可以检测到由混合物压制而成的片剂中的咖啡因基质。不同基质以及不同孔网络的存在决定了片剂的物理变化以及溶解试验期间咖啡因的释放机制。当片剂仅包含咖啡因基质时,片剂迅速崩解且咖啡因总量立即释放。单一的醋酸淀粉基质导致片剂保持完整,尽管形成了裂缝。两种材料基质的共存导致片剂表面侵蚀。对保持完整或出现侵蚀的片剂的咖啡因释放曲线用一个包含扩散和松弛因素的方程进行拟合,以描述片剂孔隙率对药物释放的影响。

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