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聚合物颗粒侵蚀控制药物释放。I. 影响药物释放的因素及释放机制的表征

Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism.

作者信息

Zuleger S, Lippold B C

机构信息

Institut für Pharmazeutische Technologie, Heinrich-Heine-Universität, Universitätsstr. 1, D-40225, Düsseldorf, Germany.

出版信息

Int J Pharm. 2001 Apr 17;217(1-2):139-52. doi: 10.1016/s0378-5173(01)00596-8.

Abstract

The present study deals with controlled drug delivery from hydrocolloid tablets by polymer particle erosion. The influence of excipients and formulation factors on the dissolution behaviour of the methyl hydroxyethyl cellulose (MHEC)-tablets is investigated. Linear drug release with low susceptibility to hydrodynamic stress is obtained. The use of drugs with higher solubility leads to a slight acceleration of the release due to the contribution of diffusion to the release process. Higher drug loading and consequently lower polymer content expedites dissolution as well as changes in the tablets' geometry resulting in enlarged release surfaces. Furthermore, alterations of the composition of the dissolution medium affect drug release. However, neither viscosity grade nor the particle size of the polymer or compaction pressure has a marked impact on the dissolution. Investigations to clarify the mechanism of polymer particle erosion include erosion studies and the comparison of different batches of MHEC, of products from different manufacturers and of fibrous trial products. There is evidence that the insoluble fibres within the water soluble MHEC are responsible for the occurrence of polymer particle erosion by disturbing swelling and formation of a thick coherent gel layer and thus, causing erosion of the hydrocolloid tablet with synchronous drug release.

摘要

本研究涉及通过聚合物颗粒侵蚀实现水胶体片剂的控释给药。研究了辅料和制剂因素对甲基羟乙基纤维素(MHEC)片剂溶解行为的影响。获得了对流体动力学应力敏感性较低的线性药物释放。由于扩散对释放过程的贡献,使用溶解度较高的药物会导致释放略有加速。较高的药物载量以及相应较低的聚合物含量会加快溶解速度,同时片剂几何形状的变化会导致释放表面积增大。此外,溶出介质组成的改变会影响药物释放。然而,聚合物的粘度等级、粒径或压实压力对溶解均无显著影响。为阐明聚合物颗粒侵蚀机制所进行的研究包括侵蚀研究,以及对不同批次的MHEC、不同制造商的产品和纤维状试验产品的比较。有证据表明,水溶性MHEC中的不溶性纤维通过干扰溶胀和形成厚的连贯凝胶层,从而导致水胶体片剂的侵蚀并同步释放药物,进而引发聚合物颗粒侵蚀。

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