Zuleger Susanne, Fassihi Reza, Lippold Bernhard C
Institut für Pharmazeutische Technologie, Heinrich-Heine-Universität, Universitätsstr 1, D-40225, Düsseldorf, Germany.
Int J Pharm. 2002 Oct 24;247(1-2):23-37. doi: 10.1016/s0378-5173(02)00362-9.
The aim of the study was a comprehensive swelling investigation of hydrocolloid tablets with drug release by diffusion, erosion and polymer particle erosion, respectively, in order to reveal differences in the swelling behaviour responsible for the diverging drug release mechanisms. Four different methods were applied to study swelling of the tablets: determination of the expansion factor, texture analysis, visual swelling observation of dye containing tablets sandwiched between plexiglas discs and photomicroscopy. Altogether they allowed the investigation of dimensional changes, swelling velocity, thickness, appearance and strength of the gel layer and front movements. However, none of the methods included a determination of all these factors. A combination of the different techniques proved to be helpful to provide information necessary for a broad understanding of the complex phenomenon of swelling. Intensive swelling was observed for matrices with diffusion controlled release (e.g. MHPC 100000), while erosion controlled systems (e.g. Pharmacoat 606) were characterized by limited swelling and fast polymer erosion. In the case of tablets exhibiting polymer particle erosion (e.g. MHEC 10000 B) the importance of the amount of insoluble fibres was confirmed. Insoluble fibres were clearly visible in the swelling zone of these tablets. They impeded the swelling, weakened the gel layer and caused attrition of polymer material, thus only a thin gel layer was formed. Synchronization of the movement of swelling and erosion fronts occurred during the swelling of tablets with a high content of insoluble fibres. The freely soluble drug proxyphylline was found to promote swelling while the poorly soluble acetophenetidin hindered the hydration of the tablet. Furthermore, the swelling study confirmed the low robustness to hydrodynamic stress of tablets with erosion control compared to tables with polymer particle erosion.
本研究的目的是对分别通过扩散、溶蚀和聚合物颗粒溶蚀实现药物释放的水胶体片剂进行全面的溶胀研究，以揭示导致不同药物释放机制的溶胀行为差异。应用了四种不同的方法来研究片剂的溶胀：膨胀因子的测定、质地分析、夹在有机玻璃圆盘之间的含染料片剂的视觉溶胀观察以及金相显微镜观察。这些方法共同使得能够研究尺寸变化、溶胀速度、厚度、凝胶层的外观和强度以及前沿移动情况。然而，没有一种方法涵盖了所有这些因素的测定。事实证明，将不同技术结合起来有助于提供全面理解溶胀这一复杂现象所需的信息。对于具有扩散控制释放的基质（如MHPC 100000）观察到强烈的溶胀，而溶蚀控制体系（如Pharmacoat 606）的特点是溶胀有限且聚合物快速溶蚀。对于表现出聚合物颗粒溶蚀的片剂（如MHEC 10000 B），证实了不溶性纤维量的重要性。在这些片剂的溶胀区域中可以清楚地看到不溶性纤维。它们阻碍溶胀，削弱凝胶层并导致聚合物材料的磨损，因此仅形成了一层薄的凝胶层。在含有高含量不溶性纤维的片剂溶胀过程中，溶胀前沿和溶蚀前沿的移动发生了同步。发现可自由溶解药物丙羟茶碱可促进溶胀，而难溶性非那西汀则阻碍片剂的水化。此外，溶胀研究证实，与具有聚合物颗粒溶蚀的片剂相比，溶蚀控制片剂对流体动力应力的耐受性较低。
