Haaser Miriam, Windbergs Maike, McGoverin Cushla M, Kleinebudde Peter, Rades Thomas, Gordon Keith C, Strachan Clare J
School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
J Pharm Sci. 2011 Oct;100(10):4452-9. doi: 10.1002/jps.22609. Epub 2011 May 10.
Matrix dosage forms are widely used for sustained drug release. As both the distribution of the matrix components and physical changes during dissolution can impact drug release behavior, a comprehensive investigation of these phenomena is required during matrix development. In this study, Raman microscopy was used to investigate different extrudate formulations in terms of component distribution and structural changes during dissolution testing. Two systems containing the model drug theophylline anhydrate were investigated: a binary system, based on a tripalmitin matrix, and a ternary system, containing tripalmitin and polyethylene glycol. The distribution of the drug and the soluble and insoluble matrix components were mapped during dissolution testing. Although a receding drug boundary was observed, it was not uniformly distant from the matrix edge. The lipid structure remained intact, whereas the water-soluble polymer rapidly dissolved and diffused from the matrix leaving a more extensive network of channels through which the dissolution medium could penetrate and the drug could diffuse. Raman mapping can be considered a useful aid in the direct analysis of multiple matrix components during drug release, and therefore a deeper understanding of factors affecting drug release can be obtained during the development of sustained-release matrices.
基质剂型广泛用于药物的缓释。由于基质成分的分布以及溶解过程中的物理变化都会影响药物释放行为，因此在基质研发过程中需要对这些现象进行全面研究。在本研究中，利用拉曼显微镜研究了不同挤出物制剂在溶出度测试过程中的成分分布和结构变化。研究了含有模型药物无水茶碱的两种体系：一种基于三棕榈酸甘油酯基质的二元体系，以及一种含有三棕榈酸甘油酯和聚乙二醇的三元体系。在溶出度测试过程中绘制了药物以及可溶和不溶基质成分的分布图。虽然观察到药物边界在后退，但它与基质边缘的距离并不均匀。脂质结构保持完整，而水溶性聚合物迅速溶解并从基质中扩散出来，留下更广泛的通道网络，溶解介质可通过这些通道渗透，药物也可通过这些通道扩散。拉曼映射可被视为在药物释放过程中直接分析多种基质成分的有用辅助手段，因此在缓释基质的研发过程中，可以更深入地了解影响药物释放的因素。
