Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Sevilla, Sevilla, Spain.
Eur J Pharm Biopharm. 2012 Apr;80(3):674-81. doi: 10.1016/j.ejpb.2011.12.005. Epub 2011 Dec 21.
A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.
先前的一篇论文涉及乙基甲基丙烯酸酯（EMA）接枝到蜡质玉米淀粉（MS）和羟丙基淀粉（MHS）的新型接枝共聚物的物理化学和技术特性。研究结果表明，这些共聚物有可能作为压缩非崩解基质片剂的赋形剂。因此，本研究的目的是研究以新型共聚物和无水茶碱或盐酸地尔硫卓作为模型药物（具有不同的溶解度）制备的基质系统中药物释放的机制。还评估了碳水化合物性质、干燥程序和初始孔网络对药物释放动力学的影响。从自由片剂进行药物释放实验。还分析了径向药物释放和前沿运动动力学，并采用了几种数学模型来确定药物释放机制。药物释放明显取决于药物的溶解度和碳水化合物的性质，但实际上不受干燥过程和初始基质孔隙率的影响。对于含有盐酸地尔硫卓的基质，与含有无水茶碱的基质相比，药物释放更快，这与药物的更高溶解度和盐酸地尔硫卓基质的更高脆性一致。事实上，尽管扩散是所有基质中占主导地位的药物释放机制，但侵蚀机制似乎在含有盐酸地尔硫卓的几种配方中也有一定的贡献。暴露于溶解介质的表面减少（径向释放研究）会降低药物释放速率，但释放机制并未发生本质改变。几乎恒定的侵蚀前沿运动证实了这些系统作为惰性基质的行为，其中药物主要通过多孔结构扩散释放。
