Yang L, Fassihi R
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
J Pharm Sci. 1996 Feb;85(2):170-3. doi: 10.1021/js950250r.
A new approach based on the three-layer matrix technology to control drug release for oral administration is presented. Polyethylene oxide polymers of various molecular weight together with theophylline as drug model and other excipients have been directly compressed into a three-layer asymmetric floatable system. The core layer contains the active drug while external layers with different thickness, composition, and erosion rates are designed to delay the hydration of the middle layer, restrict the early drug diffusion only through cylindrical side surfaces of the tablet, and provide controlled drug release. Results show that during a 16 h dissolution study drug is completely released following the zero-order kinetics with no burst effect. The release rate remains around 0.1 mg min-1 throughout the dissolution study. The release kinetics is independent of changes in pH and compression force but dependent on layer thickness and formulation components. It appears that the operating release mechanism is based on the existence of a balance between the velocities of advancing glassy/rubbery front and erosion at the swollen polymer/dissolution front.
提出了一种基于三层基质技术的口服控释药物新方法。将不同分子量的聚环氧乙烷聚合物与作为药物模型的茶碱及其他辅料直接压制成三层不对称漂浮体系。核心层含有活性药物，而具有不同厚度、组成和侵蚀速率的外层旨在延迟中间层的水化，仅通过片剂的圆柱形侧面限制药物早期扩散，并实现药物的控释。结果表明，在16小时的溶出度研究中，药物完全按照零级动力学释放，无突释效应。在整个溶出度研究中，释放速率保持在约0.1毫克/分钟。释放动力学与pH值和压力的变化无关，但取决于层厚度和制剂成分。看来，其释放机制基于玻璃态/橡胶态前沿推进速度与溶胀聚合物/溶出前沿侵蚀速度之间的平衡。
