盐酸氨溴索缓释片研究及填充剂对其中试的潜在影响

摘要

Objective: To study the release profiles of Ambroxol hydrochloride in matrix tablets with different fillers and controlled release materials, and investigate the potential impact on different fillers on the matrix tablet's scale-up. Methods: Ambroxol hydrochloride was chosen as the model drug to make single-layer matrix tablets with different types of hydroxylpropyl methylcellulose as matrix material, and lactose or microcrystalline cellulose as the filler. In vitro dissolution test was used to evaluate the drug release performance of the matrix tablets made. Also ethyl cellulose was used to prepare double-layer matrix tablets to investigate how different kinds of hydroxypropyl methylcellulose ( HPMC) and fillers would affect the drug release in double-layer matrix tablets. Results: The drug release rate of single-layer tablets with lactose and HPMC decreased significantly with the increase of the level and viscosity of HPMC. However the release profile only slightly slowed down with the increase of the content and viscosity of HPMC for single-layer matrix tablets of microcrystalline cellulose (MCC). Compared with the single-layer tablets, the level and viscosity of HPMC had less impact on the drug release of the double-layer matrix tablets. Conclusion: The matrix tablet with lactose and HPMC has greater flexibility to design formulations with different drug release rate, however the introduction of other process parameters during the scale-up could lead the shifting of the drug release profile from small scale batches. The drug release profiles of matrix tablets with insoluble filler-MCC only change within a small range with the increase of the level and viscosity of HPMC. From the formulation design point of view, it could be necessary to select different type of controlled release polymers to meet the design requirement.%目的:考察不同填充剂和缓释材料组合对盐酸氨溴索骨架片药物释放的影响,同时探索不同填充剂对盐酸氨溴索缓释片中试放大的潜在关系.方法:以盐酸氨溴索为模型药物,选用不同型号的羟丙甲纤维素( hydroxypropyl methylcellulose,HPMC)为骨架材料,乳糖或微晶纤维素为填充剂,设计不同处方制备单层片,考察药物释放与辅料的相互关系；选用乙基纤维素为阻滞材料,制备双层片,考察不同处方药物体外释放规律.结果:单层缓释片,乳糖作填充剂时,不同聚合物黏度和比例对药物释放速率影响较大；微晶纤维素作填充剂时,改变聚合物黏度和比例对药物释放速率影响不大.与单层片相比,改变双层片中辅料的种类和用量对药物的释药速率影响较小.结论:乳糖作为填充剂的处方易于调节缓释片药物释放速度,但是中试放大过程中其他工艺参数的引入常常导致中试产品药物溶出与小试处方药物释放度的差异；难溶性填充剂制备的缓释片,缓释辅料用量的改变对缓释片药物溶出速度的影响较小,因此可能需要在处方设计过程中选用不同类别缓释辅料达到药物释放的设计要求.