Wang Meng-yuan, Yang Ya-peng, Chang Jun-biao, Guo Min-tong
School of Pharmacy, Zhengzhou University, Zhengzhou, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2012 Oct 18;44(5):742-8.
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.
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.
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.
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.
研究不同填充剂和控释材料的盐酸氨溴索骨架片的释放曲线，并探讨不同填充剂对骨架片放大生产的潜在影响。
选用盐酸氨溴索作为模型药物，以不同类型的羟丙基甲基纤维素为骨架材料，乳糖或微晶纤维素为填充剂制备单层骨架片。采用体外溶出试验评价所制骨架片的药物释放性能。还使用乙基纤维素制备双层骨架片，以研究不同种类的羟丙基甲基纤维素（HPMC）和填充剂如何影响双层骨架片中的药物释放。
含乳糖和HPMC的单层片的药物释放速率随HPMC用量和粘度的增加而显著降低。然而，对于微晶纤维素（MCC）单层骨架片，随着HPMC含量和粘度的增加，释放曲线仅略有减慢。与单层片相比，HPMC的用量和粘度对双层骨架片的药物释放影响较小。
含乳糖和HPMC的骨架片在设计不同药物释放速率的制剂方面具有更大的灵活性，然而在放大生产过程中引入其他工艺参数可能导致小规模批次药物释放曲线的偏移。含不溶性填充剂MCC的骨架片的药物释放曲线随HPMC用量和粘度的增加仅在小范围内变化。从制剂设计的角度来看，可能有必要选择不同类型的控释聚合物以满足设计要求。
