Reza Md Selim, Quadir Mohiuddin Abdul, Haider Syed Shabbir
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh.
J Pharm Pharm Sci. 2003 May-Aug;6(2):282-91.
The present study was undertaken to investigate the effect of plastic, hydrophilic and hydrophobic types of polymers and their content level on the release profile of drug from matrix systems. As the physico-chemical nature of the active ingredients influence the drug retarding ability of these polymers, three different drugs were used to evaluate their comparative release characteristics in similar matrices.
Matrix tablets of theophylline, diclofenac sodium and diltiazem HCl using Kollidon SR, Carnauba wax and Hydroxypropyl methylcellulose (HPMC-15cps) were prepared separately by direct compression process. The USP Basket method was selected to perform the dissolution test carried out in 250 ml 0.1N HCl for first two hours and 1000 ml phosphate buffer of pH 6.8 for ten hours.
Statistically significant differences were found among the drug release profile from different classes of polymeric matrices. The release kinetics was found to be governed by the type and content of polymer in the matrix system. Higher polymeric content (75%) in the matrix decreased the release rate of drug because of increased tortuosity and decreased porosity. At lower polymeric level (25%), the rate and extent of drug release was elevated. Carnauba wax was found to cause the strongest retardation of drug. On the otherhand, highest drug release was from HPMC matrices while Kollidon SR gave an intermediate release profile between these two polymers. Release rate was also found to be the function of physico-chemical nature of drug molecule. Theophylline and diltiazem HCl, being soluble in nature, released faster than diclofenac sodium from all matrix systems. The release mechanism was explored and explained with biexponential equation. Release profile showed a tendency to follow zero-order kinetics from HPMC matrix systems whereas Fickian (Case I) transport was predominant mechanism of drug release from Kollidon SR matrix system. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with Carnauba wax for all the drugs under investigation.
The results generated in this study showed that the profile and kinetics of drug release were functions of polymer type, polymer level and physico-chemical nature of drug. A controlled plasma level profile of drug can be obtained by judicious combination of polymers and modulation of polymer content in the matrix system.
本研究旨在探讨塑料、亲水性和疏水性聚合物类型及其含量水平对药物从基质系统中释放曲线的影响。由于活性成分的物理化学性质会影响这些聚合物的药物缓释能力，因此使用三种不同的药物来评估它们在相似基质中的相对释放特性。
分别采用直接压片法制备了含聚维酮SR、巴西棕榈蜡和羟丙基甲基纤维素（HPMC - 15cps）的茶碱、双氯芬酸钠和盐酸地尔硫䓬基质片剂。选择美国药典篮法进行溶出度试验，前两小时在250 ml 0.1N盐酸中进行，后十小时在1000 ml pH 6.8的磷酸盐缓冲液中进行。
不同类型聚合物基质的药物释放曲线存在统计学上的显著差异。发现释放动力学受基质系统中聚合物的类型和含量控制。基质中较高的聚合物含量（75%）由于曲折度增加和孔隙率降低而降低了药物释放速率。在较低的聚合物水平（25%）下，药物释放的速率和程度有所提高。发现巴西棕榈蜡对药物的阻滞作用最强。另一方面，HPMC基质的药物释放最高，而聚维酮SR在这两种聚合物之间呈现中间释放曲线。还发现释放速率是药物分子物理化学性质的函数。茶碱和盐酸地尔硫䓬本质上是可溶的，在所有基质系统中比双氯芬酸钠释放得更快。用双指数方程探索并解释了释放机制。释放曲线显示从HPMC基质系统有遵循零级动力学的趋势，而菲克（I型）转运是聚维酮SR基质系统中药物释放的主要机制。计算了所有制剂的平均溶出时间（MDT），在所研究的所有药物中，巴西棕榈蜡获得的MDT值最高。
本研究结果表明，药物释放曲线和动力学是聚合物类型、聚合物水平和药物物理化学性质的函数。通过明智地组合聚合物并调节基质系统中聚合物的含量，可以获得药物的可控血浆水平曲线。
