Jeong Seong Hoon, Berhane Nahor Haddish, Haghighi Kamyar, Park Kinam
Department of Pharmaceutics and Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
J Pharm Sci. 2007 Mar;96(3):618-32. doi: 10.1002/jps.20677.
Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes.
尽管离子交换树脂已被广泛用作药物递送系统,但其确切的释放动力学尚未见报道。通常只考虑限速步骤,而其余步骤则被视为瞬时过程而被忽略。为了研究聚合物包衣的药物/离子交换树脂复合物用于持续药物递送的确切释放动力学,将新的数学建模结果与实验结果进行了比较。制备了含有模型药物右美沙芬的药物/树脂复合物,并用作流化床包衣的核心。使用聚(醋酸乙烯酯)的水性胶态分散体进行包衣。通过考虑扩散、溶胀和离子交换过程,采用数值技术求解,建立了一个综合的数学模型。未包衣树脂颗粒的限速因素是通过核心基质的扩散。同样,在包衣颗粒中,限速因素是通过包衣膜的扩散。该数学模型捕捉了实验评估过程中观察到的现象,并准确预测了未包衣和包衣(不同包衣水平)颗粒的释放动力学(最大均方根误差为2.4%)。该数学模型是从理论上评估包衣离子交换复合物药物释放特性的有用工具,因此可用于设计目的。