Abdekhodaie Mohammad J, Wu Xiao Yu
Faculty of Pharmacy, University of Toronto, 44 College Street, Toronto, ON, Canada M5S 2S2.
Biomaterials. 2008 Apr;29(11):1654-63. doi: 10.1016/j.biomaterials.2007.11.044. Epub 2008 Jan 14.
This paper presents for the first time a mathematical model for a mechanism of controlled drug release involving both ion exchange and transient counter diffusion of a drug and counterions. Numerical analysis was conducted to study the effect of different factors on drug release kinetics including environmental condition, material properties, and design parameters. The concentration profiles of counterions and drug species, the moving front of ion exchange, and three distinct regions inside a microsphere, namely unextracted region, ion-exchange region and drug diffusion region, were revealed by model prediction. The numerical results indicated that the rate of drug release increased with an increase in the initial drug concentration in the microspheres, the salt concentration in the external solution, or the valence of the counterions, whereas it decreased with increasing Langmuir isotherm constant. The mathematical and experimental procedures for determination of the equilibrium constant and the usefulness of the model were demonstrated using verapamil hydrochloride and sulfopropyl dextran microsphere system as an example. This work has provided a very useful mathematical tool for predicting kinetics and equilibrium of drug release and for optimizing the design of ion-exchange drug delivery systems.
本文首次提出了一种涉及药物和抗衡离子的离子交换及瞬态反向扩散的控释机制数学模型。进行了数值分析以研究不同因素对药物释放动力学的影响，这些因素包括环境条件、材料特性和设计参数。通过模型预测揭示了抗衡离子和药物物种的浓度分布、离子交换的移动前沿以及微球内部的三个不同区域，即未提取区域、离子交换区域和药物扩散区域。数值结果表明，药物释放速率随着微球中初始药物浓度、外部溶液中盐浓度或抗衡离子价态的增加而增加，而随着朗缪尔等温线常数的增加而降低。以盐酸维拉帕米和磺丙基葡聚糖微球系统为例，展示了测定平衡常数的数学和实验程序以及该模型的实用性。这项工作为预测药物释放动力学和平衡以及优化离子交换药物递送系统设计提供了非常有用的数学工具。
