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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...