The release of active principles from microencapsulated drugs has been studied and treated extensively in the literature. However, only empirical or semiempirical models have been proposed. Often, such models are not able to describe correctly the articulated behavior of the release phenomenon. This paper, based on a first principles approach, defines a fully theoretical model of the release process within the human body. The key point of this work is the penetration theory that describes the experimental evidence of release dependency from square root of time. In addition, the paper deals with the observed lead-lag time characterizing the release dynamics of active principle that diffuses towards the external solution. A detailed analysis of the transport phenomena involved, focuses. the attention on the diffusive mechanism, which is strictly related to the existing affinity between active principle and polymer coating. Finally, the good agreement between experimental release data, for different active principles, and corresponding simulated curves allows the proposed model to be considered of real value for predictive design purposes. (C) 2003 Elsevier Science Ltd. All rights reserved.