Modelling of Drug Release from Reservoir and Matrix Formulations - Multiple Unit Dosage Forms and Swelling and Dissolving Matrix Systems
Abstract: In this work, mathematical models have been developed describing drug release from film-coated reservoir systems as well as drug release and polymer dissolution from swelling and dissolving polymer tablets. The model derivation of both systems is based on a mechanistic approach. The model describing drug release from reservoir systems, i.e. from single, film-coated pellets, was validated against experimental release data from single ethyl-cellulose-coated pellets. The model was also expanded to account for the simultaneous release from an ensemble of single pellets, i.e. a multiple-unit model. This study was verified against release data from ensembles of ethyl-cellulose-coated pellets. Qualitative studies using SEM on the film-coated pellets together with the information gained from the model evaluation of the experimental release data, indicated that a major release mechanism from these pellets is drug transport through cracks and holes in the polymer film. This finding confirms the view that it is essential to obtain information on release characteristics on the single-unit level in order to increase our knowledge concerning release-controlling mechanisms.The model for polymer swelling and dissolution, i.e. the polymer dissolution model, and the model for drug release from a swelling and dissolving polymer matrix, i.e. the drug release model, are based on mass transfer in cylindrical geometry. Diffusive and convective contributions to mass transfer are accounted for. The polymer dissolution model was fitted to experimental polymer dissolution and front position data of the dissolution of poly (ethylene oxide). The information gained from fitting was applied to the drug release model, which was validated against drug release data for a soluble drug and a slightly soluble drug. It was concluded that the convective contribution to drug mass transfer can be of considerable importance, leading to erroneous fitting results if neglected.
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