Kinetics of release from enteric-coated tablets.

Controlled and localized release of drugs in the intestine can be achieved by enteric coating. The design of enteric-coated tablets has so far remained empirical, in part because of the lack of a quantitative description of the drug release kinetics. In this paper, a mathematical model is presented that describes the dissolution of the polymer coating and release kinetics of weakly acidic drugs from enteric-coated tablets in buffered media. This model can also be used to predict the time of onset of core disintegration. The model assumes that the release rate is limited by diffusion, and furthermore, all the reactions are considered as reversible and instantaneous. Dissolution and reaction are assumed to take place in the polymer layer and a hypothetical stagnant liquid film adjacent to the polymer layer (the classical film theory approach). The dissolution of the enteric coating is found to depend on the intrinsic solubilities and pKa's of the drug and polymer and the medium properties. The release rate of the drug is found to depend on the intrinsic solubilities and pKa's of drug and polymer, the medium properties, i.e., pH and buffer capacity, and a mass transfer coefficient. Explicit relationships between the release rates and all these factors are derived. Successful prediction of experimental data indicates that the model provides an adequate description of release from enteric coated tablets. Limitations of the model and its potential application to the design of appropriate in vitro testing conditions and to the formulation of enteric coated tablets are also discussed.