Theoretical analysis of the release of slowly dissolving drugs from spherical matrix systems.

Drug release from spherical matrix systems has been investigated theoretically, with numerical as well as analytical methods. The model used combines the Noyes-Whitney and diffusion equations, and thus takes the effects of a finite dissolution rate into account. The release profile has been determined numerically, by using well-established FORTRAN routines. An approximate analytical formula for the amount of released drug has been derived, which is valid during the early stages of the release process. This analytical short-time approximation was compared to the numerical result, and to drug release models existing in the literature. From this comparison it was concluded that the analytical approximation provided a good description of the major part of the release profile, irrespective of the dissolution rate. Existing literature models, based on instantaneous dissolution, provided a good description of the release only when drug dissolution proceeded very rapidly in comparison with the diffusion process. Consequently, the new analytical short-time approximation complements the formulas existing in the literature, since it provides a superior description of the release of slowly dissolving drugs.