Slow release of drug through deformed coating film: effects of morphology and drug diffusivity in the coating film.

摘要

The effects of the morphology and drug diffusivity in the coating film on the slow release characteristics have been analyzed numerically under the constraint that the volume of the coating film and the drug matrix is maintained constant. Two different systems of coated particles with deformed coating films were studied and their release characteristics compared with those of the coated particles having spherical coating films. The average release rate, fractional release, drug concentration profiles, and the initial burst of drug were found to be strongly influenced by the ratio of drug diffusivity in the coating film to that in the drug matrix D(r) (i.e., dimensionless drug diffusivity in the coating film). Increasing D(r) always increased the release rate, the fractional release, and the initial burst of drug, but reduced the initial lag times of drug release. The effect of shape deformation was very significant in the drug concentration profiles and the initial lag times; in contrast, it was not so substantial on the fractional release and the average release rates. The morphology difference in the deformed systems was also found to affect the release characteristics to different extents. Increasing the degree of the shape deformation, represented by the perturbation parameter epsilon, always reduced the effective surface area for the controlled release of drug. Because of the compensation effects between decreasing surface area and the non-uniform mass flux distribution, even though the heterogeneity of surface mass flux distribution would become more considerable, the effects of increasing shape deformation to the overall release rate would be less than expected unless the coating film was deformed significantly enough. The effect of the shape deformation and the morphology difference become less effective to differentiate the release characteristics with increasing D(r).