Journal of the Chinese Institute of Chemical Engineers, Vol.35, No.6, 667-676, 2004
The effects of the finite dissolution rate on the drug release of spherical particles loaded with uniformly dispersed drugs
Higuchi's well known model, which has traditionally been applied to describe the release of non-swellable and non-erodible drug-loaded microspheres, neglects the effects of the finite drug dissolution rate and assumes that a depletion layer extending inward leaches drugs. Although many release models have amended Higuchi's model, the effects of the finite dissolution rate are generally still ignored. This study takes the effects of the finite dissolution rate into account and proposes a more generalized drug release model. The numerical solution of the present generalized model was validated by its agreement with a short time analytical solution. The solution reveals that the dynamic curves showing the moving boundary of the depletion layer and the remaining drugs exhibit a sinusoidal shape of decrease with time. Results also indicate that due to the assumption of instantaneous dissolution, Higuchi's model can be applied only when the ratio of diffusion rate/dissolution rate B is small. It is also found that in spite of the pseudo-steady state approximation, drug release curves predicted by Higuchi's model for a drug loading ratio K as low as 1 are still close to the present results. This suggests that the significant difference between the present solution and Higuchi's solution for a large K is mainly due to the effects of the finite dissolution rate.