Modeling and analysis of dispersed-drug release into a finite medium from sphere ensembles with a boundary layer

Mathematical models were developed and analytical solutions were derived for describing kinetics of dispersed-drug release into a finite external medium from multi-particulate systems, such as ensembles of matrix spheres and microcapsules with a diffusion boundary layer. The solutions can be used to compute profiles of the moving boundary of a dispersed drug and the amount of drug released for multiparticulate ensembles with various ratios of initial drug loading (C-0) to drug solubility (C-s) in a finite to infinite medium. They are also applicable to a single sphere without a boundary layer in a perfect sink. The determinants of release kinetics, such as the liquid volume, the initial drug loading, the boundary layer thickness, and the number of spheres in a population, were analyzed using the derived solutions. The effect of coating thickness and material on the release profiles of microcapsules was studied as well. Criteria were established for finding the conditions when drug release would stall due to saturation of the medium, which can be used to determine suitable liquid volume and time for refreshing the medium. (C) 2003 Elsevier Science B.V. All rights reserved.