Theoretical analysis of inward hemispheric release above and below drug solubility

A detailed analysis of inward diffusional drug release from devices with he mispheric and related geometries is presented. When drug is loaded below it s solubility, an infinite series describes drug concentration profiles and release kinetics, with an excellent approximation resulting when only one t erm of this series is retained. A connection between this geometric setting and diffusion in constricted porous domains is pointed out, as is the util ity of mean first passage times and mean residence times derived for this m odel. For the case of drug loaded above its solubility, the pseudosteady st ate (PSS) approximation of Bechard and McMullen [J. Pharm. Sci. 77 (1988) 2 22] is compared against numerical results calculated for the full model in which the PSS assumption is removed. A close match is observed. Asymptotic analysis of the PSS expressions shows that the previously used zero-order r elease assumption is not quite correct, even at later times, and this affec ts parameter estimation procedures. A comparison between the model of Becha rd and McMullen and earlier obtained experimental data [J. Pharm. Sci. 72 ( 1983) 17] reveals some qualitative discrepancies that are yet to be explain ed. (C) 2000 Elsevier Science B.V. All rights reserved.