Size distribution effects in multiparticulate dissolution

The evaluation of models for single-particle dissolution, based on multiparticulate dissolution data, is complicated by the distribution effect present when the particles are not truly monodispersed. By using simulated data, it is shown that remarkably good linearity can be obtained with log-normal powders using an incorrect model. It is suggested that particle-size analysis is necessary to enable calculation of the distribution effect and to prevent this type of misinterpretation. The change in particle-size distribution during dissolution is calculated and shows potential for distinguishing between two, but not all three, of the models investigated. Four theoretical rules for multiparticulate dissolution are stated and discussed. The concept of "time scaling" is presented. By using this procedure, it should be possible to reduce considerably computational errors arising from nonlinear dissolution data. It is demonstrated that dissolution profiles can be transformed to a standard form, enabling the distribution effect to be evaluated without interference from rate or particle-size parameters.