Simulation of the release from a multiparticulate system validated by single pellet and dose release experiments.

A previously described single-pellet release model has been simplified and modified to give predictions of the release from multiple-pellet systems, besides describing the release from single pellets. The simplified single-pellet model has been verified using single-pellet data and has been used to estimate three release-controlling parameters, namely the pellet core radius, the overall mass transfer coefficient, and the lag time. Single-pellet release experiments showed that the release from the individual film-coated drug cores resulted in a wide distribution of release profiles, a phenomenon not observed on the dose level. Therefore, the parameter estimations resulted in distributions of these parameter values. The core radius and the lag times compared well with the experimental data. The distributions were used as input data for the multiple pellet model, in order to predict the release profiles on the dose level, showing results consistent with the measured dose release. The dose-predictive ability of the model was demonstrated in simulations by studying the effect of a change in the size of the single subunits (of constant total dose), showing that smaller pellets give an increased release rate with less variation. The model for predicting dose-release profiles could be of great value in optimising the performance of an existing formulation, as well as in the development of a new controlled-release pharmaceutical.