A new modelling approach for dissolution of polydisperse powders.

A new modelling approach for dissolution of polydisperse powders is developed within the framework of the classical Noyes-Whitney/Nernst-Brunner analysis. Its distinguishing feature is that the underlying continuous particle-size distribution is retained. Two different but related dependencies of the diffusion-layer thickness on particle size are considered. First, a power-law dependence that interpolates between a thickness that is proportional to (or equals) the particle radius (obtained when the exponent equals 1) and a constant thickness (obtained when the exponent is 0). Second, a piecewise linear function such that the thickness equals the particle radius for sufficiently small particles and is constant for larger ones. The modelling approach is exemplified by consideration of a lognormal particle-size distribution. Highly accurate closed-form expressions for the fraction of dissolved drug are obtained for dissolution under sink conditions (which are exact if the diffusion-layer thickness is radius-independent). Moreover, it is demonstrated that any result derived under sink conditions can be reused to determine the fraction of dissolved/absorbed drug under non-sink conditions, using the concept of a retarded time. Comparison with literature data and experiments are used to validate the modelling approach and to demonstrate its usefulness in a practical context.