Dissolution of irregularly-shaped drug particles: mathematical modelling

The prediction of drug dissolution profiles is crucial for elucidating the pharmacokinetic behaviour of drugs and the bioavailability of dosage forms. In this work, we develop a mathematical model to describe the dissolution process of irregularly shaped particles. We use a complete dissolution model that accounts for both surface kinetics and convective diffusion. The mechanistic relationship between the mass transfer coefficient and the local curvature is derived from the fundamental physical laws governing these processes. Our model theoretically shows that the dissolution rate depends nonlinearly on the surface curvature. The subsequent recrystallization process in the bulk fluid is also considered. The main result of this work is its simplicity, since only two coupled nonlinear ordinary differential equations are needed to describe the dissolution process. Another remarkable advantage is the possibility to determine the model parameters using common independent techniques, so that the importance of the wettability of solids on the dissolution process can be evaluated. Finally, the proposed model demonstrated the importance of particle shape in describing the experimental dissolution data of theophylline monohydrate.