ANALYSIS AND MODELLING OF THE DISSOLUTION OF POLYDISPERSED SPHERICAL DRUG PARTICLES

In virtue of its simplicity and reliability, the Dissolution Rate Test (DRT), that is the dissolution of an ensemble of drug particles in water or in a physiological medium, is commonly used in the pharmaceutical field to study the in vivo drug performance. This is also the reason why it originated a lot of modelling attempts starting with the seminal works of Hixon and Crowell in the far 1931 [1], despite its intrinsic physical complexity. A reliable mathematical model should account for different aspects such as particles shape and size distribution, mass transfer resistance at the solid-liquid interface (due to surface wettability and the presence of a hydrodynamic thin liquid film coating each particle), relative velocity between liquid and particles, possible drug recrystallization on solid surface and in the bulk liquid, and the effect of a finite volume of liquid [2]. The model proposed in this work, which considers all the aspects mentioned above with the only simplifying hypotheses of particles sphericity, aims to understand the interplay among several factors with particular focus on the relation among wettability, hydrodynamic film and the relative particles-fluid velocity, which has never been studied in much details. Our simulations evidence that in case of low solid wettability, the hydrodynamic film thickness and the particles-fluid relative velocity play a minor role in determining the dissolution kinetics. On the other hand, these phenomena become very important when no wettability problems occur. Interestingly, despite the physical complexity, the mathematical model solution (a set of ordinary differential equations) can be achieved by means of the implicit Euler method.