A convective-diffusion model for dissolution of two non-interacting drug mixtures from co-compressed slabs under laminar hydrodynamic conditions.

Abstract

A numerical convective-diffusion dissolution model has been extended to describe dissolution of two neutral non-interacting drugs co-compressed in a slab geometry. The model predicted the experimental dissolution rates of naproxen/phenytoin mixtures and hydrocortisone/nitrofurantoin mixtures quite accurately, except for phenytoin in the naproxen/phenytoin mixture at low weight proportions. A non-linear dependence of dissolution rate on weight proportion with a positive deviation from linearity was observed. An increase in flow rate increased the dissolution rate and the cube-root dependency of dissolution rate on the flow rate for a given weight proportion of the component in the slab, as proposed earlier by Shah and Nelson for pure compounds, was also observed here, suggesting that the changes in dissolution profile were caused by changes in surface area only. As expected from the model an increase in particle size of the powders used to make the slab decreased the dissolution rate. This was explained by an increase in the average length of the component resulting in a bigger 'carryover' of material from one section of the component in the slab to the next section of the same component, due to convection, and hence lower flux.