Modeling and predicting the influence of variable factors on dissolution of crystalline pharmaceuticals

Abstract In this work, the dissolution profiles of different crystalline active pharmaceutical ingredients (APIs), which show a diverse water solubility (paracetamol>hydrochlorothiazide>trimethoprim>naproxen>indomethacin>cinnarizine) were measured in water at different temperatures and stirring speeds using a rotating disk system. Meanwhile, the dissolution mechanism of these APIs was analyzed by using a two-step chemical-potential-gradient model. The solubilities and activity coefficients of the investigated APIs were calculated by using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). It was found out, that the dissolution mechanism of different crystalline APIs in water can be different dependent on their water solubilities. Additionally, an increase in both, the surface reaction and diffusion rate constants for all investigated crystalline APIs was observed with an increase in temperature and stirring speed. By the use of linear correlations between the API surface reaction and diffusion rate constants with the temperature and stirring speed, the dissolution profiles of the selected APIs could be predicted as function of temperature and stirring speed with high accuracy compared to the experimental data.