A novel theoretical strategy for predicting dissolution kinetics and mechanisms of pharmaceuticals in complex biorelevant media

The influence mechanism of biorelevant media on the dissolution of active pharmaceutical ingredients (APIs) is the key to their formulation design. The dissolution kinetics of naproxen (NAP) and indomethacin (IND) in biorelevant media was systematically investigated. The dissolution mechanism was analyzed by chemical po-tential gradient model to explore the influence of surfactant type, pH and ionic strength. Hexadecyl trimethyl ammonium bromide (CTAB) is superior to sodium dodecyl sulfate (SDS) in promoting the dissolution of NAP and IND by increasing the solubility and accelerating the surface reaction processes. The electrostatic repulsion between SDS and NAP and IND with the same negative charge facilitates the diffusion of API, while the mutual attraction between CTAB and NAP and IND is not conducive to diffusion. High pH was favorable for the dissolution of acidic NAP and IND, as the simultaneous increase in solubility, surface reaction constant, and diffusion constant. High ionic strength was beneficial for the surface reaction of NAP and IND, but hindered their diffusion. It was shown that the modeling results were in conformity with the in vitro experimental data. These results are expected to provide theoretical supports for the design of biorelevant media and pharmaceutical formulations in the pharmaceutical development.