Computational fluid dynamics-based modeling of drug dissolution in non-Newtonian media

This study extends an existing computational fluid dynamics (CFD)-based dissolution prediction framework to shear-thinning non-Newtonian media. Salicylic acid tablets were selected as the model drug, and hydroxypropyl methylcellulose (HPMC) aqueous solutions of different concentrations were used as dissolution media. Based on the mass balance equation, a drug dissolution model was developed by correlating the mass transfer coefficient with the average flow velocity and the viscosity of the medium. CFD simulations were performed to obtain local hydrodynamic parameters, while the model parameters were calibrated using a subset of the experimental dissolution data and subsequently validated using the remaining independent datasets. The results showed that HPMC solutions exhibited shear-thinning behavior. Increasing HPMC concentration reduced the saturation concentration of salicylic acid and significantly slowed drug dissolution, while increasing paddle speed enhanced the local flow velocity. The proposed model accurately predicted the dissolution profiles of salicylic acid tablets in water and HPMC media under different rotation speeds, with similarity factors (f₂) greater than 90 (maximum 99.7) and an average maximum absolute percentage error of 2.70%. The present study demonstrates the feasibility of extending CFD-based dissolution prediction from Newtonian to shear-thinning HPMC media through a mechanistically informed and experimentally calibrated framework. The proposed approach provides a basis for future extension and validation of CFD-assisted dissolution prediction models in other pharmaceutical systems.