Supplementary file 1_Mechanistic mass transport analysis of dissolution of weak-base drugs considering the influence of surface pH in formulations with and without acidifying agents.docx

These compounds frequently show pH-dependent solubility and reduced bioavailability when co-administered with acid-reducing agents, which presents significant difficulties for formulation design and clinical efficacy. Despite advances in physiologically based biopharmaceutics modeling, most existing dissolution modeling frameworks fail to account for microenvironmental pH changes induced by functional excipients such as acidifying or basifying agents.

To address this critical gap, we developed a mechanistic mass-transport-based dissolution framework that explicitly quantifies surface pH as a function of excipient diffusion and acid–base equilibria. The model integrates coupled diffusion–reaction kinetics within the diffusion boundary layer, enabling accurate prediction of interfacial pH under both buffered and unbuffered conditions. Building on the classical framework, we numerically captured the impact of monoprotic and diprotic acidifying agents on surface pH.