2026-10-10T20:43:56Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34045626 2026-10-01T12:15:27Z category_19 portal_316 item_type_3 month_year_10_2026

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 Venkata Krishna Kowthavarapu (25156470) Nitin Bharat Charbe (17249689) Tatiana Iakovleva (12857826) Cordula Stillhart (9146417) Neil John Parrott (18534569) Stephan Schmidt (394425) Rodrigo Cristofoletti (18939973) Pharmacology acidifying agents diffusion dissolution modeling mass transport analysis surface pH <p>At the solid–liquid interface, the dissolution of weakly basic drugs, particularly those exhibiting poor solubility, is highly sensitive to local pH conditions. 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. Model validation was performed using entrectinib, a clinically relevant weak base, across formulations with and without acidifying agents, supported by experimental dissolution data generated under different media conditions. The results demonstrate that bulk pH-based modeling is insufficient to capture critical formulation-driven dissolution behavior and establish surface pH as a primary determinant of dissolution kinetics. Overall, this study establishes surface pH modeling as a key advancement for mechanistic dissolution prediction of oral drug products containing functional pH-modifying excipients.</p> 2026-10-01T12:15:27Z Dataset Dataset 10.3389/fphar.2026.1924679.s001 https://figshare.com/articles/dataset/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/34045626 CC BY 4.0