Development of a Quantitative Method for Formulation Microenvironmental pH Assessment

• Published in: Molecular pharmaceutics
• Main Authors: Romero-Gonzalez, Mariana, Van Horn, Robert D., Liu, Youlin, Jonuzaj, Suela, Hanson, Jeff C., Sperry, David C., Salehi, Niloufar
• Format: Journal Article
• Language: English
• Published: United States 05.08.2025
• Subjects: dual-emission pH-sensitive fluorescent dyes; microenvironmental pH; pH modifier; solid dispersion; confocal laser scanning microscopy
• ISSN: 1543-8384; 1543-8392; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.5c00514

The purpose of this research was to develop a quantitative method for assessing the microenvironmental pH of pharmaceutical formulations containing acidic or basic pH modifiers. pH modifiers are included in formulations to improve the dissolution of ionizable drugs that exhibit pH-dependent solubility or to improve the chemical stability of the drug in the formulation by adjusting the microenvironmental pH to a range that is more favorable. The study utilized dual-emission pH-sensitive fluorescent dyes and confocal laser scanning microscopy to image the dissolving compacts of drug formulations. The images were analyzed using Python code to generate pH maps reflecting the spatial pH changes across the distinct layers formed as the compacts dissolve. This technique allowed for pH mapping over a broad pH range by using two different dyes with distinct working pH ranges. The technique is a robust tool for optimizing oral pharmaceutical formulations. By providing a reliable method for assessing microenvironmental pH, this technique can help ensure the performance or stability of formulations, reduce the need for extensive testing and reformulation, and ultimately expedite the process of bringing new products to market.