PHARMACEUTICAL SOLUBILITY AS A CRITICAL DETERMINANT OF DRUG QUALITY AND PERFORMANCE

In pharmaceutical research, solubility plays a key part in the assessment of pharmacokinetic risks. Poor drug absorption, reduced efficacy, excessive metabolism, and adverse reactions are frequently related to issues of drug solubility. During early discovery research at pharmaceutical companies, many thousands of molecules are considered. Most are rejected due to perceived unfavorable properties. Pharmaceutical solubility along with permeability link drug quality with its bioavailability and overall performance. For ionizable drugs, solubility depends on pH, ionic strength, ionization, self-association, complex formation, and solid-phase transformations. Studies demonstrate that apparently simple solubility measurements may conceal multiple aqueous and solid-state equilibria. Our research findings obtained within the physicochemical framework developed by Serajuddin and Avdeef, demonstrate that rigorous solubility measurement and mechanistic analysis are essential for salt selection, formulation design, dissolution testing, and reliable assessment of drug quality and performance.