Interaction of drug molecules with surfactants below (Benesi-Hildebrand equation) and above the critical micelle concentration (Kawamura equation)

Drug molecules can interact with surfactant molecules either in their monomeric form, where the Benesi-Hildebrand equation determines the binding constant, or when a micellar pseudophase is formed, where the Kawamura equation assesses the partition coefficient. Benesi-Hildebrand plots represent the differential absorbance as a function of surfactant concentration below the critical micelle concentration (CMC), while Kawamura plots show this relationship above the CMC, where the drug can influence the CMC and needs consideration. This review aims to provide an overview of methods for evaluating drug-surfactant interactions in aqueous solutions, particularly below and above the CMC, using spectroscopic data. Understanding these interactions is crucial for pharmacodynamics, affecting drug binding, enzymatic activity, and formulation. Various surfactants were analyzed with diphenhydramine hydrochloride, levofloxacin, phenothiazine, moxifloxacin, and chlorpromazine hydrochloride to determine monomeric binding constants, while sulfathiazole, sodium valproate, cefotaxime, losartan, and metformin hydrochloride were assessed for partitioning coefficient values. Errors in Benesi-Hildebrand plots may arise from considering surfactant concentrations above the CMC, while mistakes in Kawamura plots may stem from neglecting to determine the CMC in the presence of drug molecules, which can alter the surfactant’s behavior.