Understanding the Effect of Differently Charged Surfactants on the Protolytic Equilibria of the Drug Naproxen in Micellar Solution

Abstract

The protonation process of the poorly water-soluble drug naproxen (NAP) was studied potentiometrically in an aqueous cosolvent mixture of ethanol (25% by v/v) at temperature (298.15 ± 0.1) K and an ionic strength of 150 mM adjusted by NaCl. The potentiometric measurements were performed in various concentrations (above the critical micelle concentration or CMC) of the surfactants sodium dodecylsulfate (SDS), dodecyltrimethylammonium bromide (DTAB), and poly­(ethylene glycol) dodecyl ether (Brij 35) with head groups of different charges but the same hydrocarbon chain length. The influence of surfactant type was evaluated on the basis of a shift in the acidic constant (pK a) determined in micellar media as compared to those in a micelle-free medium. The calculations of thermodynamic function Δp G m ° (standard Gibbs free energy change) for the protonation process of NAP suggest that the differences in the values are attributed to the electrostatic and nonelectrostatic interactions between the drug and the micelle head groups. Based on the results obtained in the micellar media, irrespective of the surfactant type, the pK a of naproxen decreases on raising the micelle concentration. Moreover, the increasing order of the pK a value of the drug in the surfactant solutions is SDS > DTAB > Brij 35.