The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil

Abstract

Protolytic equilibria and solubility of verapamil were investigated in the presence and in the absence of nonionic surfactant Brij 35 at a constant ionic strength (0.1 mol/L NaCl) and temperature 25 degrees C. In surfactant free media the intrinsic solubility, S-o = 4.51 X 10(-5) mol/L (only the neutral form is present in the solution) and pH dependent solubility, S (neutral and ionized form in solution) of verapamil were determined. On the basis of the solubility data, the apparent pK(a) value 9.15 of verapamil was indirectly obtained. In micellar media (10(-3) mol/L Brij 35) the solubility of verapamil free base (S-0,S-s = 2.76 X 10(-3) mol/L) and the apparent pK(a,s) = 6.35, were determined. The shift in the protolytic equilibria (Delta pK(a) = -2.80) and the increased solubility of verapamil free base (approximately 60 times) caused by Brij 35 point out to specific interactions between verapamil and the inner part of Brij 35 micelles. The most significant changes in distribution of verapamil equilibrium forms were observed at biopharmaceutically important pH 7.4 which potentially indicates interactions with biomolecules in blood plasma.