Binding ability of sodium valproate with cationic surfactants and effect on micellization: calorimetric, surface tension, light scattering and spectroscopic approach

The interactions of surfactant molecules with biologically active pharmaceutical ingredients remain an important area of research due to the necessity to improve drug delivery and solubilization systems. In the present study, the various interactions present between a hydrophilic drug sodium valproate (SV) and cationic surfactants, viz. dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB), hexadecyltrimethylammonium bromide (HTAB) and cetylpyridinium chloride (CPC), in aqueous media have been explored by using various techniques. The partitioning of SV in the micelles of respective surfactants has been studied by using isothermal titration calorimeter (ITC), and various parameters like binding/partitioning constant (K), enthalpy, entropy, free energy and stoichiometry of binding have been determined in post-micellar regions. The outcomes reveal that CPC binds strongly to the SV as it provides more hydrophobic interactions, and the positive values of enthalpy (Δ_rH) are overcome by higher positive value of entropy (Δ_rS) which makes the overall process thermodynamically favorable. The binding parameters obtained for TTAB, HTAB and CPC are further compared with the double-tailed surfactants, i.e., didodecyldimethylammonium bromide (DDAB) and dihexadecyldimethylammonium bromide (DHDAB). In addition, the effect of SV on the micellization behavior of TTAB, HTAB and CPC was also studied using ITC and surface tension measurements, and various thermodynamic and interfacial parameters have been derived. Dynamic light scattering and proton (¹H) NMR studies have been performed to determine the locus of SV molecules within micelles of HTAB, TTAB and CPC.