Investigation on the effect of surfactant on solubility of carbamazepin-cinnamic acid cocrystal

Abstract

Introduction: Solubility is among the important parameters of the drugs to reach therapeutic concentration in the circulation and desirable pharmacologic response. Low level of solubility is a major problem in the formulation of the drugs. Pharmaceuticals co-crystals are composed of two crystalline compounds via noncovalent interactions, predominantly composed of hydrogen bonding in certain stoichiometric rations. It is a novel method to enhance physicochemical properties of pharmaceuticals. However, instability in solution is one of the challenging issues of co-crystals and surfactants/ polymers could have a positive effect on co-crystal solubility and stability. Aim: The aim of this study is to evaluate the solubility and stability of co-crystal form of carbamazepine with cinnamic acid (in the solution) in the presence of sodium lauryl sulfate as a surfactant and polyvinyl pyrrolidone K17 (PVPK17) as a polymer in the aqueous media. Method: The solubility of the carbamazepine, cinnamic acid as well as co-crystal were evaluated in different media, including phosphate buffer solution, sodium lauryl sulfate surfactant with 0.5% and 2% concentration, and PVP polymer with 0.5%, 1% and 2% concentration. The solubility was measured using spectrophotometry and results were compared. Results: Carbamazepine-cinnamic acid co-crystal has more solubility than carbamazepine in phosphate buffer solution. Improving solution stability by PVP and especially sls (0/5%) could increase the solubility but SLS decreased its solubility in high concentration (2%) because of solubilizing agents preferential solubilization for the drug despite the stability of co-crystal Conclusion: SLS and PVP polymer have significant effects on the solubility and solution stability of carbamazepine-cinnamic acid co-crystal and it should be considered in developing co-crystal formulation.