Preparation and investigation on the stability of salt or cocrystal forms of valproic acid and carbamazepine

Abstract

Introduction: Solubility and dissolution rate of drugs directly affect their oral bioavailability. Another important physicochemical property of drugs is hygroscopicity. This property has an important role in physical stability of drugs. Sodium valproate is the most usual used form of valproic acid. One of the biggest problems of sodium valproate is its weak physical stability in high humidity. Aim: The aim of this study is preparation of a solid form of valproic acid with less hygroscopicity than sodium valproate and to provide a better soluble form of carbamazepine. Carbamazepine has low aqueous solubility, therefore improvement of this property has been a purpose for many researches. In this study formation of salt was used as a method to improve hygroscopicity of valproic acid and formation of cocrystal was used to improve dissolution rate of carbamazepine and hygroscopicity of valproic acid. Methods: Equal stoichiometric amounts of valproic acid and tris were grounded in a mortar using ethanol 96% as catalyst. To form the cocorystal, equal stoichiometric amounts of valproic acid and carbamazepine were added to methanol and stirred until dissolved, then the solution was left still in a plate for 24 hours for solvent evaporation. To study hygroscopicity, saturated solutions of mineral salts in a desiccator were used to produce specific relative humidities. The samples were placed in desiccator and the amount of mass increase represented the amount of absorbed moisture. Dissolution studies were done using e beaker and stirrer and concentration of solutions were obtained from a UV-Vis spectrophotometer. Results: Valproate tris salt had good physical stability in comparison with sodium valproate. Carbamazepine-Valproic acid cocrystal had more Carbamazepine concentration in the solution after 24 h. Conclusion: Crystal engineering techniques such as salt and cocrystal formation are some of the most functional methods to improve the physicochemical properties of drugs.