Solubilization of Biphenyl Dimethyl Dicarboxylate by Cosolvency

Abstract

Biphenyl dimethyl dicarboxylate (BDD) is a synthetic analogue of schizandrin C, one of the components isolated from Fructus schizandrae, and has been widely prescribed for improvement of liver functions and symptoms of patients with liver disease. However, its oral preparations have been known to have limited bioavailability due to its extremely low solubility in water, and its solubility problem also limits preparation of its parenteral dosage forms. In this research, we searched for solvent systems to solubilize BDD to overcome these problems. The ternary solvent systems of N,N′- dimethylacetamide (DMA)/alcohol/water and Cremophor EL/DMA/alcohol were studied intensively for this purpose. BDD was solubilized effectively in these cosolvents, and the results showed that the cosolvent systems were effective for solubilizing BDD up to the concentration that might be employed for preparation of parenteral dosage forms. Formulation of a BDD concentrate for intravenous infusion was proposed employing the cosolvent system of Cremophor EL/DMA/alcohol.