Factors Affecting Tautomeric Phenomenon of a Novel Potent Immunosuppressant (FK506) on the Design for Injectable Formulation

Abstract

Due to its poor solubility in water, immunosuppressive drug substance FK506 was aimed to use nonaqueous solvent such as dehydrated ethanol for designing the injectable formulation. Ethanol, however, has been known to generate the tautomeric compounds from FK506. Herein, factors affecting the tautomeric phenomenon have been studied. Polyoxyethylene hydrogenated castor oil 60 (HCO-60, nonionic surfactant), employed as a solubilizer to avoid producing precipitates in FK506 admixtures, restrained the formation of tautomeric compounds. High temperature accelerated the equilibrium among FK506 and tautomeric compounds, whereas pH and concentration of FK506 solution had no effect on the tautomeric phenomenon.