FACTORS AFFECTING TAUTOMERIC PHENOMENON OF A NOVEL POTENT IMMUNOSUPPRESSANT (FK506) ON THE DESIGN FOR INJECTABLE FORMULATION

Due to its poor solubility in water, immunosuppressive drug substance FK506 was aimed to use nonaqueous solvent such as dehydrated ethanol f or designing the injectable formulation. Ethanol, however, has been kn own to generate the tautomeric compounds from FK506. Herein, factors a ffecting 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, res trained the formation of tautomeric compounds. High temperature accele rated the equilibrium among FK506 and tautomeric compounds, whereas pH and concentration of FK506 solution had no effect on the tautomeric p henomenon.