Zn(II)-theophylline-ethylenediamine: structure and pH stability

A zinc-containing salt of theophylline, Zn(II)-aminophylline, was synthesized and its structure determined by X-ray diffraction techniques. The zinc ion is coordinated to two theophylline anions and a molecule of ethylenediamine in a tetrahedral arrangement. The solubility of the compound in water at 30 degrees (0.047 mg/ml) is 180-fold lower than that of theophylline (8.40 mg/ml). The complex is relatively stable in the alkaline pH range, but it hydrolyzes, releasing theophylline in acidic environments. The rate of theophylline release is pH dependent. These properties are useful in formulating chewable tablets and liquid suspension dosage forms that overcome the characteristic bitter taste of theophylline, yet provide for efficacious treatment of diseases involving the respiratory tract.