Preparations of solid particulates of theophylline--ethylenediamine complex by a spray-drying technique

Aqueous solutions of ethylenediamine and theophylline were spray dried to obtain solid particulates of theophylline--ethylenediamine complex to improve solubility of theophylline. Packing and flow properties of the spray-dried products were much improved when compared with those of original theophylline particles, due to their spherical shapes which were confirmed by a scanning electron microscope. The solubility of theophylline in the resultant products was found to be three to five times higher than that of original theophylline. The solubilities of the products decreased with increasing drying temperature and rotation speed of the atomizer, which was interpreted in terms of the contents of ethylenediamine in the products. The products were confirmed to be a mixture of aminophylline, alpha-aminophylline, and theophylline by X-ray analysis and NMR spectroscopy. The logarithm of the relative intensity of the X-ray diffraction peak of alpha-aminophylline to that of theophylline decreased linearly with drying temperature and rotation speed of the atomizer. Thermal decomposition of the spray-dried products involved liberations of crystal water at 100 degrees and ethylenediamine between 110 and 127 degrees. Liberation of ethylenediamine occurred via three steps for aminophylline, but with different steps for the spray-dried products.