Solid Complexes of Theophylline with Several Aliphatic Monoamines

The formation of solid complexes of theophylline with 16 aliphatic monoamines was attempted from aqueous and absolute ethyl alcohol solutions. Theophylline forms solid complexes with methylamine, ethylamine, n-propylamine, monoethanolamine, n-propanolamine, and isopropanolamine, in a molar ratio of 1 : 1. The solid complex of methylamine contains one molecule of water of crystallization. The ability to form solid complexes was considered to be related to the pKa value, type, and hydrophobic property of the amine. The thermal and physico-chemical properties of these solid complexes were investigated by differential thermogravimetry, differential scanning calorimetry, X-ray powder diffractometry, and infrared spectroscopy. It was found that the thermal stabilities of the solid complexes of amines with a hydroxyl group are higher than those of amines without a hydroxyl group ; however, the incremental thermal stabilities of the complexes of amines without a hydroxyl group are higher than those of amines with a hydroxyl group upon formation of the solid complex. The heats of reaction for formation of the solid complexes of theophylline with monoamines and the activation energies of deamination reactions of the solid complexes were determined and are discussed.