Abstract
The solubility at 30° C of theophylline in mixtures of water and the cosolvents ethanol, propylene glycol, dimethylformamide and PEG 400 has been measured. In all these systems the solid phase in equilibrium with the solution depended on the solvent composition; theophylline monohydrate was present for water-rich solutions and anhydrous theophylline for cosolvent-rich solutions. The volume fractions of water at which the transition between the solid phases occurred was f′ = 0.18, 0.35, 0.35 and 0.25 for ethanol, propylene glycol, dimethylformamide and PEG 400, respectively. Maxima in the solubility vs composition profiles occurred for ethanol and propylene glycol, but not for dimethylformamide. The effects of hydrate formation on the solubility are analysed quantitatively in the case of ethanol/water mixtures. Hydrate formation depresses the solubility in water-rich solutions and distorts the shape of the solubility profile. In comparing experimental solubilities with the predictions of regular solution theory in the extended Hildebrand approach it is necessary to take account of the effect of hydrate formation.
Published Version
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