Solubility Of Theophylline Research Articles

Soluble complex formation of theophylline with aliphatic di- and monoamines in aqueous solution.

The interactions of theophylline with aliphatic diamines and aliphatic monoamines were studied by measurements of solubility in aqueous solution. Diamines such as 1, 3-propanediamine, 1, 4-butanediamine, 1, 6-hexanediamine and ethylenediamine, and monoamines such as triethylamine, diethylamine, n-propylamine, allylamine, 2-methoxylamine, ethanolamine and triethanolamine were used. The solubility of theophylline increased in the presence of amine and increased in proportion to the pKa of the amine. The amount of the complex formed was found to be proportional to the pKa of the amine and the apparent stability constant of complex formation tended to increase as the pKa of the amine increased.

Extended Hildebrand Solubility Approach: Methylxanthines in Mixed Solvents

The solubility profiles of theobromine, theophylline, and caffeine at 25° were examined in binary solvent systems including dioxane-formamide, water-polyethylene glycol 400, and glycerin-propylene glycol. Theobromine solubility was studied in dioxane-water mixtures, a solvent system that was investigated earlier for the solubility of theophylline and caffeine. Solubilities were calculated in these polar systems by a regression method, based on an extension of the Hilde-bland-Scatchard equation of regular solution theory. A linear relationship between the mixed solvent solubility parameter, δ1, and dielectric constant, ϵ, was introduced earlier and was confirmed in the present study. In addition, it was observed that a regression of log(activity coefficient) on ϵ in a second or higher degree polynomial provides reasonable solubility values for the methylxanthines in mixed solvents. A direct regression of molal or mole fraction (but not molar) solubility against δ1, ϵ, or against volume percent of one or the other solvent in a binary solvent mixture provided a suitable measure of solubility for these crystalline drugs in mixed polar solvents. The drug's solubility parameter as determined from peak solubility in mixed polar solvents varied somewhat, depending on the specific solvent system employed. It is suggested that a drug may exhibit one (or more) solubility parameters in nonpolar solutions and multiple solubility parameters in polar systems. The extended solubility approach serves for the back-calculation of solubilities in mixed solvent systems, even though the solubility parameter of the solute may vary from one solvent system to the next.

Extended hildebrand solubility approach: Solubility of theophylline in polar binary solvents

A quantitative approach is presented for predicting solubilities of crystalline compounds in binary solvent systems. The solubility of theophylline in mixed solvents consisting of dioxane and water was determined at 25 ± 0.1°. The solubilities across this range of polar solvents were back-calculated using a technique involving an interaction energy term, W. This parameter is regressed against a polynomial expression in δ1, the solubility parameter for the mixed solvents. Except for the end-points, solubilities were predicted within <12% and with considerably better accuracy in most cases. The new approach modifies the well-known Hildebrand solubility equation to make it applicable to polar systems. Although the method may be used with solutes in pure solvents, its greatest application appears to be the prediction of drug solubility in binary solvent mixtures.

The Solubility of Theophylline in Aqueous Amine Solutions

A study has been made of the solubility of theophylline in aqueous solutions of certain amines. The molar solubility of theophylline has been plotted against molar concentrations of monomethylamine, dimethylamine, trimethylamine, monoethylamine, diethylamine, moao-n-propylamine, di-n-propylamioe, mono-n-butylamine, and di-n-butylamine. The solubilizing effect decreases with increasing length of the carbon chain; thus monomethylamine has an effect greater than that of any other amine investigated. Monomethylamine has greater solubilizing effect than does dimethylamine, which in turn is more effective than trimethylamine. The solubility increases with increasing concentration of primary amine until a point of maximum solubility is reached, thereafter solubility decreases with increasing amine concentration. The maximum solubility increases with increasing length of the carbon chain.