Effect of aromatic hydrotropies on the solubility of carbamazepine part I: effect of sodium salt of hydroxy and amino derivatives of benzoic acid

It was found that the hydrotropic agents enhance the water-solubility of carbamazepine as a function of their concentration. The solubilizing power of these hydrotropes was shown to be highly dependent on their chemical structure. The solubilizing power of the amino derivatives is generally higher than that of the hydroxy derivatives. The position of the hydroxyl or amino groups relevant to the carboxylate group in the hydrotrope molecule plays a major role in its solubilizing effect. The spectral pattern of carbamazepine was found to undergo a change in presence of these compounds. Applying the continuous variation method revealed formation of 2:1 carbamazepine complex with each of sodium salicylate and sodium anthranilate as well as a 1:2 complex with sodium p-amino benzoate. Also, the drug forms 1:1 complexes with both sodium m-hydroxybenzoate and sodium p-hydroxybenzoate. On the other hand, two species of complexes appear to be formed in carbamazepine-sodium p- aminosalicylate system, viz., 1:2 and 2:1 complexes. An apparent correlation seems to exist between the solubilizing power of the investigated hydrotropes and the stability constant of their respective complexes with the drug. Calculating the amount of drug solubilized in free as well as in complexed forms in these systems revealed that the decrease in the activity coefficient of carbamazepine in presence of the investigated hydrotropes may be responsible for the increase in carbamazepine solubility beside complex-formation