Solubility, melting point and salting-out relationships in a group of secondary amine hydrochloride salts

The solubilites of eight hydrochloride salts of some alpha adrenergic agonists, and beta adrenergic agonist/blocker drugs were determined in water al 25 degrees C. An inverse relationship was observed between log X(+) and the melting points of the salts where X(+) is the mole fraction solubility of drug. The entropy of fusion values were not constant, as suggested by the observed log solubility-melting point correlation, and ranged from 16 to 26 cal K-1 mol(-1). It is therefore unlikely that crystal forces alone are responsible for the observed relationship between log X(+) and melting point. Setchenow salting-out constants were determined from the solubilities of the hydrochloride salts in sodium chloride-water and were found to be greatest for those compounds that possessed the lowest aqueous solubility and highest melting point. The number of aromatic rings and aromatic ring substituents also appear to have a significant influence on the values of the salting-out constants.