Precaution on use of hydrochloride salts in pharmaceutical formulation

Previous reports suggested that the formation of hydrochloride salts does not always enhance solubility due to the common ion effect. The extent of the common ion effect seems to be related to aqueous solubility, with slightly soluble hydrochlorides being more sensitive to the common ion, i.e., chloride ion. The relationship between solubility in water and the extent of the common ion effect was examined, and a high correlation was found, suggesting that hydrochlorides possessing solubilities in water at least of the order observed for papaverine and demeclocycline hydrochlorides (approximately 32 mg/ml at 25 degrees and 42 mg/ml at 37 degrees) are less soluble than the corresponding free base at gastric pH.