Surfactants and ureas affect the cloud point of amphiphilic drug, clomipramine hydrochloride

Clomipramine hydrochloride (CLP) is an antidepressant drug which shows temperature dependent phase separation, also known as the cloud point (CP). Increase in pH decreases the CP of the drug solution. Addition of ureas/thioureas at a fixed pH (6.25) decreases/increases the CP. In ureas, presence of >CO bond causes a decrease in repulsions among positively charged drug molecules. However, >CS bond (of thioureas) behaves oppositely and hence CP increases. Cationic and non-ionic surfactants form mixed micelles and hence increase the CP. Anionic surfactants, at low concentrations, retard micellization and increase the CP. At higher concentrations, these surfactants also form mixed micelles and, due to charge opposite to the drug molecules, reduce the repulsion among micelles and act as CP suppressors. Increase in solution pH/drug concentration at different fixed concentrations of CTAB causes the CP to decrease/increase. Dye solubilization results with the drug have provided proof to the above explanation.