Energetics of Clouding Phenomenon in Amphiphilic Drug Imipramine Hydrochloride with Pharmaceutical Excipients

The clouding behaviour of an amphiphilic antidepressant drug imipramine hydrochloride (IMP) with several additives (hydrotropes, bile salts, fatty acids and sugars) over the entire composition range at pH = 7.6 was investigated in the present study. The magnitude of clouding (increase or decrease) of IMP in the presence of additives (pharmaceutical excipients) depends on the nature and types of additives. Bile salts and fatty acids showed peak behaviour i.e., cloud point (CP) increases at lower concentrations while decrease in cloud points was observed at higher concentrations. Thermodynamics at the CP were also evaluated (except for sugars, because sugars does not form mixed micelles with IMP), assuming that the clouding indicates the solubility limit when phase separation occurs. Thus, the various thermodynamic parameters e.g., standard Gibbs free energy (ΔGso), the enthalpy (ΔHso) and entropy (TΔSso) were calculated at this point. The results showed that the ΔGso, was found to be negative for all the additives, however ΔHso and TΔGso of the clouding phenomenon were found to be positive or negative depending upon the types and nature of additives.