A thermodynamic study of the amphiphilic phenothiazine drug thioridazine hydrochloride in water/ethanol solvent

A comparative study of the thermodynamic properties at the air–water interface and in the bulk of structurally related phenothiazine drugs aqueous solutions

“…These values are of the same order as those reported for other tricyclic drugs [12,[44][45][46][47]. The distance between drug monomers in the surface monolayer is mainly due to the linkage of the phenyl rings of the structure in the form of a rigid planar nucleus that causes the drug molecules to be fairly separated at the interface.…”

“…This shows that there is practically no effect of the temperature on the outer hydrated molecules, E (STR). Besides that, the values are positive indicating the predominance of hydrophobic hydration over electrostriction of water molecules around the solute ions [64], and of similar magnitude to those of other tricyclic drugs [47,55]. The slightly higher values for the expansibility of the monomer for triflupromazine suggest a little larger hydration of the monomer when free in solution than that of promazine.…”

“…Such hydrophobic interactions become increasingly insignificant with the partial breakdown of the structure of water as the temperature rises and the aggregation becomes primarily an enthalpic process; the negative DH m values suggest the importance of the London dispersion interactions as the major force of aggregation. Similar changes from entropic to enthalpic aggregation with temperature increases have been observed for many surfactants and amphiphilic drugs [31,46,47]. In this regard, it has been shown that van der Waals interactions between the amino side chain of phenothiazines and the 2-substituent on ring A can promote a conformation mimicking dopamine [49].…”

“…Negative DV m / values were also obtained for other tricyclic drugs [12,47,56,62] and suggest that there is less mobility in the interior of the aggregates than in typical micelles as might be expected if a stacked aggregate were formed. The relatively small increase in free space of drug molecules on transition to the micellar state is a possible consequence of the stacked arrangement of the almost planar structure of the molecules.…”

“…The same behaviour has been found for triflupromazine, although the second critical concentration, cmc 2 , is found at lower concentrations, mainly due to its higher hydrophobicity. The second critical concentration emerges as a structural rearrangement of the previously formed aggregates in order to minimize the energy of the solution, as occurred for other tricyclic drugs including other phenothiazine and antidepressant drugs [12,13,47]. Table 2 shows the values of the critical concentrations at different temperatures for both drugs.…”