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

Surface tension, conductivity, density, and ultrasound velocity measurements have been performed in order to determine in a systematic manner some of the aggregation properties of the phenothiazine drugs promazine and triflupromazine hydrochlorides. Both drugs are structurally related, differing in an extra CF3 group in the triflupromazine molecular structure. Surface tension data showed that the presence of an extra CF3 in the molecular structure of triflupromazine involves a higher hydrophobicity of this drug and a restriction in the number of conformations molecules can adopt due to the presence of this bulkier atomic group. This involves a larger surface area in order to accommodate triflupromazine molecules at the interface. From conductivity measurements at different temperatures, the thermodynamic quantities of the micellization process of these drugs indicate that the aggregation is a spontaneous process, mainly enthalpic, where the London-dispersion forces play an active role. Using density and ultrasound velocity measurements, apparent molar volume and adiabatic compressibility of aqueous solutions of the amphiphilic cationic drugs have been determined. Positive deviations from the Debye–Hückel limiting law of the apparent molar volume were obtained from both drugs over the whole temperature range, which provides evidence of possible pre-association at concentrations below the critical concentration. Apparent molar adiabatic compressibility of the aggregates formed by these drugs was typical of those corresponding for an aggregate formed by a stacking process.