Interaction of gelatin with promethazine hydrochloride: Conductimetry, tensiometry and circular dichroism studies

• Aggregation behavior of promethazine hydrochloride–gelatin mixtures has been investigated.
• PMT interacts with gelatin in a surfactant-like manner.
• The critical aggregation concentration (cac) and free energy of aggregation (ΔGagg) are evaluated.
• CD spectra show attractive electrostatic interactions between drug molecules and exposed binding sites of gelatin.
• The results have applicability in drug delivery.

The interaction of amphiphilic phenothiazine drug promethazine hydrochloride (PMT) with gelatin in aqueous as well as aqueous-electrolyte (50 mM NaCl) solutions has been studied by using conductimetry, tensiometry and circular dichroism (CD) techniques. The drug interacts with gelatin similar to the interaction of surfactants and polymers. Hence, we have considered the gelatin–amphiphile interaction approach using conductimetry and tensiometry. The plots of specific conductivity versus concentration of drug were nonlinear with three different linear regions with two clear breaks. The critical aggregation concentration (cac), i.e., first break point, appeared well below the usual critical micelle concentration (cmc). Second break is regarded as polymer saturation point (psp) which is similar to cmc. The interaction starts with the formation of a highly surface-active complex as revealed by the lowering of surface tension on the addition of drug to the macromolecule (gelatin). The results further show that the cac decreases on increasing the gelatin concentration, while psp increases for all concentrations of gelatin which is a clear indication of the interaction between the drug and gelatin. By the use of degree of ionization, free energies of aggregation (ΔGagg) and micellization (ΔGmic) were also evaluated. As inorganic salts increase the ionic strength, the solubility of amphiphile (drug) is lowered by ionic screening effects, resulting in a greater tendency to aggregate at lower concentration. Therefore, both the cac and psp/cmc values decrease. Effect of PMT on the secondary structure of gelatin in aqueous solutions was also investigated using CD measurements. The measurements demonstrated that the random coil content of gelatin increases with increasing the drug concentration.