Effect of salt and urea on complexation behavior of pharmaceutical excipient gelatin with phenothiazine drug promazine hydrochloride

Abstract

An evaluation of the interactions of cationic phenothiazine drug promazine hydrochloride (PMZ) with gelatin in aqueous solution as well as in the presence of 50mM NaCl and 100mM urea, investigated through different physicochemical measurements is presented in the present study using conductometric method. PMZ is used for the control of mania and schizophrenia. The drug interacts with gelatin similar to the interaction of surfactants and polymers. The plots of specific conductivity versus concentration of the drug were nonlinear with three different linear regions with two clear breaks. The first break point, i.e., critical aggregation concentration (cac), appeared well below the typical critical micelle concentration (cmc). The second break point is considered as polymer saturation point (psp) that is akin to cmc. The cac value decreases on increasing the gelatin concentration, whereas the psp value increases for all fixed concentrations (%w/v) of gelatin which is a clear signal of the interaction of the drug with gelatin. As inorganic salts increase the ionic strength, the solubility of amphiphile (drug) is lowered by ionic screening effects, ensuing in a greater tendency to aggregates at lower concentration. As a result, both the cac and psp/cmc values decrease. By the addition of urea an increase in the surface charge of the micelles was observed followed by halt of the aggregation of the drug hence both the cac and psp/cmc values increase. Free energies of aggregation (ΔGagg), micellization (ΔGmic), polymer saturation (∆Gpsp) and transfer (ΔGt) were also evaluated.