Effect of pressure on the colloidal solution behavior of aqueous local anesthetic tetracaine solutions

Abstract

The solution behavior of two local anesthetics, tetracaine hydrochloride (TC·HCl) and tetracaine hydrobromide (TC·HBr), in water was studied. The temperature-pressure diagrams of aqueous TC·HCl and TC·HBr solutions of different concentrations were determined by observing the sudden change in transmittance accompanying the phase transition from the coagel phase to the micellar solution under high pressure up to 170 MPa. The transition temperature was linearly elevated by applying pressure. It was seen that the temperature-pressure slopes of both anesthetics increase with increasing concentration and become constant above 0.3 mol kg −1. We obtained the concentration-temperature phase diagram of TC·HCl solution from the solubility vs. temperature curves at different pressures, which were determined from the concentration dependence of the temperature-pressure diagrams, and the critical micelle concentration (CMC) vs. temperature curves. The solubility curve intersects the CMC curve at a certain temperature under atmospheric pressure, which is regarded as the Krafft temperature of TC·HCl. The volume change associated with the phase transition from coagel to micelle was estimated from the Clapeyron-Clausius equation using the values of the temperature-pressure slope above 0.3 mol kg −1 and the transition enthalpy taken from the DSC study. The values were determined to be 8.4 cm 3 mol −1 for TC·HCl and 9.5 cm 3 mol −1 for TC·HBr, respectively. Further, by considering the volume change of transition for TC·HCl among three states of anesthetic assembly, it was concluded that the solution behavior of these anesthetics in water bears a striking resemblance, with respect to volume, to that of typical cationic surfactants such as alkyltrimethylammonium salts.