Kinetics of Tetracaine Solvolysis in Propylene Glycol

Tetracaine is a potent ester-type local anesthetic. Recent publications describe the use of TC free base in topical anesthetic formulations containing propylene glycol. While solvolysis of tetracaine in propylene glycol solutions has been reported, there are no detailed reports on the kinetics of tetracaine reaction with propylene glycol. The objectives of the study were to characterize the kinetics and temperature dependence of tetracaine solvolysis in PG solutions. In this study, products of tetracaine degradation in propylene glycol solution at 60°C were collected and analyzed by high-performance liquid chromatographymass spectrometry and nuclear magnetic resonance. The kinetics of tetracaine reaction with propylene glycol was studied at 22°C, 30°C, 40°C, and 60°C. The reaction of tetracaine with n-propanol and isopropanol was also studied. Analysis was performed by high-performance liquid chromatography-mass spectrometry with ultraviolet detection using a gradient elution method. Tetracaine concentrations were quantitated using a four-point standard curve. Tetracaine degradation rates were consistent with apparent first order kinetics at all temperatures studied. The data indicated that tetracaine degrades via transesterification with propylene glycol. The rate constants ranged from 2.26 x 10^-3 d^-1 at 22°C to 7.06 x 10^-2 d^-1 at 60°C. Arrhenius analysis indicated an activation energy for the reaction of 74.1 kJ/mol, which is similar to published values for the hydrolysis of pharmaceutical esters.