Degradation kinetics of benzonatate in aqueous solutions

The decomposition of benzonatate in aqueous solutions followed apparent first-order kinetics. One major hydrolysis product, 4-(butylamino)benzoic acid, was efficiently and completely separated from benzonatate with a validated HPLC. The apparent activation energies obtained from an Arrhenius plot was 16.07, 20.54 and 18.23 kcal mol−1 in buffer solutions with pH 3.61, 9.42 and 10.46, respectively, which indicated that hydrolysis dominated the degradation process. The buffer concentration showed significant effect on the hydrolysis of benzonatate (P<0.05). Specific acid-, specific base- and buffer catalyzed hydrolysis of benzonatate were observed in solutions with pH in the range of 0.31–12.21. The decomposition of benzonatate in basic solutions was faster than in acidic solutions by about 2000-fold. The prominent base-catalyzed breakdown of the ester bond and slower acid-catalyzed hydrolysis suggested that benzonatate should be prepared in the solutions with pH 3–7 to maximize its stability.