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. (C) 1999 Elsevier Science B.V. All rights reserved.