Degradation kinetics of benzonatate in aqueous solutions
Journal
International Journal of Pharmaceutics
Journal Volume
176
Journal Issue
2
Pages
179-186
Date Issued
1999
Author(s)
Abstract
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. Copyright (C) 1999 Elsevier Science B.V.
SDGs
Type
journal article