Abstract
It has been found that diphenhydramine undergoes fairly rapid decomposition in the presence of a strong acid and, in order to find its decomposition in gastric juice and its stability in a preparation, kinetic studies were made of its decomposition in aqueous solution. Diphenhydramine is hardly decomposed in alkaline solution. The decomposition in acid solution was found to be due to hydrolysis of the ether linkage and the reaction velocity constants were calculated at 40.0°, 50.0°, 59.6°, and 95.0°, between pH 0.7 and pH 4.7. It was found that this decomposition is a pseudofirst-order reaction and that it was catalyzed by hydrogen ion in the range of pH measured. The hydrogen ion catalytic constant, kH, could be represented by the following equation:
kH=8.63×1015⋅e-23, 900/RT (L./mole/hr.)
Rates of decomposition during digestion in the stomach, during sterilization at pH 5.5, and during storage were calculated from the above equation and all were found to be below 0.4%, negligible from the point of compounding. It is assumed, therefore, that the rapid decomposition of diphenhydramine in the body is mainly due to their decomposition in the organs and tissues.
