BEHAVIOUR OF SUCCINIC ANHYDRIDE AND BENZOCAINE IN THE SOLID-PHASE REACTION

The possibility of obtaining benzocaine succinamide under the conditions of mechanochemical reaction of succinic anhydride with benzocaine (a local anesthetic) is demonstrated. It has been established that mechanical treatment in a ball mill results in amorphisation of initial substances, promoting adsorption of succinic anhydride on the surface of drug crystals, which leads to the chemical interaction between initial components. An intensive development of solid-phase interaction was determined to proceed intensively during 10 days after the load was removed. The maximum transformation degree (~90 %) was detected for the mechanical treatment of an equimolar mixture of benzocaine and succinic anhydride, in the amount of 4 g, in a ball mill for ~2 h. With a decrease in the mixture mass or increase in the load applied, the maximum yield is achieved within a shorter time. The conversion degree was determined to decrease with an increase in the time of mechanical action in all cases. The detected feature can be related to the equilibrium amidation under the conditions of heating during the long-term action of the impact load.