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Prodrugs Of Ibuprofen II-Kinetics Of Decomposition Of N-Mannich Base Prodrugs

Author(s): Abha Doshi, S. G Deshpande

The kinetics of decomposition of N-Mannich base derivatives of ibuprofenamide was studied to assess their utility as a prodrug for ibuprofen. These kinetic studies were performed in aqueous buffers at different pH values, in simulated gastric and intestinal fluids and in human plasma at 37o. Kinetic studies in aqueous buffers at different pH showed that these derivatives undergone pH dependent hydrolysis. The pH-rate profile for these compounds had a sigmoidal shape. These N-Mannich bases were hydrolyzed to ibuprofenamide but in no case ibuprofen was released. Kinetic studies performed in simulated gastric and intestinal fluid showed that there was not much effect of gastric and intestinal constituents on the release rate. But the kinetic studies performed in human plasma showed that some amount of ibuprofenarnide was converted to ibuprofen which might be due to the presence of proteolytic enzymes in human plasma.


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