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Hydrolysis Kinetic Studies of Mutual Prodrugs of Diclofenac Sodium

S. Chhajed, Manisha Puranik, M. Padwal, Z. Deshmukh, S. Agarwal and P. Yeole

Mutual prodrugs of diclofenac with paracetamol, salicylamide and N-Mannich bases of salicylamide were synthesized with a view to reduce its ulcerogenic potential, which is attributed to the presence of free –COOH group and inhibition of endogenous prostaglandins. Therefore, blocking this group by synthesizing functional derivatives carboxylic acid, may reduce these side effects. In vitro hydrolysis of the prodrug in hydrochloric acid buffer pH 1.2 indicated that it was resistant to acidic hydrolysis and hence, may not produce irritation of the gastrointestinal tract, where as in phosphate buffer (pH 7.4), it is hydrolyzed following first order kinetics, releasing free drug and linker moiety.