Synthesis and evaluation of some amino acid conjugates of suprofen

Amino acid conjugates of suprofen were synthesized by coupling the carboxylic group (as acid chloride) of suprofen and various amino acid methyl ester hydrochlorides. The structures of the synthesized conjugates were characterized by analytical and spectral data. Release of the drug from the conjugates was investigated by performing hydrolytic studies in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF + 80% human plasma at pH 7.4. The results revealed that the drug was readily released from the conjugates in SIF at pH 7.4 and SIF + 80% human plasma at pH 7.4 following first order kinetics except for SGF at pH 1.2 where it exhibited negligible hydrolysis. The amino acid conjugates were evaluated for analgesic, acute and chronic anti-inflammatory and ulcerogenic activities. The results suggest that the amino acid conjugates showed comparable analgesic and anti-inflammatory activities to free drug with marked reduction in ulcerogenicity.