Synthesis and Pharmacological Evaluation of Tyrosine and Glycine Prodrugs of Aceclofenac

The gastrointestinal toxicity associated with aceclofenac (AC) can be reduced by synthesis of its prodrugs. Itinvolves condensing the carboxylic acid group of AC with methyl esters of amino acids like tyrosine and glycineto give tyrosine conjugated aceclofenac (3a) and glycine conjugated aceclofenac (3b), respectively.Physicochemical characterization of the prodrugs by various analytical and spectral methods was carried out. Invitro hydrolysis in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and human plasma showed anencouraging hydrolysis rate in SIF and human plasma than in SGF. This indicated that the prodrugs do not breakin stomach but release aceclofenac in SIF and human plasma. The pharmacological evaluations showed acomparable increase in anti-inflammatory activity and marked reduction of ulcer index for the prodrugs. Normalhistological findings revealed that the prodrugs are not producing any ulceration in the gastric region. Theprodrugs thus possess better pharmacological response than the parent drug