Abstract
Aspirin chlorzoxazone ester linked mutual prodrug was synthesized with the aim of improving the thera peutic index through prevention of gastrointestinal irritation and bleeding. The structure of the synthesized ester prodrug was con firmed by IR and 1H NMR spectroscopy and their purity was established by elemental analysis, HPLC and TLC. The release of ASP as well as CZX, from the ester prodrug was studied. A validated analytical HPLC method for the estimat ion of the ASP , and the pr odrug was developed. The kinetics of ester hydrolysis was studied in four different non - enzymatic buffer solutions, at pH 3 , 4, 5 and 7.4 as well as in experimental plasma . Study of skeletal muscle relaxant and anti - in flammatory properties in comparison wit h the reference compounds has shown that both skeletal muscle relaxant and anti - in flammatory activities were present at the same doses of the investigated compounds. The ester was found to be less irritating to gastric mucosal membrane than the parent drugs . These results sugge st that the synthesized prodrug is characterized by better therapeutic index than the parent drugs.
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