As a therapeutic group, non-steroidal anti-inflammatory drugs (NSAIDs) are among the
most widely used, prescribed and over the counter (OTC) medications for the treatment of inflammatory
diseases, but suffering from several undesired side effects, the most important being
ulcerogenicity, mucosal hemorrhage and gastritis. Most of the NSAID moieties are chemically composed
of carboxylic functional groups and this could be one of the reasons for the damage to the mucosal
lining. The prodrug designing is one of the several strategies used to overcome this drawback.
Hence, in the last decade, the design and the synthesis of prodrugs of NSAIDs have been explored and
given much attention by medicinal chemists. The rationale behind the prodrug concept is to achieve
temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption.
This review is aimed to highlight and provide important information on NSAID prodrugs that have
been designed and reported to be safe and more effective. This review will also focus on NSAID prodrugs
that have been designed for improving therapeutic i.e. anti-inflammatory action as well as improving
drug delivery at the target site. The most common derivatives of carboxylic NSAIDs that are
discussed here belong to the chemical classes of esters, amides, anhydrides, acetals and the other derivatives
with completely masked carboxylic groups. The successful prodrugs were listed and their molecular
structures were also demonstrated here. The present review covers the recent updates present in
literature and will surely provide a greater insight into the designing of safer NSAIDs in the future.