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Drug delivery is an extremely demanding science, that seek to address the site specificity to the tissues in order to maximize drug activity and minimize side effects. In addition to bioavailability and pharmacokinetics, site specific or targeted drug delivery system is highly needed. The prodrug approach has emerged as a tool in overcoming the obstacles to drug formulation and targeting. Prodrugs may help to overcome several barriers by improving low chemical stability, aqueous solubility, or oral absorption/bioavailability, or by preventing rapid pre-systemic metabolism and potential toxicity, inadequate site specificity, or poor patient acceptance/compliance. Novel NSAIDs prodrugs of Aceclofenac with antioxidants like Quarcetin, Vanilin and metharylates showed better therapeutical action than the parent drug without loss of desired pharmacological activity. The prodrug approach proved to be successful.