Amide Codrug Approach: Synthesis and Biopharmaceutical Evaluation of Nonsteroidal Anti-Inflammatory Drug and Calcium Channel Blocker Conjugates

Background and Aim Geriatric patients often suffer from osteoarthritis and hypertension comorbidity. The codrugs approach was shown to be an effective strategy for targeting diseases synergistically hence improving the quality of life of patients. The present study aimed to synthesize various Nonsteroidal Anti-inflammatory Drugs NSAIDs and Calcium channel blocker CCB Co-drugs and biopharmaceutical study to eliminate the adverse gastrointestinal effects of the NSAIDs to treat comorbid conditions in geriatric patients with significant reduction of polypharmacy.Methods Various conjugates were synthesized by a one-pot amidation reaction of Amlodipine with various NSAIDs. Further characterization by melting point TLC Fourier transform infrared nuclear magnetic resonance and mass spectroscopy followed by solubility partition coefficient and hydrolysis study in SGF and SIF.Results The synthesized codrugs satisfied the structural criteria of the proposed plan. From the biopharmaceutical and hydrolysis study it was observed that the co-drugs underwent significant hydrolysis in SIF pH 7.4 and have showed delayed onset of action with respect to the standard drugs. The delayed onset may be due to the hydrolysis of amide linkage followed by the release of the prodrug which finally releases the active drug.Conclusion The findings illuminated the codrugs pros and cons aiding optimization and development. This research advances amide-based mutual prodrugs and their use in pharmaceutical research. The outcome of this exploration confirmed that the described co-drug can offer desirable safety and therapeutic benefits. Hence these conjugates could be considered for further development.