Synthesis and Evaluation of Amide Codrug of Ibuprofen and Amlodipine for Dual Inhibition of Inflammation and Hypertension

Abstract

The codrugs approach showed as an effective strategy for targeting diseases synergistically, hence improving the quality of life of patients. The main goal is to address comorbid conditions of hypertension and osteoarthritic pain and inflammation in geriatric patients, eliminate the adverse gastrointestinal adverse effects of the drug, reducing dose with significant reduction of polypharmacy and improve patient compliance. The present study aimed to synthesize amide linked codrugs of Ibuprofen (nonsteroidal anti-inflammatory drug) and Amlodipine (Calcium channel Blocker), its biopharmaceutical study and evaluation of anti-inflammatory and antihypertensive activity. Codrug conjugates were synthesized by a one-pot amidation reaction of Amlodipine with Ibuprofen using DCC as coupling agent and DMAP as catalyst. The obtained compound Ibuprofen-Amlodipine amide linked codrug (IBAM) was characterized by determination of melting point, TLC, DSC, FT-IR, NMR, and mass spectroscopy. The solubility, partition coefficient, plasma protein binding and in vitro hydrolysis study in SGF and SIF were studied to determine biopharmaceutical properties.The anti-inflammatory and antihypertensive activity of synthesized compounds were tested in a carrageenan-induced rat paw oedema model and Fructose induced diabetic hypertensive model and it was discovered that the codrugs underwent significant hydrolysis in SIF (pH 7.4) and IBAM showed effective reduction in hypertension, inflammation in comparison to parent drug. Finally, it is concluded that the codrug approach could be successfully used in drug design and development for overcoming undesirable difficulties without losing the desired activities of the parent drugs.