Development of Novel Combination Drug Treatment for Arthritis Using Chronopharmacological Approach

Concomitant therapy of anti inflammatory agent and disease modifying drug in pulsatile pattern proves the best treatment for pain relief and in remission of disease. In the current work, combination therapy of aceclofenac and leflunomide was studies for rheumatoid arthritis. Tab in tab formulation was developed with inner leflunomide and outer aceclofenac fraction. Outer fraction provides instant relief from symptomatic pain and inner part provides disease remission. pH sensitive polymers were investigated for coating and coating parameters were optimized. Considering the pH solubility of Eudragit S 100 and Eudragit L 100 in different ratio, final composition was derived. With final composition, desired lag phase observed in the drug release study. Further, X-ray studies and Pharmacokinetic study with final formulation also proves the efficacy of the final formulation w.r.t. desired lag phase and drug plasma concentration in-vivo. Final formulation found stable in 3 months stability study w.r.t. physical and chemical parameters. Optimized novel pulse release combination therapy developed to provide the relief to arthritis patient.