Design, Formulation, Evaluation and Statistical Optimization of Coated Floating Pulsatile Tablets for Modified Chronopharmacotherapy of Rheumatoid Arthritis

Objective: Rheumatoid arthritis is a condition that needs early morning medication according to biorhythms. Hence, the main aim of designing Chronomodulated Floating Pulsatile Tablets (CFPT) of opioid analgesic and to perform in vitro drug release, in vitro buoyancy for modified chronopharmacotherapy of rheumatoid arthritis. Methods: The formulation was designed with the immediate core covered with buoyant composition and followed by immediate release layer. The best formulations of core tablets were compression coated with Methocel K100M, Plantago Ovate Gum (POG), and Tamarindus gum (TG) to assign a suitable lag time for formulation as a preliminary trial. Further 32 factorial designs was utilized to study polymer and Sodium Bicarbonate (SB) composition, Statistical optimization was done on dependent parameters such as FLT, FD, %DR5H, and % DR10H. Results: In this chronomodulated formulation, immediate release layer and core tablets were optimized with formulation IF4 which contains sodium starch Glycolate and Cross Carmellose sodium 8%, and then in buoyant formulation, CFPT was optimized by DoE optimization showing FF9 exhibiting good floating behavior and lag time. FLT of 125 sec, FD of 10h, % DR5H of 15.24% and maximum drug release of 98.28% were obtained for formulation FF9. Conclusion: As the formulation showed immediate and delayed drug release in vitro and also showed in-vitro buoyancy, hence nighttime administration could be beneficial to reduce the rheumatoid arthritis complications in the early morning.