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

Abstract

Objective The main aim of designing Coated Floating Pulsatile Tablets (CFPT) of Tramadol hcl for statistical optimization and to perform in vitro and in vivo buoyancy evaluation for modified chronopharmacotherapy of rheumatoid arthritis. Methods The formulation was designed with the immediate core covered with a compression coat followed by the upper buoyant layer. Best formulations of Immediate burst release core tablets were compression coated with polymer HPMC K15M, Ispaghula gum (IG), and Tamarindus gum (TG) to assign suitable lag time to formulation. HPMC K100M, Ispaghula gum, and their combination were compressed as the buoyant layers. Parameters such as BLT, TFT, %SI,% CDR were Statistical optimized by surface and contour plots AND invivo buoyancy was also done. Results Immediate release core tablets were optimized with formulation IF2 which contains sodium starch Glycolate 8% as immediate release agent, and then in compression coated buoyant formulation CFPT was optimized by DoE optimization showing BF4 and BF8 exhibiting good floating behavior and lag time, drug release for a period of 11 hrs. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. Conclusion As the formulation showed delay in drug release both in in vitro and showed in vivo buoyancy, hence nighttime administration could be beneficial to reduce the rheumatoid arthritis complications in the early morning.