Colon-Specific Delivery of Naproxen Pellets for Rheumatoid Arthritis: Development, Optimization, and Evaluation Using a 3-Level Randomized Full Factorial Design

Rheumatoid arthritis (RA) is characterized by increased joint pain and stiffness, particularly in the morning, which requires medication for treatment. Our research described here was aimed to develop, evaluate, and optimize coated naproxen pellets for colon-specific delivery using the carboxymethyl Leucaena leucocephala gum for the chronotherapy of RA. The extrusion-spheronization process was used for the preparation of the pellets followed by coating in a fluidized bed processor with materials such as Eudragit (R) S 100 and L 100. An 11-run, 2-factor, 3-level, randomized full factorial design was used to analyze the impact on the responses by varying the levels of independent factors to obtain the optimized formulation. The drug release of all the formulation batches at the 4th hour varied from 1.24 to 17.22% in the upper gastrointestinal (GI) tract; while the release of the drug at the 10th hour varied from 76.87 to 98.39% at the colonic pH. Furthermore, it was observed that the optimized formulation exhibited an increased release of naproxen in the presence of cecal matter collected from rats. We suggest that the prepared optimized formulation of the coated pellets of naproxen shows promise for the chronotherapeutic treatment of early morning symptoms associated with RA.