Chronotherapeutic Delivery of Lornoxicam Pellets for Rheumatoid Arthritis: Formulation Development and Optimization Using a Randomized Factorial Design

Rheumatoid arthritis (RA) is a chronic condition marked by joint pain and stiffness, especially in the morning, necessitating medication for management. This study focused on developing, evaluating, and optimizing coated lornoxicam pellets for targeted colon delivery, utilizing carboxymethyl Caesalpinia spinosa gum to address the chronotherapeutic needs of RA. The pellets were prepared using an extrusion-spheronization technique and subsequently coated in a fluidized bed processor with polymers such as Eudragit^® S 100 and RL 100. An 11-run, 2-factor, 3-level randomized full factorial design was employed to assess the influence of varying independent factors on the responses, leading to the identification of an optimized formulation. The drug release profiles of the formulation batches showed that at the 4th hour, release in the upper gastrointestinal (GI) tract ranged from 0 to 16.79%, while at the 10th hour, release at colonic pH ranged from 71.95 to 95.64%. Additionally, the optimized formulation demonstrated enhanced drug release in the presence of rat cecal matter, indicating its potential for targeted colonic delivery. In vivo pharmacokinetic studies of the optimized formulation showed a clearance of 0.022 L/hr and a volume of distribution of 0.319 L, indicating slow elimination and limited tissue distribution. The high area under curve values (44.53 and 96.12 µgh/mL) reflected effective absorption and good systemic exposure. The mean residence time of 21.30 h suggested prolonged residence time, supporting sustained therapeutic levels in the colon. These findings suggest that the optimized lornoxicam-coated pellet formulation holds promise for the chronotherapeutic management of early morning RA symptoms.