Formulation and in Vitro Evaluation of Nabumetone Pulsatile Drug Delivery

The present study aimed to design and evaluate an oral pulsatile drug delivery system (Pulsincap) for Nabumetone, a nonsteroidal anti inflammatory drug (NSAID) used in the management of rheumatoid arthritis (RA), osteoarthritis (OA), and juvenile rheumatoid arthritis. The Pulsincap system consists of a water-insoluble hard gelatin capsule body cross-linked with formaldehyde vapors, filled with an optimized Nabumetone tablet blend, and sealed with a hydrogel plug prepared from Ethyl Cellulose and HPMC K15M in varying ratios. Twelve tablet formulations (F1–F12) were prepared using different super-disintegrants (Crospovidone, Ludiflash, Lycoat). Formulation F12 (Lycoat 20 mg) was selected as optimized, showing maximum drug release of 98.16% within 30 minutes. Capsule bodies exposed to formaldehyde for 6 hours maintained the required 6-hour lag time. Among five pulsincap formulations (P1F12–P5F12), P5F12 — containing Ethyl Cellulose:HPMC K15M (2:1) — was identified as optimal, achieving 99.84% drug release after a 6-hour lag time. Drug release followed Korsmeyer-Peppas kinetics with super case-II transport. Stability studies at 40°C/75% RH for 3 months confirmed formulation stability. This system offers a promising chronotherapeutic approach for timed drug delivery aligned with the circadian pattern of arthritic symptoms. Keywords: Pulsatile drug delivery, Nabumetone, Pulsincap, Chronopharmaceutics, HPMC K15M, Ethyl Cellulose, Rheumatoid Arthritis, Lag time