Development and evaluation of a time-specific pulsatile-release tablet of aceclofenac: a solution for morning pain in rheumatoid arthritis.

The objective of this study was to develop and evaluate an oral chronomodulated drug delivery system (CDDS) for the treatment of rheumatoid arthritis with a distinct predetermined lag time of 6 h (+/- 0.25 h). The basic design of the system consisted of an inner core, an intermediate swelling layer and an external acid-resistant enteric layer applied by pan coating. Croscarmellose sodium was used as a disintegrant and swelling agent to create the desired rupturing pressure. A mixture of hydroxypropyl cellulose M (175 mg) and ethyl cellulose (25 mg) was used as an intermediate swelling layer. The lag time for the system was found to be independent of the effect of various parameters such as compression load, paddle rotation speed and pH of dissolution medium. For the enteric coating of the press-coated tablet an aqueous dispersion of Eudragit L30 D55 containing 15% of total solid content plasticized with 20 triethyl citrate was applied by conventional pan coater. An in vitro dissolution study of the prepared tablet was conducted initially for 2 h in simulated gastric fluid, and after that medium was changed to simulated intestinal fluid pH 6.8. A pharmacokinetic study was also used to establish in vitro methodology capable of predicting the subsequent in vivo performance of the time-dependent pulsatile-release system. Various pharmacokinetic parameters studied in rabbits as the animal model demonstrated that drug absorption was not influenced by the in vivo behavior of the pulsatile system. As per guidelines provided by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use and the World Health Organization, the formulation was found to be stable.