Formulation development and statistical optimization of chronotherapeutic tablets of indometacin

Chronotherapeutic drug delivery offers a new approach in the pharmacologic interventions design for the effective treatment in the diseases which follows circadian rhythm. In the present study chronotherapeutic tablets of indometacin was designed to match the timing of rheumatoid arthritis treatment with the intrinsic illness timing. The developed chronotherapeutic delivery system consists of a core tablet containing the active ingredient along with osmogents and other excipients, which was coated with a swellable polymer, hydroxyl propyl methyl cellulose by compression coating technique. The time controlled release was achieved by coating the entire system with a combination of pH-independent polymer, Eudragit RS 100 and Eudragit RL 100 (1:1). The optimization technique using Box-Behnken design was employed for the selection of the ideal formula. The optimization procedure was validated, and the observed value of the ideal batch was found to be similar with the predicted values within 5% of predicted error. The formulation when administered at bed time starts releasing the drug after a lag time of 4 h and provides sufficient plasma concentration after 6 h of normal sleep. Thus, the tablets can be successfully used for the chronotherapeutic drug delivery of indometacin in the treatment of rheumatoid arthritis.