Chronotherapy: Formulation and Evaluation of Pulsatile Floating Drug Delivery of Tramadol HCl

This study attempts to design and evaluate a chronomodulated drug delivery system of tramadol hydrochloride, it a NSAID drug for the treatment of arthritis, fibromyalgia. It was aimed to have a lag time of six hours that is, the system is taken at the bed time and expected to release the drug after a period of 6 hr at early morning time. Such time-controlled pulsatile drug delivery can be achieved mainly with cores containing tramadol hydrochloride as bioactive agent were prepared by direct compression method using different ratios of microcrystalline cellulose with effervescent agent. The tablets were coated sequentially with an inner swelling layer containing a HPMC K4M (100mg, 200mg and 300mg) and an outer rupturable layer having Eudragit RL 100 + PGE 6000 (1:1) with 1 and 2%. Which act as release controlling layers. The core serves as reservoir and the release controlling layers protect the core from the environment e.g., water, acidic pH and enzymes until the drug is released after a predetermined lag phase. Single unit rupturable pulsatile drug delivery system was chosen as the model system over erodible pulsatile drug delivery system because of ease of manufacturing, better reproducibility of the lag time and rapid drug release after a lag time. The rupture and dissolution tests were studied using the USP paddle method at 100 rpm in 0.1 N HCl for first 2hrs and then phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. All the results obtained in the present study suggest that osmotic pumping effect was involved which eventually lead to the drug release.