A novel system for three-pulse drug release based on "tablets in capsule" device.

The objective of the present study was to obtain programmed drug delivery from a novel system, which contains a water-soluble cap, impermeable capsule body, and two multi-layered tablets. Types of materials for the modulating barrier and its weight can significantly affect the lag time (defined as the time when drug released 8% of the single pulse dosage). We chose sodium alginate and hydroxy-propyl methyl cellulose (HPMC E5) as the candidate modulating barrier material. Through adjusting ratio of sodium alginate and lactose, lag time was controllable between the first two pulsatile release. Linear relationship was observed between the ratio and the lag time. Through adjusting the ratio of HPMC E5/lactose, lag time between the second and the third pulse can be successfully modulated. In further studies, drug release rate of the second pulsatile dose can be improved by adding a separating layer between the third and the modulating barrier layer in the three-layered tablet. To evaluate contribution of bulking agent to drug release rate, lactose, sodium chloride, and effervescent blend were investigated. No superiority was found using sodium chloride and effervescent blend. However, lactose favored it. The results reveal that programmed drug delivery to achieve pulsatile drug release for three times daily can be obtained from these tablets in capsule system by systemic formulation approach.