AIMTo develop a novel pulsatile drug delivery system of which the lag-time is controlled by an erodible plug (EP) and evaluate its release characteristics in vitro.

METHODSThe impermeable capsule body was prepared by fulfilling method and the drug tablet and the erodible plug were made by wet granulating compression. Tetramethylpyrazine phosphate (TMPP) pulsincap capsule was prepared by sealing the drug tablet and fillers inside the impermeable capsule body with the EP. The influence factors on the lag-time such as the EP pharmaceutical properties and the dissolution condition were investigated by dissolution testing.

RESULTSBoth the composition and the weight of EP influenced the lag-time of the tetramethylpyrazine phosphate pulsincap capsule significantly. The lag-time prior to the drug release was enhanced when the content of gel-forming excipient (hydroxypropylmethylcellulose, HPMC) in the EP or the weight of EP was increased. The hardness of EP showed minor influence on the lag-time. In addition, the lag-time was shortened when the paddle speed was higher, while the pH value of the dissolution medium exhibited no significant influence on it.

CONCLUSIONTo meet the chronotherapeutic requirements, a pulsatile drug delivery system with a suitable lag-time can be achieved by adjusting the composition and the EP weight.