An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets

Abstract

To develop new pulsatile release tablets, which can suppress drug release in stomach and release the drug rapidly after a predetermined lag time of about 3 h in intestine, the use of tablets with ethylcellulose/Eudragit L as a coating film and cross-linked polyvinylpyrrolidone in the core tablets was investigated. The release of diltiazem hydrochloride (DIL) as a model drug in the core tablets was investigated in vitro. The lag time ( t 10) was prolonged with an increase of the coating level, whereas the drug release rate was almost constant, irrespective of the coating level. The water-uptake study and electron microscope photographs suggested the mechanism of pulsatile release of drug. Pulsatile release tablets containing 60 mg DIL with 4.4 h of lag time ( t 10) in vitro were administrated to eight volunteers. The mean plasma concentration curves showed 4.9 h of lag time ( t lag), 8.0 h of time to maximum concentration ( t max) and 3.1 h of time between t max and t lag ( t psi) in vivo. Relative bioavailability was 1.05 for pulsatile release tablets compared to conventional tablets.