An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets.
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 (t10) 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 (t10) in vitro were administrated to eight volunteers. The mean plasma concentration curves showed 4.9 h of lag time (tlag), 8.0 h of time to maximum concentration (tmax) and 3.1 h of time between tmax and tlag (t(psi)) in vivo. Relative bioavailability was 1.05 for pulsatile release tablets compared to conventional tablets.
Fan
T Y
TY
Department of Pharmacy, Peking University School of Pharmaceutical Sciences, 100083, Beijing, China.
Wei
S L
SL
Yan
W W
WW
Chen
D B
DB
Li
J
J
D000328:Adult; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002482:Cellulose / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004110:Diltiazem / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D010592:Pharmaceutic Aids / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000493:pharmacokinetics*; D011205:Povidone / Q000493:pharmacokinetics*; D013608:Tablets, Enteric-Coated
D000959:Antihypertensive Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D010592:Pharmaceutic Aids; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose; D004110:Diltiazem; D011205:Povidone