Absorption of diltiazem in beagle dog from pulsatile release tablet.
An orally applicable pulsatile drug delivery system in dry-coated tablet form was prepared using diltiazem hydrochloride as the model drug, and a polyvinyl chloride-hydrogenated castor oil-polyethyleneglycol mixture as the outer shell of the tablet. In vitro drug release from the prepared tablet exhibited a typical pulsatile pattern with a 7 h lag phase (non-drug release period). This dosage form was orally administered to three beagle dogs under non-fasting and fasting conditions, and the plasma concentration level of diltiazem was determined according to time after administration. The result of the in vivo study in non-fasting dogs suggested that the drug could be released in the gastrointestinal tract as in the in vitro test. However, under the fasting condition, a large difference in the plasma concentration profile was found, suggesting that the disintegration time of the tablet tended to be influenced by the feeding condition of subject.
Ishino
R
R
Pharmaceutics Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Yoshino
H
H
Hirakawa
Y
Y
Noda
K
K
D000284:Administration, Oral; D000818:Animals; D002368:Castor Oil / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism*; D004110:Diltiazem / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D005215:Fasting; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D011143:Polyvinyl Chloride / Q000737:chemistry; D013608:Tablets, Enteric-Coated
D003692:Delayed-Action Preparations; D013608:Tablets, Enteric-Coated; D011092:Polyethylene Glycols; D002368:Castor Oil; D011143:Polyvinyl Chloride; D004110:Diltiazem