Evaluation of the correlation between in vivo and in vitro release. Effect of the force of contraction and food on drug release.
The effects of the force of contraction in the gastrointestinal (GI) tract and of food on drug release were investigated. Two dosage forms were administered orally to beagle dogs. Dosage form A was a matrix in which drug release was affected by the force of contraction in the GI tract, and dosage form B was not affected by the contraction force. The in vitro dissolution curves from dosage forms A and b using the paddle-beads method were similar to in vivo drug release, with the respective release of up to at least 50%. The in vitro release by means of the paddle-beads method was characterized by the in vivo drug release. The in vivo drug release profile from dosage form A was affected by food. A 1:1 relationship between in vivo and in vitro release was observed up to 6 h in those dogs under the fed condition, but only up to 2.5 h in those under the fasted condition. In the earlier stage of oral administration there was no difference in drug release profile between dogs of the fed and fasted conditions; however, the drug release rate in the fed condition was faster than that in the fasted condition 2-4 h after administration. It was thus assumed that in the fed condition, drug release from dosage form A was affected by gastro-duodenal transit time or by the different environment in the distal parts of the GI tract rather than by the force of contraction.
Aoki
S
S
Research Laboratories of Pharmaceutical Development, Eisai Co., Ltd., Gifu, Japan.
Ando
H
H
Ishii
M
M
Ida
K
K
Watanabe
S
S
Ozawa
H
H
D000284:Administration, Oral; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004068:Digestive System Physiological Phenomena; D004285:Dogs; D004304:Dosage Forms; D004435:Eating; D005769:Gastrointestinal Motility; D066298:In Vitro Techniques; D008297:Male; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D004304:Dosage Forms; D010665:Phenylpropanolamine; D002482:Cellulose; C008079:hydroxypropylcellulose