Preparation and evaluation of Eudragit gels. IV: Rectal gel preparations for sustained release and avoidance of first-pass metabolism of propentofylline.
Formulations of a high-viscosity acrylic resin gel (Eudispert hv) containing propentofylline, a new cerebral microcirculation-improving agent, were prepared and tested for avoidance of the first-pass metabolism of propentofylline through the liver and for sustained release of propentofylline. The absolute bioavailability of propentofylline after oral administration was only 4% in rabbits. The relative bioavailabilities of propentofylline from polyethylene glycol (M(r), 2000) and Witepsol H-15 suppositories were approximately 8- and 16-fold, respectively, compared with oral administration. Furthermore, the absolute bioavailability of propentofylline from Eudispert hv hydrogel and xerogel preparations was approximately 100%. The results indicate that, in principle, drug loss caused by first-pass metabolism may be avoided completely by placing Eudispert hv hydrogel and xerogel formulations in the lower part of the rectum for long periods.
Kim
N S
NS
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ito
T
T
Kawata
M
M
Uchida
T
T
Goto
S
S
D000180:Acrylic Resins / Q000008:administration & dosage*; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003692:Delayed-Action Preparations; D005782:Gels; D008297:Male; D011109:Polymethacrylic Acids; D011817:Rabbits; D014970:Xanthines / Q000008:administration & dosage* / Q000378:metabolism
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D005782:Gels; D011109:Polymethacrylic Acids; D014970:Xanthines; C038300:methylmethacrylate-methacrylic acid copolymer; C032114:propentofylline