An original intragastric delivery system for oral administration of solid formulations to fully conscious rats: its application to oxodipine studies.
The purpose of this paper is to describe an original intragastric delivery system for powders to conscious rats. This system is an administration cannula composed of a simple polypropylene tube, long enough to reach the stomach and an adapted metallic stem in the lumen of the tube. A finite dose of powder, set on the free extremity of the cannuly, is expulsed into the stomach. This delivery system is applied to study oxodipine absorption from oral solid forms containing appropriate vehicles. Different test formulations were administered to rats: solution by I.V. (1 mg/kg) and P.O. (2mg/kg) routes, and oral dry powders (2 ng/kg). Blood samples were collected until 12 hours post-dose. Oxodipine plasma levels are measured by a HPLC method. Results indicated that the rate and extent of absorption can be modulated by the administration of oxodipine in different formulations. The formulations studied can be classified as a function of the vehicles added to the solid formulation. In fact, the limiting factor of absorption in rats is the in vivo dissolution rate. Absolute bioavailability can be modulated by different formulations. The apparent elimination half-life was dependent on the dissolution rate of oxodipine from formulations.
Egros
F
F
Département de Biopharmacie, Laboratoires Delagrange, Chilly-Mazarin, France.
Lhot
O
O
Stypulkowski
M
M
Hulot
T
T
Dufour
A
A
D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients; D006207:Half-Life; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal / Q000295:instrumentation*; D008297:Male; D011092:Polyethylene Glycols; D011208:Powders; D051381:Rats; D011919:Rats, Inbred Strains; D012967:Sodium Dodecyl Sulfate
D001647:Bile Acids and Salts; D004095:Dihydropyridines; D005079:Excipients; D011208:Powders; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; C053783:oxodipine