Colonic delivery of sodium butyrate via oral route: acrylic coating design of pellets and in vivo evaluation in rats.
Few pharmaceutical studies, with the exception of those on rectal solutions, are described on short chain fatty acid (SCFA) formulations-especially for sodium butyrate, which is a colonocyte preferential substrate. Highly dosed butyrate pellets (90%) were prepared and their coating was designed for colonic delivery. In vivo determination (pH and transit time of pellets in rats) allowed to respectively choose the grade and thickness (resistance of 6 h) of the pH-dependent coating (Eudragi L+S, 1:1). The coated pellets were administered to naturally butyrate-deprived rats. The rats' colonic mucosa had the particularity to weakly express mitochondrial HMG-CoA synthase, an enzyme that responds to luminal butyrate. The results did not show early absorption of butyrate, but a probable cecal loss in the rat cecum as cecal residence time of the pellets was important and as pH was propitious for the coating hydrolysis. It seemed that butyrate, given daily for 7 days without the other main SCFA. was unable to induce the enzyme and/or that the dose (0.32 mmol/day) was insufficient.
Tuleu
C
C
Laboratoire de Galénique, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes-Paris, Paris, France. catherinetuleu@minitel.net
Andrieux
C
C
Cherbuy
C
C
Darcy-Vrillon
B
B
Duée
P H
PH
Chaumeil
J C
JC
D000284:Administration, Oral; D000818:Animals; D020148:Butyric Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002329:Carmine / Q000493:pharmacokinetics; D002432:Cecum / Q000737:chemistry; D003066:Coenzyme A Ligases / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004396:Coloring Agents; D005753:Gastric Mucosa / Q000737:chemistry / Q000201:enzymology; D005766:Gastrointestinal Contents / Q000737:chemistry; D005772:Gastrointestinal Transit; D006863:Hydrogen-Ion Concentration; D006904:Hydroxymethylglutaryl-CoA Synthase; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids; D051381:Rats; D011916:Rats, Inbred F344; D013607:Tablets
D004396:Coloring Agents; D011109:Polymethacrylic Acids; D013607:Tablets; D020148:Butyric Acid; C038300:methylmethacrylate-methacrylic acid copolymer; D002329:Carmine; D006904:Hydroxymethylglutaryl-CoA Synthase; D003066:Coenzyme A Ligases; D009638:Norepinephrine