A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon.

AIM To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid (500 mg) was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects. The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentration-time curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

[1]  G. Corazza,et al.  Oral butyrate for mildly to moderately active Crohn's disease , 2005, Alimentary pharmacology & therapeutics.

[2]  German and Austrian ImipenemCilastatin Study Group,et al.  Treatment of distal ulcerative colitis with short-chain fatty acid enemas a placebo-controlled trial , 1996, Digestive Diseases and Sciences.

[3]  E. di Giulio,et al.  Combined Oral Sodium Butyrate and Mesalazine Treatment Compared to Oral Mesalazine Alone in Ulcerative Colitis , 2000, Digestive Diseases and Sciences.

[4]  V. Annese,et al.  Topical butyrate improves efficacy of 5‐ASA in refractory distal ulcerative colitis: results of a multicentre trial , 2003, European journal of clinical investigation.

[5]  C. Tuleu,et al.  Colonic delivery of sodium butyrate via oral route: acrylic coating design of pellets and in vivo evaluation in rats. , 2001, Methods and findings in experimental and clinical pharmacology.

[6]  S. Polak‐Charcon,et al.  Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition. , 2001, Oncology research.

[7]  W. Hörl,et al.  Anti‐inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL‐12 and up‐regulation of IL‐10 production , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  D. Coradini,et al.  Sodium butyrate modulates cell cycle‐related proteins in HT29 human colonic adenocarcinoma cells , 2000, Cell proliferation.

[9]  I. Macdonald,et al.  In vivo measurement of colonic butyrate metabolism in patients with quiescent ulcerative colitis , 2000, Gut.

[10]  M. Chapman,et al.  In vivo colonic butyrate metabolism and colonic permeability in extensive ulcerative colitis. , 1998, Gastroenterology.

[11]  F. Azzaroli,et al.  Sluggish small bowel motility is involved in determining increased biliary deoxycholic acid in cholesterol gallstone patients , 1999, American Journal of Gastroenterology.

[12]  P. Rutgeerts,et al.  In vivo butyrate metabolism and colonic permeability in extensive ulcerative colitis. , 1998, Gastroenterology.

[13]  J. Baker,et al.  Treatment of left‐sided ulcerative colitis with butyrate enemas: a controlled trial , 1996, Alimentary pharmacology & therapeutics.

[14]  J. Patz,et al.  Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas. , 1996, The American journal of gastroenterology.

[15]  A. Roda,et al.  Intestinal absorption of bile acids in the rabbit: different transport rates in jejunum and ileum. , 1996, Gastroenterology.

[16]  M. Chapman,et al.  Butyrate metabolism in the terminal ileal mucosa of patients with ulcerative colitis , 1995, The British journal of surgery.

[17]  Boyle,et al.  Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. , 1994, Gut.

[18]  I. Finnie,et al.  Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism. , 1993, Gut.

[19]  T. Kirchner,et al.  Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. , 1992, Gastroenterology.

[20]  R. Frizzell,et al.  Intestinal absorption and secretion , 1991 .

[21]  S. Hakomori,et al.  Antibody-mediated targeting of differentiation inducers to tumor cells: inhibition of colonic cancer cell growth in vitro and in vivo. A preliminary note. , 1989, Biochemical and biophysical research communications.

[22]  W. Roediger,et al.  Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. , 1986, British journal of experimental pathology.

[23]  O. Fausa,et al.  Absorption of short-chain fatty acids from the human colon measured by the 14CO2 breath test. , 1982, Scandinavian journal of gastroenterology.

[24]  J. Cummings.  Short chain fatty acids in the human colon. , 1981, Gut.

[25]  F. Wilson,et al.  Intestinal transport of bile acids. , 1981, The American journal of physiology.

[26]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.

[27]  F. Plum.  Handbook of Physiology. , 1960 .