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


CONCLUSIONS
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.
Roda
Aldo
A
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, Bologna 40126, Italy. aldo.roda@unibo.it
Simoni
Patrizia
P
Magliulo
Maria
M
Nanni
Paolo
P
Baraldini
Mario
M
Roda
Giulia
G
Roda
Enrico
E
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D002087:Butyrates / Q000008:administration & dosage* / Q000378:metabolism* / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D002432:Cecum / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000188:drug therapy; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D013655:Taurochenodeoxycholic Acid / Q000097:blood
D002087:Butyrates; D002247:Carbon Isotopes; D013608:Tablets, Enteric-Coated; D002245:Carbon Dioxide; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D012964:Sodium