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World J Gastroenterol. Feb 21, 2007; 13(7): 1079-1084
Published online Feb 21, 2007. doi: 10.3748/wjg.v13.i7.1079
A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon
Aldo Roda, Patrizia Simoni, Maria Magliulo, Paolo Nanni, Mario Baraldini, Giulia Roda, Enrico Roda
Aldo Roda, Maria Magliulo, Paolo Nanni, Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, Bologna 40126, Italy
Patrizia Simoni, Mario Baraldini, Giulia Roda, Enrico Roda, Department of Internal Medicine and Gastroenterology, University of Bologna, via Massarenti 9, Bologna 40126, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Aldo Roda, Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, Bologna 40126, Italy. aldo.roda@unibo.it
Telephone: +39-51-343398 Fax: +39-51-343398
Received: November 10, 2006
Revised: December 1, 2006
Accepted: January 22, 2007
Published online: February 21, 2007
Abstract

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.

Keywords: Sodium butyrate; Inflammatory bowel diseases; Ulcerative colitis; Crohn’s disease; Controlled release formulation; Pharmacokinetics; Stable isotope; Breath test