title: Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.
abstract: BACKGROUND
  ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.
  
  
  METHODS
  Release from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.
  
  
  RESULTS
  Full analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of 13C) was 5:42 h (95% CI 5:18-6:18 h, range 2:36-6:36 h,) There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT) based on pH (median 5:42 vs 5:31 h p = 0.903). In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.
  
  
  CONCLUSIONS
  From the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.
  
  
  BACKGROUND
  ISRCTN Registry 18301880.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Jacoba M
authors.initials: JM
authors.lastname: Maurer
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Reinout C A
authors.initials: RC
authors.lastname: Schellekens
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Hèlen M
authors.initials: HM
authors.lastname: van Rieke
authors.affiliation: Medimetrics Personalized Drug Delivery BV, Eindhoven, The Netherlands.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanke
authors.affiliation: Medimetrics Personalized Drug Delivery BV, Eindhoven, The Netherlands.
authors.forename: Ventzeslav
authors.initials: V
authors.lastname: Iordanov
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.affiliation: University of Rostock, Children's Hospital, Research Laboratory Gastroenterology and Nutrition, Rostock, Germany.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Wutzke
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.affiliation: University of Groningen, Department Pharmacy, Section of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
authors.forename: Margot
authors.initials: M
authors.lastname: van der Zee
authors.affiliation: University of Groningen, Department Pharmacy, Section of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
authors.forename: Herman J
authors.initials: HJ
authors.lastname: Woerdenbag
authors.affiliation: University of Groningen, Department Pharmacy, Section of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands; University of Groningen, Department Pharmacy, Section of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001682:Biological Availability; D003106:Colon / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D065546:Drug Liberation; D005260:Female; D005772:Gastrointestinal Transit; D064368:Healthy Volunteers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D013607:Tablets; D055815:Young Adult
chemical_list: D004337:Drug Carriers; D013607:Tablets