title: A non-invasive, low-cost study design to determine the release profile of colon drug delivery systems: a feasibility study.
abstract: OBJECTIVE
  Conventional bioavailability testing of dosage forms based on plasma concentration-time graphs of two products in a two-period, crossover-design, is not applicable to topical treatment of intestinal segments. We introduce an isotope dual-label approach ((13)C- and (15)N(2)-urea) for colon drug delivery systems that can be performed in a one-day, non-invasive study-design.
  
  
  METHODS
  Four healthy volunteers took an uncoated or a ColoPulse-capsule containing (13)C-urea and an uncoated capsule containing (15)N(2)-urea. In case of colon-release (13)C-urea is fermented and (13)C detected as breath (13)CO(2). Absorbed (13)C-urea and (15)N-urea are detected in urine.
  
  
  RESULTS
  C and (15)N in urine released from uncoated capsules showed a ratio of 1.01 ± 0.06. The (13)C/(15)N-recovery ratio after intake of a ColoPulse-capsule was constant and lower >12 h post-dose (median 0.22, range 0.13-0.48). The (13)C/(15)N-ratio in a single urine sample at t ≥ 12 h predicted the 24 h non-fermented fraction (13)C of <26 %. Breath (13)CO(2) indicated delayed (>3 h) release and a fermented fraction (13)C >54 %.
  
  
  CONCLUSIONS
  Breath and urine (13)C and (15)N data describe the release-profile and local bioavailability of a colon delivery device. This allows non-invasive bioavailability studies for evaluation of colon-specific drug delivery systems without radioactive exposure and with increased power and strongly reduced costs.
authors.affiliation: Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands. m.maurer@umcg.nl
authors.forename: Marina J M
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Reinout C A
authors.initials: RC
authors.lastname: Schellekens
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Wutzke
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.forename: Herman J
authors.initials: HJ
authors.lastname: Woerdenbag
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
mesh_terms: D000328:Adult; D001944:Breath Tests; D002214:Capsules; D002247:Carbon Isotopes / Q000032:analysis / Q000493:pharmacokinetics / Q000652:urine; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009587:Nitrogen Isotopes / Q000032:analysis / Q000493:pharmacokinetics / Q000652:urine; D012107:Research Design; D014508:Urea / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002214:Capsules; D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D014508:Urea