Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets

Jacoba M. Maurer; Reinout C. A. Schellekens; Helen M. van Rieke; Christoph Wanke; Ventzeslav Iordanov; Frans Stellaard; Klaus D. Wutzke; Gerard Dijkstra; Margot van der Zee; Herman J. Woerdenbag; Henderik W. Frijlink; Jos G. W. Kosterink

doi:10.1371/journal.pone.0129076

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets

Jacoba M. Maurer^*, Reinout C. A. Schellekens, Helen M. van Rieke, Christoph Wanke, Ventzeslav Iordanov, Frans Stellaard, Klaus D. Wutzke, Gerard Dijkstra, Margot van der Zee, Herman J. Woerdenbag, Henderik W. Frijlink, Jos G. W. Kosterink

^*Corresponding author voor dit werk

Onderzoeksoutput › Academic › peer review

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Introduction

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.

Materials and 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 C-13-urea and an uncoated, immediate release tablet containing N-15(2)-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 C-13-urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of C-13) 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 C-13 from the ColoPulse tablet occurred.

Discussion and Conclusions

From the combined data from the IntelliCap system and the C-13-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.

Originele taal-2	English
Artikelnummer	e0129076
Aantal pagina's	17
Tijdschrift	PLoS ONE
Volume	10
Nummer van het tijdschrift	7
DOI's	https://doi.org/10.1371/journal.pone.0129076
Status	Published - 15-jul.-2015

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10.1371/journal.pone.0129076Licentie: CC BY

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse TabletsFinal publisher's version, 722 KBLicentie: CC BY

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Maurer, J. M., Schellekens, R. C. A., van Rieke, H. M., Wanke, C., Iordanov, V., Stellaard, F., Wutzke, K. D., Dijkstra, G., van der Zee, M., Woerdenbag, H. J., Frijlink, H. W., & Kosterink, J. G. W. (2015). Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets. PLoS ONE, 10(7), Artikel e0129076. https://doi.org/10.1371/journal.pone.0129076

@article{e2efa39090c64e19aa5fa50deb568548,

title = "Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets",

abstract = "IntroductionColoPulse 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.Materials and MethodsRelease 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 C-13-urea and an uncoated, immediate release tablet containing N-15(2)-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.ResultsFull analysis could be performed in 12 subjects. Median bioavailability of C-13-urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of C-13) 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 C-13 from the ColoPulse tablet occurred.Discussion and ConclusionsFrom the combined data from the IntelliCap system and the C-13-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.",

keywords = "INFLAMMATORY-BOWEL-DISEASE, DOSAGE FORMS, INTRALUMINAL PH, CROHNS-DISEASE, LUMINAL PH, DEVICE, DELIVERY, BEHAVIOR, DRUG",

author = "Maurer, {Jacoba M.} and Schellekens, {Reinout C. A.} and {van Rieke}, {Helen M.} and Christoph Wanke and Ventzeslav Iordanov and Frans Stellaard and Wutzke, {Klaus D.} and Gerard Dijkstra and {van der Zee}, Margot and Woerdenbag, {Herman J.} and Frijlink, {Henderik W.} and Kosterink, {Jos G. W.}",

year = "2015",

month = jul,

day = "15",

doi = "10.1371/journal.pone.0129076",

language = "English",

volume = "10",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "7",

}

Maurer, JM, Schellekens, RCA, van Rieke, HM, Wanke, C, Iordanov, V, Stellaard, F, Wutzke, KD, Dijkstra, G, van der Zee, M, Woerdenbag, HJ , Frijlink, HW & Kosterink, JGW 2015, 'Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets', PLoS ONE, vol. 10, nr. 7, e0129076. https://doi.org/10.1371/journal.pone.0129076

TY - JOUR

T1 - Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets

AU - Maurer, Jacoba M.

AU - Schellekens, Reinout C. A.

AU - van Rieke, Helen M.

AU - Wanke, Christoph

AU - Iordanov, Ventzeslav

AU - Stellaard, Frans

AU - Wutzke, Klaus D.

AU - Dijkstra, Gerard

AU - van der Zee, Margot

AU - Woerdenbag, Herman J.

AU - Frijlink, Henderik W.

AU - Kosterink, Jos G. W.

PY - 2015/7/15

Y1 - 2015/7/15

N2 - IntroductionColoPulse 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.Materials and MethodsRelease 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 C-13-urea and an uncoated, immediate release tablet containing N-15(2)-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.ResultsFull analysis could be performed in 12 subjects. Median bioavailability of C-13-urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of C-13) 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 C-13 from the ColoPulse tablet occurred.Discussion and ConclusionsFrom the combined data from the IntelliCap system and the C-13-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.

AB - IntroductionColoPulse 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.Materials and MethodsRelease 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 C-13-urea and an uncoated, immediate release tablet containing N-15(2)-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.ResultsFull analysis could be performed in 12 subjects. Median bioavailability of C-13-urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of C-13) 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 C-13 from the ColoPulse tablet occurred.Discussion and ConclusionsFrom the combined data from the IntelliCap system and the C-13-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.

KW - INFLAMMATORY-BOWEL-DISEASE

KW - DOSAGE FORMS

KW - INTRALUMINAL PH

KW - CROHNS-DISEASE

KW - LUMINAL PH

KW - DEVICE

KW - DELIVERY

KW - BEHAVIOR

KW - DRUG

U2 - 10.1371/journal.pone.0129076

DO - 10.1371/journal.pone.0129076

M3 - Article

C2 - 26177019

SN - 1932-6203

VL - 10

JO - PLoS ONE

JF - PLoS ONE

IS - 7

M1 - e0129076

ER -

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets

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