A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers

Jason T. McConville, Lee Ann Hodges, Tamara Jones, Janet P. Band, Bridget O'Mahony, Blythe Lindsay, Alistair C. Ross, Alastair J. Florence, Adrian J. Stanley, Michael J. Humphrey, Clive Wilson, Howard Stevens

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release characteristics of the TDC relied on the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug release scintigraphically (theophylline was a marker compound). Three formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were shown to compare favourably with mean in vivo scintigraphic release times of 2.7, 3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC concentrations respectively. An increase in HPMC concentration was associated with a delayed technetium release time, and followed the same rank order as the in vitro dissolution study. Observed radiolabel dispersion always occurred in the small intestine. In conclusion, the study established that the TDC performs and demonstrates an in vitro-in vivo correlation. Additionally, time and site of release were accurately visualized by gamma scintigraphy, and confirmed with determination of theophylline absorption.
Original languageEnglish
Pages (from-to)4251-4263
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume98
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Capsules
Healthy Volunteers
Technetium
Theophylline
Tablets
Pentetic Acid
Indium
Riboflavin
Photography
Radio
Radionuclide Imaging
Cross-Over Studies
Small Intestine

Keywords

  • controlled delivery
  • gastrointestinal transit
  • scintigraphy
  • site-specific delivery
  • targeted drug delivery

Cite this

McConville, Jason T. ; Hodges, Lee Ann ; Jones, Tamara ; Band, Janet P. ; O'Mahony, Bridget ; Lindsay, Blythe ; Ross, Alistair C. ; Florence, Alastair J. ; Stanley, Adrian J. ; Humphrey, Michael J. ; Wilson, Clive ; Stevens, Howard. / A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers. In: Journal of Pharmaceutical Sciences. 2009 ; Vol. 98, No. 11. pp. 4251-4263.
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author = "McConville, {Jason T.} and Hodges, {Lee Ann} and Tamara Jones and Band, {Janet P.} and Bridget O'Mahony and Blythe Lindsay and Ross, {Alistair C.} and Florence, {Alastair J.} and Stanley, {Adrian J.} and Humphrey, {Michael J.} and Clive Wilson and Howard Stevens",
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McConville, JT, Hodges, LA, Jones, T, Band, JP, O'Mahony, B, Lindsay, B, Ross, AC, Florence, AJ, Stanley, AJ, Humphrey, MJ, Wilson, C & Stevens, H 2009, 'A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers', Journal of Pharmaceutical Sciences, vol. 98, no. 11, pp. 4251-4263. https://doi.org/10.1002/jps.21739

A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers. / McConville, Jason T.; Hodges, Lee Ann; Jones, Tamara; Band, Janet P.; O'Mahony, Bridget; Lindsay, Blythe; Ross, Alistair C.; Florence, Alastair J.; Stanley, Adrian J.; Humphrey, Michael J.; Wilson, Clive; Stevens, Howard.

In: Journal of Pharmaceutical Sciences, Vol. 98, No. 11, 11.2009, p. 4251-4263.

Research output: Contribution to journalArticle

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AU - McConville, Jason T.

AU - Hodges, Lee Ann

AU - Jones, Tamara

AU - Band, Janet P.

AU - O'Mahony, Bridget

AU - Lindsay, Blythe

AU - Ross, Alistair C.

AU - Florence, Alastair J.

AU - Stanley, Adrian J.

AU - Humphrey, Michael J.

AU - Wilson, Clive

AU - Stevens, Howard

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AB - Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release characteristics of the TDC relied on the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug release scintigraphically (theophylline was a marker compound). Three formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were shown to compare favourably with mean in vivo scintigraphic release times of 2.7, 3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC concentrations respectively. An increase in HPMC concentration was associated with a delayed technetium release time, and followed the same rank order as the in vitro dissolution study. Observed radiolabel dispersion always occurred in the small intestine. In conclusion, the study established that the TDC performs and demonstrates an in vitro-in vivo correlation. Additionally, time and site of release were accurately visualized by gamma scintigraphy, and confirmed with determination of theophylline absorption.

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KW - gastrointestinal transit

KW - scintigraphy

KW - site-specific delivery

KW - targeted drug delivery

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DO - 10.1002/jps.21739

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JO - Journal of Pharmaceutical Sciences

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