Pharmaceutical Research

, Volume 25, Issue 5, pp 1075–1084 | Cite as

In Vivo Performance of an Oral MR Matrix Tablet Formulation in the Beagle Dog in the Fed and Fasted State: Assessment of Mechanical Weakness

  • Fiona McInnes
  • Nicola Clear
  • Michael Humphrey
  • Howard N E Stevens
Research Paper



To evaluate the behaviour of an oral matrix modified release formulation in the canine gastrointestinal tract, and establish if a mechanical weakness previously observed in clinical studies would have been identified in the dog model.

Materials and Methods

In vitro release profiles were obtained for two modified release matrix tablets containing UK-294,315, designed to release over either 6 (formulation A) or 18 (formulation B) hours. Tablets were labelled with 153samarium and in vivo pharmacoscintigraphy studies were performed in four beagle dogs in the fasted state for both formulations, and following ingestion of an FDA high fat meal for formulation B.


The matrix tablet formulations displayed significantly different in vitro release profiles (F 2 < 50), with time to 80% release for formulation A and B of 406 and 987 min respectively. Complete in vivo disintegration occurred at 339 ± 181 and 229 ± 171 for formulation A and B respectively in the fasted state, and at 207 ± 154 min for formulation B in the fed state, in disagreement with in vitro release.


The fed/fasted dog model would have predicted a lack of physical robustness in the matrix tablet formulation B, however it would not have predicted the clear fed/fasted effects on performance observed previously in man.

Key words

food effects gamma scintigraphy IVIVC matrix tablet pharmacoscintigraphy 



Analysis of variance


Area under the curve


Area under the plasma concentration curve from 0–8 h.

\( {\rm{AUC}}_{{{\left( {0 - \infty } \right)}}} \)

Area under the plasma concentration curve from 0 h extrapolated to infinity.


Complete tablet disintegration time


Maximum plasma concentration


Gastric emptying complete






Initial tablet disintegration time




Elimination rate constant




migrating myoelectric complex


Modified release


Region of interest


Small intestinal transit time




samarium oxide-152




Time to reach maximum plasma concentration


Time to 50% of parameter


Plasma half life


Technetium-99m-diethylenetriaminepentaacetic acid



These studies were funded by Pfizer Global Research and Development, UK.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Fiona McInnes
    • 1
  • Nicola Clear
    • 2
  • Michael Humphrey
    • 2
  • Howard N E Stevens
    • 1
  1. 1.Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK
  2. 2.Pfizer Global Research and DevelopmentSandwichUK

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