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Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet

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Abstract

The objective of this work is to develop a biorelevant dissolution method to support the clinical study for In Vitro In Vivo Correlation (IVIVC) of the first commercially approved single-layer extrudable core system (ECS) osmotic tablet — the 11 mg tofacitinib modified-release tablet. The dissolution conditions were selected through analysis of experimental work including several designed experiments (DoE). The Apparatus 2 (paddles) was selected over the Apparatus 1 (baskets) to minimize the dissolution test variability. The paddle speed was kept at 50 rpm to be conservative and because higher paddle speed did not offer statistically significant improvement in dissolution test variability. The buffer of 50 mM potassium phosphate at pH 6.8 was selected over other buffers at lower or acid pH as the in vivo drug release is expected to occur in the small intestinal region, where the pH is approximately neutral. Finally, the statistically designed experiments proved that use of the Japanese basket sinkers was effective in reducing dissolution variability and eliminating the artificial shift in dissolution profile caused by final pink color-coated tablets sticking to the dissolution vessel. Discriminatory power of the method was verified and the method was validated per ICH and FDA guidelines. Since a Level A IVIVC is established from the analysis of the results of both in vivo clinical study and in vitro dissolution testing, the method is proven to be biorelevant. It also serves a suitable quality control dissolution method.

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Abbreviations

ECS:

Extrudable Core System

DoE:

Design of Experiments

IVIVC:

In Vitro/In Vivo Correlation

BE:

Bioequivalence

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Acknowledgements

The authors wish to thank the following Pfizer colleagues for their helpful discussions: Ling Zhang, Alfred Berchielli and John Larmann.

Funding

The work was funded by Pfizer Inc.

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Authors and Affiliations

  1. Analytical Research and Development, Worldwide Research, Development and Medical, Pfizer Inc., Groton, Connecticut, 06340, USA

    Raymond Chen, Andrew Blanchard & Vincent DeMatteo

  2. Drug Product Design, Worldwide Research, Development and Medical, Pfizer Inc., Groton, Connecticut, 06340, USA

    Joseph Kushner

  3. Pharmaceutical Sciences & PGS Statistics, Analytical Research and Development, Worldwide Research, Development and Medical, Pfizer Inc., Groton, Connecticut, 06340, USA

    Brent Harrington & Jia Liu

Authors
  1. Raymond Chen
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  2. Andrew Blanchard
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  3. Joseph Kushner
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  4. Brent Harrington
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  5. Jia Liu
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  6. Vincent DeMatteo
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by Vincent DeMatteo and Andrew Blanchard. The statistical analysis was performed by Jia Liu and Brent Harrington. The first draft of the manuscript was written by Raymond Chen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Raymond Chen.

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Conflict of Interest

The authors are employees of Pfizer Inc. and own stocks of Pfizer Inc.

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Chen, R., Blanchard, A., Kushner, J. et al. Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet. AAPS PharmSciTech 23, 5 (2022). https://doi.org/10.1208/s12249-021-02110-x

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  • DOI: https://doi.org/10.1208/s12249-021-02110-x

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