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Physiologically Based Pharmacokinetic Modeling in the Development and Evaluation of Hydrophilic Matrix Tablets

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Hydrophilic Matrix Tablets for Oral Controlled Release

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 16))

Abstract

Physiologically based pharmacokinetic (PBPK) modeling has evolved to its present biopharmaceutics approach that makes it useful in the development and evaluation of oral dosage forms including hydrophilic matrix tablets. Useable models involve the detailed representation of the gastrointestinal tract, including how gastric emptying (such as the effect of fed/fasted state) influences drug absorption profiles and how different release rates from matrices interact with this variable, along with overall transit time, role of transporters, and first-pass metabolism to yield the simulated drug pharmacokinetic profile. The need for, and determination of, human intestinal permeability as a key input parameter is described, including the use of radiofrequency-controlled capsules and gamma scintigraphy to determine intestinal and, important, colonic drug permeability. The use of in vitro dissolution data as an input for PBPK modeling is described and the development of an in vitro–in vivo correlation (IVIVC) is covered. Finally, the limitations of PBPK modeling applied to hydrophilic matrix tablets are indicated.

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Authors and Affiliations

  1. Drug Product Science and Technology, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, NJ, 08903, USA

    John R. Crison Ph.D.

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  1. John R. Crison Ph.D.
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Correspondence to John R. Crison Ph.D. .

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Editors and Affiliations

  1. Drug Product Science and Technology, Bristol-Myers Squibb, Moreton, Merseyside, United Kingdom

    Peter Timmins

  2. Commercial Trade Channels, Merck, Sharp and Dohme, Hoddesdon, Hertfordshire, United Kingdom

    Samuel R. Pygall

  3. School of Pharmacy, University of Nottingham, Notthingham, Nottinghamshire, United Kingdom

    Colin D. Melia

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© 2014 American Association of Pharmaceutical Scientists

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Crison, J.R. (2014). Physiologically Based Pharmacokinetic Modeling in the Development and Evaluation of Hydrophilic Matrix Tablets. In: Timmins, P., Pygall, S., Melia, C. (eds) Hydrophilic Matrix Tablets for Oral Controlled Release. AAPS Advances in the Pharmaceutical Sciences Series, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1519-4_8

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