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Mol Pharm. 2017 Dec 4;14(12):4192-4201. doi: 10.1021/acs.molpharmaceut.7b00198. Epub 2017 Aug 23.

Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.

Author information

1
Pharmaceutical Technology & Development, AstraZeneca , Macclesfield, U.K.
2
Institute of Pharmaceutical Technology, Goethe University , Frankfurt am Main, Germany.
3
Drug Product Development, AbbVie Deutschland GmbH & Co. KG , Ludwigshafen, Germany.
4
Chemical and Pharmaceutical Development, Bayer AG , Wuppertal, Germany.
5
Pharmaceutical Development, Boehringer Ingelheim Pharma GmbH , Biberach an der Riß, Germany.
6
Drug Product Science and Technology, Bristol-Myers Squibb , Moreton, U.K.
7
Pharmaceutical Development & Supply, GlaxoSmithKline R&D , Harlow, U.K.
8
Pharmaceutical Sciences, Janssen Pharmaceutica, Johnson & Johnson , Beerse, Belgium.
9
Drug Delivery and Disposition, University of Leuven , Leuven, Belgium.
10
Biologics and Pharmaceutical Science, H. Lundbeck A/S , Valby, Denmark.
11
Department of Biopharmaceutics and Pharmaceutical Technology, University of Mainz , Mainz, Germany.
12
Analytical Sciences, MRL, Merck & Co., Inc. , Kenilworth, New Jersey, United States.
13
Technical Research and Development, Novartis Pharma AG , Basel, Switzerland.
14
Pharmaceutical Sciences, Analytical Development, Orion Pharma , Turku, Finland.
15
Analytical Research and Development, Pfizer Ltd. , Sandwich, U.K.
16
Research & Development, Sanofi-Aventis , Vitry-sur-Seine, France.

Abstract

Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a single intestinal medium, FaSSIF, to simulate release in the small intestine, and a "transfer" (two-stage) protocol to simulate the concentration profile when conditions are changed from the gastric to the intestinal environment. The test products chosen were commercially available ibuprofen tablets and zafirlukast tablets. The biorelevant dissolution tests showed a high degree of reproducibility among the participating laboratories, even though several different batches of the commercially available medium preparation powder were used. Likewise, results were almost identicalbetween the commercial biorelevant media and those produced in-house. Comparing results to previous ring studies, including those performed with USP calibrator tablets or commercially available pharmaceutical products in a single medium, the results for the biorelevant studies were highly reproducible on an interlaboratory basis. Interlaboratory reproducibility with the two-stage test was also acceptable, although the variability was somewhat greater than with the single medium tests. Biorelevant dissolution testing is highly reproducible among laboratories and can be relied upon for cross-laboratory comparisons.

KEYWORDS:

FaSSIF; OrBiTo; biorelevant; dissolution testing; in vivo predictive testing; ring study; transfer model

[Indexed for MEDLINE]

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