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Research ArticleResearch

Modeling the Migration Behavior of Extractables from Mono- and Multilayer Polyolefin Films to Mathematically Predict the Concentration of Leachable Impurities in Pharmaceutical Drug Products. Part 1: Experimental Details and Modeling Experimental Results

Peter V. Mercea, Manfred Ossberger, Regina Wyrwich, Matthias Herburger, Vishal Barge, Rajendra Aluri and Valer Toşa
PDA Journal of Pharmaceutical Science and Technology January 2024, 78 (1) 3-32; DOI: https://doi.org/10.5731/pdajpst.2022.012816
Peter V. Mercea
1FABES Forschungs-GmbH, Schragenhofstr. 35, 80992 Munich, Germany;
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Manfred Ossberger
1FABES Forschungs-GmbH, Schragenhofstr. 35, 80992 Munich, Germany;
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Regina Wyrwich
1FABES Forschungs-GmbH, Schragenhofstr. 35, 80992 Munich, Germany;
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  • For correspondence: regina.wyrwich@fabes-online.de
Matthias Herburger
1FABES Forschungs-GmbH, Schragenhofstr. 35, 80992 Munich, Germany;
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Vishal Barge
2Medicinal Sciences, Pharmaceutical Sciences Small Molecule, Pfizer Inc., 375 North Field Drive, Lake Forest, IL 60045;
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Rajendra Aluri
3Medicinal Sciences, Pharmaceutical Sciences Small Molecule, Pfizer Inc. SIPCOT Industrial Park, Sriperumbudur, 602117 Tamil Nadu, India; and
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Valer Toşa
4National Institute for Research and Development of Isotopic and Molecular Technologies, Str. Donath 67-103, 400293 Cluj-Napoca, Romania
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Abstract

An important step in the development of a pharmaceutical drug product is to demonstrate acceptable levels of leachable impurities during the shelf-life and therapeutic use of the drug product. If the diffusion and partition coefficients are known, the concentration profile of a leachable impurity in the drug product can be predicted theoretically at a given temperature and time. With this objective in mind, kinetic experiments were performed to study the migration of low- to high-molecular-weight organic compounds from mono- and multilayer polyolefin films. Migration curves at different temperatures were generated for each compound when these films were brought in contact with aqueous solutions with varying pH or with another plastic film made from a different polyolefin material. “Best fit” migration curves and the corresponding diffusion and partition coefficients (about 300 pieces) were obtained by using numerical software developed by FABES. The results obtained show that, in general, the correlation between the calculated diffusion and partition coefficients and temperature, between 30°C and 85°C, obeys the Arrhenius and Van’t Hoff equations. In this temperature range, the diffusion and partition coefficients can be used to model and predict migration of the investigated compounds from the same pharmaceutical packaging materials. A comparison of these coefficient values with other polyolefin films also provides insights into the chemistry of the mono- and multilayers and the impact it has on the migration behavior of the compounds. In a consecutive paper, an approach to overestimate the diffusion and partition coefficients to account for the variability in experimental data is explained and finally, the use of these overestimated parameters to predict the concentrations for other compounds leaching from the multilayer films into aqueous drug product formulations is discussed.

  • Extractables and leachables (E&L)
  • Pharmaceutical packaging
  • Diffusion and Partition coefficients
  • Predictive modeling
  • Migration modeling
  • © PDA, Inc. 2024
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PDA Journal of Pharmaceutical Science and Technology: 78 (1)
PDA Journal of Pharmaceutical Science and Technology
Vol. 78, Issue 1
January/February 2024
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Modeling the Migration Behavior of Extractables from Mono- and Multilayer Polyolefin Films to Mathematically Predict the Concentration of Leachable Impurities in Pharmaceutical Drug Products. Part 1: Experimental Details and Modeling Experimental Results
Peter V. Mercea, Manfred Ossberger, Regina Wyrwich, Matthias Herburger, Vishal Barge, Rajendra Aluri, Valer Toşa
PDA Journal of Pharmaceutical Science and Technology Jan 2024, 78 (1) 3-32; DOI: 10.5731/pdajpst.2022.012816
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Keywords

  • Extractables and leachables (E&L)
  • Pharmaceutical packaging
  • Diffusion and Partition coefficients
  • Predictive modeling
  • Migration modeling

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Modeling the Migration Behavior of Extractables from Mono- and Multilayer Polyolefin Films to Mathematically Predict the Concentration of Leachable Impurities in Pharmaceutical Drug Products. Part 1: Experimental Details and Modeling Experimental Results
Peter V. Mercea, Manfred Ossberger, Regina Wyrwich, Matthias Herburger, Vishal Barge, Rajendra Aluri, Valer Toşa
PDA Journal of Pharmaceutical Science and Technology Jan 2024, 78 (1) 3-32; DOI: 10.5731/pdajpst.2022.012816

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