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Simulated Leaching (Migration) Study for a Model Container-Closure System Applicable to Parenteral and Ophthalmic
Dennis Jenke1, Thomas Egert2, Alan Hendricker3
1Baxter Healthcare Corporation, Round Lake, IL, USA; dennisjenke@triadscientificsolutions.com.
PDA Journal of Pharmaceutical Science and Technology
|December 16, 2016
Summary
This study shows that substances can migrate from pharmaceutical packaging into drug products, even without direct contact. Packaging material composition and solvent chemistry influence extractable migration into parenteral and ophthalmic drug products.
Area of Science:
- Pharmaceutical Science
- Materials Science
- Analytical Chemistry
Background:
- Parenteral and ophthalmic drug products require robust container-closure systems to maintain product integrity.
- Understanding the potential for extractables to leach from packaging materials into drug products is critical for patient safety.
- Model systems are essential for predicting the behavior of real-world pharmaceutical packaging under various conditions.
Purpose of the Study:
- To investigate the leaching (migration) of substances from a model container-closure system into simulated drug product solutions.
- To correlate extractables profiles with the materials of construction and the nature of the extracting medium.
- To assess the impact of direct contact versus indirect contact on leachables migration.
Main Methods:
- A model container-closure system was assembled using a linear low-density polyethylene bottle, polypropylene cap, elastomeric liner, adhesive label, and foil overpouch.
- The system was filled with simulating solvents (pH 2.5, pH 9.5, and 1:1 isopropanol/water) and stored at 40 °C for up to 6 months.
- Leaching solutions were analyzed using multiple analytical techniques to identify volatile, semi-volatile, and non-volatile organic and inorganic extractables.
Main Results:
- The extractables profile could be qualitatively correlated with the known composition of the container-closure system materials.
- The chemical nature of both the simulating solvents and the individual extractables significantly influenced the migration profile.
- Substances leached from the label into the simulated drug product, even without direct contact with the solution.
Conclusions:
- The composition of container-closure systems directly influences the types and amounts of extractables that can migrate.
- Environmental factors, such as solvent chemistry and storage conditions, play a crucial role in the leaching process.
- Leachables can migrate into drug products through mechanisms other than direct contact, highlighting the importance of considering all packaging components.
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