PT  - JOURNAL ARTICLE
AU  - Jenke, Dennis
AU  - Egert, Thomas
AU  - Hendricker, Alan
AU  - Castner, James
AU  - Feinberg, Thomas
AU  - Houston, Christopher
AU  - Hunt, Desmond
AU  - Lynch, Michael
AU  - Nicholas, Kumudini
AU  - Norwood, Daniel L
AU  - Paskiet, Diane
AU  - Ruberto, Michael
AU  - Smith, Edward J
AU  - Holcomb, Frank
TI  - Simulated Leaching (Migration) Study for a Model Container-closure System Applicable to Parenteral and Ophthalmic Drug Products (PODPs)
AID  - 10.5731/pdajpst.2016.007229
DP  - 2016 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2016.007229
4099  - http://journal.pda.org/content/early/2016/12/13/pdajpst.2016.007229.short
4100  - http://journal.pda.org/content/early/2016/12/13/pdajpst.2016.007229.full
AB  - A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products (PODP). This container-closure system consisted of a linear-low density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling) and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1(v/v) IPA/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch and the filled and pouched units were stored either upright or inverted for up to 6 months at 40°C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables. The leaching data generated supported several conclusions, including that (a) the extractables (leachables) profile revealed by a simulating leaching study can qualitatively be correlated with compositional information for materials of construction, (b) the chemical nature of both the extracting medium and the individual extractables (leachables) can markedly affect the resulting profile and (c) while direct contact between a drug product and a system's material of construction may exacerbate the leaching of substances from that material by the drug product, direct contact is not a prerequisite for migration and leaching to occur.