Sealing technology manual for the process industry - Extractables

EXTRACTABLES Particularly high purity requirements apply to elastomers in the pharmaceutical industry, including the desire for disclosure of the ingredients of the compounds. This does not provide the desired information about the interac- tions that can take place during the production process. That is why manufacturers in the pharmaceutical industry want to examine materials for a possible interaction with the pharmaceutical preparation. For example, they want to know how an O-ring for the sealing of an inhalation spray head be- haves in contact with the drug. It is also of interest to mini- mize the influence of the seals from production on the prod- uct. In addition to studies at ambient temperatures – with respect to the completeness of the packaging, the stor- age conditions and test substances (leachables study) – tests are slated in the worst-case scenario with more stringent conditions such as elevated temperatures and solvent strengths (extractables study). Apart from the quantifica- tion, the identification of the migrated substances is particu- larly important for a subsequent toxicological evaluation. Compared to storage, a multiple of the volume flows by the seal in the production process. The ratio of surface area to volume and hence the concentration of possibly leached compounds is therefore much smaller. Nevertheless, an interaction between the sealing material or the soluble components of the elastomeric compound and the active pharmaceutical ingredient can occur. This interaction might alter the pharmaceutical product and, in the worst case, adversely affect its efficacy. If the interactions between the seals in valves and other system components and the prod- ucts therein are known to the pharmaceutical manufactur- ers, possible contamination can already be evaluated during the production process. This safeguards the processes and ensures the necessary purity of the products. Extractables study Freudenberg conducted an extractables study on O-rings with different media at high temperatures. The tested O-rings were extracted, without prior cleaning steps, in a low ratio of elastomer to extract medium for 24 hours under reflux to achieve the most stringent conditions possible for evaluation. To ensure the comparability of re- sults of different O-rings, the ratio between surface and media volume was kept constant. In line with the recom- mendations of the FDA, the BfR and other relevant sources, four media were used: • Ethanol • N-hexane • Phosphate buffer pH 2.5 • Phosphate buffer pH 9.5 In addition to a gravimetric evaluation, the extractable contents were analyzed by means of gas chromatography- mass spectrometry (GC-MS). For this purpose, the eva- porated extracts were absorbed in the respective extract- ing agent and the extracts of the buffer solutions in meth- anol and injected into the gas stream. The chromatograms were plotted with the same scale size for evaluation. The sum of the detected substances was assessed by an evalu- ation of the entire surface and by the determination of the main compounds found. DESIGNATION COLOR HARDNESS SHORE A EPDM 291 black 70 EPDM 292 black 85 EPDM 253815 white 70 Fluoroprene® XP 41 blue 75 Fluoroprene® XP 43 blue 85 Simriz® 494 black 75 Simriz® 506 white 75 APPENDIX PRODUCT PORTFOLIO MATERIALS RESISTANCE & PURITY ENGINEERING PLASTICS ELASTOMERIC MATERIALS TECHNICAL FUNDAMENTALS INTRODUCTION 61

Pages Overview