Category: Formulation and Quality
Purpose: In the pharmaceutical industry, it is important to identify extractables and leachables from pharmaceutical packaging and container closure systems for patient safety and submissions to regulatory authorities. Many of the substances reported in extractables and leachables studies are additives that provide a variety of technical effects to the polymer formulations of the packaging and container closure systems. To facilitate the identification of extractables, we acquired and compiled data on hundreds of examples across seven major categories of polymer additives: accelerants, antioxidants, antidegradants, bisphenol analogues, cross-linkers, plasticizers, and UV stabilizers.
Methods: Standards of over 120 plastic additives were prepared at 100 ppm and chromatographed using HPLC-DAD or HPLC-ELSD. To obtain mass pattern data, standards were further diluted and analyzed with LC-MS. In addition, standards from a commercially available library of 24 plastic additives were analyzed with GC-MS.
Results: For the polymer additive library, 71 standards were resolved with HPLC-DAD. Of these 71, 60 were analyzed using a C18 analytical column and a further nine standards were resolved with a C8 column. Two more standards were resolved using THF as an isocratic mobile phase and a styragel column. An additional five standards were chromatographed with HPLC-ELSD. These analyses generated a library of retention times, as well as UV absorption for those additives with UV activity. Adding MS pattern data to the library, mass spectra of 102 of the compounds were generated with LC-MS and 24 were generated with GC-MS. Extracts generated from pharmaceutical packaging and container closure systems were analyzed using the same methods developed in building the library. Polymer additives were identified in the extracts using the data on retention time, UV absorption, and MS pattern from the library.
Conclusion: The development of a polymer additive library facilitates rapid identification of polymer additives in extractables and leachables screenings.