Gas-phase transfer of polymer cross-linking agents and by-products to solid oral pharmaceuticals.
In the pharmaceutical industry, solid oral compressed tablets (OCT) are frequently transported in bulk containers prior to packaging. While in this state, the product is generally protected from interaction with liquid and solid contaminants by physical barriers (e.g., polyethylene bags, drums, etc.). Vapor phase contamination, although generally less frequently observed, is possible. A specific example of the detection and identification of volatile by-products (acetophenone and 2-phenyl-2-propanol) of a common polymer cross-linking agent (dicumyl peroxide) is presented. The product tablets were compressed, placed into double polyethylene bags, and subsequently placed into a polyethylene drum for shipment overseas. To cushion the product during transit, a cross-linked polyethylene foam disk (designed to fit into the bottom of the drum) was placed below the bag of tablets. Initially, these contaminants were detected by HPLC with UV detection at the receiving laboratory, and assumed to be degradates of the active components of the product. Further analysis showed that neither the collected UV absorbance data nor the observed levels of the contaminants were consistent with known degradates of the product. Liquid extraction followed by GC-MS analysis of the product as well as the cross-linked foam disk exhibited measurable quantities of the contaminants in question. Vapor phase transfer of these cross-linking agent by-products, originating in the cross-linked foam pads, was determined to be the root cause for the presence of these compounds in the product.
Maus
Russell G
RG
Pharmaceutical Analytical Chemistry, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486, United States. russell_maus@merck.com
Li
Min
M
Clement
Christopher M
CM
Kinzer
Jeffery A
JA
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control; D004349:Drug Packaging / Q000592:standards; D008401:Gas Chromatography-Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D013607:Tablets
D003432:Cross-Linking Reagents; D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets