Glass delamination is a serious and costly problem for pharmaceutical manufacturers, and has led to several drug recalls in recent years. Delamination occurs when injectable solutions and suspensions react with glass packaging, resulting in contamination of drug products with glass flakes and residues formed during glass dissolution. Reaction of glass with a drug may also lead to formation of secondary products. The severity of glass delamination depends upon several factors, including glass composition and presence of defects, glass container manufacturing methods, sterilization techniques, and drug storage conditions. Characteristics of the drug product such as pH or presence of buffers will also influence the glass delamination process.
A variety of analytical techniques may be used to verify that glass delamination has occurred, beginning with examination of the liquid drug product in the glass container, both visually and using a stereomicroscope. Particulate and fine residues are then typically isolated from liquid products by filtration, followed by examination of the filtered solids using light microscopy. The filtered particulate may then be analyzed using scanning electron microscopy with energy dispersive X-ray spectrometry (SEM/EDS), a technique recommended for use in glass container screening studies as outlined in USP <1660>. The interior surfaces of empty glass containers may also be characterized by wrapping them with tape and breaking them to expose inner surfaces while maintaining the spatial relationship of the fragments. This is critical because specific areas such as the base or neck of a vial are more susceptible to delamination due to stresses incurred during the manufacturing process. Interior surfaces may exhibit possible delamination precursors such as etching and pitting. If the process is more advanced, flaking glass will be evident when surfaces are examined using light microscopy or SEM.
In some cases, visual examination, light microscopy and SEM imaging may be enough. However, elemental analysis is key to identifying particulate as having resulted from glass delamination, peeling of a coating, dissolution of glass to form a residue, or reaction of glass with a drug to form a secondary product. SEM/EDS is the most commonly used technique for obtaining compositional information about delamination materials, and there are some drawbacks to this approach. Removal of extremely thin samples such as delamination flakes or residues from filters for transfer to SEM substrates can be difficult. An alternative is to mount the entire filter on a substrate. Either preparation technique typically results in EDS spectra dominated by a signal from the substrate or by carbon from a filter material such as polycarbonate (PC), and containing much smaller peaks for major elements present in the thin samples. Peaks for minor or trace elements may be entirely absent, thereby lessening the value of SEM/EDS for discrimination between glass and other materials that may be present.
Transmission electron microscopy (TEM) with EDS has been shown to offer advantages over scanning electron microscopy SEM/EDS for analysis of very thin particulate resulting from delamination of glass vials and syringes. Such samples are usually electron transparent as isolated and require no further thinning, particularly when analysis is done in a high voltage materials science TEM. A representative spectrum displays major silicon and oxygen peaks, as well as peaks for minor and trace elements that can aid in identification of specific glass formulations.
View a related on-demand webinar "Identification of Glass Delamination Products Using TEM"