An essential role of packaging material for the storage and delivery of drug products is to provide adequate protection against contamination and loss of sterility. This is especially important for parenteral containers, as lack of sterility or contamination can result in serious adverse events including death. Nonetheless, cracked parenteral containers are an important source of container integrity failures for injectable drugs and pose a serious risk for patients. Despite significant investments in inspection technology, each year many injectable drugs are investigated and recalled for sterility risks associated with cracked borosilicate containers. Multiple studies and the many difficulties in detection of cracked containers suggest that the magnitude of the public health risk is even larger than the recall rate would suggest. Here we show that the root cause of cracked parenteral containers (low internal energy following annealing) is inherent to the glasses currently used for primary packaging of the majority of injectable drugs. We also describe a strengthened aluminosilicate glass that has been designed to prevent cracks in parenteral containers through the use of an engineered stress profile in the glass. Laboratory tests that simulate common filling line damage events show that the strengthened aluminosilicate glass is highly effective at preventing cracks. Significant safety benefits have been demonstrated in other industries from the use of special stress profiles in glass components to mitigate failure modes that may result in harm to humans. Those examples combined with the results described here suggest that a significant improvement in patient safety can be achieved through the use of strengthened aluminosilicate glass for parenteral containers.LAY ABSTRACT: Cracks are small cuts or gaps in a container which provide a pathway for liquid, gas, or microbes through a glass container. When these defects are introduced to conventional glass containers holding injectable medicines, the affected drug can pose serious risks to the patient receiving that medication. Specifically, the drug product may become less effective or even non-sterile, which could lead to bloodstream infections and, in some cases, death. This article presents a review of some previously documented cases of cracked glass containers that led to patient infections and deaths. Following a survey of common crack locations in glass vials, lab-based methods for replicating these cracks are presented. These methods are then used to compare the fracture response of vials made from conventional borosilicate glass and strengthened aluminosilicate glass. The results show that stable cracks are essentially prevented (at least 31 times less likely to occur) in the strengthened aluminosilicate glass containers (relative to conventional borosilicate glass). This improvement in safety is similar to improvements already engineered into other glass product designs by utilizing stored strain energy to mitigate certain failure modes.

While normally thought of as brittle, glass undergoes a brittle-to-ductile transition (BDT) as temperature increases and viscosity decreases. Understanding this transition is important both in glass manufacturing, particularly for thin sheet applications such as display glass, and in fundamental studies. A high-temperature double-torsion test apparatus has been developed and used to determine the BDT temperature of two commercial calcium aluminosilicate glasses. The BDT temperature can be found with high precision and compared with other characteristic temperatures such as the glass transition temperature or the softening point. The strain rate sensitivity of the BDT temperature is demonstrated.

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The feasibility of producing high-hardness ceramic sandwich structures, with compressive residual stresses in the faces, was evaluated in this study. The faces were originally chosen to be SiAlON with an SiC core. To produce structures that did not crack during processing, however, it was necessary to hybridize the faces by adding SiC particles to the SiAlON. This modification resulted in a composite face that reduced the thermal expansion mismatch with the core. The residual stresses in the face were measured with an indentation technique and these values agreed well with those measured by X-ray diffraction and calculated from the theory using experimental values.

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