Search

Lyophilization Glass Vials Problems

Updated: Jun 8

Glass vials are nowadays one of the most important components in the pharmaceutical industry, protecting delicate active ingredients which require aggressive and complex excipient solutions to prevent their degradation due to changes in pH, oxidation, and other processes.


Breakage, cracks, particulates and delamination are longstanding problems associated with existing compendial glasses, and they have resulted in numerous recent products recalls. Breakage and cracks are related to handling issues (during transport, filling and storage), while flake production (delamination and precipitation) can be tied to the container and its interaction with the drug product.


Breakage

Breakage is a problem for the pharmaceutical industry because it creates particulate contamination in aseptic filling areas, increases manufacturing cost and waste, and may lead to drug shortages and recalls. Glass breaks when applied loads create tensile stresses that act on existing flaws at the glass surface and cause them to propagate. Alternatively, as glass contacts materials of similar or higher hardness (including other glass containers), strength-reducing damage can be introduced that makes subsequent loading more likely to cause breakage. This damage can be introduced during glass manufacturing, pharmaceutical filling, or subsequent handling and distribution. Regardless of the mechanism, glass breakage is observed both within pharmaceutical filling lines and during customer use. Some pharmaceutical manufacturers are turning to filling lines that reduce glass-to-glass contact minimize glass damage and reduce breakage.


Cracks

Cracks are problematic because they present pathways for microbes and other contaminants to pass into the container’s sterile contents, escape of the product dosage form and allowing change of gas in the landscape content. In the most severe cases, contaminated does are undetected and used, causing sepsis and death. Current methods for addressing cracked containers include increased visual inspection during container manufacture and after filling improved handling procedures during filling, improved handling procedures during filling, and advancements in leak detection technologies. These methods may reduce the frequency of cracked containers leaving the manufacturing environment, but they do not address cracks introduced in the field. Despite these advances, recalls due to cracked and broken containers continue today.


Precipitation

Precipitation refers to creation of a solid from components of a solution which exceed their solubility limit. In parenteral solutions, this might occur by reaction of leachables of the packaging components (glass or plastic container, stopper, etc.) with the drug product (or excipient) to produce insoluble solid phases. For example, this can occur when barium leached from packaging components (glass, plastic, or rubber) reacts with sulfate solutions to product barium sulfate precipitates. Phosphate solutions are similarly prone to forming various precipitates. Precipitates can take several shapes, including flat sheets built upon the container walls. If these sheets release from the container walls, they appear as solid flakes.


Delamination

During the tubular converting process (and less-so the molding process), the high temperatures cause evaporation and deposition of low-melting glass constituents and formation of altered composition surface layers. Commonly located in the heel region, there surface layers are enriched in sodium and boron species and therefore have reduced chemical durability and corrode at higher rates than surrounding glass. The corrosion observed for these regions depends upon the degree of composition alteration during the forming process, the aqueous solution strength (pH, concentration, ionic strength, etc.) and accelerating conditions (autoclaving, pasteurization, lyophilization, storage temperature, etc.) but is substantially faster than the unaltered borosilicate glass.


After more than 100 years since the introduction of the borosilicate glasses for parenteral packaging, there is a clearly a need for improvement and new materials are on the horizon.


*Extracted article from: “Historical review of glasses used for parenteral packaging”

fondo.jpg

LYOPHILIZATIONWORLD