Glass materials are often used in pharmaceutical packaging. There has been a recent trend in the pharmaceutical market toward the increased use of biological (protein-based) drugs that are more “sensitive” than traditional drugs. With these types of drugs, the topic of drug/container interaction becomes increasingly important due to the lower stability of these drugs and their propensity to degrade during storage, especially when formulated as a liquid. Because of this, extractable substances (e.g. dissolved cations) coming from the pharmaceutical packaging container can cause issues with regard to efficacy and purity of these drugs (including drug instability, toxicity, etc). A Review of Glass Types Available for Packaging, S. V. Sangra, Journal of the Parenteral Drug Association, Mar.-pr., 1979, Vol. 33, No. 2, pp. 61-67.
Cationic extraction from traditional glasses used in pharmaceutical packaging can create issues with the purity and/or effectiveness of such protein-based drugs. The mechanism of cationic extraction is typically hydronium/alkali ion exchange that causes a pH increase, which is then followed by bulk dissolution, especially in Type I (e.g., borosilicate glass, such as Schott Fiolax®) and Type II (treated soda-lime silicate) glasses. The poor chemical durability of these glasses arises from the fact that soluble cations, such as Na+, Li+, K+, Mg2+, Ca2+ and/or Ba2+ are used to flux these glasses to achieve a suitably low working point temperature that makes them highly processable with standard glass melting equipment (see, e.g., U.S. Pat. Nos. 5,782,815 and 6,027,481).
Glass particle generation due to delamination is one of the major concerns in pharmaceutical packaging industries when Type I and Type II glasses are used as the container for pharmaceutical products. Delamination occurs when top layers of a glass separate at a scale that is barely visible or invisible to the naked eyes as shown in FIG. 1 of Ronald G Iacocca, “The Cause and Implications of Glass Delamination”, Pharmaceutical Technology, 2011, pp s6-s9, the disclosure of which is incorporated herein by reference in its entirety. The particles become suspended in drug solutions, posing a serious risk to the consumer.
Glasses without chemical modifiers (e.g., alkali metals, borates, alkaline earth metals) such as fused quartz glass are preferable from a chemical purity (low extractables) and chemical durability perspective, but it was previously believed such glasses may be difficult to manufacture due to the high processing temperatures required (typically >2,000° C.). Even when fused quartz glasses can be melted and formed into tubing, it is then often difficult to flame convert them into pharmaceutical packages (vials, syringe barrels, ampoules, etc), due to a high working point temperature (>1,700° C.). Thus, such glasses have generally not been used to manufacture pharmaceutical packaging. U.S. Pat. Nos. 6,200,658 and 6,537,626 show that efforts have been made to coat the interior surfaces of traditional glass containers with a layer of silica to reduce extractables (e.g., Schott Type I Plus®) and glass particles that are produced through delamination. Providing coated articles, however, are cumbersome and expensive and, therefore, not widely accepted in the pharmaceutical packaging market. Thus, there is a need for a cost-effective process to produce pharmaceutical packaging glass that exhibits low extractables and leachables that can be used in pharmaceutical packaging applications.
Further, glass compositions formed to be of high purity can still contain contaminants from the glass formation process. Such contaminants can still be present in a concentration that the glass would not be suitable for use in pharmaceutical applications. Thus there is a need for a robust “clean” process to ensure the surface purity of pharmaceutical packaging glasses.