A Contribution to an Understanding of Complexing Agents and Salt Solutions Reaction Mechanism on Chemical Attack of Type I Molded Glass Containers

Abstract

An enhancement of the glass surface chemical attack was shown in type I molded borosilicate glass containers because of the synergy between the presence of complexing agents in the aqueous solution and basic pH. However, flake development (delamination) is not easily correlated with even a strong glass surface chemical attack. A few homologue series of carboxylic and dicarboxylic acids were investigated. We considered the presence of functional groups (NH₂, COOH, OH), alkyl chain length (three to six carbon atoms), and C=C bonds. Tests were performed at 0.024 M constant concentration, in the 5.8–10 pH range, in small-volume 23 mL type I molded glass containers, and by autoclaving for 1 h at 121°C. The extracted silicon data confirm that both the dissociation constant pKa and the molecular structure of the complexing agent are determinant enhancing factors of glass surface chemical attack. The second part of the work concerned the glass surface chemical attack in the 5.8–9 pH range by alkali chloride solutions (NaCl and KCl 0.9% w/v and 0.0154 M) widely used in parenteral therapies. This last study was extended to also include LiCl and CsCl, even if they are not used in injectables, to evaluate a possible influence of the molecular weight on the glass chemical attack. A correlation between alkali chloride's molecular weight and glass chemical attack as a function of pH was found. Therefore, in a preliminary way, the complexing powers of acetic acid and EDTA (ethylenediaminetetraacetic acid) were examined in the presence of Na or Li ions, which showed different chelating propensities as a function of the alkali ion. The present research provides valuable information to the chemists involved in new pharmaceutical formulation to consider some possible compatibility limitations with the packaging in type I borosilicate glass containers.

LAY ABSTRACT: The glass surface degradation particles appearing in vials (delamination) has forced a number of drug product recalls in recent years. Some drug formulations can contain active components or excipients with a known ability to corrode glass silica networks. Sometimes these ingredients are dissolved in an alkaline medium that dramatically increases the glass corrosion and potentially causes the issue. Flaking may become visible after a long period of storage; it could be affected by the surface glass composition but no correlation even with strong glass surface chemical attack was found. Generally, the synergy of complexing agents and concentrated salt solutions at alkaline pH increases the glass attack rate. The glass attack rate was investigated by analyzing extracted silicon in aqueous solution under controlled test conditions (autoclaving for 1 h at 121°C), in the 5.8–10 pH range, by a homologue series of 0.024 M solutions of complexing agents with different functional groups, alkyl chain lengths, etc. Data showed that both complexing agent acid dissociation constant, pKa, and molecular structure are determinant enhancing factors for glass surface chemical attack. The role of alkali chloride solutions at constant concentration and molarity was also examined.