A contribute to the comprehension of complexing agents and salt solutions reaction mechanism on chemical attack of type I molded glass containers

The commonly named ″glass delamination″ that is flakes or particles' appearance in injectables, is an important issue sometime at the origin of recalls from the market and of possible health issues to patients. In a previous work (1) the enhancement of glass surface chemical attack was shown in type I tubing and molded borosilicate glass containers, due to the presence of complexing agents in the aqueous solution in synergy with basic pH. In any case neither flakes development nor cloudy solutions were found also in the present work, to emphasize that flakes development (delamination) is not easily correlated even with a strong glass surface chemical attack. To understand the correlation between complexing agent chemical structure and the rate of glass 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 (3 to 6 carbon atoms) and the presence of double C=C bonds. Testing conditions were performed at 0.024M constant concentration, in the 5.8 - 10 pH range, in small-volume 23 mL type I molded glass containers, by autoclaving for 1 h at 121 °C according to the European Pharmacopoeia or United States Pharmacopoeia. The extracted silicon was analyzed by inductively coupled plasma atomic emission spectrometry. The collected data confirm that both dissociation constant pKa and molecular structure of the complexing agent are determinant enhancing factors of glass surface chemical attack. The second part of the work concerns with the glass surface chemical attack in the 5.8 - 9 pH range by alkali chloride solutions (NaCl and KCl 0.9% w/v and 0.0154M) widely used in parenteral therapies. For reason of completeness, this last research was extended also to LiCl and CsCl even if not used in injectables, to evaluate a possible influence of the molecular weight on the glass chemical attack. A correlation between alkali chlorides molecular weight and glass chemical attack as a function of pH was found. Therefore, in a preliminary way also acetic acid and EDTA (ethylenediaminetetraacetic acid) complexing power were examined in presence of Na or Li ions, showing some different chelating propensity as a function of the alkali ion. The present research can give precious information to the chemist involved in new pharmaceutical formulation or new molecules development, to prevent or consider some possible compatibility limitation with the packaging in type I borosilicate glass containers