Factors Affecting the Chemical Durability of Glass Used in the Pharmaceutical Industry

Abstract

Delamination, or the generation of glass flakes in vials used to contain parenteral drug products, continues to be a persistent problem in the pharmaceutical industry. To understand all of the factors that might contribute to delamination, a statistical design of experiments was implemented to describe this loss of chemical integrity for glass vials. Phase I of this study focused on the effects of thermal exposure (prior to product filling) on the surface chemistry of glass vials. Even though such temperatures are below the glass transition temperature for the glass, and parenteral compounds are injected directly into the body, data must be collected to show that the glass was not phase separating. Phase II of these studies examined the combined effects of thermal exposure, glass chemistry, and exposure to pharmaceutically relevant molecules on glass delamination. A variety of tools was used to examine the glass and the solution contained in the vial including: scanning electron microscopy and dynamic secondary ion mass spectroscopy for the glass; and visual examination, pH measurements, laser particle counting, and inductively coupled plasma-optical emission spectrometry for the analysis of the solution. The combined results of phase I and II showed depyrogenation does not play a significant role in delamination. Terminal sterilization, glass chemistry, and solution chemistry are the key factors in the generation of glass flakes. Dissolution of silica may be an effective indicator that delamination will occur with a given liquid stored in glass. Finally, delamination should not be defined by the appearance of visible glass particulates. There is a mechanical component in the delamination process whereby the flakes must break away from the interior vial surface. Delamination should be defined by the observation of flakes on the interior surface of the vial, which can be detected by several other analytical techniques.

Effects of Phosphate Buffer in Parenteral Drugs on Particle Formation from Glass Vials

“…10,29) Considering the fact that sulfur treatment suppressed the particle formation, dealkalization might have an effect on the suppression of particle formation. In contrast, SiO 2 coating is also known to protect the surface from alkali elution, 2,12) however, no suppression effects of the SiO 2 coating on the particle formation were shown in this study.…”

“…At that time, we also measured the concentration of Si, which is known as indicator of delamination. 12) This extraction was conducted at a high temperature for short time (121± 1°C, 10 min) to keep the concentrations from any undesirable effects during extracting.…”

“…Ennis et al 10) evaluated the tendencies of delamination from borosilicate glass vials based on the fact that the cidofovir injectable drug product formed glass delamination, and they concluded that the high pH of the solution enhanced the corrosive attack on the inner surface of the glass container, resulting in delamination. Iacocca et al 11,12) also investigated causes of glass delamination using some drug products with borosilicate glass vials, suggesting a scheme of corrosive attacks by the drug solution on the glass surface, which relates to the delamination. From these reports, the corrosive attacks by drug solutions on glass surfaces have induced delamination, and their study results are expected to eliminate the delamination potential of injectable drugs during future drug development.…”

Comparisons of Aluminum and Silica Elution from Various Glass Vials

“…4,16) On the other hand, SiO 2 coating, a technique to coat the surface with silica, is known to be able to avoid delamination from the glass surface. 2,6) However, our previous study showed that sulfur-treated vials showed a protective effect against the Al-containing particles' formation, while otherwise the SiO 2 coating did not have any protective effects.…”

“…Delamination, which is indicated by the presence of glass flakes, is the most well-known phenomenon and is the result of corrosive attack on the inner surface of the glass container. [4][5][6][7][8][9][10] United States Pharmacopeia (USP) ‹1660› describes factors of delamination on the surface of glass vials filled with drug solution, and also introduces tools for selecting an appropriate glass container from the point of view of avoiding delamination. 11) Among several literatures describing the propensity of forming delamination, Guadagnino has suggested that the silicon dioxide (SiO 2 ) concentration in an extract solution is an efficient indicator of glass dissolution.…”