Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination

Abstract

Purpose: Studies were initiated to examine the effect of formulation and process variables on the delamination process and also the influence of the glass manufacturing process, supplier, and glass surface treatment.

Methods: Stress testing was performed by exposing filled vials to multiple sterilization cycles followed by accelerated stability testing. Delamination incidence was determined by visual examination, light obscuration (HIAC), and microscopical methods. The inner surface of vials from each supplier and lot were also examined by scanning electron microscopy.

Results: Vials sourced from Supplier A had smooth surfaces as demonstrated by SEM examination, whereas vials sourced from Suppliers B and C displayed extensive surface imperfections such as pitting and/or deposits. These imperfections were localized to the vial wall, adjacent to the vial bottom, and increased with sulfate treatment. Delamination incidence increased in those vial lots with increased surface imperfections. Thus, vials sourced from Supplier A had the lowest frequency of delamination. Sulfate treatment and high pH increased delamination incidence to as high as 100%.

Conclusion: These results demonstrate the importance of the surface morphology created during the vial forming process. Given the diferences observed, final vial selection should include extensive microscopical and product stress testing studies on multiple vial lots.