Microscopic evaluation of pharmaceutical glass container-formulation interactions under stressed conditions

Chemical incompatibility of the formulation with glass container can adversely impact the quality of parenteral products. The objective of this study is to investigate formulation-glass interactions at the inner surface of the glass containers that lead to the generation of particulates under stressed conditions (i.e., combinations of high pHs, temperatures and prolonged exposure selected to purposely cause failure of glass containers) using advanced microscopic techniques. The optical, electron microscopy and X-ray spectroscopy were used in tandem to investigate the nature of these interactions at the vial inner surface. These interactions were characterized by surface roughness and reaction zones on the inner surface of the vials and particulates in the formulation using two commercially available pharmaceutical glass containers (Vials 1 and 2). A nanoscale level examination of the inner surface of Vial 1 revealed layers flaking off from the inner surface of the vial resulting in typical particulate generation, while the reaction zone on the inner surface of Vial 2 exhibited a different layered structure. The results suggest that particulates observed in Vials 1 and 2 were generated through different failure modes.