When heat strikes: Investigating unexpected particles in sodium bicarbonate injections

Abstract

The presence of particles in injectable formulations presents significant risks, such as embolism, phlebitis, and thrombophlebitis. Moreover, visible particles violate pharmacopeial standards and may lead to regulatory actions. Therefore, it is crucial to identify the underlying cause and eliminate visible particles to ensure both patient safety and regulatory compliance. Sodium Bicarbonate Injection, a straightforward formulation containing only the active pharmaceutical ingredient and water for injection, is commonly packaged in glass vials for commercial use. This study reports an unexpected observation that, when subjected to sterilization at 121 °C, Sodium Bicarbonate Injection can develop particulate matter. Through thorough analysis, we discovered that the particles as crystals of sodium dawsonite; surprisingly, this forms at high temperatures due to the interaction between the drug product and aluminium leached from the glass vial. This important finding highlights the risks associated with exposing the drug product to elevated sterilization temperatures, emphasizing the need for alternative sterilization methods or careful optimization of heat-based conditions. It also underscores the importance of particle identification through the use of a combination of techniques that help identify the root cause and prevent formation, thereby ensuring safety and efficacy.