Formulation Matters: Influence of Water Content and Packaging on Stability and Safety of Sevoflurane

Abstract

Inhalation anesthetic agents have the foundational roles in modern anesthesia practice. These agents offer ease of administration and titration. Understanding the distinctions of each agent enables anesthesiologists to maximize patient safety, comfort, and perioperative efficiency.1 Sevoflurane was first introduced for clinical use in 1995 by Abbott Laboratories under the brand name Ultane® (or Sevorane® in some markets) in the United States. In 2006, Baxter Healthcare Corporation launched a generic formulation, Sevoflurane Inhalation Anesthetic, approved by the U.S. Food and Drug Administration as therapeutically equivalent to Ultane, the reference listed drug.2 Although these formulations are considered clinically interchangeable, recent investigations have highlighted differences in specific physicochemical parameters, specifically water content and container composition, which may influence the chemical stability of sevoflurane and its interaction with anesthesia vaporizers and glass container.2,3 A key safety concern arises from the potential formation of hydrofluoric acid (HF), a toxic degradation product, particularly in the presence of Lewis acids found in certain vaporizer components.3 These acids may leach from materials used in vaporizers or containers, especially under conditions involving low water content or reactive surfaces. The interaction between formulation variables and device materials underscores the need for critical appraisal beyond the therapeutic equivalence. This growing body of evidence underscores the need for clinicians to critically evaluate not only therapeutic equivalence but also formulation-specific properties when selecting sevoflurane products for clinical use.