Effectiveness of manufacturing annealing temperature on sterilization and depyrogenation of closed ampoules compared with other techniques.

Abstract

The presence of endotoxin in the bloodstream can lead to unexpected fever and, in severe cases, endotoxemia and bacteremia that can lead to death. The reduction of bacterial endotoxin, known as depyrogenation, is crucial for preparing primary packaging components like ampoules for use in injectable drug products. The durability of glass ampoules depends on the proper annealing process. If glass is not annealed correctly, it is prone to cracking or shattering from even small changes in temperature or from mechanical shock or stress. To evaluate the effectiveness of sterilization and depyrogenation, a dry heat oven at 250°C was used for 30 minutes. The Limulus Amebocyte Lysate (LAL) assay was utilized to detect endotoxin, and efficient sterilization and depyrogenation were observed at this temperature. The impact of heating glass ampoules to various temperatures on the process of sterilization and depyrogenation was studied. This investigation covered a range of temperatures (250°C - 550°C), and included holding stage times (105, 120, and 200 seconds) corresponding to the belt speed. The removal of endotoxins was achieved by exposing to temperatures from 350°C to 550°C for specific time intervals and at 300°C with an exposure time of 200 seconds. The absence of endotoxin was observed when annealing glass ampoules at 500°C for 105 seconds, regardless of the ampoules' size. Alternative methods for testing depyrogenation of sealed ampoules, such as ethylene oxide (EtO), sodium hydroxide (NaOH), and hydrochloric acid (HCl), were also demonstrated to have a clear comparison against temperature which considered the best effective economic method . This research indicates that annealing sealed glass ampoules at specific temperatures can serve as a replacement for sterilization and depyrogenation processes prior to filling, leading to savings in time, labor, machine work, energy, and cost.