Particulate contamination of lyophilized amphotericin B preparation during reconstitution process

J Clin Pharm Ther. 2001 Apr;26(2):87-91. doi: 10.1046/j.1365-2710.2001.00328.x.

Abstract

Objective: To investigate the effect of the reconstitution methods for the commercial amphotericin B preparation with respect to particulate contamination.

Methods: The particle counts in amphotericin B solutions reconstituted according to three different methods and amphotericin B fluids made with intravenous fluids after reconstitution were performed using a light extinction method. The particle contaminants were identified with X-ray emission spectrometry attached to a scanning electron microscope.

Results: Amphotericin B in a vial induced particle contamination during the reconstitution process, and the contamination was especially marked by shaking vigorously after injecting water into the vial. From the X-ray analysis, it appeared that the increased number of particles was derived from the amphotericin B-deoxycholate complex containing substances such as silicone released from the vial components. Amphotericin B fluid made with intravenous fluids after reconstitution also contained particles over the acceptable limits according to the Japanese or US pharmacopoeia.

Conclusion: These findings suggest that reconstituted solutions should be filtered with membrane filters and diluted fluids with in-line filters.

MeSH terms

  • Amphotericin B / administration & dosage*
  • Amphotericin B / chemistry
  • Amphotericin B / standards*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / standards*
  • Chemistry, Pharmaceutical
  • Drug Contamination*
  • Filtration
  • Microscopy, Electron, Scanning
  • Particle Size
  • Silicones
  • Solubility
  • Spectrometry, X-Ray Emission

Substances

  • Anti-Bacterial Agents
  • Silicones
  • Amphotericin B