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Particulate contamination of lyophilized amphotericin B preparation during reconstitution process
T Sendo1, M Hirakawa, K Makino
1The Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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.
Insights
Reconstituting amphotericin B can cause particulate contamination, particularly when shaken vigorously. Filtering solutions with membrane filters and diluted fluids with in-line filters is recommended to reduce particle load.
Area of Science:
- Pharmaceutical Science
- Drug Formulation
- Quality Control
Background:
- Amphotericin B is a critical antifungal medication.
- Proper reconstitution is essential for safe administration.
- Particulate contamination poses a risk to patient safety.
Purpose of the Study:
- To evaluate particulate contamination in reconstituted amphotericin B.
- To compare different reconstitution methods.
- To identify the sources of particle contaminants.
Main Methods:
- Particle counts were measured using a light extinction method.
- Contaminants were identified using X-ray emission spectrometry and scanning electron microscopy.
- Three reconstitution methods and post-reconstitution dilution were tested.
Main Results:
- Vigorous shaking during reconstitution significantly increased particle counts.
- Contaminants included silicone originating from vial components within the amphotericin B-deoxycholate complex.
- Diluted amphotericin B solutions exceeded pharmacopoeial limits for particles.
Conclusions:
- The reconstitution process itself introduces particulate contamination.
- Filtering reconstituted amphotericin B solutions is crucial.
- In-line filters should be used for diluted amphotericin B fluids.