Particulate contamination of lyophilized amphotericin B preparation duringreconstitution process

Objective: To investigate the effect of the reconstitution methods for the commercial amphotericin B preparation with respect to particulate contamina tion. Methods: The particle counts in amphotericin B solutions reconstituted acco rding to three different methods and amphotericin B fluids made with intrav enous fluids after reconstitution were performed using a light extinction m ethod. The particle contaminants were identified with X-ray emission spectr ometry 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 sha king vigorously after injecting water into the vial. From the X-ray analysi s, 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 intraveno us 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 f iltered with membrane filters and diluted fluids with in-line filters.