AMPHOTERICIN-B IN LIPID EMULSION - STABILITY, COMPATIBILITY, AND IN-VITRO ANTIFUNGAL ACTIVITY

Newer formulations of amphotericin B (AmB) complexed,vith liposomes or lipid suspensions have been developed. Preliminary studies have sugge sted that AmB in Intralipid (IL) mag be as effective as, but less toxi c than, conventional formulations of AmB, but few data are available r egarding its stability, compatibility, or in vitro antifungal activity . A compatibility study was done to evaluate the effects of AmB concen trations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid ch romatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was det ermined by using a broth macrodilution method in accordance with Natio nal Committee for Clinical Laboratory Standards guidelines (M27-T). Sa mples of AmB-IL which were lightly shaken retained more than 90% of th e AmB concentration over 21 days when stored at either 4 or 23 degrees C. Varying the AmB concentration did not appear to affect the stabili ty of AmB-IL. However, a precipitate was formed when mixtures with mor e than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities again st reference strains of yeasts. Further pharmacologic and clinical stu dies with AmB-IL are warranted, although AmB should dot be combined wi th IL in concentrations capable of producing a precipitate.