Amphotericin B in oil-water lecithin-based microemulsions: formulation and toxicity evaluation.
A novel lecithin-based microemulsion containing AmB was developed to reduce the toxic effects of the drug, comparing it with the commercial formulation Fungizone. Phase diagrams containing the microemulsion region were constructed for pseudoternary systems composed of isopropil myristate (IPM)/Brij((R)) 96V/lecithin/water. The incorporation of AmB to the microemulsions was done following the Phase Inversion Temperature (PIT) method or by diluting the drug in the aqueous phase of the disperse system before forming the microemulsion. The percentage of drug entrapped in the microemulsion was analyzed by an HPLC method obtaining recoveries > 98%. Mean droplet size of the microemulsions chosen for the acute toxicity evaluation was of 45 nm, and the rheological studies showed that those microemulsions mentioned followed a Newtonian behavior. Different studies are described in this work to prove the stability of these new dosage forms. Acute toxicity results, determined by a graphic method, the probit binary model and the Reed and Muench method showed that lethal dose 50 (LD(50)) for AmB microemulsions was of 2.9 mgkg(-1) compared to 1.4 mgkg(-1) for the commercial deoxycholate suspension, Fungizone. The overall results indicate that treatment with AmB microemulsions was less toxic than Fungizone, suggesting a potential therapeutic application.
Brime
Begoña
B
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain. begonab@farm.ucm.es
Moreno
Marco A
MA
Frutos
Gloria
G
Ballesteros
Ma Paloma
MP
Frutos
Paloma
P
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D004655:Emulsions; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009821:Oils / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D012212:Rheology; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D014783:Viscosity; D014867:Water / Q000008:administration & dosage / Q000737:chemistry
D000935:Antifungal Agents; D004655:Emulsions; D009821:Oils; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D014867:Water; D000666:Amphotericin B