Lyophilized lecithin based oil-water microemulsions as a new and low toxic delivery system for amphotericin B.
OBJECTIVE
To develop and investigate lecithin based oil-water microemulsions as potential amphotericin B (AmB) delivery systems and to evaluate their in vivo acute toxicity.


METHODS
AmB was added to the microemulsion and its location was evaluated by partitioning studies and UV-visible spectrophotometric analysis of the drug. Both, non-lyophilized and reconstituted microemulsions were characterised and assessed for their stability. Single-dose acute toxicity of the AmB microemulsion was studied on male albino Webster-derived CD-1 mice and compared with Fungizone.


RESULTS
The studies performed showed that AmB was intercalated on the oil-water interface of the microemulsion as a complex formed with lecithin molecules. AmB addition did not seem to modify the rheological properties of the original system, but had an effect on its particle size distribution. Lyophilization of the microemulsion led to an oily cake, easily reconstituted and stable at the conditions studied. Single-dose acute toxicity studies proved that the LD50 of AmB microemulsions was of 4 mg kg(-1) of animal weight, compared with 1 mg kg(-1) found for Fungizone.


CONCLUSIONS
Lyophilized lecithin based oil-water microemulsions appear to be valuable systems for the delivery of AmB in terms of easy and low-cost manufacturing, stability and safety compared with the formulations already in market.
Moreno
M A
MA
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain. marco@eucmax.sim.ucm.es
Frutos
P
P
Ballesteros
M P
MP
D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004655:Emulsions; D005079:Excipients; D005612:Freeze Drying; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D012212:Rheology; D013056:Spectrophotometry, Ultraviolet; D014783:Viscosity
D000935:Antifungal Agents; D004655:Emulsions; D005079:Excipients; D010713:Phosphatidylcholines; D000666:Amphotericin B