چکیده (انگلیسی):

The present studies were designed to develop a formulation of amphotericin B in a lipid-based
preparation as a microemulsion and to compare its toxicity with the commercial formulation Fungizone.
The final product developed is a lyophilized amphotericin B, oil and surfactant blend for reconstitution in
water to yield a microemulsion containing 5 mg/ml of the drug. Pseudoternary phase diagrams were
constructed to identify areas of existence of microemulsion composed of Peceol (glyceryl monooleate)
as oil phase and Mys 40 (polyethylene glycol 40 stearate) and Solutol HS 15 (polyethylene glycol 15
hydroxy stearate) as surfactants. Amphotericin B was co-evaporated with oil - surfactant mixture to
produce a microemulsion pre-concentrate. The co-evaporate was diluted in water, filtered for sterilization
and lyophilized to obtain the final product. The lyophilized as well as the reconstituted products were
separately studied for stability and the latter was also characterized for various physicochemical aspects
including droplet size of the dispersed phase, osmolarity and aggregation state of drug. The dispersion
showed no evidence of precipitation of drug for 48 h, and resisted destabilization due to freeze–thaw
cycles or centrifugation. The dispersed phase globules measured a mean size of 84 nm and uv–
spectrophotometric studies indicated the presence of self-aggregated amphotericin B. The present
formulation showed a 92% decrease in haemolysis of human RBC in vitro when compared with the
commercially available Fungizone. The LD50 in mice was estimated to be 3.4 mg/kg. The results
indicate that the formulation holds promise for development as a safer and efficacious alternative for
amphotericin B therapy.