PHYSICOCHEMICAL CHARACTERIZATION AND ACUTE TOXICITY EVALUATION OF A POSITIVELY-CHARGED SUBMICRON EMULSION VEHICLE

Fine, homogeneous, positively-charged emulsions with a mean droplet si ze of 138 +/- 71 nm and a zeta potential value of 41.06mV were prepare d using a combination of emulsifiers comprising phospholipids, poloxam er 188, and stearylamine. The pH of these emulsions decreased with tim e. However, the extent of decrease was dependent on the storage temper ature. The mean droplet size of the emulsions that had been prepared w ith 1% poloxamer began to increase slightly after six months' storage, particularly when stored at 23 and 37 degrees C. However, emulsions p repared with 2% poloxamer remained stable for at least 10 months at 4 degrees C, suggesting that the poloxamer 188 concentration is critical for prolonged emulsion stability. The results of the ocular tolerance study in rabbit eye indicate that hourly administration of a positive ly-charged emulsion vehicle was well tolerated without any toxic or in flammatory response to the ocular surface during the five days of the study. Scanning electron microscopy revealed a normal corneal surface, which was not different from that of the animals treated with physiol ogical saline. No marked acute toxicity was observed when 0.6mL of pos itively-charged emulsion was injected intravenously to BALB/c mice. Fu rthermore, no difference was noted between this group of animals and t he group injected with the marketed Intralipid emulsion. These results were further confirmed in a rat study where there were no deaths foll owing intravenous injection of 3.3 mL per rat of the positively-charge d emulsion or Intralipid. Neither emulsion elicited any hepatotoxic or nephrotoxic effects. The overall results suggest that the novel posit ively-charged emulsion is suitable for parenteral use, and for ocular application.