Physicochemical Characterization and Acute Toxicity Evaluation of a Positively-charged Submicron Emulsion Vehicle

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Abstract
Fine, homogeneous, positively-charged emulsions with a mean droplet size of 138 ± 71 nm and a zeta potential value of 41.06 mV were prepared using a combination of emulsifiers comprising phospholipids, poloxamer 188, and stearylamine. The pH of these emulsions decreased with time. However, the extent of decrease was dependent on the storage temperature. The mean droplet size of the emulsions that had been prepared with 1% poloxamer began to increase slightly after six months’ storage, particularly when stored at 23 and 37°C. However, emulsions prepared with 2% poloxamer remained stable for at least 10 months at 4°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 positively-charged emulsion vehicle was well tolerated without any toxic or inflammatory 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 physiological saline. No marked acute toxicity was observed when 0.6 mL of positively-charged emulsion was injected intravenously to BALB/c mice. Furthermore, no difference was noted between this group of animals and the group injected with the marketed Intralipid emulsion. These results were further confirmed in a rat study where there were no deaths following intravenous injection of 3.3 mL per rat of the positively-charged emulsion or Intralipid. Neither emulsion elicited any hepatotoxic or nephrotoxic effects. The overall results suggest that the novel positively-charged emulsion is suitable for parenteral use, and for ocular application.