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

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 degrees C. However, emulsions prepared 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 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.

Design and Synthesis of Some Substituted 1H‐Pyrazolyl‐oxazolidines or 1H‐Pyrazolyl‐thiazolidines as Anti‐inflammatory‐Antimicrobial Agents

“…Moreover, these compounds were tested for their toxicity through the parenteral route. A modified method of Klang was used [28].The results revealed that all the test compounds were non-toxic up to 100 mg/kg. [mg/kg] …”

Formulation and Evaluation of Submicron Emulsion Containing Entrapped Fluoroquinolone for Ocular Delivery

“…Cosurfactant is very essential for the stability of SE [24,25]. Poloxamer 188 concentration is critical for prolonged emulsion stability [26]. Formulations were prepared below 70°C as higher temperature degrades lecithin.…”

Effect of Oil-in-Water Submicron Emulsion Surface Charge on Oral Absorption of a Poorly Water-Soluble Drug in Rats

“…Usual formulations of positively charged submicron emulsions include the use of lecithin with poloxamer 188 (Elbaz et al 1993;Klang et al 1994;Klang, Abdulrazik, and Benita 2000;Tamilvanan et al 2005). Our formulations with lecithin and poloxamer were not submicronic (data not shown), so we substituted poloxamer 188 by polysorbate 85 (data not shown).…”

“…The use of cationic lipids, stearylamine (Elbaz et al 1993;Klang et al 1994;Zeevi et al 1994;Klang, Abdulrazik, and Benita 2000;Fang et al 2004) or oleylamine (Rabinovich Guilett et al 2004), has already been described for the formulation of positive submicron emulsions. Usual formulations of positively charged submicron emulsions include the use of lecithin with poloxamer 188 (Elbaz et al 1993;Klang et al 1994;Klang, Abdulrazik, and Benita 2000;Tamilvanan et al 2005).…”