Application of response surface methodology in the development of parenteral emulsion using ultrasonic emulsification

Abstract: Intravenous lipid emulsion is a critical component of parenteral nutrition. Long-term administration of such therapy lead to liver dysfunction. As the cause of liver failure can be the size of lipid emulsion droplets, their reduction can positively affect the clinical condition of patients. This study aimed to develop and optimize the preparation process of intravenous lipid emulsions with reduced droplet size compared to commercially available formulations. The response surface methodology was applied to optimize the ultrasonic emulsification. The reduction of lipid droplet size was achieved by the use of a combination of 1.2% (w/w) soy phospholipids and various concentrations of Tween 80 (2, 3, and 4% (w/w)). The other variables were sonication amplitude and time of sonication. During the optimization process, fifteen soybeans oil-based intravenous lipid emulsions were developed. All formulations were characterized by the physicochemical properties appropriate for intravenous administration, i.e., MDD ranging from 119.1 ± 0.6 nm to 177.1 ± 2.1 nm, PdI below 0,219 ± 0,009. The pH and osmolarity ranged from 6.23 ± 0.01 to 6.58 ± 0 and from 328 ± 3 to 568 ± 8 mOsm/kg, respectively. The Box Behnken methodology allowed for optimizing the preparation of intravenous lipid emulsion using ultrasonic emulsification.