Role of phospholipids and copolymers in enhancing stability and controlling degradation of intravenous lipid emulsions

• Emulsifier mixture can alter the emulsion activation energy and stability.
• Emulsions prepared with the emulsifier mixture have low degradation rate.
• Emulsifiers with high transition temperature and steric hindrance enhance stability of oil droplets.
• Insight on the rational design of submicron emulsions for intravenous administration.

Understanding the factors that control the stability at the oil–water interface continues to be a major focus to optimize the formulation of intravenous emulsion. In this study, we investigated how phospholipids and nonionic polymeric surfactants influence the emulsifying capacity, stability, and lipolysis kinetics of emulsions under physiological conditions. 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and Pluronic P123, either alone or in combination were used as emulsifiers to prepare emulsions. Then, in vitro methods were applied to study the emulsifying capacity during the manufacturing process, and emulsion stability under both heat treatment and intravenous lipolysis conditions. Our results showed that an emulsifier blend with DOPC, DOPE, and Pluronic P123 resulted in a higher surface activity and produced smaller and more uniform droplet sizes in comparison to the use of DOPC alone. In addition, mixed emulsifier-stabilized emulsions showed more stable droplet sizes and surface tensions under heating and lipolysis treatments, as well as decreased lipolysis rates under physiological conditions. The reason for this seems to be the high transition temperature and steric hindrance produced by DOPE and Pluronic P123. Mixed emulsifier-stabilized emulsions resulted in increased activation energy values. A better understanding of the relationship between the surfactant and oil droplets may be applied in the development of novel strategies to rationally design submicron emulsions as lipophilic drug carriers.

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