Studying the effect of different factors on partitioning of propofol between aqueous and organic phases of injectable emulsions

Abstract

Introduction: Propofol is one of the most widely used agents for anesthetic induction and for sedation in the intensive care unit. Due to its high hydrophobicity, propofol has been formulated as an oil in water microemulsion. As an alkyl phenol, it has an irritating effect on skin and mucous membranes which leads to irritation of vein endothelium. Pain on intravenous injection of propofol is a common side effect, which is related to increased concentration of propofol in aqueous phase. Objective: Present study was designed to investigate the probable effect of different factors on concentration of propofol in aqueous phase, as follows: (1) type of the osmotic agent, (2) type of the oil used in organic phase, (3) volume of organic phase, and (4) type of surfactant. Method: Water-soluble agents were dissolved in water, and insoluble ingredients were dissolved in oil phase. After adding aqueous phase to oil phase, formulations were put in shaker incubator at 150 rate per minute in room temperature for 48 hours to reach balance. In order to separate the aqueous phase, each formulation was transferred to a separatory funnel. The HPLC method was used to determine the concentration of propofol in aqueous phase. Results: Our findings shows that type of the osmotic agents has not a significant effect on propofol concentration in aqueous phase. Type of oil phase and surfactant notably effect propofol concentration in aqueous phase. Conclusion: Changing the types of oil or surfactant, can lead to a new formulation which has lower concentrations of propofol in aqueous phase. It can result in decrease of pain of injection.