Preparation and evaluation of injectable propofol microemulsion

Abstract

Background: Propofol is an intravenous drug used for induction and maintenance of anesthesia. In its pure form high lipophilicity and low water solubility leads to low bioavailability, which renders it unusable.

Aim: The main purpose of this study was to develop a stable propofol microemulsion, study physicochemical properties including: pH, zeta potential and particle size and perform storage stability tests in accelerated conditions.

Materials and methods: Propofol, soybean oil, glycerol, egg lecithin, mannitol and EDTA with different amounts were mixed to form the 3 sets of emulsions which are named initial, reevaluation and final formulations. Afterwards the prepared formulations went through a two step high pressure homogenizer system (HPH). These samples were then evaluated for active drug ingredient using high performance liquid chromatography (HPLC), droplet sizes were measured by LASER diffraction particle size analyzer and DLS technique, pH values were measured using pH meter. A set of each formulation was stored in the refrigerator, room temperature and accelerated conditions.

Results: Propofol – a poor water soluble agent – was solubilized in microemulsion system using egg lecithin as emulsifier. Active drug assessment using HPLC method showed that propofol is a stable agent – owing to its phenol structure – and the concentration of propofol remained within the defined range (NLT 90.0% and NMT 110.0%). Particle size analysis indicated that the prepared formulations all passed the particle size upper limit of 5 μm for injectable emulsions and met with the microemulsion particle size criteria of 700 nm. Conclusion: Formulations were prepared and storage stability showed that propofol microemulsion was stable under accelerated conditions for 6 months. Further experiments are needed to be done in vivo to study the efficacy and safety of prepared formulation.