Studies On Preparation And Pharmacological Efficacy Of Propofol-lidocaine Hydrochloride Nanoemulsion

Objective: To prepare propofol-lidocaine hydrochloride nano-emulsion and evaluate itsstability,security properties and pharmacological efficacy.Methods:?a?The optimum formulation of propofol-lidocaine hydrochloride nano-emulsion was selected based on the related stability and security principles of intravenous fluid and pseudo-ternary phase diagram,and then the nano-emulsion was prepared.?b?The type of nano-emulsion was identified by staining method.The shape of nano-emulsion droplet was determined by TEM,and the particle size and its distribution was detected using LPSA.The drug content was determined by HPLC.We tested the stability and shelf life of nano-emulsion by stress testing,accelerated testing and long-term testing.?c?The hemolysis and vascular stimulation assay was evaluated.?d?The pharmaceutical efficacy was evaluated by tail-flip,and acetic acid induced writhing.Results:?a?The propofol-lidocainehydrochloride nano-emulsion was light yellowtransparent liquid,and its optimum formula was follows: propofol?1%?,lidocaine hydrochloride?0.1%?,pluronic F68?10%?,1,2-propylene glycol?10%?and saline?78.9%?.?b?The structure pattern of nano-emulsion was O/W.The shape of the nano-emulsion droplet under TEM was equally distributed spherical particles,the range of particle size was 43.82¹41.8nm,and its average particle size was 86.82 nm.The stability of this nano-emulsion was goodand its shelf life was 12 months under the condition of 25±2? and relative humidity of 60±10%.It was no obvious difference in viscosity between nano-emulsion and water.The best detection wavelength of propofol and lidocaine hydrochloride was 275 nm and 254 nm respectively.The concentrations of propofol and lidocaine hydrochloride had good linear relationships with its own peak areas in the range of 0.03125mg/mL to 1mg/mL and 0.00625mg/mL to 0.1mg/mL respectively;the average recovery rate of propofol and lidocaine hydrochloride were 99.51%and 99.89%,respectively.?c?Hemolysis and vascular stimulation assay showed that the security of nano-emulsion had no significant difference withcommercial lipid emulsion.?d?In the anesthesiatest,the ED₅₀ of nano-emulsion is 8.43 mg/Kg.In the tail-flip test,the ED₅₀ of nano-emulsion is 7.04mg/Kg.In the acetic acid induced writhing test,the ED₅₀ of nano-emulsion is 14.52 mg/Kg,there is no significant difference in both analgesia and anesthesia between nano-emulsion and commercial lipid emulsion.Conclusion: Propofol-lidocaine hydrochloride nano-emulsion was successfully prepared,its stability and security was goodand its storage time was long.Besides,its vascular stimulationwas low and its analgesia and anesthesia effects had no significant differencewith commercial lipid emulsion,which could be effectively used in veterinary clinicalanesthesia.