Experimental Investigation On The Preparation Of Hydrophobic Drugs Liposomes By Supercritical Technology

The supercritical reverse phase evaporation process is a new preparation technology based on supercritical fluid processing techniques.The SCRPE process has the unique superiority in preparating low-water soluble medicine liposomes.It avoids using the organic solvent massively,eliminates the harms to the environment,and changes the modes of system through adjusting pressure,temperature and density(solvent dissolving capacity),thus provides the controllable medium for the preparation and separation of liposomes,this method is a breakthrough of liposomes preparing technology,It can widely extend the application fields of supercritical CO₂.In this paper takes the water-soluble medicine glucose as the object for the experimental study of preparing liposomes by the SCRPE process.The morphologies of liposomes,the particle size and dispersibility of liposomes and the trapping efficiency of liposomes are characterized by a ZETA electric potential analyzer,a biological sensing analyzer and the dialysis law.The effects of the operation parameters,such as the temperature,the pressure,the equilibrium time,the ratio of phospho-lipin and the ethylalcohol,the pH value of solution as well as the amount of cholesterol are investigated.In the range of experiments,T:60℃,P: 25MPa,Ethanol:460μL,DPPC:0.0361g,Cholesterol:0.003g,pH=7,Glucose:0.2mol/L, the liposomes with average diameter distribution of 365nm,the trapping efficiency of 39.7% are obtained;The experimental results show that this method can prepare liposomes with high trapping efficiency.The membrane matcriai of liposomcs uses with L-α-Phosphatidylcholincphosphatide,the Mctronidazole liposomes arc experimentally prepared by SCRPE process.In the range of experiments,T:50℃,P:25MPa,Ethanol:230μL,DPPC:0.0182g,Cholesterol:0.006g,pH= 7,liposomes with average diameter distribution of 328nm,the trapping efficiency of 37.2% are obtained.Aciclovir liposomcs arc experimentally prepared by SCRPE process.In the range of experiments,T:40℃,P:25MPa,Ethanol:230μL,DPPC:0.0187g,Cholesterol:0.0045g,pH =7,liposomcs with average diameter distribution of 332nm,the trapping efficiency of 27.6% are obtained.The properties,morphologies,trapping efficiency and the particle size of the obtained liposomes are respectively characterized by a transmission scanning electron microscope,an Agilcnt1100 highly cffcctivc liquid chromatography,a ZETA electric potential analyzer,an ultraviolet obvious spectrophotomctcr.The effects of the operation paramctcrs, such as the pH value of solution,the best ratio of phospho-lipin and the medicine,operating pressure,temperature,the medicine density,the reaction balance time,the amount of phosphatide and the cholesterol as well as the flux density on the liposomes particle size and the trapping efficiency are investigated.In this work,both the liposomes preparation by SCRPE technique and the effects of the operation parameters on the average particle size and size distribution are understood more deeply.That provides an essential basis for the theoretical research of this process.