The operation method of the continuous liposome extruder can be divided into four core steps: pretreatment, equipment assembly, operation control, and safety protection. The specific process is as follows:
1、 Preprocessing stage
1. Material pretreatment
Crude liposomes need to be prepared through methods such as thin film dispersion and solvent injection. If they contain large particles or agglomerates, they need to be homogenized under high pressure or treated with ultrasound to avoid clogging the filter membrane.
When the purity of the solvent and solute is high, they can directly enter the extrusion process.
2. Equipment cleaning and sterilization
Before use, thoroughly clean the system piping and membrane components with alcohol or high-temperature steam to ensure sterility.
2、 Membrane module assembly
1. Install filter membrane system
Place the polycarbonate track etching film (PC film) between two O-rings and embed it into the plastic component of the film support unit, ensuring that the film is centered and sealed without leakage.
After confirming the correct position of the membrane through the inspection hole, manually tighten the end cap.
2. Pressure system connection
Connect the nitrogen cylinder to the equipment inlet, check the sealing of the gas path, and open the pressure relief valve to discharge residual gas.
3、 Operation control process
1. Material loading and pressurization
Open the lid of the material tank and pour in the liposome suspension. Close the pressure relief valve and slowly open the main valve of the nitrogen cylinder. Adjust the pressure precisely to the target value (usually ≤ 100 bar) through the pressure relief valve to avoid sudden pressure rise.
2. Continuous extrusion operation
Under conditions slightly above the phospholipid phase transition temperature (adjusted according to the formula), activate nitrogen pressure drive to continuously pass the suspension through the PC membrane group.
Observe the discharge status: The initial extruded liquid returns to the material tank for circulation, and after the particle size stabilizes, it is connected to the receiving tank to collect the finished product.
3. Dynamic parameter adjustment
Replace the filter membrane with different pore sizes according to the particle size distribution requirements (such as gradually changing from 200nm to 80nm), or increase the extrusion frequency (usually 3-10 times).
Real time monitoring of pressure fluctuations, stopping the machine to check for filter membrane blockage when the set threshold is exceeded.
4、 Key points of safety and maintenance
1. Operation protection
Wear goggles and pressure resistant gloves throughout the entire process to avoid spray injuries caused by high-pressure pipeline rupture.
2. Shutdown procedures
Close the main valve of the nitrogen cylinder → open the equipment pressure relief valve → remove the membrane component after the pressure gauge returns to zero.
Immediately rinse the membrane and flow path with pure water to prevent lipid residue from solidifying.
3. Component maintenance
Check the integrity of the O-ring before each use, and replace worn parts with original accessories to prevent pressure relief risks.
Regularly check the permeability of the PC membrane and replace it with a new membrane when there is an abnormal decrease in flow rate.
Key process control points: The extrusion temperature should be stable at 10-15 ℃ above the lipid phase transition point (such as about 55-60 ℃ for DPPC liposomes). Excessive temperature can lead to degradation, while insufficient temperature can cause membrane blockage; The extrusion pressure is negatively correlated with particle size, and precise control of shear force needs to be achieved through flow regulation.