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When performing liposome extrusion, the corresponding equipment must be used. However, when each device is finalized as a standard product, various performance requirements, versatility, price, ease of use and other factors will be comprehensively considered, and a certain degree of trade-offs will be made. Because of this trade-off process, each device has its own projects and fields that are suitable, as well as projects and fields that have certain disadvantages when used. Therefore, how to choose the right extrusion equipment is particularly important. This article gives a more detailed introduction to the commonly used liposome extruders.
Micro push extruder
The principle of the micro-hand-push liposome extruder is:
A sealed glass syringe is used, and the hand push force is used as the power to squeeze the liposome sample in the syringe at one end and force it through the PC filter membrane in the middle. The shear force of the PC filter membrane reduces the particle size of the liposome and improves the distribution, and then returns to the syringe on the other side; the push rod of the syringe on the other side is pushed again for secondary extrusion. Repeat the above process for multiple extrusions. If the extrusion process requires temperature control, the entire device can be placed in a hot water bath for extrusion.
The advantages of this equipment: it can extrude very small sample amounts (0~1ml) without sample loss, and the entire extrusion process is visible, which is very suitable for the extrusion requirements of laboratory trace samples.
Disadvantages: Manual extrusion, unknown pressure, and the extrusion process is generally very difficult, and the glass syringe is easily damaged.
The overall price of this equipment is low, so it is very suitable for exploratory experiments in the laboratory.
Tank type liposome extruder
The principle of the tank-type liposome extruder is:
Using high-pressure nitrogen as the power, the liposome sample is squeezed to pass through the PC filter membrane and its supporting components at the bottom. The shear force generated by the PC membrane during the passage can reduce the particle size of the liposome sample and improve its distribution.
Advantages of this device:
The gas directly pressurizes the sample through the PC membrane, with stable pressure and no pulse fluctuation, which can effectively ensure that all liposome samples are extruded with the same extrusion force and have good uniformity.
Another advantage is that the high-pressure chamber can be customized according to the volume of the sample (such as 10ml, 50ml, 100ml, 200ml, 800ml, 1000ml, etc.), and the specifications of the corresponding extrusion disc assembly are also different (diameters such as 25mm, 47mm, 90mm, 142mm).
shortcoming:
The extrusion pressure that can be provided is relatively low. Many liposome varieties with less mature formulations or drug-loaded liposomes are generally difficult to extrude. The extrusion speed is very slow and many samples cannot be extruded.
Another disadvantage is that the chamber of such commercially available standard equipment generally has its own jacket for insulation, but there is no insulation jacket at the extrusion disk, so there will be a certain low-temperature area during the extrusion process, which sometimes has a greater impact on the extrusion effect.
This type of equipment is generally used for laboratory liposome sample extrusion (1ml~1000ml), and is particularly suitable for the extrusion of blank liposome samples with mature prescriptions. Some equipment can also be used in parallel to meet the needs of pilot and production capacity.
Gas booster extruder
The principle of this type of liposome extruder is:
Nitrogen or compressed air is used as the power source input. After the cylinder pressurizes the input gas source, the liposome sample pre-loaded in the cavity is squeezed through the piston to pass through the PC filter membrane and its supporting components. The shear force generated when passing through the membrane can reduce the particle size of the liposome sample and improve its distribution.
Advantages of this device:
The extrusion pressure that can be provided is high, which can basically meet the extrusion pressure requirements of all types of liposome samples (blank liposome samples with mature/immature prescriptions, various drug-loaded liposome samples, etc.); and the pressure during the extrusion process is constant without fluctuation;
The extrusion speed is faster (generally about 10~15 times faster than that of tank liposome extruder);
The sample chamber and extrusion unit are equipped with insulation jackets, and the whole extrusion process is kept at a constant temperature without temperature fluctuation.
Disadvantages: The extrusion speed is too fast. Sometimes the preset pressure is too high, which causes the extrusion speed to be too fast, making the extrusion effect fail to meet the required requirements. Therefore, when using this equipment, special attention should be paid to finding a more appropriate extrusion pressure and extrusion speed.
This equipment is relatively versatile and suitable for extrusion of various types. However, due to the principle, its single extrusion volume will not be too large (usually 1ml~100ml), so it is only suitable for laboratory use.
Continuous Extruder
The continuous liposome extruder is composed of a high-pressure pump and an extrusion disk connected by valves and pipe fittings.
The high-pressure pump sucks the sample and delivers it to the extrusion disk. The high-pressure pump provides high-pressure power to extrude the sample from the extrusion disk to achieve the effect of controlling the particle size of the liposomes.
Since the pump runs continuously, the feeding and discharging of the extruder are also carried out continuously and simultaneously, so this type of extruder is called a continuous liposome extruder.
There are three key aspects of this type of extruder:
1. High-pressure pump
There are generally two types of high-pressure pumps: high-pressure plunger pumps and high-pressure diaphragm pumps. Both types of pumps are widely used in liposome research and development, pilot tests and production projects.
2. Extrusion disc
The extrusion discs for this type of extruder are generally recommended to be 47mm, 90mm and 142mm in diameter.
19mm and 25mm are not suitable for use with high-pressure pumps due to their small flux. 293mm extrusion discs are rarely used due to their large sample loss and inconvenient purchase of filter membranes.
After determining the specifications of the extrusion disc, it is generally combined with the extrusion process requirements, such as how many different membrane groups are to be extruded? Extrusion time requirements? Residual volume requirements? Combining these three factors can determine the diameter, quantity and connection method of the extrusion disc, and then achieve a good connection with the pump to complete the main configuration design or selection.
3. Process control components
Process control components generally include valves, pipes, and instruments (temperature instruments and pressure instruments).
Reasonable selection of valves and pipes can ensure that the extrusion process is continuous until completion. There is no need to stop the machine to change the membrane and other operations. Different times of extrusion of the same membrane group, different times of extrusion of different membrane groups, etc. can be completed by switching valves.
The selection of temperature and pressure instruments can monitor the pressure and temperature at various points in the extrusion process. If necessary, they can also be linked with the control system to ensure the stability and real-time adjustability of the core parameters in the extrusion process.
The relevant exchanges on liposome particle size control have been basically introduced in this article. In general, when choosing extrusion equipment, comprehensive consideration should be given based on actual needs and budget.
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