www.6662016.com www.sparta-cuss.com As the liposome has many advantages, such as targeting delivery, cell affinity, histocompatibility, slow release profile and is easy to reduce drug toxicity, etc. It prevails worldwide market to produce this drug delivery system nowadays.
According to the different mechanism of drug loading, the synthesis process of liposome can be classified into passive drug-loaded method and active drug-loading method. Here, we mainly introduce passive drug-loaded method. Firstly, drugs are dissolved in the aqueous phase or organic phase (fat-soluble drugs), and then prepared in appropriate conditions. Liposomes prepared in this way are usually fat-soluble and with higher affinity for phospholipids. The preparation methods generally include film hydration method, injection method, reverse evaporation method, double emulsion method and so on.
Due to raw materials and the process of prescription, it’s always difficult to realize the industrialization of the liposome preparation from lab. Here, we will introduce how to prepare liposome in industry, mainly on film hydration method.
Film hydration production process includes: film, hydration, high pressure homogenization / high pressure extrusion, filtration and machine filling.
Simple process description: Firstly, the liquid from the water phase tank and the organic phase tank is added to the rotary evaporator and mixed to form the phospholipid bilayers. Then, the phospholipid bilayers are added to the hydration solution, and then after passing through a high pressure homogenizer / micro jet / high pressure extruder, the desired liposome is formed and filtered into the finished tank for filling.
The main control point of the process:
1. The dissolution of lecithin and drug in the organic phase: before the preparation, the organic phase tanks should be vacuum dried by nitrogen. It’s necessary to use the high-speed shearing machine to achieve the dissolution of phospholipids (the minimum amount for shearing should be considered), shear line speed 20m / sec or so, the stirring speed can be 2900rpm, for the whole process, the tank temperature should be carefully controlled by the jacket through heat medium, temperature deviation should be controlled at ± 2 °C.
2. Preparation of the aqueous phase: The amount of feeding water should be accurately controlled by weighing module, then adding accessories while solution is controlled by magnetic stirring, temperature control is also needed while mixing.
3. Liposome film formation: the aqueous phase and the organic phase are sequentially added to the rotary evaporator, then add the compound into rotary evaporation in a certain degree of vacuum. After getting the visible lipid film, continue to vacuum drying after a certain time, get loose lipid film. The whole process requires full monitoring (can be linked to PLC).
4. Hydration: The amount of feeding water should be accurately controlled by weighing module, adding raw materials, dissolved after stirring, then the compound should be cooled to room temperature through the jacket. After the production instructions are obtained, the hydration solution is transferred to rotary evaporator through sterilizing filter by inert gas, meanwhile, the water temperature of the rotary evaporator is controlled within the appropriate range, and the evaporation is working at a certain degree of vacuum (intermittent high speed), finally, the solution will be altered to yellow and visible suspension. In the process, inert gas should always be in the evaporator bottle to prevent phospholipid oxidation.
5. High pressure homogenization or high pressure extrusion: Reducing the average particle size and particle size distribution the formationed large particles of liposomes through a certain method, such as high pressure homogeneous or high pressure micro-shot method, or high pressure homogenization + high pressure Extrusion method, or high pressure extrusion method. Choose the right method according to the different processes. The whole process needs to ensure uniform temperature which could be achieved by heat exchanger and jacket temperature control system.
6. Products are sterilized in place through sterilizing filter, and then transferred by nitrogen to filling machine. The sterilization filter can achieve the integrity testing after SIP.
Summary: It's easy for the product prepared in this way to meet the product testing standards, if the preparation can be completed within the specified time. As a professional automatic solution preparation system provider, Tofflon-Top is able to provide a one-button operation and control system to reduce the labor intensity, to offer recipe-type management (supply custom parameters set due to different product), to conduct a complete cleaning and sterilization process, to meet the cGMP and FDA standards, and can provide customized solutions.
Many details are not mentioned due to limited space. More valuable advices are favorable.