The method of the freeze-drying system involves freezing the material and then warming it in a vacuum system so that the ice sublimes. This method is used for drying food freeze, blood plasma or tissues, and pharmaceuticals without affecting their physical structure.
Principle
The principle of freeze-drying involves the removal of water molecules from the frozen material by sublimation. The experimental conditions required for freeze-drying times can be decided by the solid-liquid-vapor equilibrium phase diagram of water. Exposing the material to temperature and pressures below the triple point. results in drying. Under these stainless steel conditions. The heat transferred is used as latent heat and sublimes (i.e., changes to vapor state directly). The water vapor is removed by condensation or a cold trap maintained at a temperature lower than the frozen material. Freeze drying is also known as lyophilization which means that for removal of the solvent, the system is made solvent loving.
Construction
The freeze dryer consists of the following parts:
1) Drying chamber for loading trays.
2) Radiation source or heating coils for supplying heat,
3) Vapour condensing or adsorption system, and
4) Vacuum levels pump or steam ejectors or both.
The vacuum chamber (suitable for batch operation) consists of shelves for loading the material to be freeze-dried. The distance between the subliming surface and condenser should be less than the molecules' mean path thus, increasing the drying rate.
The condenser has a large surface area, which is cooled by solid carbon slurred with acetone or ethanol. The condenser temperature should be less than the evaporated surface of the frozen material. This condition can be maintained by frequent cleaning of the condenser surface.
Working
1) Preparation and Pre-Treatment: Limited volume of solution is fed into the container. Since the freeze-drying process cannot be done beyond a certain limit of the depth of liquid, pre-treatment is necessary. The solution is pre-concentration using tray drying technique under normal conditions of vacuum, reducing the actual drying rate by 8-10 times. The end product obtained is more porous. Liquid or solid desiccants are also used for this purpose.
2) pre-Freezing to Solidify Water: Aqueous solutions are packed in vials, ampoules, or bottles and frozen at —50C on cold shelves. The cabinet is maintained at a low temperature and atmospheric pressure. 1-3 K/min is the normal cooling rate so that large ice crystals with larger holes are formed when the ice sublimes. This also results in a porous end product.
3) Primary Drying (Sublimation of Ice under Vacuum): The material to be dried products is spread for sublimation over a large surface area. The temperature and pressure are maintained below the triple point of water (i.e., 0.0098C and 0.533 kilopascals (4.58mm of Hg), respectively for sublimation), when only water is present.
When the material solution is dried, depression of the freezing point of water occurs. Therefore, maintaining the temperature below the eutectic point (pressure and temperature at which the frozen material evaporates without converting into liquid) is required. The eutectic point usually ranging from — 10 to 300C is determined depending on the drug substance dissolved in water. The condition of 1-8K below the eutectic point is sufficient.
About 3mm of Hg (0.4 kilopascals) vacuum is applied to the frozen sample.
Within 2 hours the temperature is increased linearly to about 300C. About 2900kJ/hr of heat is supplied which gets transferred as latent heat causing the sublimation of ice. The inward movements of the ice layer are controlled by heat in such a manner that the highest possible water vapor is obtained at the ice surface without melting the material. The temperature difference and also the vapor pressure difference between the evaporating surface and condenser is the driving force. The thickness of the frozen layer decreases while that of the partially dried solids increases with the process of drying. In the primary drying phase stage of drying, the easily removable moisture (98-99% water) is eliminated. The sample still contains a few traces of moisture.
4) Secondary Drying (Removal of Residual Moisture under High Vacuum): In this step, the traces of moisture still present are eliminated by heating the solid at 50-60C under vacuum lower than 50mm of Hg. The secondary drying rate is very slow, taking approximately 10-20 hours for its completion.
5) Packing: After replacing the vacuum with inert gas, the bottles and vials are closed.
Uses freeze dryer has the following uses:
1) It is used for manufacturing injections, solutions, and suspensions.
2) It can be also be used for drying:
i) Blood plasma and its fractionated products,
ii) Bacterial and viral cultures,
iii) Human tissue (arteries and corneal tissue),
iv) Antibiotics and plant extracts, and
v) Steroid, vitamins, and enzymes.
3) Foods dried items like prawns, mushrooms, meat and poultry products,shelf life coffee and tea concentrates, and citrus fruit juices can also be dried.
Merits
Freeze dryer has the following merits:
1) It is used for drying thermolabile materials.
2) The porous and uniform product obtained retains its bulk volume as reconstitution of the material is easy.
3) Product denaturation does not occur.
4) Migration of salts and other solutes does not occur.
5) Less volatile material is lost.
6) Moisture level can be kept low without decomposition.
7) Drying can be carried out in the final container (single-dose and multiple-dose vials) of the material.
8) Maintaining sterility is easy.
9) The end product can be stored at ambient temperature if it is sealed properly by providing an inert atmosphere.
Demerits
Freeze dryer has the following demerits:
1) The product with high porosity and large surface area is likely to oxidize. To prevent oxidation, the product should be packed in a vacuum or using inert gas or in a container impermeable to gases.
2) Equipment and running costs are high.
3) Solutions containing non-aqueous solvents cannot be dried by this method.
4) It is a time-consuming process (it takes around 10 hours) and the time cannot be shortened.
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