Freeze drying is also known as cryodesiccation or lyophilization. It is a dehydration process with a variety of applications in the preservation of perishable products, and vital biological substances and assays needed to be stored for a long time. The process works by reducing the pressure in the substance so that frozen water can evaporate from solid to gas in a method known as sublimation. The first use of freeze drying was during the Second World War when it was used to preserve blood serum. Since then, technology has advanced and there have been a myriad of applications in multiple industries. Currently, the process is being used in industries such as pharmaceuticals, food processing, laboratory and testing, preservation of nutraceuticals, and preservation of dietary nutritional supplements among others.
When a product or a substance is undertaken through this method of drying, it loses the ability to reabsorb moisture even if it is stored under room temperature conditions once the process is over. With the reduced water content in the substance, it is impossible for enzymes and other microorganisms to degrade the product in any way. Through this process, wasteful processes such as spoilage and shrinkage will not occur, and consequently, the substances will retain their flavor, smells, and nutritional content for a much longer period of time.
The freeze drying process
The freeze drying process takes place in three primary stages. As noted earlier, it is the process of removing water by first freezing the substance and then evaporating the water through a process known as sublimation. Typically, the substance is frozen, the pressure reduced, and then heat is added to allow the frozen water to evaporate through a process known as sublimation. Below is a detailed overview of the three main processes involved in the freeze drying process-:
This is the very first step in the freeze drying process and there are various ways this can be achieved. It can be done in a chilled bath, inside a freezer, or simply on a shelf on the freeze dryer. During this phase, the material will be cooled below its triple point, and this is to ensure that the water molecules don’t melt, but instead they sublime – transforming directly from the solid state into vapor or gas. This process can be easily accomplished with the help of large ice crystals that are usually easy to obtain by processes such as annealing or slow freezing. However, when dealing with biological materials, there are instances when the crystals may be too large causing them to easily break the cell walls. This type of situation may lead to a not-so-pleasing freeze drying results. To stop this from happening, the freezing process must be done rapidly for the case of biological substances. For materials known to be prone to precipitation, annealing is the best approach for this freezing phase. The process involves fast freezing before the rapid raising of the product temperature to allow for the formation of large crystals.
The primary drying part is a two-part process that features the actual Primary Drying and the Secondary Drying. A good amount of water is removed from the product during the freezing phase through the process of sublimation, which is also the process used to remove most of the organic solvents.
The primary drying phase is a slow process that is done at relatively cooler temperatures – usually below the product’s collapse temperature. In the sublimation process, heat energy is usually necessary to drive the phase change so that the water molecules can change directly from solid state to gas without melting into a liquid first.
When this process is done in a simple manifold dryer, the transfer of heat from the flask or product will happen mainly through convection and radiation from the surrounding. When dealing with products whose collapsible temperatures are low, it may be important to insulate or wrap the flask to lower the rate of heat transfer and to avoid the collapse of the substance.
When this process is done in a shelf freeze dryer, the bulk of the heat transfer to the product will be through conduction. As such, it is important to ensure maximum surface contact between the product, tray or container with the shelf. This is how to maximize heat transfer through conduction. However, the effects of heat transfer through radiation and convection can also not be overlooked because it is important to consider product uniformity as well as process control.
The heat generated through radiation from the walls of the product chamber may lead to the products or vials located near the walls of the shelf to dry quicker than the products or vials located at the center or near the middle of the shelf. This phenomenon is known as the “edge effect” in the freeze drying process. Radiation originating through the acrylic doors of some freeze dryers are also known to have a greater effect on the products or vials located at the front of the dryers, and as such, they are always the fastest to dry. Due to this, most of the freeze dryers intended for mass production feature a metal door design with very tiny viewports.
How to determine the end of primary freeze drying
There are a variety of analytical methods that can be used to determine if the process of primary drying is complete. One of the most basic methods and the preferred one by most freeze drying service providers is to monitor the temperature of the product by using a thermocouple probe. When primary drying is complete, the measured temperature by the thermocouple probe will be lower than that of the shelf temperature since the heat of the shelf is what was being used for the sublimation process. Upon the completion of the sublimation of ice crystals, the temperature of the product will rise to approach that of the shelf temperature. When the temperature of the product becomes equal to the shelf temperature, it can then be concluded that the primary drying process is over.
While checking for the end of primary drying with the use of a thermocouple probe, however, it should be noted that the vial that contains the thermocouple probe is likely to dry faster compared to the rest of the vials on the shelves, and this is because the wire in the thermocouple probe will be helping in the conduction of more heat in that specific vial. Additionally, in the case of bulk drying, it will be observed that the areas around the thermocouple wire tend to dry quickly compared to the rest of the areas far from the thermocouple wire. As such, a modest amount of time must be allowed for additional drying after the rise of the thermocouple temperature to ensure that all the ice that might still be present in the entire batch has all been sublimated.
Also, since the drying process will start from top down, it is necessary that the tip of the thermocouple touches the bottom of the vial and be placed right at the center of the container. There is no problem with the tip of the thermocouple touching the very bottom of the container. If the drying is being done in vials, it is recommended that the thermocouple be inserted in the vials located in the middle of the shelf. This is because the vials located at the perimeter of the shelf may dry more quickly due to the effects of radiant heating.
Once the free ice has been sublimated during the primary drying process, there will still be a significant amount of water molecules still bound to the product or substance. This is the water that is targeted with the secondary drying phase. Due to the fact that all the free water molecules present in the substance have been sublimated at this point, it will now be safe to increase the product temperatures considerably without any fears of the product collapsing or melting.
The secondary drying phase normally sets in during the primary drying phase, except it takes place at slightly elevated temperatures. The rate at which it takes place, however, is dependent on the temperature of the product. For amorphous products, it may be necessary to increase the temperature from primary to secondary drying at a low ramp rate to avoid any instances of collapse in some parts of the product.
The process of secondary drying will go on until the acceptable moisture content levels are attained in the product – levels which will be ideal for long term storage. Based on the application, the typical moisture content in most of the fully dried products is between 0.5% and 3%. As is usually the norm, the drier the product, the longer its shelf life. However, some complex biological products may become too dry for long term optimal storage, and in which case, the process of secondary drying should be done with great caution.
Industrial applications of freeze-drying
Freeze drying has a variety of industrial applications. They include, but are not limited to the following-:
Food processing – the food processing industry has been a major beneficiary of freeze-drying technology. Foods such as vegetables, meats, and fish can be freeze-dried without compromising their tastes or nutritional value. With food substances, freeze drying techniques have been in use since the 1970s, and the process is now common practice for all types of food items, including juices, cereals, coffee, ice creams, as well as instant meals and soups.
Pharmaceuticals – the pharmaceutical industry is another major beneficiary of freeze-drying technology. The technology has brought a lot of versatility in the storage and application of products such as hormones, enzymes, proteins, vaccines, and peptides among others. With freeze drying, the shelf life of vaccines, hormones, collagen, and peptides can be extended, and they can also be transported over long distances under normal or varying conditions without worrying about compromising their integrity. As a matter of fact, it is possible to preserve mot materials in a glass vial after all the water is removed, and this makes it easy to store and ship materials.
Laboratory and testing
In the field of research and development, the process of freeze-drying is used for the stabilization and storage of various biological components. The process doesn’t have any effects on the chemical structure of the substances, and it will also reduce the risks of contamination. Substances such as antibiotics, pathological samples and cultures, vaccines, bacteria, viruses, and other active pharmaceutical and biological ingredients can now be safely and easily preserved in lab freeze dryers for prolonged durations.
Nutritional supplements like Echinacea and aloe vera are currently being preserved and stored with the help of commercial freeze dry machines. This is also done for culinary herbs such as mussels which can now be stored, shipped and even sold when they are freeze-dried. Yogurts, cheese, and probiotics can also be subjected to the same treatments to enhance their longevity without compromising their nutritional values.
In addition to the above, the freeze-drying process has also been used as a recovery method for documents and books that might have undergone water damage. In bacteriology, the technology is also being used to preserve special strains, while in ceramics, it is being used to create a formable powder that can then be used for spraying slurry mist. The concept of floral freeze drying is also picking up a lot of steam, and with this, the method is being used to preserve flowers for memorials, weddings or decorations, hence, reducing the overall cost of such events because you will not need to buy new flowers for decorations.
From the above, the process of freeze drying is such a vital and complex one. If you are in the market looking for service providers, therefore, it is imperative that you take your time to do some research so that you choose the very best service providers. The last thing you want is to spend your money only to have your products go bad because not all the necessary water was removed during the process.