Pharmaceutical freeze drying for the preservation of active ingredients

Freeze drying, also known as sublimation drying, is the lyophilization/drying of products using thermal energy. It is used to dry pharmaceutical products such as vaccines and bacteria.The dried material is called lyophilizate.

Water-containing products, such as medicines, food or organic and other porous materials, are deep-frozen to -55 °C and then dried under vacuum conditions. The sublimation drying process is used here. The water is converted directly from a solid state to a gas state. The product is dried in the freeze dryer at a negative pressure of less than 6 mbar.

What is lyophilization?

Lyophilization is a technical process for removing water by sublimation drying. This takes place through a freezing phase and a drying phase of the product.The structural properties of the product are retained when water is removed, which leads to longer shelf lives and improved stability. 

When an amorphous substance is dissolved, it becomes glassy. The starting products are stabilized in the freezing phase by cryoprotectors. This is achieved by increasing viscosity or prefentional exclusion. Prefentional exclusion means that the protein is kept in its native form by adding certain substances such as polyols or carbohydrates.
A vacuum is then applied for sublimation drying, which sublimates the ice and removes the water from the frozen solution.

The lyophilization process consists of several steps. First, the product is filled into containers or vessels in liquid form. Next, it is quickly frozen, often using refrigerants such as liquid nitrogen or R729. Once the product is frozen, the pressure in the freeze dryer is reduced and the water in the product is removed by sublimation. The water passes directly from the solid phase into the gaseous phase. This process step is known as primary drying. This process can take several hours or even days, depending on the size and type of product. In the following secondary drying stage, the temperature in the product is increased in order to remove any residual water. The dissolved substance remains as a porous cake with a large surface area, which can later be easily dissolved in water again. In the final step, the dried product is sealed to keep moisture out of the environment.

Principle of lyophilization in the pharmaceutical industry

In the pharmaceutical industry, lyophilization plays an important role in the production and conservation of medicines. The freeze-dried form makes medicines more stable and gives them a longer shelf life. This is particularly important for vital medicines that have to be stored and transported under certain conditions. Lyophilization enables the production of powder formulations that can be quickly rehydrated, making dosing and application easier.

Vials for use Pharmaceutical freeze-drying
Vials for use Pharmaceutical freeze-drying

Principle of lyophilization in the food industry

In the food industry, foods such as fruit, instant coffee or soups are freeze-dried. By removing the water, the shelf life is extended and the weight is reduced, making it easier to transport and store in a frozen state. Freeze-dried food also retains its nutritional composition and taste, which helps to offer high-quality products.

Freeze-dried raspberries
Freeze-dried raspberries

Applications and advantages of lyophilization

Lyophilization, as explained above, is used in various industries, including food and pharmaceuticals. Freeze-drying offers several advantages over conventional drying processes such as hot air drying. Freezing the goods preserves their structural properties, which results in better rehydration. Lyophilization also makes many food and pharmaceutical products lighter and more compact, which makes logistics and storage easier. In addition, the taste and nutritional composition is preserved, as no high temperatures are used that could lead to losses or changes.

Lyophilization is a complex process that requires careful planning and monitoring. The selection of suitable freezing and drying agents and the control of temperature and pressure are crucial in order to obtain a high-quality end product. In addition, the right packaging materials must be used to protect the dried product from humidity and other environmental influences.

Another important aspect of lyophilization is the validation of the process. This involves carrying out tests to ensure that the product has the necessary characteristics and fulfills the requirements. Tests include determining the residual moisture, particle size and stability of the product.

Freeze-drying is also used in R&D to develop new products and formulations. By combining lyophilization with other techniques such as microencapsulation, innovative products with improved properties can be manufactured.

Overall, lyophilization is an important process that is used in various industries to extend the shelf life of products and improve their stability. By removing water, the structural characteristics of the product are preserved, resulting in better quality. The controlled environment and careful planning are crucial to achieving ideal results.

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Advantages of freeze-drying

Drying of the product
Drying of the product

No mold formation and extended half-life

Proven drying process for paper
Proven drying process for paper

Careful conservation of historical books & papers

Preservation of the flavorings
Preservation of the flavorings

Increased intensity of flavorings in food

Preservation of proteins & medicines
Preservation of proteins & medicines

Substances in the pharmaceutical industry are preserved for a longer time

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Disadvantages of freeze-drying

High investment costs
High investment costs

High acquisition costs

High energy consumption
High energy consumption

High amount of thermal energy required

Freeze-drying systems for the industry

Industrial freeze dryers usually consist of two chambers. One chamber contains storage surfaces on which the product or the filled aqueous solution is placed in vials (glass bottles). Cryogenic or heated silicone oil flows through the chamber and temperatures from - 55 °C to + 40 °C are realized.

The second chamber is the condenser, where the sublimated moisture from the product is collected. The condenser is cooled via cooling coils, which are also flooded with silicone oil. Temperatures of -60 °C to -80 C are reached via a circuit with compressors and evaporators. It is the coldest point in the system. Both chambers can be separated from each other by a flap (intermediate valve). During drying, they are connected to each other. A vacuum pump is also connected to the condenser.

The first chamber, which is also a vacuum chamber, enables the water to be removed by sublimation, while the refrigeration system is responsible for freezing the product. The containment system protects the dried product from moisture and other harmful influences.The respective degree of the drying process can be precisely determined using attached measuring instruments. This is made possible by a pressure gauge. Both Pirani pressure gauges and conductometric pressure gauges are used.

HOF CryoBlizzard" freeze-drying system
HOF CryoBlizzard" freeze-drying system

History & future of lyophilization

Lyophilization has a long history and was first developed in the 1940s. Initially, the process was mainly used to preserve blood and sera in medical research. However, they quickly realized that lyophilization could also be beneficial for other food and pharmaceutical products, and so lyophilization began to gain importance in various industries.

In the early years of lyophilization, applications were mainly focused on medical and military areas. Freeze-drying enabled the long-term storage of medicines, blood plasma and vaccines, which was particularly important in military supplies. It also enabled the production of blood products in powder form, which could be rehydrated if required.

In recent decades, significant advances have been made in lyophilization technology. The equipment and machines have been improved to make the process more efficient and controllable. New refrigerants and vacuum systems have been developed to speed up sublimation and shorten drying times. In addition, there are increased efforts in the formulation of products to further improve stability and rehydration properties.

Lyophilization could be used in other areas in the future. For example, lyophilization techniques are being developed for the manufacture of personal care products such as creams and lotions. Lyophilization could also be used in nanotechnology to produce nanostructured materials. With advancing technology and research, the possibilities for lyophilization are endless.

Overall, lyophilization offers an effective method for preserving and stabilizing products in various industries. With advances in technology and continued research, lyophilization will continue to play an important role and provide new opportunities for product development.

Here you will find suitable products and services

Suitable products

Suitable services

For the right system technology, it is important to analyze the parameters from the formulation and define the production cycles with simultaneity. This defines the requirements such as temperatures and capacities for the refrigeration technology. That is the only way to select the optimum system for the process.

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