Ins and Out of Lyophilization for Bio-Pharmaceutical (Nano or Micro)
Abstract
Lyophilization involves the removal of water by first freezing it then extracting it through a principle known as sublimation. It is the first step of drying known as primary drying. The second step, known as secondary drying, involves the reabsorption of water. After the final drying, water content is reduced by 95%. At this point, there is no chemical reaction that occurs, nor any biological activities that can take place. It is the most vital and effective method to conduct thermolabile and thermostable drug formulations. The lyophilization provides advantages over other methods. It is not only stable but provides cost-effective ways of transportation and storage. Despite these advantages, it is time and energy-consuming, and the equipment used to conduct the process is costly (Gamiz, et al).
Introduction
Lyophilization is a drying method used to extract water from pharmaceutical and food products. Research shows that pharmaceutical companies use lyophilization in 35% of biological drugs. They are mainly divided into two types; thermolabile and thermostable. Thermo labile drying processes are limited, unlike thermostable. One of their methods that is efficient and accurate is the lyophilization. Freeze drying was first put into practice by Loire, Stokes, Edwards, among others. However, they experienced some problems when the process was used to preserve antibiotics (Heldner). The process was later used to produce vaccines and blood fractions. Some of the examples of products that undergo the lyophilization process include vaccines such as BCG, smallpox, and varicella. Proteins and peptides are also freeze-dried such as LDH, Beta-galactosidase catalase, protein G, G-6 PDH, and white fish protein. Drugs are also freeze-dried. They include loperamide, calcitonin, domperidone maleate, and fluorescein. The main principle of lyophilization is sublimation, where solids are changed from their original state directly to a gas state. Sublimation occurs in the presence of atmospheric pressure and powerful energy to transform it from solid to gas. . Don't use plagiarised sources.Get your custom essay just from $11/page
Definition & working principles
Lyophilization, also known as freeze-drying, is a drying process used in the preservation of items. The process begins by freezing at a very high speed and later subjected to vacuum drying to get rid of the ice. It is one of the most successful preservation of cells for a long period. It is used to make injection dosages that have been reconstituted.
Lyophilizer can be defined as a piece of freeze-drying equipment used in the lyophilization process.
Sublimation is the conversion of a product from its solid state to a gaseous state. Mainly occurs in the primary drying stage.
Thermodynamics can be defined as a process in the physics field that involves heat combined with other types of energy and how they are related. It deals with the conversion of thermal energy from one form to another and its effects on substances.
The working principle of lyophilization is sublimation. It involves changing a substance from solid to gas. It mainly works in three main stages. The first stage is the pretreatment process. At this stage, products are subjected to treatment methods before proceeding to the freezing stage. It includes material concentration, component addition so as to stabilize a product, preserve its natural state, and refine its processing. The second stage is freezing. This is the most vital step in the whole process. It can influence the reconstitution speed, the time it takes to complete the whole process, the stability of the product, and the crystal formation process. Here, the product is frozen using a freezer, a chilled compartment, or a freeze dryer using shelves. The temperatures used for the process are -40oC (Kasper, Christina, and Friess). The main reason for using these temperatures is to ensure that instead of melting taking place, sublimation will take place. Biological elements require fast and rapid freezing to prevent rapture to the cell walls. The procedure involves rapid freezing then increase if temperatures to promote the development of crystals. For other products where precipitation occurs, the preferred method of freezing is slow freezing.
After which the products are moved to the third stage known as primary drying. Between freezing and drying, thawing is not a requirement. At this point, the temperatures are increased, and the pressure brought to a minimum. The reason for this action is to enable the process of sublimation to take place. With the help of the vacuum, the process is speeded up. Condensation takes place whereby the water vapor produced forms of ice. The condenser inside the vacuum provides the vacuum pump with a protective layer. In this stage, the water content is reduced up to 95%. The stage is very slow and takes time where the heat is monitored to prevent too much heat that may damage the cell structure of the product (Goldman, et al).
The fourth stage is secondary drying, where the product is now converted to dry powder, which is a gaseous state or form. The products may take from 12 to 72 hours to complete the whole process. The amount of time depends on the type of product being sublimated or the quantity of the products. The process is also known as adsorption. At this stage, ion bound water particles. The products retain pores after the whole process. Using one of the inert gases, the vacuum is disintegrated. After which the products are sealed. The residual moisture of most products is between 1 to 5% (Kasper, Christina, and Friess).
Importance of lyophilization in Biopharmaceuticals
Lyophilization is important in the preservation of the specimen. It is important as it maintains the original structure of the specimen. Pharmaceutical companies prefer a process that is able to keep the specimen intact even after the process. This is to give it a form that, when being studied, is not altered. Transportation is also a challenge when moving the specimen from one location to another. The use of lyophilization solves the problem. The products are safely stored and transported, minimizing the damages that may occur during movement. The industry is also faced with the challenge of the expiration of drugs, among other products. They choose a process that may extend the shelf life of these products. Lyophilization is the best procedure to provide them with these needs. It is, therefore, an important process in the pharmaceutical industry. Another significance of the lyophilization to the industries is that they are cost-effective. The companies are a profit-making business. They prefer processes that minimize damages and increase profits. The process does exactly that. It does not only minimize damages, but it is also lightweight, and its transportation is simple. The companies suffer minimal losses (Zhang, et al).
Thermodynamics of lyophilization
The heat and mass transfer of a freeze dryer allows the top part of the sample to dry first. It then proceeds to the bottom of the sample in the vial. Drying takes place in three systematic procedures. The top layer is dry, the middle front part of sublimation, and the frozen bottom layer. During the drying process, a barrier is created, and the transmission of mass from the vial is difficult. The main reason for this is because of the continued increase in the dried sample. An indication that when the products being freeze-dried, the volume of the samples in the vial has to be standard. An increase in the product means an increase in the surface area as well. Therefore for large quantities, if products going through lyophilization have to be put in large vials or the process has to take place with slanted vials. Factors that lead to the drying of the product from the top include thermal conduction rate while the frozen product is determined by the condensation temperatures.
For an optimal operation to take place, there is a need to widely open the surface routes between the product and the condenser. In large lyophilizer, the surfaces of the condenser may be placed in the same chamber as the samples or differently connected using a duct or the drying room. Reducing the system is important to avoid cases of collisions that may occur with air particles. Additionally, the pressure of residual has to be more than that of solid vapor pressure. Consequently, it may cause the ice to evaporate then taken up to the pump, which may destroy the pump. The speed at which products may take to dry is influenced greatly by the size of the ice crystals, the quantity of the product, and the thermal conductivity of the product. The degree of the cooling point and crystallization rate determine the process of freezing and the primary drying effectiveness. The size of the pores formed is mainly determined by the size of the crystals and the rate of drying. The faster the rate cooling produces small crystals, hence small pores. Therefore, it creates resistance to the transportation of water vapor in the primary drying stage. Poor thermal conduction factors in the products contribute to the slow transfer of heat from frozen samples to the drying stage. Because of the slowness in the drying process, the time taken to complete the process is usually a minimum of 24 hours. It is important to figure out the time needed for the process, the rate of heat, and the temperatures of the product. The main reason for this is to give a successful process by conducting a careful reproduction process.
Advantages and disadvantages
There are a number of lyophilization merits and a few disadvantages. Beginning with the advantages, it is stable as it is stored in a dry condition. The process is multifunctional as it can be used in the cosmetic industry to prepare face creams, dyes used in the hair coloring, and beauty masks. Additionally, the preparation of catalysts, refined chemicals, and filters is another use of freeze-drying practiced in the chemical industries. Another advantage of the process is that the materials are well dried without necessarily apply high temperatures. The process is perfect for drugs that air-sensitive and those with oxygen. For pharmaceutical use, it is a useful process mainly because of the pores made after sublimation. Pharmaceutical products can stay for long periods without expiring. The products contain pores from the ice formed hence making them easy to rehydrate when necessary.
Another advantage is that the method has rapid time rebuilding. Because of the low levels of water content, preserving materials is a guarantee. The growth of microorganisms is not possible. Even enzyme activity cannot take place with this type of process. Lack of water content also gives preserved food lightweight. It is a cost-effective way of preserving materials and substances. It is a convenient method as it reduces damages that may result in losses as compared to other dehydration processes. It is very difficult for items to alter their original smells hence, being a perfect choice for food preservation. Products that are freeze-dried do not require refrigeration; therefore, they greatly reduce the costs of storage and transportation.
The disadvantage of the process may be a lack of conclusive research hence deeming it as an immature process that needs more practice and experiment, especially with the equipment used. There is a need for improved manufacturing instruments to produce large quantities of products that are reliable and efficient. The equipment used for the process is very expensive. They are thrice the price of other types of equipment used in other methods. The process is energy-consuming, using unto three times more energy than any other method. It is time-consuming. The process uses up to 72 hours to complete the drying cycle. Another disadvantage involves the cleaning protocols of the equipment. They require high maintenance, where the cleaning procedure may be overlooked.
Application
The process is applicable in several fields. It can be applied both in the pharmaceutical and food industries. The main reason is that it has minimal water content. The absence of water in products reduces microbial growth and enzyme activity. Therefore, the products are able to have a long shelf life (Izutsu and National Institute of Health Sciences). For instance, the presence of bacterial in products produces diseases causing substances that are harmful, which, apart from causing illnesses, alters the taste of food and medications. Moreover, enzyme activity in food contributes to oxygen production in food that hastens the process of ripening or spoilage. Pharmaceutical products are also affected by the presence of water just as food. Water content in drugs facilitates quick spoilage and short shelf life. The main reason why drugs are stored in airtight containers to prevent moisture and oxygen absorption. With the lyophilization, water is extracted up to 95%. Pharmaceutical companies use lyophilization to make tablets and powder that are used for reconstitution in vials. Also, they use them for pre-filled self administrative medication syringes. The industry applies lyophilization in the production of pharmaceutical raw materials such as APIs (“Applications of Freeze-Drying in Pharmaceuticals, Biopharmaceuticals, and Foods.”). The top 16 percent of pharmaceutical companies out 100 use the process of freeze-drying for their products. Lyophilization is vital in that it provides stability to bacterial cultures. By so doing, it promotes a long shelf life and reduces the chances of damage resulting from harsh sample drying. As a result, the products that have been lyophilized are easily used in the development of culture media after rehydration. Another importance of lyophilization is its use in the biotechnology industry. Together with the biomedical companies, lyophilization is used to safeguard vaccines, decontaminated proteins, blood specimens, among other biological substances.
The weight of food and pharmaceutical products is very light. Water content in products makes them heavy. The military and camping organizations use the freeze-drying method for their foods. The method provides the soldiers and camping people an easy time carrying their food products because of the lightweight. NASA also uses the lyophilization method in its food products because of its lightweight in their spaceships.
Freeze drying is applied in insect preservation mainly for consumption purposes. They are later sold in different parts of the world. When they are converted to powder form, they are used in animal feeds as a protein and nutritional supplements for humans. In technology industries, the process is used to purify products and the extraction of solvents. Lyophilization is used in the nanotechnology industries to perform nanotube purification. It is used to avoid the aggregation of thermal vaporization as a result of capillary forces. The process is also applicable in the taxidermy field for preserving animals. Some of the animals preserved through lyophilization are reptiles, insects, mammals, amphibians, and crustaceans. Other applications include in the field of bacteriology to preserve special strains. In ceramic industries to produce powder extracted from the slurry mist. In burials where it is environmentally friendly as compared to cremation and casket burying.
Available lyophilization equipment used in biopharmaceuticals
Lyophilizer is an equipment used to free dry products. There are different types of lyophilizers. It contains a vacuum assembly room comprising shelves that are able to carry products containing containers in the process of cooling and bring heated. The vacuum system of 50 to 100 microbar is used. The main function of this is to extract solvents. It presses gases that do not condense using a condenser. It also contains a refrigeration compartment that is connected to the main chamber. The main function if the system is to cool shelves and process condenser by the use of compressors. Liquid nitrogen can also be used to supply the energy needed for freezing to take place. The products are put in vials, which are then placed on the shelves of the chamber. The cooling segments on the shelves freeze the products. Once the process is complete, the vacuum pump removes the products to the heating elements where the heating process starts. The process of heat transmission from the shelf to the vials and finally to the product is known as thermal conduction. Shelf liquid (silicone oil) is used to circulate in the system with a pump to regulate heat temperatures in the primary and secondary drying stage. The control system is part of the lyophilizer that standardizes the shelf temperatures, the pressure, and time to complete the process.
A contact freeze dryer is a type of lyophilizer that uses conduction to supply energy for sublimation. Radiant freeze dryer uses infrared radiation. It is used to heat up materials put in a tray. The trays used in the lyophilizer should be flat. It is limited to the low capacity of penetration. It is appropriate for homogeneous materials. A microwave-assisted freeze dryer uses a microwave to allow sublimation to take place. It is complicated to use due to the electrical charge, which produces gases. The samples may be transformed into plasma, which may burn the product (“Freeze Drying and Microwave Freeze Drying as Encapsulation Methods”).
Conclusion
Lyophilization has been an important discovery, especially in the pharmaceutical industry. It has provided a way off drying drugs that normally are heat resistant. It is practical and gives hands-on solutions to most of the challenges faced by the pharmaceutical industry. Through its invention, it has become useful in many industries making work easier. The process has very many advantages that have led to institutions like the military force; NASA and camping organizations adopt it for food preservation. Stability, long shelf life, and lightweight are among the advantages of freeze-drying. As discussed, lyophilization through useful has some shortcomings. The equipment in itself is very expensive and needs careful cleaning. It is time and energy-consuming. Despite these challenges, many industries are adopting their application. It has made work easier for organizations in the pharmaceutical, biomedical, and biotechnological fields. There are different types of lyophilizer used to carry out the process of sublimation. As the process continues to be improved, it is the most appropriate drying method that exists for the pharmaceutical industry. It will continue to remain the most suitable method, even in the future.
Works Cited
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