Principles of Lyophilization

Lyophilization is a high-technology method of preserving chemicals or sensitive biological materials from humidity enzymes, hormones, vitamins, blood products, antibiotics, drugs, radiopharmaceutical kits, etc. 

Lyophilized products are characterized by prolonged shelf-life, and chemical bacteria or enzymatic changes do not easily occur. The sterility is more guaranteed and solubility assured. In addition, transportation is easier. Finally, certain compounds or radiopharmaceutical kits exist only as lyophilized products. However, freeze-dried products suffer from certain disadvantages. The reentry of moisture may destroy the products. Direct optical control of lyophilized products cannot be performed. Therefore, the risk of particle contamination of the final product is high. Bacterial contamination can only be avoided by using the proper installations (clean rooms) for manufacturing injectable lyophilized products. 

The lyophilization method is similar to ordinary vacuum distillation with one essential difference the material to be dried must first be solidly frozen and then subjected to a very low absolute pressure (high vacuum) and controlled heat input. Under these conditions, the water content, in the form of an ice matrix, is selectively removed via sublimation, completely bypassing the intermediate liquid phase. The solid particles are locked into the matrix during drying and cannot interact. The following conditions are necessary for freeze-drying  

The product must be solidly frozen, usually below its eutectic point (-10 to -50°C). 

A condensing surface must be provided (-40 to -50 °C) for trapping ice vapors. 

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Lyophilization (Freeze Drying) Lyophilization is most frequently used for heat-labile dosage forms that are unstable in aqueous formulation. The principle of lyophilization can be seen by reference to the phase equilibrium diagram for water (Fig. 15). Water at atmospheric pressure and ambient temperatures is stable in its liquid phase at lOO C the liquid phase attains an equilibrium with its vapor phase. Above 100 C water is stable in its vapor phase. At atmospheric pressures and 0 C the solid (ice) and liquid phases of water are in equilibrium with each other. At vacuum pressures a temperature (the eutectic point) can be reached where the three phases, solid, liquid, and vapor are all in equilibrium with each other. At even lower temperatures and pressures the solid phase comes into equilibrium with the liquid phase. The significance of this is that an aqueous solution can be concentrated by evaporation (sublimation) at low pressures without any necessity for significant heat input. 

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