LYOPHILIZER.pptx

LYOPHILIZER

1. LYOPHILIZER

2. What is a lyophilizer? How does it work? Lyophilizer and freeze dryer are synonymous names for the same equipment. A lyophilizer executes a water removal process typically used to preserve perishable materials, to extend shelf life or make the material more convenient for transport. Lyophilizers work by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate.

3. Table of Contents 1.Principle 2.Construction of Freeze Dryer 3.Diagram of Freeze Dryer 4.Working of Freeze Dryer 5.Freeze Drying Steps 6.Advantage of Freeze Dryer 7.Disadvantage of Freeze Dryer 8.Applications of Freeze Dryer

4. 1.Principle  The principle involved in freeze-drying is sublimation, where water passes directly from solid-state (ice) to the vapour state without passing through the liquid state. Sublimation of water can take place at pressures and temperatures below the triple point of water. (The temperature and pressure at which a substance can exist in equilibrium in the liquid, solid, and gaseous states. The triple point of pure water is at 0.01°C and 4.58 mm Hg.) The material to be dried is first frozen and then subjected under a high vacuum to heat (by conduction or radiation or by both) so that frozen liquid sublimes leaving only non-volatile solid, dried components of the original liquid.

5. 2.Construction of Freeze Dryer Generally, there are three types of freeze dryers, for example, manifold freeze-dryer, rotary freeze dryer and tray-style freeze-dryer. These freeze-dryers differ in the method by which the dried substance is interfaced with a condenser. The components common to all of them are a vacuum pump to reduce the ambient gas pressure and a condenser to remove the moisture by condensation on a surface cooled to -20 to -80 °C. A freeze dryer consists of a vacuum chamber wherein products to be dried are kept on shelves and capable of cooling and heating containers and their contents. A vacuum pump, a refrigeration unit, and associated controls are connected to the vacuum chamber.

6. 3.Diagram of Freeze Dryer

7. 4.Working of Freeze Dryer Traditional freeze-drying is a complex process that requires a careful balancing of sample, equipment and processing techniques.  In this process, water is removed from a sample after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. It is performed at temperature and pressure conditions below the triple point of the liquid, to enable sublimation of frozen material. The entire process is performed at low temperature and pressure. Steps involved in lyophilization start from sample preparation followed by freezing, primary drying and secondary drying, to obtain the final dried product. The vapour pressure of water increases with an increase in temperature during the primary drying. Therefore, primary drying temperature should be kept as high as possible, but below the critical process temperature, to avoid a loss of cake structure. There are four important stages in the complete freeze drying process namely pretreatment, freezing, primary drying, and secondary drying.

8. 5.Freeze Drying Steps Preparation and pretreatment ↓ Pre freezing for solidifying water ↓ Primary Drying ↓ Secondary Drying ↓ Packing

9. Pretreatment: It includes any method of treatment of the product before freezing. This may include concentrating the product, the revision of the formulation (ie, the addition of components to increase stability and/or improve processing), decreasing a high vapor pressure solvent, or increasing the surface area.  Pretreatment methods include freezing concentration, solution-phase concentration, formulation to preserve the appearance of the product, formulation to stabilize reactive products, formulation to increase the surface area, and decreasing high vapor pressure solvent.

10. Pre freezing: The product should be frozen at a temperature low enough to solidify completely. Since freeze-drying is a change in the state from the solid phase to the gas phase, the material to be freeze-dried must first be adequately pre-frozen. The pre-freezing method and the final temperature of the frozen product can affect the ability to successfully freeze the material. The rapid cooling results in small ice crystals, useful for preserving structures that will be examined microscopically, but it produces a product that is more difficult to lyophilize. Slower cooling results in large ice crystals and a less restrictive channel in the matrix during the drying process. The products are frozen in two ways, most of the products that are lyophilized consist mainly of water. Most of the samples to be lyophilized are eutectic, which are mixtures of substances that freeze at a lower temperature than the surrounding water. It is very important in lyophilization to pre-freeze the product below the eutectic temperature before beginning the lyophilization process. The second type of frozen product is a suspension that is subjected to the formation of glass during the freezing process.

11. Primary drying: After pre-freezing the product, conditions must be established in which the ice can be removed from the frozen product through sublimation, resulting in a dry, structurally intact product. This requires very careful control of the two parameters: Temperature and Pressure involved in the lyophilization system. The sublimation rate of a frozen product depends on the difference in vapor pressure of the product compared to the vapor pressure of the ice collector. The molecules migrate from the high-pressure à lower pressure area. As the vapor pressure is related to the temperature, the temperature of the product must be warmer than the temperature of the cold trap (ice collector). The temperature at which a product is lyophilized is balanced between the temperature that maintains the frozen integrity of the product and the temperature that maximizes the vapor pressure of the product. This balance is key to optimum drying.

12. Heat enters the products by one of several mechanisms: 1.By direct contact between the container base and the shelf or 2.By conduction across the container base and then through the frozen mass to the drying front or 3.By gaseous convection between the product and residual gas molecules in the chamber or 4.By radiation.

13. Secondary Drying: After primary freeze-drying is complete, and all ice has sublimed, bound moisture is still present in the product. The product appears dry, but the residual moisture content may be as high as 7-8%. Continued drying is necessary at a warmer temperature to reduce the residual moisture content to optimum values. This process is called ‘Isothermal Desorption’. Secondary drying is usually carried out for approximately 1/3 or 1/2 of the time required for primary drying.

14. Packing: By replacing vacuum with inert gas, bottles and vials are closed.

15. 6.Advantage of Freeze Dryer This is suitable for drying heat sensitive products Freeze-dried product is porous and easy to be rehydrated and instantly dissolved. Drying takes place at very low temperatures, so that enzyme action is inhibited and chemical decomposition, particularly hydrolysis, is minimized. Denaturation of protein does not occur. Loss of volatile material is less. Sterility can be maintained.

16. 7.Disadvantage of Freeze Dryer The process is very slow Expensive process. It is not a general method of drying, but it is limited to certain types of valuable products that can not be dried by any other means. The period of drying is high The product is prone to oxidation, due to the high porosity and large surface area. Therefore, the product must be vacuum packed or with inert gas or in a container

17. 8.Applications of Freeze Dryer Freeze-drying is used to increase the shelf life of thermolabile products, such as vaccines and other injectable. It is used to enhance stability of products during storage, shipping, and transportation. Freeze-drying is used to reduce weight of products. It is used to preserve blood products in freeze-dried form. It is used in chemical synthesis to make products more stable and easier to dissolve in water. Freeze-drying can effectively be used in bio-separations in purification procedures. It can be used to concentrate low molecular weight substances that are too small to be removed by a membrane filtration.

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