Lyophilization Principle Pdf

Primary drying is a top-down process with a well-defined sublimation front moving through the product as it dries. In many cases, freezing induced by these conditions may be necessary to achieve successful freeze drying of a sensitive product. Essential control aspects during freeze drying. One such method entails comparison of parallel pressure readings between a Pirani gauge and a capacitance manometer. Sublimation is when a solid ice changes directly to a vapor without first going through a liquid water phase.

General Principles of Freeze Drying. For the Batman episode, see Instant Freeze. If drying in vials, it is good practice to insert the thermocouple in a vial located in the middle of the shelf. The tray is loaded with vials, placed on a shelf in the freeze dryer and then the bottom part of the tray is slid out. The process condenser consists of refrigerated coils or plates that can be external or internal to the chamber.

Insure the necessary low temperature saturated suction during the secondary drying to deliver the lower vacuum levels needed for this phase. Find a Product Specialist Request a Quote. Because product will dry from the top down, the tip of the thermocouple should always be placed at the very bottom and center of the container. By a series of reproducible runs on a scaleable the optimum cycle can be established. The higher the sublimation temperature, the faster the drying cycle.

To facilitate faster and more efficient freeze drying, larger ice crystals are preferable. The conditions of low temperature and high vacuum, can have, if they are unnecessarily prolonged, an effect on living organisms, which form the great bulk of freeze dried products.

These crystals seem to be contained in an interstitial state, still liquid, but which constitutes the principal active element of the solution. Frozen products can be categorized as either crystalline or amorphous glass in structure. The use of organic solvents requires more attention in the freeze drying process. These products can benefit from a thermal treatment process, which is also called annealing.


The control of vacuum in the lyophilization process can become a useful means of controlling heat transfer, principles of web design pdf and the means of getting energy to the product. The ideal curve of lyophilization is depicted on Curve A of Fig. Understanding the physical properties of materials that are freeze-dried is a key part in developing a successful lyophilization process.

At the completion of the process, the treated product will have retained its form, volume and original structure-as well as all its physical, chemical and biological properties. This section needs additional citations for verification. This is especially important when it comes to pharmaceutical uses. The duration of the primary and secondary drying phases. In other projects Wikimedia Commons.

It is extremely important that the sample be fully and completely frozen prior to pulling a vacuum and starting the drying process. In high-altitude environments, the low temperatures and pressures can sometimes produce natural mummies by a process of freeze-drying. We are recognized experts in applications, methodologies, lab processes and many other areas that directly impact your day-to-day operations.

Aseptic Pharmaceutical Processing Equipment

By controlling chamber pressure, you can reduce the heat transfer coefficient between the warm shelves and the product. The vacuum in the drying chamber.

Larger ice crystals improve the speed of the freeze drying process because of the larger vapor pathways left behind in the dried portion of the product as the ice crystals are sublimated. This structure is ideal for sublimation.


It is good practice to characterize the collapse temperature for all new injectable or ingestible drug formulations to be freeze dried. Prevent vapors from contaminating the oil in the vacuum pump. Shell bath freezing involves rotating a flask containing the sample in a freezing bath so the sample freezes on the walls of the flask.

Because of the lack of control over the rate of heat transfer into the product, most manifold dryers are operated conservatively at lower pressures to help keep the product temperature lower. The refrigeration system can also be employed to cool shelves in the product chamber for the freezing of the product. The curve of shelf temperature is shown in schematic form in B of Fig. Provide a simple cleaning operation.

General Principles of Freeze Drying

Product chambers are typically either a manifold with attached flasks, or, a larger chamber with a system of shelves on which to place the product. This plasma could potentially burn the sample, so maintaining a microwave strength appropriate for the vacuum levels is imperative.

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Microwave-assisted freeze dryers utilize microwaves to allow for deeper penetration into the sample to expedite the sublimation and heating processes in freeze-drying. Water can also cause mold to grow or make inks bleed. An isolation valve can be added to the vapor port that connects the product chamber to the condenser.

Contact freeze dryers use contact conduction of the food with the heating element to supply the sublimation energy. The Pirani gauge, however, will give a false high reading in the presence of water vapor. Because shelf contact is often inconsistent, convective heat transfer can help promote uniform product drying. Advanced ceramics processes sometimes use freeze-drying to create a formable powder from a sprayed slurry mist.

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