The Lyophilization glossary
Source: Fact.MR Analysis, 2022
The pressure exerted at the earth's surface by the atmosphere. A standard atmosphere is 760 torr or millimeters of mercury or 760,000 microns.
A process that occurs at low chamber pressures where hydrocarbon vapors from the vacuum system can enter the product chamber.
Freeze-drying multiple samples of the same product in similar-sized vessels simultaneously in a shelf tray dryer.
This is the ultimate pressure the pump or system can attain.
BLOWER (see Mechanical Booster Pump)
This pump is positioned between the mechanical pump and the chamber. It operates using two lobes, turning at a high rate of speed. It is used to reduce the chamber pressure to less than 20 microns.
Admitting air or a selected gas to an evacuated chamber, while isolated from a vacuum pump, to raise the pressure towards, or up to, atmospheric.
Freeze-drying a large sample of a single product in one vessel, such as the bulk drying pans designed for shelf tray dryers
A pump for conveying the heat transfer fluid.
A phenomenon causing the collapse of the structural integrity of a freeze-dried product due to too high a temperature at the drying front.
The temperature above which collapse occurs.
CONDENSER (Cold trap)
In terms of the lyophilization process, this vessel collects the moisture on plates and holds it in the frozen state. Protects the vacuum pump from water vapor contaminating the vacuum pump oil.
In terms of refrigeration, this unit condenses (changes) the hot refrigerant gas into a liquid and stores it under pressure to be reused by the system.
The lowering of the temperature in any part of the temperature scale.
A device to pass thermocouple wires through and maintain a vacuum-tight vessel.
ln the vacuum system, the introduction of water vapor into the oil in the vacuum pump causes the pump to lose its ability to attain its ultimate pressure.
The removal of ice from a condenser by melting or mechanical means.
DEGREE OF CRYSTALLIZATION
The ratio of the energy released during the freezing of a solution to that of an equal volume of water.
DEGREE OF SUPERCOOLING
The number of degrees below the equilibrium freezing temperature where ice first starts to form.
Free from liquid and moisture.
The removal of moisture and other liquids by evaporation.
EQUILIBRIUM FREEZING TEMPERATURES
The temperature where ice will form in the absence of supercooling.
A point of a phase diagram where all phases are present and the temperature and composition of the liquid phase cannot be altered without one of the phases disappearing.
Cooling of a liquid at reduced pressures caused by loss of the latent heat of evaporation.
This tank is located in the circulation system and is used as a holding and expansion tank for the transfer liquid.
FILTER OR FILTER/DRIER
There are two systems that have their systems filtered or filtered/dried. They are the circulation and refrigeration systems. In the newer dryers, this filter or filter/dryer is the same and can be replaced with a new core.
The free water in a product is that water that is absorbed on the surfaces of the product and must be removed to limit further biological and chemical reactions.
This is the absence of heat. A controlled change of the product temperature as a function of time during the freezing process to ensure a completely frozen form.
Used in the vacuum system on the vacuum pump to decontaminate small amounts of moisture in the vacuum pump oil.
GAS BLEED (Vacuum control)
To control the pressure in the chamber during the cycle to help the drying process. In freeze-drying, the purpose is to improve heat transfer to the product.
GLASS TRANSITION TEMPERATURE
The temperature at which certain products go from a liquid to a vitreous solid without ice crystal formation.
This exchanger is located in the circulation and refrigeration systems and transfers the heat from the circulation system to the refrigeration system.
HEAT TRANSFER FLUID
A liquid of suitable vapor pressure and viscosity range for transferring heat to or from a component, for example, a shelf or condenser in a freeze-dryer. The choice of such a fluid may depend on safety considerations. Diathermic fluid.
HOT GAS BYPASS
This is a refrigeration system. To control the suction pressure of the BIG FOUR (20-30 Hp) compressors during the refrigeration operation.
HOT GAS DEFROST
This is a refrigeration system. To defrost the condenser plates after the lyophilization cycle is complete.
The solid, crystalline form of water.
Any gas of a group, including helium, radon, and nitrogen, was formerly considered chemically inactive.
In a two-stage compressor system, the cross-over piping on top of the compressor connects the low side to the high side. One could also think of it as a low side, intermediate, and high side.
INTERSTAGE PRESSURE REGULATING VALVE
This valve controls the interstage pressure from exceeding 80 - 90 psi. This valve opens to suction as the interstage pressure rises above 80 - 90psi.
The process of desorbing water from a freeze-dried product by applying heat under a vacuum.
LIQUID SUB-COOLER HEAT EXCHANGER (see Sub-cooled Liquid)
The liquid refrigerant leaving the condenser/receiver at cooling water temperature is sub-cooled to a temperature of +15oF (-10oC) to -15oF (-25oC).
A process in which the product is first frozen and then, while still in the frozen state, the major portion of the water and solvent system is reduced by sublimation and desorption to limit biological and chemical reactions at the designated storage temperature.
MAIN VACUUM VALVE (see Vapor Valve)
This valve is between the chamber and external condenser to isolate the two vessels after the process is finished. This is the valve that protects the finished product.
MANIFOLD FREEZE DRYING
A freeze drying process where each vessel is individually attached to a manifold port, resulting in a direct path to the collector for each vessel.
A system of ice crystals and solids that are distributed throughout the product.
MECHANICAL BOOSTER PUMP (see Blower)
A roots pump with a high displacement for its size but a low compression ratio. When backed by an oil-seal rotary pump, the combination is an economical alternative to a two-stage, oil-sealed rotary pump, with the advantage of obtaining a high vacuum.
MECHANICAL VACUUM PUMP
The mechanical pumping system lowers the pressure in the chamber to below atmospheric pressure so that sublimation can occur.
MELTING TEMPERATURE (Melt-back)
The temperature where mobile water first becomes evident in a frozen system.
MICRON (see Torr)
A unit of pressure is used in the lyophilization process. One micron = one Mtorr or 25,400 microns = 1" Hg., or 760,000 microns = one atmosphere.
A mixture of gases such as nitrogen, hydrogen, chlorine, and hydrocarbons. They may be drawn into the system through leaks when part of the system is under a vacuum. Their presence reduces the system's operating efficiency by increasing the condensing pressure.
The formation of ice crystals on foreign surfaces or as a result of the growth of water clusters.
In vacuum terminology, a filter is attached to the discharge (exhaust) of an oil-sealed rotary pump to eliminate most of the "smoke" of suspended fine droplets of oil that would be discharged into the environment.
OIL SEALED ROTARY PUMP
A standard type of mechanical vacuum pump used in freeze-drying with a high compression ratio but having a relatively low displacement (speed) for its size. A two stage pump is effectively two such pumps in series and can obtain an ultimate vacuum.
Separates the oil from the compressor discharge gas and returns the oil through the oil float trap and piping to the compressor crankcase.
The process of cooling a product to below its eutectic temperature prior to freeze drying.
PRESSURE GAUGE (Vacuum Gauge)
An instrument used to measure very low pressures in a freeze-drying system. Thermocouple Gauge: A pressure gauge that measures only the condensable gases in the system. This gauge can be used as an indicator of drying endpoints.
McLeod Gauge: A mercury gauge used to measure total pressure in the system (i.e., condensable and noncondensable gases.)
The process of removing all unbound water that has formed ice crystals in a product undergoing freeze- drying.
A real leak is a source of atmospheric gases resulting from penetration through the chamber.
The dissolving of the dried product into a solvent or diluent.
Used for safety purposes to prevent damage in case excessive pressure is encountered.
ROTARY VANE PUMP
A mechanical pumping system with sliding vanes as the mechanical seal. It can be single- or two-stage.
After primary drying, the process of reducing the bound water in a freeze-dried product is complete.
During secondary drying, heat is applied to the product under very low pressures.
SELF-LIQUID HEAT EXCHANGER
Heat transfer from the shelf fluid to the refrigeration system through tubes in the exchanger causes compressor suction gas to warm.
In terms of the lyophilization process, they are a form of the heat exchanger within the chamber with a serpentine liquid flowing through them, entering one side and flowing to the other. They are located in the circulation system.
Freezing a product in a thin layer coats the inside of the product container. Shell freezing is accomplished by swirling or rotating the product container in a low temperature bath.
This is a normal type compressor used in refrigeration . In the lyophilization process, it is used to control the shelf temperature, both for cooling and keeping the shelf temperature from overheating using a temperature controller.
A heat transfer fluid.
The use of steam and pressure to kill any bacteria that may be able to contaminate that environment or vessel.
The conversion of material from a solid phase directly to a vapor phase, without passing through the liquid phase. This is referred to as the primary drying stage.
SUB-COOLED LIQUID (See Liquid Sub-cooler Heat Exchanger)
The liquid refrigerant is cooled through an exchanger so that it increases the refrigerating effect, as well as reduces the volume of gas flashed from the liquid refrigerant in passage through the expansion valve.
SUCTION LINE ACCUMULATOR
To provide adequate refrigerant liquid slug protection (droplets of liquid refrigerant) from returning to the compressor and causing damage to the compressor.
Trichloroethylene - A heat transfer fluid.
The degree of hotness or coldness of a body.
Metal-to-metal contact between two dissimilar metals produces a small voltage across the free ends of the wire.
THERMOSTATIC EXPANSION VALVE
An automatic variable device controlling the flow of liquid refrigerant.
TORR (See Micron)
A unit of measure equivalent to the amount of pressure in 1000 microns.
TWO-STAGE COMPRESSOR (see Interstage)
This is a specially built compressor. Its function is to be able to attain low temperatures by being able to operate at low pressures. It is two compressors built into one. A low-stage is connected internally and a high stage connected externally with piping, called interstage.
This valve connects the interstage with suction to equalize both pressures during pump-down.
A space in which the total pressure is less than atmospheric.
VACUUM CONTROL (Gas Bleed)
To assist in the rate of sublimation, by controlling the pressure in the lyophilizer.
A mechanical way of reducing the pressure in a vessel below atmospheric pressure to where sublimation can occur. There are three types of pumps, rotary vane, rotary piston and mechanical booster.
A target shaped object placed in the condenser to direct vapor flow and to promote an even distribution of condensate.
The pressure of the vapor in equilibrium with the sample.
The vacuum valves used are of a ball or disk type that can seal without leaking. The balI types are used for services to the chamber and condenser. They are also used for drains and isolation applications. The disk types are used in the vacuum line system and are connected to the vacuum pump, chamber, and condenser.
VAPOR VALVE (See Main Vacuum Valve)
The vacuum valve between the chamber and external condenser. When this valve is closed the chamber is isolated from the external condenser. Also known as the main vapor valve.
A small glass bottle with a flat bottom, short neck, and flat flange designed for stoppering.
In the vacuum system, a virtual leak is the passage of gas into the chamber from a source that is located internally in the chamber.