products, inactivated vaccines, and polymerase chain reaction
(PCR) components for medical diagnostics; bone and other body
tissues for surgical or medical use; and living organisms for vaccine
or seed culture use, which must grow and multiply to produce new
progeny after drying and reconstitution. However, freeze-drying is
less appropriate for:
1. Oily or nonaqueous solutions where the material has a low
melting temperature and/or low vapor pressure.
2. Products that form an impervious surface skin (typically a layer
of concentrated solute) or excluded liquid phase (e.g., glycerol
rising to the top of the otherwise frozen structure), which can
prevent vapor migration from the product.
3. Biological materials that are able to retain viability only when in
the presence of additives that are incompatible with practical
freeze-drying.
2 The Process of Freeze-Drying
For convenience, the freeze-drying process may be divided into a
number of discrete steps that may be summarized as:
1. Product freezing, which reduces thermal denaturation of product, immobilizes solution components, and prevents foaming
when the vacuum is applied. Freezing also induces a desired ice
crystal structure within the product, which facilitates drying.
2. Primary drying (sublimation) where conditions must be maintained in the drying chamber to sustain water migration from
the product ice during drying. During primary drying, the
product temperature (strictly freeze-drying interface temperature) must be maintained below the eutectic, glass transition,
collapse, or melt temperature as appropriate, to minimize product damage during drying.
3. A secondary drying stage during which resident moisture
adsorbed to the apparently dry structure is removed by desorption.
4. Sealing the dried product in a vacuum or under an inert gas at
the end of the process, both of which exclude the entry of
reactive, destabilizing, atmospheric gases such as oxygen or
carbon dioxide into the dried product and prevent the ingress
of damp air into the freeze-dried product. Note that a freezedried product will have a vastly expanded dry surface area and is
therefore particularly sensitive to air denaturation or moisture
uptake.
5. The products are then removed from the freeze-dryer, stored,
and/or distributed for use prior to reconstitution for injection,
application, or regrowth.
Principles of Freeze-Drying
101
(PCR) components for medical diagnostics; bone and other body
tissues for surgical or medical use; and living organisms for vaccine
or seed culture use, which must grow and multiply to produce new
progeny after drying and reconstitution. However, freeze-drying is
less appropriate for:
1. Oily or nonaqueous solutions where the material has a low
melting temperature and/or low vapor pressure.
2. Products that form an impervious surface skin (typically a layer
of concentrated solute) or excluded liquid phase (e.g., glycerol
rising to the top of the otherwise frozen structure), which can
prevent vapor migration from the product.
3. Biological materials that are able to retain viability only when in
the presence of additives that are incompatible with practical
freeze-drying.
2 The Process of Freeze-Drying
For convenience, the freeze-drying process may be divided into a
number of discrete steps that may be summarized as:
1. Product freezing, which reduces thermal denaturation of product, immobilizes solution components, and prevents foaming
when the vacuum is applied. Freezing also induces a desired ice
crystal structure within the product, which facilitates drying.
2. Primary drying (sublimation) where conditions must be maintained in the drying chamber to sustain water migration from
the product ice during drying. During primary drying, the
product temperature (strictly freeze-drying interface temperature) must be maintained below the eutectic, glass transition,
collapse, or melt temperature as appropriate, to minimize product damage during drying.
3. A secondary drying stage during which resident moisture
adsorbed to the apparently dry structure is removed by desorption.
4. Sealing the dried product in a vacuum or under an inert gas at
the end of the process, both of which exclude the entry of
reactive, destabilizing, atmospheric gases such as oxygen or
carbon dioxide into the dried product and prevent the ingress
of damp air into the freeze-dried product. Note that a freezedried product will have a vastly expanded dry surface area and is
therefore particularly sensitive to air denaturation or moisture
uptake.
5. The products are then removed from the freeze-dryer, stored,
and/or distributed for use prior to reconstitution for injection,
application, or regrowth.
Principles of Freeze-Drying
101