Often regarded as a gentle method of drying materials, freezedrying is in reality a potentially damaging process where the individual process stages should be regarded as a series of interrelated
stresses, each of which can damage sensitive bioproducts. Damage
sustained during one step in the process chain may be exacerbated
at succeeding stages and even apparently trivial changes in the
process. One example is that of a change in container or closure
to an apparently identical one but whose freeze-drying characteristics may differ markedly from the original, such as the heat transfer characteristics of a vial or a different vapor resistance from a
stopper [6]; such a change may be sufficient to transform a successful process into one that is unacceptable.
Freeze-drying will not reverse damage incurred prior to formulation and care must be exercised when selecting an appropriate cell
type or technique used to culture or purify the cell or its extracts
prior to freeze-drying. The essence of the formulation exercise
should be to minimize freeze-drying damage, loss of viability, or
activity. To ensure minimal losses of activity, the product may
require dilution in a medium containing protective additives, specifically selected for the product or application. Although frequently described as “protectants,” these additives may not be
effective at all stages of the process but may protect only during
particular steps in the freeze-drying cycle. At other stages, the
additive may fail to protect the active component and indeed may
be incompatible with the process. It is also important to appreciate
that individual stages in the process can result in damage, which
initially remain undetected, becoming evident only when the dried
product is rehydrated [7, 8]. Particular attention must be applied to
the selection and blending of the additive mixes in the formulation,
and the importance of formulation will be discussed at greater
length later.
Products should be formulated to ensure batch product uniformity, whereas there may be particular requirements relating to
product use. In this context, vaccines freeze-dried for oral or aerosol delivery may require the inclusion of excipients that minimize
damage when the dried product is exposed to moist air, since
different materials can display different rates and extents of moisture uptake under identical conditions [9].
A wide range of containers can be used to freeze-dry vaccines,
microorganisms, and others, including glass ampoules, rubber
stoppered vials, double-chambered vials, and prefilled syringes
that hold both dried vaccine and diluent, bifurcated needles, and
so on. Alternatively, vaccines can be dried in bulk in stainless steel
or plastic trays and the resultant powder tableted, capsulated,
sachet filled, or dispensed into aerosol devices for lung or nasal
delivery.
Principles of Freeze-Drying
103
stresses, each of which can damage sensitive bioproducts. Damage
sustained during one step in the process chain may be exacerbated
at succeeding stages and even apparently trivial changes in the
process. One example is that of a change in container or closure
to an apparently identical one but whose freeze-drying characteristics may differ markedly from the original, such as the heat transfer characteristics of a vial or a different vapor resistance from a
stopper [6]; such a change may be sufficient to transform a successful process into one that is unacceptable.
Freeze-drying will not reverse damage incurred prior to formulation and care must be exercised when selecting an appropriate cell
type or technique used to culture or purify the cell or its extracts
prior to freeze-drying. The essence of the formulation exercise
should be to minimize freeze-drying damage, loss of viability, or
activity. To ensure minimal losses of activity, the product may
require dilution in a medium containing protective additives, specifically selected for the product or application. Although frequently described as “protectants,” these additives may not be
effective at all stages of the process but may protect only during
particular steps in the freeze-drying cycle. At other stages, the
additive may fail to protect the active component and indeed may
be incompatible with the process. It is also important to appreciate
that individual stages in the process can result in damage, which
initially remain undetected, becoming evident only when the dried
product is rehydrated [7, 8]. Particular attention must be applied to
the selection and blending of the additive mixes in the formulation,
and the importance of formulation will be discussed at greater
length later.
Products should be formulated to ensure batch product uniformity, whereas there may be particular requirements relating to
product use. In this context, vaccines freeze-dried for oral or aerosol delivery may require the inclusion of excipients that minimize
damage when the dried product is exposed to moist air, since
different materials can display different rates and extents of moisture uptake under identical conditions [9].
A wide range of containers can be used to freeze-dry vaccines,
microorganisms, and others, including glass ampoules, rubber
stoppered vials, double-chambered vials, and prefilled syringes
that hold both dried vaccine and diluent, bifurcated needles, and
so on. Alternatively, vaccines can be dried in bulk in stainless steel
or plastic trays and the resultant powder tableted, capsulated,
sachet filled, or dispensed into aerosol devices for lung or nasal
delivery.
Principles of Freeze-Drying
103