indeed, there are many factors that can damage freeze-dried products, including temperature, moisture content, reactive gases,
light, free radicals, and specific chemical reactions such as Maillard
reactions. Indeed, even when the residual moisture level in a sealed
container of freeze-dried material remains constant, there may be
an equilibrium between “sorbed” (adsorbed or absorbed) water in
the lyophilized cake and free water in the headspace, which may
fluctuate with time and temperature [42].
As highlighted above, MDSC can be used to measure the
thermal properties of a freeze-dried product and also to evaluate
the plasticization effect of water. However, the thermal properties
of the lyophilized material (such as the dry state T g ) are not the only
influence on the long-term stability of biological materials; in addition, the chemical nature of the formulation ingredients may play a
role, including those components that stabilize during freezing and
drying, which may not necessarily be the optimal choice for ensuring long-term stability. This has been demonstrated in a number of
cases, including a study of the role of reducing sugars [19], which
are known to undergo Maillard reactions with proteins in the dried
state, while nonreducing sugars do not. As such, a formulation will
ideally take into account the dry state characteristics of the final
product as well as the behavior of the formulation during the
freeze-drying process itself.
The specific aspects and challenges associated with the stabilization of different materials by freeze-drying—including proteins,
vaccines, bacteria, sperm, and bioscaffolds—are discussed in later
chapters in this volume.
A further factor receiving significant attention is that of the
physical properties of the freeze-dried product, particularly with
regard to its robustness to handling and transport. It is well understood that cosmetically acceptable “cakes” are often endowed with
concomitantly superior properties compared with their collapsed
counterparts, such as lower residual moisture and more rapid
reconstitution; however, it could be argued that this is a property
that needs to extend to the entire shelf life of the product, not just
immediately post-manufacture, because a product that becomes
powdery during transport and handling can also lead to difficulties
for the end user. As such, strides have been made to commercially
develop mechanical testing devices that are suitably sensitive to
quantify parameters such as the stiffness (Young’s Modulus) and
strength of lyophilized cakes in situ, as described by Hedberg et al.
[43]. Imaging techniques are also available that can provide a visual
representation of the interior of the freeze-dried cake in three
dimensions [44].
Any analytical method that can provide reliable quantification
of measurable product attributes assists not only in the conventional approach to formulation and process development in freezedrying but also in the Quality by Design approach [45].
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Kevin R. Ward and Paul Matejtschuk
light, free radicals, and specific chemical reactions such as Maillard
reactions. Indeed, even when the residual moisture level in a sealed
container of freeze-dried material remains constant, there may be
an equilibrium between “sorbed” (adsorbed or absorbed) water in
the lyophilized cake and free water in the headspace, which may
fluctuate with time and temperature [42].
As highlighted above, MDSC can be used to measure the
thermal properties of a freeze-dried product and also to evaluate
the plasticization effect of water. However, the thermal properties
of the lyophilized material (such as the dry state T g ) are not the only
influence on the long-term stability of biological materials; in addition, the chemical nature of the formulation ingredients may play a
role, including those components that stabilize during freezing and
drying, which may not necessarily be the optimal choice for ensuring long-term stability. This has been demonstrated in a number of
cases, including a study of the role of reducing sugars [19], which
are known to undergo Maillard reactions with proteins in the dried
state, while nonreducing sugars do not. As such, a formulation will
ideally take into account the dry state characteristics of the final
product as well as the behavior of the formulation during the
freeze-drying process itself.
The specific aspects and challenges associated with the stabilization of different materials by freeze-drying—including proteins,
vaccines, bacteria, sperm, and bioscaffolds—are discussed in later
chapters in this volume.
A further factor receiving significant attention is that of the
physical properties of the freeze-dried product, particularly with
regard to its robustness to handling and transport. It is well understood that cosmetically acceptable “cakes” are often endowed with
concomitantly superior properties compared with their collapsed
counterparts, such as lower residual moisture and more rapid
reconstitution; however, it could be argued that this is a property
that needs to extend to the entire shelf life of the product, not just
immediately post-manufacture, because a product that becomes
powdery during transport and handling can also lead to difficulties
for the end user. As such, strides have been made to commercially
develop mechanical testing devices that are suitably sensitive to
quantify parameters such as the stiffness (Young’s Modulus) and
strength of lyophilized cakes in situ, as described by Hedberg et al.
[43]. Imaging techniques are also available that can provide a visual
representation of the interior of the freeze-dried cake in three
dimensions [44].
Any analytical method that can provide reliable quantification
of measurable product attributes assists not only in the conventional approach to formulation and process development in freezedrying but also in the Quality by Design approach [45].
124
Kevin R. Ward and Paul Matejtschuk