rate of the shelf post-nucleation. Methods employed in initial
attempts to achieve controlled ice nucleation are numerous and
are covered in a comprehensive review by Winter and Geidobler
[17]; however, only two methods have been commercialized to
date, namely, the pressurization-depressurization technique [12]
and the ice fog method, although other emerging methods also
show promise [13].
In addition to the above benefits, controlled nucleation may
also yield improvements in the uniformity of dried product appearance, a tighter range of intra- and inter-batch moisture content
values, more rapid reconstitution and more predictable scalability.
2.2.2 Shelf-Cooling Rate
The shelf-cooling rate is the simplest parameter to control, and
programmed rates of cooling are standard options on research and
production freeze-dryers. Because shelf temperature and product
responses are not identical, defining shelf-cooling rate will not fully
define product behavior. Although we are concerned with the cooling rate achievable within each individual production container
(typically a vial), this parameter is less easy to monitor compared
with shelf cooling, and freeze-drying cycles generally are controlled
by programmed shelf cooling rather than feedback control from the
sample. Cooling rates of the product/cell suspension will vary
considerably from vial to vial, and even throughout the sample
within the vial, and, consequently, measuring the temperature of
vial contents at a fixed position will give only an approximation of
the sample temperature variation.
Observing the freezing pattern of a number of vials arranged on
a shelf will demonstrate that while the contents of some vials will
freeze slowly from the vial base, neighboring vials may remain
unfrozen and supercool appreciably before freezing instantly. This
random freezing pattern will reflect differences in ice structure from
vial to vial and be translated into different drying geometries. In
summary, freezing patterns will be related to:
1. The ice forming potential within each container (e.g., vial
or tray).
2. The relative position of the vial on the shelf causing exposure of
individual containers to cold or hot spots.
3. Edge effects where samples in vials on the periphery of each
shelf will be subjected to heat transmitted through the chamber
walls or door.
4. The insertion of temperature probe into the container, which
will induce ice crystallization.
5. The evolution of latent heat as samples freeze, which will tend
to warm adjacent containers.
6. Variations in container base geometry, which may impede thermal contact between container and shelf.
106
Kevin R. Ward and Paul Matejtschuk
attempts to achieve controlled ice nucleation are numerous and
are covered in a comprehensive review by Winter and Geidobler
[17]; however, only two methods have been commercialized to
date, namely, the pressurization-depressurization technique [12]
and the ice fog method, although other emerging methods also
show promise [13].
In addition to the above benefits, controlled nucleation may
also yield improvements in the uniformity of dried product appearance, a tighter range of intra- and inter-batch moisture content
values, more rapid reconstitution and more predictable scalability.
2.2.2 Shelf-Cooling Rate
The shelf-cooling rate is the simplest parameter to control, and
programmed rates of cooling are standard options on research and
production freeze-dryers. Because shelf temperature and product
responses are not identical, defining shelf-cooling rate will not fully
define product behavior. Although we are concerned with the cooling rate achievable within each individual production container
(typically a vial), this parameter is less easy to monitor compared
with shelf cooling, and freeze-drying cycles generally are controlled
by programmed shelf cooling rather than feedback control from the
sample. Cooling rates of the product/cell suspension will vary
considerably from vial to vial, and even throughout the sample
within the vial, and, consequently, measuring the temperature of
vial contents at a fixed position will give only an approximation of
the sample temperature variation.
Observing the freezing pattern of a number of vials arranged on
a shelf will demonstrate that while the contents of some vials will
freeze slowly from the vial base, neighboring vials may remain
unfrozen and supercool appreciably before freezing instantly. This
random freezing pattern will reflect differences in ice structure from
vial to vial and be translated into different drying geometries. In
summary, freezing patterns will be related to:
1. The ice forming potential within each container (e.g., vial
or tray).
2. The relative position of the vial on the shelf causing exposure of
individual containers to cold or hot spots.
3. Edge effects where samples in vials on the periphery of each
shelf will be subjected to heat transmitted through the chamber
walls or door.
4. The insertion of temperature probe into the container, which
will induce ice crystallization.
5. The evolution of latent heat as samples freeze, which will tend
to warm adjacent containers.
6. Variations in container base geometry, which may impede thermal contact between container and shelf.
106
Kevin R. Ward and Paul Matejtschuk