in the freeze-casting process we can draw the following conclusions: - when cooling starts from room temperature the suspension enters a supercooled state before nucleation and subsequent crystals growth can occur driving the system away from equilibrium - the nucleation stage is controlled by the particle size the surface of the ceramic the incorporation of the controlled ice nucleation of the freezing step Recently a successful attempt of incorporating controlled ultrasound-assisted nucleation to freeze-drying of solid samples was presented by Dai et al [16] The benefits of controlled nucleation

Innovative ideas

during freezing and following freeze-drying Micrograph by courtesy of IDT Biologika [1] Allmendinger A et al (2016) Controlled nucleation during freeze drying using vacuum-induced surface freezing Data base no 633018 Figure 1: Crystal growth after vacuum-induced nucleation

Until now the freezing step of lyophilization was uncontrolled due to the random nature of the nucleation or crystal-forming process Praxair's new ControLyo TM technology now makes nucleation control a reality by regulating the nucleation temperature to within 1C of its freezing point The results are improved product uniformity quality

Cryopreservation in a controlled-rate freezer removes water from the cells A seeding dip can improve repeatability by initiating ice nucleation Further sources of information: Berz D McCormack E Winer E Colvin G Quesenberry P Cryopreservation of hematopoietic stem cells American Journal of Hematology [Internet] 2007 [31 May

During the freezing step of a typical freeze drying process the temperature at which nucleation is induced is generally stochastically distributed resulting in undesired within-batch heterogeneity Controlled nucleation techniques have been developed to address this problem these make it possible to trigger the formation of ice crystals at

In addition uncontrolled nucleation means vials nucleate at different times creating a heterogeneous batch Controlled ice nucleation is the key step in a freeze-drying cycle and control therefore characterization of the degree of supercooling provides a solution to what is perhaps the biggest freeze-drying scale-up challenge

Influence of controlled ice nucleation on the freeze

May 30 2017Typically the controlled freezing methods induce the nucleation event at higher temperature with respect to the conventional freezing producing larger ice crystals that on the one hand speed up primary drying because of lower resistance to vapor flow and on the other hand should reduce the specific area of the lyophilized product and

May 25 2001Kyuya Nakagawa Aurelie Hottot Severine Vessot Julien Andrieu Modeling of freezing step during vial freeze‐drying of pharmaceuticals—influence of nucleation temperature on primary drying rate Asia-Pacific Journal of Chemical Engineering 10 1002/apj 424 6 2 (288-293) (2011)

Mar 15 2007Modeling of freezing step during freeze‐drying of drugs in vials H Hammouri A Hottot Model predictive control during the primary drying stage of lyophilisation Control Engineering Effect of ultrasound-controlled nucleation on structural and morphological properties of freeze-dried mannitol solutions Chemical Engineering

Controlled nucleation is now an important step in a freeze drying cycle and our development work with ControLyo Technology has shown significant benefits Its function is to control the nucleation of the product solution in the freeze dryer i e the solution in all vials (or bulk syringes etc ) allowing nucleation at the same time and the

Aug 21 2017Controlled nucleation is one of the most topical trends in the industry as the freezing step is of paramount importance for stability of products The temperature range between 0C and the real crystallisation temperature is called supercooling spanning over 10C in a freeze-dryer

secondary drying steps may be well controlled the lack of control of the ice nucleation temperature (the temperature at which the freezing starts) can adversely affect product uniformity and lead to suboptimal freeze drying cycles Colder nucleation temperatures cause ice crystals

To address the nucleation problem Praxair has developed a step-change technology that adds consistent control to the freezing step of lyophilization This low-capital plug-and-play option can be readily implemented on most existing freeze-dryers with

Cryopreservation in a controlled-rate freezer removes water from the cells A seeding dip can improve repeatability by initiating ice nucleation Further sources of information: Berz D McCormack E Winer E Colvin G Quesenberry P Cryopreservation of hematopoietic stem cells American Journal of Hematology [Internet] 2007 [31 May

Ice Fog as a Means to Induce Uniform Ice Nucleation During

Controlling ice nucleation during the freezing cycle of lyophilization is one such tactic that is currently under investigation as a means to achieve more robust and scalable lyophilization cycles The importance of ice nucleation temperature The onset of freezing or ice nucleation is one of the most important steps in the lyophilization cycle

The ice nucleation temperature (or degree of supercooling) is a potential critical process parameter during the freezing step 1 The pore structure in the dried matrix is a reflectance of how the solution was frozen with every 1 C increase in ice nucleation temperature resulting in a 1%-3% reduction in primary drying time 2 A higher degree of

Due to high interfacial energy ice crystallization is primarily controlled by heterogeneous nucleation events because the homogeneous nucleation barrier of ice is extremely high In addition to the interfacial energy the interfacial morphology or nanostructure of foreign bodies plays a diverse role under different supercooling regimes due to

in the freeze-casting process we can draw the following conclusions: - when cooling starts from room temperature the suspension enters a supercooled state before nucleation and subsequent crystals growth can occur driving the system away from equilibrium - the nucleation stage is controlled by the particle size the surface of the ceramic

In-situ X-ray computed tomography (CT) was used to observe microstructure formations during freeze-drying of a dextrin solution A specially designed freeze-drying stage was equipped at the X-ray CT stage Frozen and dried microstructures were successfully observed The CT images of the frozen solution clarified the ice crystal size increase and obvious boundary formation between the ice and