LYOSPARK®

The lyophilization process comprises three main stages: freezing (solidification), primary drying (ice sublimation) and secondary drying (moisture desorption). The nucleation of ice crystals (the initial stage of ice formation during freezing) is a naturally spontaneous and protracted process. As such, forcing ice crystals to nucleate at a specific temperature, rate and time can improve the homogeneity of the batch and reduce the cycle duration.

Historically, because of the random nature of the nucleation process, lyophilization has been difficult to control. For a typical pharmaceutical formulation filled in vials, for example, crystals might form at temperatures ranging from –5 to –20 °C).

As the nucleation temperature has a direct impact on the developing ice structure and crystal size — as well as the appearance of the dried product cake — it can negatively influence the product’s critical quality attributes (CQAs), such as residual moisture or dissolution behavior.

A new patent-pending technology from GEA, which is fully compatible with all our currently available freeze dryers, provides a novel and scalable method to control the nucleation process without having to develop new pharmaceutical formulations.

Graph showing process data without LYOSPARK

Process without LYOSPARK®

Simultaneous Crystal Nucleation

LYOSPARK® enables the user to control the temperature at which nucleation crystals form inside the product, thereby ensuring that, at any time, every vial in the chamber is subjected to the same process conditions, irrespective its specific location on the shelf.

Combining LYOSPARK® technology with conventional freeze-drying processes is very simple. The vials are loaded into the freeze dryer as usual and cooled to the optimal (product dependent) nucleation temperature. As soon as the nucleation temperature is reached, the chamber is vented with gas from a condenser.

A filter-equipped cooling trap is mounted on the chamber. Ice crystals form on the cooled surface of the trap and are entrained in the gas stream during venting. Inside the supercooled product solution, the ice crystals undergo immediate and homogenous nucleation in each vial.

As the formation of ice crystals at higher temperatures results in larger pores, drying times can be shortened. Furthermore, LYOSPARK® offers better scalability, sterility and higher throughput speeds than conventional systems, resulting in optimized performance and productivity.

Graph showing process data with LYOSPARK

Process with LYOSPARK®

Process Optimization

LYOSPARK®, which eliminates issues such as the denaturation of active ingredients or unpredictable scale-up, also provides several technical advantages, including improved product quality, better vial uniformity per batch and a more homogenous, aesthetically pleasing cake.

In summary, LYOSPARK® controlled nucleation technology facilitates uniform ice crystal formation in laboratory and production-scale freeze dryers with a minimum degree of supercooling. This is reflected in more consistent and larger ice crystal sizes with a more open product structure. As a result, faster drying and reconstitution times can be achieved.

QbD-compliant, GEA’s LYOSPARK® delivers a more uniform, higher quality product, reduces process times and provides a cost-effective solution to controlled nucleation.

At a glance advantages

Larger ice crystals
Shorter drying times
Better process control
Better reconstitution
Less vial cracking
Less stress on biological agents
Better looking cake

This cost-efficient technology will be offered as an option for all GEA freeze dryers and will also be available as a retrofit option for existing plant.