A knowledge-based approach to designing and developing successful freeze drying formulations and cycles requires information about how the product responds to different processing conditions. Candidate formulations should be analyzed in terms of their visible physical structure, thermal characteristics and frozen state mobility, in order to gain a sufficient understanding of its behaviour throughout the freeze drying process. This ensures that cycles can be developed that are tailored to the specific needs of every product, making them efficient, safe, robust and reproducible.
Optimisation of the lyophilisation process starts with a deep understanding of the Active Product Ingredient (API) being used and its interaction with excipients. Knowledge of phase transitions occurring in the frozen state directly leads to efficiency and promotes stability during and after the lyophilisation process. One of the most powerful methods used to find these phase transitions is Zsinϕ analysis, performed using the Lyotherm3.
The Lyotherm3 identifies the temperature that transitions occur at using variations in Zsinϕ, a function of electrical impedance, and supplements this with differential thermal analysis (DTA). As Zsinϕ is a metric of molecular mobility this is sensitive enough to identify protein folding and other small reorientation events.