Rational freeze-drying process design is based on a representative and accurate measurement of the critical formulation temperature. To avoid product shrinkage or collapse, it is indispensable to control the product temperature just below this key temperature during primary drying. Over the last decades, DSC was routinely used to determine the glass transition temperature of the maximally freeze concentrated solute (Tg’), information which was then applied to freeze-drying process design. Recently, Freeze-Dry Microscopy (FDM) was introduced as a new technology to determine an even more representative critical temperature: the collapse temperature (Tc). Today, important technological improvements in FDM even allow more sophisticated observations of collapse behaviour and therefore, further cycle optimization.

During the past 10-15 years, close attention has been paid to the development of optimal lyophilization cycles for different types of pharmaceuticals. Recent advances in process control, such as the Smart Freeze-Dryer^TM technology or similar approaches, make cycle development a routine procedure.

Freeze drying is generally known to be a time consuming and therefore expensive process. In order to lower costs during manufacturing, the effective cycle time must be reduced. This goal can be achieved by optimising a freeze drying cycle in the laboratory – in particular the primary drying phase. Applying PAT in the laboratory can provide valuable information about product and process behaviour and may help to identify the critical process parameters during cycle development and optimisation.

Over the last decade, the development of new drug delivery methods and devices for dry powder inhalation, needle-free intradermal powder injection or sustained parenteral drug delivery has led to an increasing demand for powder formulations incorporating an active pharmaceutical ingredient (API).