ABSTRACT
Together with the number of products and formulations that require a freeze-drying step for the stabilization, the requirements in terms of efficiency, quality, and safety of the products have increased in recent years. To meet these challenges, the right equipment and process analytical technologies (PATs) are required. In this chapter we present one of the most promising technologies for the real-time monitoring of the product during a lyophilization process, namely infrared (IR) imaging. After a brief introduction on the fundamentals of the technology, and the cautions that must be taken in order to obtain a reliable measurement, the main applications are discussed, together with their advantages and drawbacks. First of all, because they are based on a contactless technology, the presented PAT allows noninvasive and reliable measurement of temperature in several vials at the same time, thus accounting also for the spatial heterogeneity of the batch. But what makes IR imaging so interesting and promising among the many other PATs proposed in the past is the quantity and quality of the information that can be extracted from what basically is just a picture (or a series of them). Not only can a full thermal characterization of the product, that is, maximum temperature, axial thermal profile, and so on, be inferred or estimated, but also the residual amount of solvent, the ending point of the primary drying phase, and the heat and mass transfer coefficients that can be used to optimize the process. Multivariate statistical process monitoring schemes able to assess whether the process is (in real-time) statistically in control, as well as the advantages of coupling this information with that provided by other variables, are also presented and discussed.
