Vacuum Induced Surface Freezing as an effective method for cycle optimization

In recent years, special attention has been given to freezing and its control. As a matter of fact, freezing suffers from the same challenges as primary and secondary drying, from performance in specific formulations to reproducibility and batch uniformity. These challenges are made further critical if we account for the fact that potential problems in freezing impact on the product behavior during both primary and secondary drying, on product morphology, as well as on intra-vial and vial-to-vial heterogeneity. Recent literature showed that the control of temperature at which nucleation occurs is beneficial to primary drying time, but also to batch uniformity [1]. In this study, we investigate how the control of nucleation temperature, and particularly the use of Vacuum Induced Surface Freezing (VISF), can effectively reduce the total cycle time, minimize batch heterogeneity, and improve intra-vial uniformity [3]. This last aspect is not secondary to the previous advantages as uncontrolled freezing can promote a non-uniform distribution of the active ingredient within the lyophilized product and potentially their aggregation/denaturation [4]. The impact of VISF on drying is here discussed referring to both primary and secondary drying.