Insights into Thermal Interactions in Frozen Pharmaceutical Vials: Effects on Ice Nucleation Times and Inhibition

Abstract

Purpose This study investigates the thermal interactions between adjacent vials during freezing and assesses their impact on nucleation times. Methods Various loading configurations were analyzed to understand their impact on nucleation times. Configurations involving direct contact between vials and freeze-dryer shelves were studied, along with setups using empty vials between filled ones. Additionally, non-conventional loading configurations and glycol-filled vials were tested. The analysis includes 2R and 20R vials, which are commonly utilized in the freezing and lyophilization of drug products, along with two different fill depths, 1 and 1.4 cm. Results The investigation revealed that configurations with direct contact between vials and freeze-dryer shelves led to substantial thermal interactions, resulting in delayed nucleation in adjacent vials and affecting the temperature at which nucleation takes place in a complex way. In another setup, empty vials were placed between filled vials, significantly reducing thermal interactions. Further tests with non-conventional configurations and glycol-filled vials confirmed the presence of thermal interactions with a minimal inhibitory effect. Conclusions These findings carry significant implications for the pharmaceutical industry, highlighting the role of thermal interactions among vials during freezing and their impact on the temperature at which ice nucleation occurs.