Investigation of the Freezing Phenomenon in Vials Using an Infrared Camera

Abstract

The freezing phenomenon has a dramatic impact on the quality of freeze-dried products. Several freezing models applied to solutions in vials have been proposed to predict the resulting product morphology and describe heat transfer mechanisms. However, there is a lack of detailed experimental observations of the freezing phenomenon in vials in the literature. Thus, the present work offers new experimental observations of the freezing phenomenon in vials by infrared (IR) thermography. IR imaging allowed each vial’s whole axial temperature profile to be collected during freezing, providing significant insights into the process. Spontaneous nucleation and vacuum-induced surface freezing (VISF), as a controlled nucleation technique, are investigated. Batches having vials in direct contact with the shelf (exchanging heat mainly through conduction) as well as suspended (exchanging heat mainly through natural convection and radiation) were tested. The study used three solutions: sucrose 5%, mannitol 5%, and dextran 10%. SEM images coupled with an automated image segmentation technique were also performed to examine possible correlations between the freezing observations and the resulting pore size distributions. IR thermography was found to be a promising tool for experimentally predicting the resulting product morphology in-line.

Infrared Thermography for Monitoring of Freeze Drying Processes—Part 2: Monitoring of Temperature on the Surface and Vertically in Cuvettes during Freeze Drying of a Pharmaceutical Formulation

“…Van Bockstal et al reported on the use of an IR camera to monitor rotating glass vials [ 14 ]. In another publication, freezing behaviour inside glass vials was also studied using an infrared camera [ 19 ]. Correct temperature readings were obtained as also shown here, but without high thermal and spatial resolution to reveal more subtle differences [ 14 , 19 ].…”

“…In another publication, freezing behaviour inside glass vials was also studied using an infrared camera [ 19 ]. Correct temperature readings were obtained as also shown here, but without high thermal and spatial resolution to reveal more subtle differences [ 14 , 19 ]. In Figure 2 a–d, spatial contour plots of the germanium and glass windows are shown for the oil–water experiment after 0 and 180 s, respectively.…”

“…The arrow indicates the time point for the spatial contour plot shown in Figure 8 a. Since freezing is such an important step in freeze-drying processes [ 11 , 19 ], controlled nucleation is a relatively new hardware and software feature that exists for some freeze-dryer models. In some configurations, an ice fog is blown over supercooled material [ 23 , 24 ].…”

“…Several other studies have since then been published describing work using an infrared camera to monitor freeze-drying processes [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Lietta et al described the use of an infrared camera mounted inside a freeze dryer compared with results from thermocouples when drying a sucrose formulation in glass vials.…”

Surface Treatment of Glass Vials for Lyophilization: Implications for Vacuum-Induced Surface Freezing

“…This is extremely useful for automatizing the controlled-freezing protocol, as the presence of an operator is not required if the values of P n and t n are already known. Moreover, this is a necessary requirement for a whole batch, where most of the vials are not in-sight of the operator, and the only way to properly select the nucleation pressure and time is by means of prior knowledge (as in this work), or alternatively, through the use of a suitable monitoring device (for instance, heat flux sensors [41] or infrared thermography [42] that were recently applied to the VISF protocol).…”