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.
Highlights
The pharmaceutical industry has undergone a deep renovation during the past decade, shifting its research and development efforts from chemically synthesised drugs to biopharmaceuticals [1]
The first trivial observation is the stochastic nature of freezing when uncontrolled freezing is used instead of when controlled freezing is applied
Some humps on the temperature profiles are observed for the spontaneous nucleation test caused by the nucleation energy released in neighbouring vials
Summary
The pharmaceutical industry has undergone a deep renovation during the past decade, shifting its research and development efforts from chemically synthesised drugs to biopharmaceuticals [1]. The several benefits of biopharmaceuticals can explain this trend shift. Their benefits include highly effective and potent action, few side effects, and the potential to cure previously untreatable diseases [2]. The pandemic caused by COVID-19 highlighted the necessity to have reliable ways to stabilise and store therapeutic liquid products, e.g., vaccines, for long times. These kinds of drug products are, often unstable in solutions and lose their activity when subjected to the high temperatures used in conventional drying [2]. Freeze-drying is a good fit for these drugs because it is a dehydration technique performed at low temperatures, increasing the product’s shelf-life while maintaining its biological activity
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