Vial design features can play a significant role in heat transfer between the shelf and the product and, consequently, in the final quality of the freeze-dried product. Our objective was to investigate the impact of the variability of some geometrical dimensions of a set of tubing vials commonly used for pharmaceuticals production on the distribution of the vial heat transfer coefficients (K) and its potential consequence on product temperature. Sublimation tests were carried out using pure water and 8 combinations of chamber pressure (4-50 Pa) and shelf temperature (-40°C and 0°C) in 2 freeze-dryers. K values were individually determined for 100 vials located in the center of the shelf. Vial bottom curvature depth and contact area between the vial and the shelf were carefully measured for 120 vials and these data were used to calculate K distribution due to variability in vial geometry. At low pressures commonly used for sensitive products (below 10 Pa), the vial-shelf contact area appeared crucial for explaining K heterogeneity and was found to generate, in our study, a product temperature distribution of approximately 2°C during sublimation. Our approach provides quantitative guidelines for defining vial geometry tolerance specifications and product temperature safety margins.

In pharmaceutical freeze-drying, the position of the product container (vial) on the shelf of the equipment constitutes a major issue for the final product quality. Vials located at the shelf edges exhibit higher product temperature than vials located at the centre, which in turn often results in collapsed product. A physics-based model was developed to represent heat transfer phenomena and to study their variation with the distance from the periphery of the shelf. Radiation, conduction between solids, and conduction through low-pressure water vapour were considered. The modelling software package COMSOL Multiphysics was employed in representing these phenomena for a set of five vials located at the border of the shelf, close to the metallic guardrail. Model predictions of heat fluxes were validated against experimental measurements conducted over a broad range of shelf temperatures and chamber pressures representative for pharmaceutical freeze-drying. Conduction through low-pressure water vapour appeared as the dominant mechanism explaining the additional heat transfer to border vials compared to central ones. The developed model constitutes a powerful tool for studying heterogeneity in freeze-drying while reducing experimental costs. Highlights:• A 3D mathematical model of heat transfer in freeze-drying is proposed.• The role of several heat transfer mechanisms is explored.• Knudsen effect is considered for conduction inside low-pressure water vapour.• Radiation heat transfer is evaluated using the surface-to-surface model.• Atypical heat transfer is explained mainly by gas conduction rather than radiation.

During the primary drying step of the freeze-drying process, mass transfer resistance strongly affects the product temperature, and consequently the final product quality. The main objective of this study was to evaluate the variability of the mass transfer resistance resulting from the dried product layer (R) in a manufacturing batch of vials, and its potential effect on the product temperature, from data obtained in a pilot scale freeze-dryer. Sublimation experiments were run at -25 °C and 10 Pa using two different freezing protocols: with spontaneous or controlled ice nucleation. Five repetitions of each condition were performed. Global (pressure rise test) and local (gravimetric) methods were applied as complementary approaches to estimate R. The global method allowed to assess variability of the evolution of R with the dried layer thickness between different experiments whereas the local method informed about R variability at a fixed time within the vial batch. A product temperature variability of approximately ±4.4 °C was defined for a product dried layer thickness of 5 mm. The present approach can be used to estimate the risk of failure of the process due to mass transfer variability when designing freeze-drying cycle.

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Thermal treatments are known to affect the textural properties of fruits and vegetables. This study was conducted to evaluate the influence of vacuum cooking process on the mechanical properties of various apple cultivars. A total of 10 apple cultivars were industrially processed by vacuum pasteurization at 95 degrees C for 25 min. The raw material was characterized by penetrometry, uniaxial double compression, soluble solid content, and titrable acidity. Textural properties of processed apples were analyzed by uniaxial double compression. As expected, for all cultivars, fruit resistance was lower after processing than before. Results showed that texture degradation due to vacuum pasteurization was different from one cultivar to another. Indeed, some cultivars, initially considered as the most resistant ones, such as Braeburn, were less suitable for processing, and became softer than others after thermal treatment. Consequently, it is worth noting that the texture classification of the investigated apple cultivars was changed by the vacuum-cooking process.