Freeze-Drying Process Development and Scale-Up: Scale-Up of Edge Vial Versus Center Vial Heat Transfer Coefficients, K v

3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

“…Even if a debate is ongoing in literature on the importance of convection during freeze-drying [7,8,30], a recent work of Pikal et al [8] has shown that convection can be considered negligible at the low pressures typically encountered during the freeze-drying of pharmaceuticals (usually below 10 Pa).…”

“…In the considered low-pressure environment, heat transfer by radiation is expected to play a non negligible role [7,8]. In the present model, it was considered that the solid surfaces are opaque, that the radiation and the absorption occur in the same spectral range and that the absorption and radiation of the low pressure water vapour are negligible [21,31].…”

“…During the primary drying step, the total heat transfer towards the sublimation interface is mainly dependent on the operating parameters (shelf temperature, chamber pressure, step duration), but also on the vial geometry and on the position of the vial on the shelf [6][7][8][9]. Vials located at the periphery of the shelf (named edge vials) receive an additional heat flow and present a product temperature up to 4 °C higher compared to vials located in the centre of the shelf (named central vials) and surrounded only by other vials at the same conditions [6][7][8]10]. This atypical heat transfer characteristic is usually known as "edge vial effect" [7].…”

“…Recently, a study of Pikal et al [8] showed that the conduction through the low-pressure water vapour contained in the gap between the metallic rail and the vial could play a relevant role in the additional heat transfer in edge vials.…”

Determining Maximum Sublimation Rate for a Production Lyophilizer: Computational Modeling and Comparison With Ice Slab Tests

“…This protocol can be used as a tool to characterize freeze dryers and for scale-up between laboratory, pilot, and production equipment as previously presented by Tchessalov et al 11 It is also interesting to observe the nonuniform nature of the heat and mass transfer in the freeze dryer. The edge vial effect, in which the vials near the edges of the shelf dry faster than the vials in the center, is discussed by Pikal et al 12 In this, the problem of scale-up from the perspective of the edge vial effect is presented. The freeze dryer operation also depends on the load as observed by Patel et al, 7,8 where product temperatures and surface area are monitored in lab, pilot, and production-scale freeze dryers.…”