Investigation of heat and mass transfer behavior of mannitol during vial freeze-drying

The vial design feature, such as the base curvature, acts as the primary heat transfer barrier in the lyophilization process. In this study, heat and mass transport characteristics of mannitol (5%) during vial freeze-drying are numerically investigated by including the vial base curvature effects. The influence of the product fill height, chamber pressure, and the vial base curvature on the product temperature, drying time, and mass transfer resistance is analyzed in detail. The diameter of the vial is taken as 15 mm, while the fill height of the product is varied from 3 to 5 mm. The chamber pressure is maintained between 5 and 50 Pa. The results revealed that the product with a 3 mm fill height experienced a 2.5 °C lower temperature than the product with a 5 mm fill height. As opposed to the flat vial predictions, if the vial base curvature effects are considered, the drying time is increased by 1.96 and 3.8 h for the 3 mm and 5 mm fill heights, respectively. The increased drying time is attributed to the reduced direct contact area between the vial and shelf and the vapor entrainment in the gap. The results showed that the dry layer mass transfer resistance contributes to 95% of the total mass transfer resistance; however, the contribution of semi-stoppered vial resistance is 1–2% only.