Heat transfer characteristics of sublimation from frozen thin films

Abstract

Thin-film freeze-drying (TFFD) is an alternative to conventional freeze-drying (CFD) where frozen films are lyophilized as a bed of particles. In this study, we investigated the heat transfer mechanisms governing TFFD and how they differ from CFD at small and large scales. Small-scale experiments showed sublimation rates in TFFD are limited by high resistance to heat transfer within the particle bed. Sublimation rates for TFFD were dependent on both chamber pressure and shelf temperature and were fastest at high chamber pressures. Scale-up trials revealed that TFFD outperformed CFD under more aggressive drying conditions, with faster drying and better product quality. However, TFFD was less efficient in more conservative drying conditions due to its reliance on both a steep temperature gradient and sufficient chamber pressure to facilitate heat transfer throughout the product bed. CFD dried quicker in the more conservative cycles but was more prone to structural defects such as cake collapse and shrinkage. Finally, trays were fabricated with additional fins to increase the available surface area for heat transfer in the bed of frozen particles. The duration of primary drying decreased proportional to the increase in surface area to volume ratio of the trays with the most dramatic efficiency improvements at lower chamber pressures. For optimal sublimation rates, TFFD requires higher shelf temperatures and chamber pressures than CFD and benefits from container designs maximizing surface area in scale-up. Understanding the interplay between heat transfer and product structure is essential for refining TFFD as a scalable and efficient freeze-drying method.

Keywords: Freeze-drying; Heat transfer; Optimization; Particles; Scale-up.