Development of freeze-drying cycles for pharmaceutical products using a micro freeze-dryer

This paper aims to investigate how a small-scale freeze-dryer can be used for process design. The system encompasses a temperature controlled metallic ring that surrounds a small batch of vials, in contact with the external vials through removable thermal conductors. The temperature of the ring can be modified to keep a constant difference with the temperature of one or more vials of the batch. In this paper an extensive validation of the system is given, considering 10% w/w sucrose and 5% w/w mannitol solutions, processed in different types of vials (6 R and 20 R) and in different operating conditions. The micro freeze-dryer was also shown to be able to provide accurate estimates of the overall heat transfer coefficient from the shelf to the product in the vials (Kv) and of the resistance of the dried cake to vapor flux (Rp): both values appeared to be very close to those obtained for the same case studies in a pilot-scale unit. Finally, the use of the micro freeze-dryer to control product temperature and drying time values to simulate a pilot-scale unit was addressed, thus demonstrating the adequacy of this system for process scale-up.