Freeze-Drying - LyoLab

Experimental Facilities for Freeze-Drying

The group operates a Lyostar freeze-dryer from SP Scientific (Gardiner, NY). The dryer is equipped with the FreezeBoost controlled nucleation technology from Millrock Technologies (Kingston, NY). The dryer is currently being used for

a) Studying key heat transfer modes and their contribution in the freeze-dryer product chamber with the ultimate aim of improving scale-up accuracy from laboratory to production scale.

b) Studying the vapor flow and ice-growth dynamics in the condenser with the ultimate aim of determining the critical parameters that affect non-uniformity of ice growth

c) To compare ice nucleation in vials with and without control mechanisms

A typical freeze-drying cycle is run for shelf temperatures ranging between -25C to 0C. The condenser reservoir contains an arrangement of coils that are maintained at a temperature varying between -90C and -40C. The condenser reservoir is connected to a vacuum pump for removal of non-condensable gases. The typical range of pressures encountered in freeze-drying ranges from 10 to 500 mTorr.

Time-lapse imaging is used to capture ice nucleation in vials and the unsteady ice-growth dynamics in a freeze-dryer condenser.

Figure 1: Lyostar Freeze-dryer equipped with FreezeBoost (Millrock Technologies- Kingston, NY)

(Above): TN Thomson of Millrock Technologies Inc. demonstrating the retrofitted Freezebooster controlled technology capabilities of the Lyostar to students of pharmacy and Aero and Astro at Purdue.

Comparison of Uncontrolled and Controlled Nucleation in a Laboratory-scale Freeze-Dryer (Lyo Lab, Purdue)

The video is a time-lapse comparison of the nucleation times and shelf temperature variation between uncontrolled ice nucleation and FreezeBooster (Millrock Technologies- Kingston, NY) controlled nucleation with 5% sucrose in 10 ml vials placed on the shelf of a laboratory-scale FTS Lyostar freeze-dryer. The shelves are cooled based on the following recipe:

Temperature, C 5 -10 -40

Ramp, min 10 30 60

Hold, min 30 15 0

We see that with uncontrolled nucleation, 27 minutes elapse between nucleation in the first and last vials, while all vials nucleate within 15 s during controlled nucleation.The ice front continues to grow beyond that for about 1 hour. Figure 3 compares the nucleation times and shelf temperature with and without nucleation control.

Figure 2 (Left): Process parameters for uncontrolled and controlled nucleation

Figure 3 (Right): Comparison of uncontrolled and FreezeBooster controlled nucleation run nucleation times and shelf temperature