Wednesday, November 14, 2012

Process Wednesday: Why is the drying taking so long?

From a 2006 Organic Process Research and Development paper [1], a reason why tray dryers don't work very well:
The model describes the drying process as a penetration process. It is assumed that there is a drying front that moves from the equipment wall into the bulk solid, parallel to the wall. Particles between the drying front and the wall are assumed to be completely dry, and particles beyond the drying front are assumed to be completely wet. This is shown schematically in Figure 2.  
The heated surface is shown at the bottom. Below the drying front there is a layer of dry solids with zero moisture content. Above the drying front a layer of wet solids is shown in black. This layer of wet solids is assumed to be at boiling temperature at the prevailing pressure. The vapour phase consists of the pure liquid component.
So as far as I can tell, this means that, in a tray dryer with no movement, the material you want to dry will always be furthest away from the heat source. Grrrrrrrrreat.

I've worked at places with tray dryers in the past; we had to routinely break the vacuum, go in there with a scoop and turn the stuff over by hand. It's remarkable how fast a 20L rotovap can work by comparison to a medium-sized tray dryer; one can only imagine how fast a double cone dryer works in comparison.

1. Hoekstra, L.; Vonk, P.; Hulshof, L.A. "Modeling the Scale-Up of Contact Drying Processes." Org. Process Res. Dev., 2006, 10 (3), pp 409–416.

1 comment:

  1. I missed this article, thanks for bringing this up.

    Drying in tray dryer is still simpler than in almost any other if an agitated filter-dryer is not available. In an early scale-up simplicity is a blessing (usually...).

    We had some success drying up to ~50 kg (depending on the bulk density of the solid) in a 5' x 5' x 5' chamber with heated shelves.

    I consider at least two factors for a successful process:

    - N2 purge flow in the dryer equivalent to a couple of linear feet/sec at the target pressure;

    - good TGA trace from a process sample showing the departure of both the bulk and the structural solvent.

    Usually I recommended drying temperature above the departure temperature of the bound (structural) solvent. A couple of TGA (or one mTGA) experiments will give enough data for some prediction of kinetics of drying.

    With the N2 sweep on, the rate of solvent removal in a typical tray with <2" bed depth is related mostly to the rate of heat transfer through the cake and the heat of evaporation of the bulk solvent (pressure and temp. are both important here).

    To remove the bound solvent some heat is needed to break the bonds, but experimentally the temperature of the process is the key. The best vacuum is not that critical unless the solvent has a very low vapor pressure. Bound solvent can be removed at fairly high pressure as long as the temperature is high enough and N2 carries the vapor away.

    For pharmaceutical scale-up I often find that the decomposition temperature of the product is lower than the temperature required to break the bonds to the solvent. When that happens it is time to revisit the crystallization step.