Wednesday, May 4, 2011

Process Wednesday: drying

In the final set of questions from Kilomentor on scaling up, he asks:
Is there a drying step in the process? If so:
  • Can the drying be done by azeotropic distillation or passing through a molecular sieve plug to avoid solid drying agents? Is there an IPC to determine completion of drying?
It seems like there's ALWAYS a drying step in the process. I've seen the powers of azeotropic drying and I believe (I believe!) that there is mostly likely some way of avoiding drying agents. But what that might entail, of course, is a different matter altogether.

Having a rotary dryer of some sort (or rigging one up) seems to be a cheap solution to the problem of drying powders, but I've suspect that they're scale- or cost-limited as well. Readers, please educate me.  

4 comments:

  1. People in process are quite fond of vacuum ovens for drying solids - you can set the heater temperature high and let inert gas bleed pass through to speed up the process. I also used coffee-can Kugelrohr/1L flask to dry inorganic solids on highvac.

    Azeotropic drying will not help you if you used brine (or NH4Cl or bicarb) wash at the end. You need some solid drying agent and filtration to take care of those insoluble inorganics. Also azeotroping water away does not work too well at reduced pressure so you need to do it typically at atmospheric pressure and that means heating things to boil for extended periods of time, not all products/reaction mixtures can tolerate that

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  2. Some azeotropes are sensitive to pressure, some are not. For example composition of ethyl acetate/water azeotrope changes from 8.5% of acetate in the distillate at 760 mm to 3.6% at 25 mm. On the other hand, i-PrOH/water doesn't change over the pressure span. See N. G. Anderson - Practical Process R&D for useful reference.

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  3. I can think of only a few unique situations (including continuous process) where would desire to "avoid solid drying agents" since typically no issues applying at scale. Most common Newbie lesson is MgSO4 not usual first choice as it is in lab due to scope of reactivity and particle size.

    For drying powders I have seen giant tumble dryers (i.e. visualize Cement mixers) for both API and drug products and indeed are pricey to purchase. install and run. Likewise seen dryers/centrifuge combos that have mechanical arms to turn over solid periodically. Milkshake is correct general a fondness for vacuum tray dryers, probably due to cost factors and ease of operation (unless you are the one assigned to conduct the manual turns every 4h).
    CMCguy

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  4. Tumble driers are great to look at (my favourite is the double cone drier) but can break down easily as the whole rig is moving and thus becomes more prone to mechanical failures.

    Another disadvantage of tumble driers can be the tendency of the product to form large lumps of product if the material that is discharged from the centrifuge has a large solvent content, and the lumps clog the discharge chute.

    Huge fun when you have to open the drier in a clean room environment...

    The list of what can go wrong when drying material can go on and on...

    Thats's why I usually prefer nutsche type driers, some of them have a temperature probe inside the filter cake which make it easier to determine the end point of your drying process

    I am usually relieved once the material made it safely into its secondary packaging and everything is labelled correctly.

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