Wednesday, March 30, 2011

Scaling up: results of the poll on 1 gram reactions

Last week, I asked two questions:
  • If a trusted colleague came to you and ask you to scale a reaction from 1 gram to 100 grams, would you expect the results to be the same?
  • What is the largest scale at which you expect the major parameters of a 1 gram reaction (product yield, purity, time, temperature) to be basically similar?
I thought 10 grams was about the limit. 20 or 50 grams, if you're lucky and anything larger than that (100 grams) is a complete crapshoot.

From the comments, we had variety of responses, mostly on the low end of the given range:
  • A4:38a: "I'd say 10 grams too - but it would depend on the purification."
  • See Arr Oh: "I would say it might be similar at 20 g, depending on temperature profile and solubility. 100g is completely out, though. I never scale anything more than 5x at a time."
  • Kay: "The general rule for production scale is 3x but that's for larger lots at the pilot plant stage. For something as small as 1 g, I think you could go up 5x or even 10x."
  • A7:14a: "10g is the highest I'd go before reevaluating."
  • CMCguy: "In reality answers mostly a function of the chemistry/reactions involved and what you know from literature or lab. I have done routine development at 100mg-10g scales then jumped with confidence immediately to 1-25kg scales."
  • NS29: "When it comes to scaling up high pressure hydrogenation reactions, my experience is definitely not. The surface/volume ratio and thus the size of the gas/liquid interphase differs too much when scaling up by a factor of 100."
  • A10:09a: "In my experience it is variation of one or more seemingly unimportant variables that ends up being the cause of a disparate result. Allowing that disparate result to guide further experimentation into determining the most important variables you need to control is actually the crux of development of a robust and repeatable process."
I'm glad that my gut feeling was more-or-less similar to some of the (dearly appreciated) longtime professionals that are reading the blog. Thanks to all for participating in the poll!

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