Flow Chemistry vs. Batch Chemistry

Technologies

Flow Chemistry vs. Batch Chemistry

From a commercial standpoint, flow chemistry is the preferred method over batch chemistry. These systems require less space, make better use of raw materials and produce a much higher volume of consistent products.  Continuous flow systems are cost-effective and becoming increasingly popular in the manufacture of pharmaceuticals, creating faster reactions with better yields.

Granted there is more complexity in setting up a continuous system as compared to batch but once that work is done, the payback is substantial.   For continuous flow systems, that would mean having the pumps set up correctly and calibrated, valving is correct and the automated system’s logic has been pre-approved. However, if one is dosing a batch system with a totalizer then the steps are almost the same in terms of set up.  Pumping is only an issue if materials of construction are not correct or solids are generated in situ.  (However, both of these are known quantities prior to commercialization and should not influence the process.)

Comparison

One major item to be considered in comparing batch vs continuous flow is that the surface area to volume ratio of batch is an order of magnitude LESS than continuous.  What this means is that the temperature difference between the heating or cooling fluid is much LESS for a continuous system vs batch.   If the heat, Q, for both is the same then and increase in Area, A, means that ΔT (delta T) can decrease.  That is because:

Q =   U x A x ΔT where Q = Heat removal in BTU/Hr or Kcal A = Surface Area in square feet or square meters U = Heat transfer coefficient in BTU/square feet-Hr-oF or Kcal/square meter-Hr-oC ΔT = oF or oC Also, for the engineers, the heat transfer coefficient, U, will be greater in a continuous system than a stirred tank, further lowering the ΔT in a continuous system.

Thus, any byproduct formation that could occur in a heated system in batch due to the larger temperature gradient at the wall is almost eliminated. (Engineers refer to this occurring in the film attached to the reactor wall).  Also, for cooling operations, the coolant is at a much HIGHER temperature for continuous ones because the system does not have to compensate for the smaller heat transfer area characteristic of batch systems in order to get the heat out.  Many batch systems have very low temperature cooling (-20oC or lower) requirements and that is because they have to get the heat out and need the higher temperature driving force.

Benefits of Continuous vs Batch That You Might Want to Consider

  • Steady state operation: For an unsteady state batch reaction, if a system is fed with reagents during the course of a reaction, there are very large concentration gradients within the poorly mixed reactor that results in some finished product seeing fresh reagents. This can hurt selectivity and yield.  In a continuous flow reaction, there is no back-mixing where significant amounts of finished product come in contact with raw materials.
  • Low inventory of materials: In a continuous flow system, all of your raw material inventory is not committed before the reaction starts. If there should be an operations problem, power outage or quality issue raised, the run can stop immediately and the issue fixed BEFORE raw materials are committed.  In a batch system, you’re stuck with the consequences of any events at time zero plus 1 second.
  • Footprint: the size of a continuous flow system is typically only 10 to 20% of a batch system, again because all of the inventory is not committed at time zero.
  • Preparation time: Batch systems usually have extensive manual preparation (cleaning, pressure check, valve positioning, inerting) steps that are automated in continuous flow systems. This makes continuous flow systems more “complex” but reduces the chance of the preparation not being done properly.
  • Safety: If the pressure should get high in a batch system one relies on a pressure relief valve, a rupture disk and a surge tank to protect operators and the environment. In a continuous flow system, one relieves the hydraulic pressure through a discharge valve (less than 1% of the reactor volume) and stops the pumps.
  • Less equipment required: Using a continuous flow system eliminates a reactor agitator, motor, seals with potential leaks or contamination.

Thus, the long term benefits of continuous flow systems far outweigh batch systems where economics, quality and safety are the primary drivers for consideration as opposed to the known comfort of batch ones.

Sentinel has over 30 years of experience developing custom chemistry systems for the pharmaceutical industry. We engineer flow chemistry processes and reactors designed to improve your bottom line, with automated production methods to ensure the mixtures produced are consistent and safe for the end-user.  If you would like to know more about our products and how we can design a system that is suited to your needs, send us a request for more information or call our team today.

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