Phase separation times in liquid–liquid extractions (LLE)

Using the software, we can:

i) develop a methodology to anticipate emulsion formation;

ii) Perform LLE troubleshooting to improve yield and cycle time.

The background of liquid liquid mixing:

  • Two immiscible liquids – a dispersed phase (drop) in a matrix (continuous) phase.
  • Mixing impacts the equilibrium between drop coalescence vs. drop breakup.
  • Lab-scale vessels provide unrealistic hydrodynamics that can mask coalescence and dispersion suspension problems.


The moon-shot: To develop an efficient and reliable methodology to anticipate emulsion formation and phase separation times at manufacturing.

Phase separation times in liquid–liquid extractions

Stage 1 – Developing in-house knowledge

Literature search of liquid mixing process:

• Define relevant parameters
o Mean drop size
o Turbulent shear rate at the blade circulation flow rate
o Relative residence time
o Maximum energy dissipation

• Prior work/knowledge
o Laboratory and/or manufacturing observations

Experimental apparatus:
• Reactor geometry
• Impeller type
• Liquid–liquid system
DoE approach:
• Exclude correlated variables
• Perform full-factorial tests

Phase separation times in liquidliquid extractions
Stage 1 – Developing in-house knowledge (bench scale DoE)


Higher maximum energy dissipation (MED) leads to longer

separation times.

  •  For the same MED, different impellers yielded similar separation times.
  •  Interaction with other mixing variables?

High maximum energy dissipation (MED) leads to larger
separation times.

  • High residence time in the zone of MED leads to centrifugal separation –
    swirl effects
  • Power and geometry effects can now be anticipated!


Stage 2 –Applying knowledge at manufacturing



Scaled-down manufacturing reactor to a 2 L bench reactor:
• A correlation exists between the maximum energy dissipation and the amount of
residual emulsion at the end of the procedure.

The new optimized mixing conditions yielded the desired
product. Besides stirring speed, no changes are made to the manufacturing

Lessons learned:

  1. Software was used to study the effect of geometric
    variables in oil-inwater systems.
    Key mixing parameters are identified!
  2. A reasonable acceptable prediction model was generated and integrated in a
    QbD methodology.
    Increased know-how! Right first time!
  3. The software was used for the optimization of an important manufacturing
    extraction process.
  4. Increased batch yield and cycle-time! $

Taken from the Second VisiMix Forum by Nuno Lousa – Hovione



VisiMix Video

The Influence of Mixing in the Process
New methodology using VisiMix software for the purpose of checking the influence of mixing in the processes.

VisiMix Demo Operation
Learning how to input data into the VisiMix software and get results the will help us understand the influence of mixing in our processes.

Lab Experiments
Learning how to set up the relevant experiments at the lab scale, to develop the processes from an engineering point of view.