Emulsion Formation during Extractions

30 March 2003

If you have ever had the problem of emulsion formation in the pilot plant production extraction, but didn’t see it during the laboratory process, it may be due to a number of factors.

1. The temperature of the extraction

Lab processes are carried out in the warm laboratory at 20-25°C, possibly higher in hot countries. Extractions in the plant, particularly in cold countries in the winter, may be at much lower temperatures. This may make the difference. Emulsions are much less stable at higher temperature and so it is often advisable to carry out an extraction at 50oC or above if your compound is stable enough. Better phase separations will be obtained and it may be possible to use less solvent. Many industrial processes operate using high temperature extractions. It is not so easy to do in the lab, but very easy in the plant. There is an energy saving aspect, too. Why cool your reaction mixture to perform the extraction, then heat the combined organic layers to distil off the solvent? Why not do all operations at high temperature?

2. The relative ratio of the organic solvent and water

Emulsions are much more likely with 50:50 mixtures of organic solvent and water, whereas at below 30:70 or above 70:30 mixtures, emulsion formation is less likely. This is why diluting with water can help to break an emulsion.

3. The way in which you mixed the solvents

Did you add the water to the organic phase or vice versa? Did you do it differently in the plant? It can make a difference! Adding the aqueous to the organic creates a water in oil (organic) emulsion which may be stable, whereas adding organic to water may create an oil (organic) in water emulsion which may be unstable (or vice-versa).

4. The composition of the layers

Some materials e.g. surfactants, certain phase transfer catalysts may cause difficulty with layer separation and a modification to the process may be the only option (e.g. change the composition of the PTC).

Certain impurities may also cause problems and if none of the above methods (changing temp, relative ratio, order of addition) work, then addition of a co-solvent, such as ethanol may help to break the emulsion.

For a detail discussion of these issues see the excellent book by John Atherton and Keith Carpenter, “Process Development: Physicochemical Concepts”, published by Oxford Univ Press, ISBN 0198503725. The price is, I think, under £10 — what excellent value for money.

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