A Further Look at the Bourne Protocol for Efficient Investigation of Mixing Sensitivities during Process Development

At the inaugural AIChE Process Development Symposium in 2003, Ed Paul stated, “Always assume there is a mixing problem until proven otherwise.”

 

Ed’s sage advice has been an important consideration in my process development work. However, with all the tasks that are necessary to achieve successful process development, we need to efficiently understand our “mixing problems” so we can effectively deal with them long before commercialization.

 

In his comprehensive review article on the influence of mixing on reaction sensitivity, John Bourne recommended an experimental protocol to determine mixing resistances in reaction processes (Bourne, 2003). We have applied the Bourne Protocol to reactive and non-reactive systems to determine when mixing needs to be carefully considered in our processes (Teich, Sarafinas, Morton 2010a+b, Sarafinas and Teich in Kresta et al, 2016). The Bourne Protocol is more efficient than some other methods that use model reactions (Sarafinas 2011).

 

This paper will extend the recommendations of Bourne’s 2003 paper, and discuss some theoretical and practical considerations when trying to understand when micromixing, mesomixing, and macromixing create “mixing problems” in your process.

 

REFERENCES

Paul, E.L., “Notes on Process Development: Pharmaceutical Intermediates and APIs,” AIChE Process Development Symposium, Poconos-Lake Harmony, PA, 2003

 

Bourne J.R., “Mixing and the Selectivity of Chemical Reactions”, Org. Process Res. Des. Dev.; 2003; 7(4) pp. 471-508.

 

Teich, C., Sarafinas, A., Morton, P., “Taking the Min to the Max: A Case Study in Small Scale Process Development Using On-Line Reaction Calorimetry and in-situ Particle Characterization,” AIChE 2010 Annual Meeting, Salt Lake City, UT, Paper 422b, 2010a.

 

Teich, C., Sarafinas, A., Morton, P., “Can This Process Be Saved? A Search for Understanding Using the Bourne Protocol and Advanced Process Development Tools,” AIChE 2010 Annual Meeting, Salt Lake City, UT, Paper 437e, 2010b.

 

Kresta, S.M., Etchels III, A.W., Dickey, D.S., and Atiemo-Obeng, V.A., Advances in Industrial Mixing: A Companion to the Handbook of Industrial Mixing, John Wiley and Sons, 2016.

Sarafinas, A., “The Evolution of Process Understanding Through Micromixing and Mass Transfer Studies in the Successful Development of a Specialty Chemical Process,” AIChE 2011 Annual Meeting, Minneapolis, MN, Paper 389e, 2011.