Cake washing process development and end-point determination based on refractive index

Abstract

The goal of the chemical development pilot plant (CDPP) of Janssen Pharmaceutica in Geel is the production of intermediates, process optimisation, scale-up and introduction of new technology in a large plant. The increasing complexity of Active Pharmaceutical Ingredients (API) demands a better understanding of the manufacturing process as costs for development of new products increases. Filter cake washing is a constant bottleneck in the production of new API. Theoretical predictions are hard, due to the strong dependence of the washing on process parameters. The goal of this master thesis is the cake washing process optimisation and endpoint determination based on refractive index.

Cake washing is executed in centrifuge dryers in this study. Refractometers are used to measure the cake washing, whereafter washing curves will be drafted. Washing curves will be used for deviation detection, endpoint determination and process optimisation.

Washing curves are very product dependent, which complicates endpoint determination. Further research for a model on endpoint determination will be needed. The refractive index is perfect for deviation detection, due to its high sensitivity. Different deviations, such as crystal morphology, reactor washing and change in solvent ratio, were detected using the refractive index as an analytical tool. The detection of these deviations resulted in a decrease of used washing solvent.