Development of a downstream separation process
This diploma thesis was elaborated in R&D centre of Lonza Ltd company in Visp, Switzerland during internship, August 2012 – March 2013.
The downstream processing of produced material involves several steps. Rough separation techniques are followed by fine techniques of purification. The most widely used technique for the production of solid materials is crystallization. As industrial process, crystallization is a separation and purification technique used to generate a broad collection of chemicals for example pharmaceuticals, agricultural products, flavours, fragrances and others. Compound X (a mixture consisting of two similar compounds, Compound A and B) is produced by fermentation (upstream processing) and is gained from the fermentation broth by solid-liquid separation, extraction and purification steps (part of the downstream processing), dissolved in an organic solvent. The main goal of this work is to crystallize Compound X using a cooling or evaporation crystallization. For the development of the crystallization the understanding of the phase diagrams, the influence of the impurity profile and the mechanisms of the nucleation and crystal growth are important fundamentals.
Preliminary experiments were made ahead of crystallization experiments. N-heptane was chosen as the most suitable solvent for cooling crystallization of Compound X as a final downstream processing step. Proper solubility dependence on temperature establishes easy and fast crystallization. Purity of Compound X increases in the order of several percents. Ratio of Compound A and B should have been increased from approximately 80:20 to 85:15. It is possible to increase this ratio by cutting of Compound B rich material at high temperature, though loss of material increases. As an alternative, increase of Compound A and B ratio in fermentation process were suggested. Process parameters were measured by turbidimetry, FBRM and Raman spectroscopy and its suitability for PAT use are discussed in the thesis.