Supercritical fluid chromatography (SFC) is already recognized as the method of choice for the preparative separation of chiral molecules in pharmaceutical industries. Even for the achiral separations , especially for the separation of natural products , SFC has a huge potential to grow as the method of choice. To harness the full potential of SFC in these separations , however , we need to develop better methods for scaling-up from analytical to preparative conditions. One of the critical procedures during the method development of a preparative separation is the scale-up procedure. Screening of competing combinations of the mobile phase compositions and the stationary phases , leading to the best separation , is time consuming and expensive to carry out directly in the preparative scale. One of the better alternatives is to first identify the optimum mobile/stationary phase combination in the analytical scale and then transfer the method to a scale where the prep separation should be carried out. Although there are standard methods available in liquid chromatography (HPLC) for scaling-up , they are not always useful in SFC. In SFC the density of the mobile phase varies significantly across the column , which results into the variation of all the mobile phase properties. The extent and the nature of variation of density in the analytical and the preparative scale can be very different , depending on (a) the dimensions of the connecting tubes and the column , (b) the particle sizes of the stationary phases , and (c) the operating temperature , pressure and flow rate. This difference in the density profiles across the column , between the analytical and the preparative system , will lead to very different chromatography unless the scaling-up procedure is guided by a systematic approach requiring additional calculations. In this presentation we will discuss a systematic approach we are developing to scale-up operations from analytical to preparative scale in SFC.
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