Determination of Elution Volumes and Flow Rates

To obtain identical retention times as under analytical conditions, the flow rate under preparative conditions has to be adjusted accordingly (see Eq. 12), assuming that the same particle size is used. 

The easy scalability of enantioselective HPLC can be demonstrated for the separation of omeprazole [29], one of the blockbuster drugs for the treatment of ulcers (see Fig. 17). The (S)-enantiomer, esomeprazole with the trade name Nexium, is used as an improved active pharmaceutical ingredient against inflammation and ulcers of the oesophagus (reflux oesophagitis), heartburn/ pyrosis (gastrooesophagal reflux), and ulcers of the duodenum after infection with helicobacter pylori. 

After method optimization using the DaicelCSP Chiralpak AS, the enantiomers can be separated using alcohols as eluents (Fig. 18). Under analytical conditions, an enantiomer separation can be achieved within 12 min. 

The enantiomer separation can be transferred to preparative scale using the same mobile and stationary phases (Fig. 19). 

When an appropriate flow rate is selected, the retention times differ only marginally between analytical and preparative columns. Preparative HPLC allows the isolation of enantiomerically pure compounds at up to the multi-kg range. However, if larger amounts are needed (10 kg up to 5001), a continuous production method has to be implemented as described in the following paragraphs. 

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