Extraction Technologies For Medicinal And Aromatic Plants - Unido

EXTRACTION TECHNOLOGIES FOR MEDICINAL AND AROMATIC PLANTS
11.5 Stepwise Operations in Process-scale HPLC
Various aspects should be taken into consideration for operating
process-scale HPLC and stepwise scale-up, as follows.
• Develop a robust analytical method and scale up the method
for process scale using the same stationary phase.
• The main objective of method development is a simple, wellautomated
and robust separation process able to run 24 h
per day.
• Optimize sample loading, fl ow rate and column pressure.
• Select the best solvent for both sample preparation and elution.
• The injection solvent should be optimized because sharp
peaks and high loadability are important goals.
• In process-scale separations, control the fi rst two runs manually
and observe the process. If no technical problems occur,
subsequent runs can be performed automatically.
• Collect fractions and re-analyze them for purity using the
analytical method.
• Peak purity at three points (i.e. up slope, apex and down
slope) should be confi rmed.
11.6 Problems Encountered in Preparative Scale-up
11.6.1 Purity of Crude Extract
A typical problem encountered in process scale-up is that the
plant material or enriched fraction used during method development had
been produced in analytical scale and differs in solubility and impurity from
the material that is being processed in pilot scale. The process-scale plant
material can be either of a different quality or show larger amounts of the
same impurities, and, in some instances, even new impurities can arise.
If an impurity profi le shows larger amounts of the same impurities or new
impurities, the chromatographer must retest the separation method at analytical
scale before starting the process-scale separation.
If during a process scale up, a compound shows higher purity,
the solubility in the weak solvent chosen during optimization may not be
good enough. In this instance, productivity can be lower than expected because
the amount separated in each run will be less. Because scale-up is
linear, the chromatographic run takes the same time in preparative scale as
in analytical scale, and the substance is not stressed longer in the separation
equipment.
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