Abstract
A laboratory-scale CCC (LCCC) of approximately 80 mL capacity was used to investigate the purification of an active pharmaceutical intermediate (API) using polar liquid-liquid systems based around water / n-butanol. Variation of pH and the polarity of the mobile phase by the use of a gradient pumping system, lead to the development of an isocratic system (where the upper organic phase was mobile). The method was then transferred to a larger (preparative PCCC) unit of 930 mL capacity. An estimated output from the large scale machine was made and compared with the production rate to current methods of purification, i.e., HPLC.
The capacity of the PCCC has been estimated to be equivalent to a 30 cm × 7.5 cm i.d. dynamic axially compressed (DAC) LC column; it is anticipated to be of comparable capital cost. The PCCC machine failed to purify the API to the product specification using the current eluent system. The potential output was comparable and the solvent consumption only 25 % of the HPLC system. Weepage or stripping of stationary phase (SP) was observed on runs with a relatively high mobile phase flow rate. From a process robustness and, hence, validation point of view, weepage is unacceptable.
ACKNOWLEDGMENTS
The help of Kate McLaughlin, Gerald Guillon, Ian Sutherland (the comments and critical review were especially welcome), and Alex Flynn is recognized in achieving the final results.