(755e) Extraction and Phase Separation of Api’s in Low Interfacial Tension Mixtures
In this work, we utilize a unique membrane module with integrated pressure control that decouples the separation from downstream disturbances. This unique module removes the need for the user to individually control the pressure of the aqueous and permeate sides of the membrane. The pressure is controlled using a thin perfluoroalkoxy (PFA) polymer diaphragm that acts to modulate the pressure between the aqueous and organic sides of the membrane. The upper and lower bounds for operating this system while achieving complete separation correspond to the capillary and permeation pressure, respectively. The capillary pressure must be greater than the diaphragm pressure and the diaphragm pressure must be greater than the permeation pressure. These pressures can be controlled by varying the pore size and type of membrane and the thickness of the diaphragm.
This system has been successfully applied to the final synthesis steps of the production of several pharmaceuticals, including lidocaine and diazepam. These complex mixtures contained several organic solvents as well as aqueous salt solutions. The goal was to extract the active pharmaceutical ingredients (APIâs) into the organic phase; hexanes for lidocaine and ethyl acetate for diazepam. In general, this type of separation would not be possible using a membrane, since the interfacial tension is too low, leading to breakthrough of the aqueous phase into the organic phase. We present a method to modulate the interfacial tension so that complete separation of the two phases is achieved.Â In addition to completely separating the two phases, 100% of the APIâs were extracted into their respective organic phases. This was not previously possible and is a step towards the reliable extraction and phase separation of APIâs in a fully continuous operation.