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Slurry Handling in the ACR - Apotex Pharma

AM Technology are pleased to share that an existing Coflore® ACR customer, Apotex Pharma in Canada, have published work on the “Continuous Flow Process for Reductive Deoxygenation of ω-Chloroketone in the Synthesis of Vilazodone” in the journal OPR&D (DOI: 10.1021/acs.oprd.8b00145).

Figure 1: Reaction scheme outlining the preparation of 3b within a Coflore® ACR

This work involves successful handling of a 23.5% w/v slurry solution within the Coflore® ACR to prepare compound 3b, as shown in Figure 1. Figure 2 shows how the team at Apotex set up their Coflore® ACR cell block. The versatility of the Coflore® ACR allows for multiple injection sites (three each per CSTR 1&10, two each per CSTR 2-9). This allowed the researchers to add sodium borohydride at both cells 2 and 6 for example.

Figure 2: Diagram showing the ACR cell block set up for the reductive deoxygenation of vilazodone precursor 2b

The authors stated that “the benefit of a continuous flow process to the synthesis of [a vilazodone precursor] intermediate is unmistakable. The limitations of controlling the exotherm in a batch reaction are now successfully overcome by conducting the reaction in a continuous flow CSTR setting that is also able to handle heterogeneous mixtures”. The authors also noted that the continuous flow process reduced the generation of a key dimeric impurity, and improved the yield of the desired product. This publication gives a clear example of the Coflore® ACR’s ability to handle solid suspensions in flow. In this example, a 23.5% w/v slurry was successfully pumped through the ACR cell block. Successful handling of hydrogen gas evolution within the system was also achieved, showing that the Coflore® ACR can handle a 3-phase, solid-liquid-gas reactive system.

For further information, please refer to technical note AM-TN02 or the paper by Gorin, B et al. both of which are linked to here:


“One of today's most important tools for modernizing the pharmaceutical industry is a process known as continuous manufacturing”

Director of the FDA’s Centre for Drug Evaluation and Research,

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