Manufacture of pharmaceutical co‐crystals using twin screw extrusion: A solvent‐less and scalable process

Clean and Efficient Synthesis Using Mechanochemistry: Coordination Polymers, Metal-Organic Frameworks and Metallodrugs

“…18,19 The techniques of LAG and of neat grinding have also recently been adapted into continuous screw-extrusion processes compatible with industrial scale-up. 20 Although the detailed mechanisms 17 underlying LAG cocrystallization, and especially control of polymorphism 21 and templating of open molecular framework, 18 are not known, simple explanations for the efficiency and speed of LAG have recently been proposed. In particular, it was proposed by several research groups 22,23 that the speed of reactions conducted by…”

Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free

“…[1][2][3][4][5] Avoiding toxic solvents not only decreases potential hazards, but can also reduce the overall cost of a process. 5 A variety of materials and compounds have been prepared mechanochemically including metal alloys, 6 metal organic frameworks (MOFs), 7 and organic compounds from reactions such as the Knoevenagel condensation [8][9][10] and Wittig reaction, 11 amongst others.…”

“…Recently, in order to overcome these drawbacks, twin screw extrusion (TSE), previously used extensively in the food, polymer and pharmaceutical industries, 15 has shown great potential for the efficient, continuous mechanochemical synthesis of fine chemicals, including co-crystals 2 and metal organic frameworks (MOFs). 3 This technique involves the conveyance of material through a confined space (barrel) by the rotation of a pair of modulated, intermeshing, co-or counter-rotating screws (Figure 1).…”

“…2 Co-crystal research to date has been directed towards the formation of pharmaceutically relevant mixtures, for example Amgen report the synthesis of the AMG 517 -sorbic acid co-crystal via TSE. 2 Those authors also highlight additional advantages of employing TSE in addition to benefits related to the process efficiency.…”

“…2 Co-crystal research to date has been directed towards the formation of pharmaceutically relevant mixtures, for example Amgen report the synthesis of the AMG 517 -sorbic acid co-crystal via TSE. 2 Those authors also highlight additional advantages of employing TSE in addition to benefits related to the process efficiency. They report that the cocrystals obtained exhibit enhanced properties (compared to solution grown cocrystals), including a higher surface area (2.9 m 2 g -1 vs. 0.9 m 2 g -1 ), thereby eliminating the need for post-synthesis processing involving milling.…”