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Pharmaceutics 2011, 3(3), 582-600; doi:10.3390/pharmaceutics3030582

Application of Twin Screw Extrusion in the Manufacture of Cocrystals, Part I: Four Case Studies

, , , *  and *
Small Molecule Process and Product Development, Amgen Inc, Thousand Oaks, CA 91320, USA
* Authors to whom correspondence should be addressed.
Received: 1 July 2011 / Revised: 17 August 2011 / Accepted: 24 August 2011 / Published: 31 August 2011
(This article belongs to the Special Issue Pharmaceutical Salts and Co-Crystals)
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The application of twin screw extrusion (TSE) as a scalable and green process for the manufacture of cocrystals was investigated. Four model cocrystal forming systems, Caffeine-Oxalic acid, Nicotinamide-trans cinnamic acid, Carbamazepine-Saccharin, and Theophylline-Citric acid, were selected for the study. The parameters of the extrusion process that influenced cocrystal formation were examined. TSE was found to be an effective method to make cocrystals for all four systems studied. It was demonstrated that temperature and extent of mixing in the extruder were the primary process parameters that influenced extent of conversion to the cocrystal in neat TSE experiments. In addition to neat extrusion, liquid-assisted TSE was also demonstrated for the first time as a viable process for making cocrystals. Notably, the use of catalytic amount of benign solvents led to a lowering of processing temperatures required to form the cocrystal in the extruder. TSE should be considered as an efficient, scalable, and environmentally friendly process for the manufacture of cocrystals with little to no solvent requirements.
Keywords: twin screw extrusion; cocrystals; environmentally friendly; green chemistry twin screw extrusion; cocrystals; environmentally friendly; green chemistry
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Daurio, D.; Medina, C.; Saw, R.; Nagapudi, K.; Alvarez-Núñez, F. Application of Twin Screw Extrusion in the Manufacture of Cocrystals, Part I: Four Case Studies. Pharmaceutics 2011, 3, 582-600.

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