title: Continuous engineering of nano-cocrystals for medical and energetic applications.
abstract: Cocrystals, solid mixtures of different molecules on molecular scale, are supposed to be tailor made materials with improved employability compared to their pristine individual components in domains such as medicine and explosives. In medicine, cocrystals are obtained by crystallization of active pharmaceutical ingredients with precisely chosen coformers to design medicaments that demonstrate enhanced stability, high solubility, and therefore high bioavailability and optimized drug up-take. Nanoscaling may further advance these characteristica compared to their micronsized counterparts - because of a larger surface to volume ratio of nanoparticles. In the field of energetic materials, cocrystals offer the opportunity to design smart explosives, combining high reactivity with significantly reduced sensitivity, nowadays essential for a safe manipulation and handling. Furthermore, cocrystals are used in ferroelectrics, non-linear material response and electronic organics. However, state of the art batch processes produce low volume of cocrystals of variable quality and only have produced micronsized cocrystals so far, no nano-cocrystals. Here we demonstrate the continuous preparation of pharmaceutical and energetic micro- and nano-cocrystals using the Spray Flash Evaporation process. Our laboratory scale pilot plant continuously prepared up to 8 grams per hour of Caffeine/Oxalic acid 2:1, Caffeine/Glutaric acid 1:1, TNT/CL-20 1:1 and HMX/Cl-20 1:2 nano- and submicronsized cocrystals.
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: D
authors.initials: D
authors.lastname: Spitzer
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: B
authors.initials: B
authors.lastname: Risse
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: F
authors.initials: F
authors.lastname: Schnell
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: V
authors.initials: V
authors.lastname: Pichot
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: M
authors.initials: M
authors.lastname: Klaumünzer
authors.affiliation: NS3E, ISL-CNRS-UdS (Nanomatériaux pour les Systèmes Sous Sollicitations Extrêmes) UMR 3208, French-German Research Institute of Saint-Louis, 5, rue du Général Cassagnou, B.P. 70034, 68301 St Louis, France.
authors.forename: M R
authors.initials: MR
authors.lastname: Schaefer
mesh_terms: D002110:Caffeine / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D005977:Glutarates / Q000737:chemistry; D006860:Hydrogen Bonding; D053758:Nanoparticles / Q000737:chemistry*; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D005977:Glutarates; D002110:Caffeine; C035736:glutaric acid