title: Reaction crystallization of pharmaceutical molecular complexes.
abstract: A mechanism for cocrystal synthesis is reported whereby nucleation and growth of cocrystals are directed by the effect of the cocrystal components on reducing the solubility of the molecular complex to be crystallized. The carbamazepine:nicotinamide cocrystal (CBZ:NCT) was chosen as a model system to study the reaction cocrystallization pathways and kinetics in aqueous and organic solvents. Fiber optic Raman spectroscopy and Raman microscopy were used for in situ monitoring of the cocrystallization in macroscopic and microscopic scales in solutions, suspensions, slurries, and wet solid phases of cocrystal components. This study demonstrates the advantages of reaction cocrystallization methods to develop rational approaches for high-throughput screening of cocrystals that can be transferable to control batch and continuous cocrystallization processes.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109-1065, USA. nrh@umich.edu
authors.forename: Naír
authors.initials: N
authors.lastname: Rodríguez-Hornedo
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nehm
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Seefeldt
authors.forename: Yomaira
authors.initials: Y
authors.lastname: Pagan-Torres
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Falkiewicz
mesh_terms: D003460:Crystallization / Q000379:methods*; D004049:Diethylcarbamazine / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*; D008859:Microscopy, Polarization / Q000379:methods; D008956:Models, Chemical; D009536:Niacinamide / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013055:Spectrophotometry, Infrared / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D046911:Macromolecular Substances; D012997:Solvents; D009536:Niacinamide; D004049:Diethylcarbamazine