title: Green production of cocrystals using a new solvent-free approach by spray congealing.
abstract: Pharmaceutical cocrystals are used as a strategy to overcome poor physicochemical properties of drugs. The use of cocrystals in the pharmaceutical industry remains to be fully exploited due, in part, to the scarcity of suitable large-scale production methods and lack of robust and cost-effective processes. To overcome these challenges, spray congealing was used for the first time in the preparation of cocrystals. The work considered a feasibility study, followed by a design of experiments to assess the impact of varying atomization and cooling-related process parameters on cocrystal formation, purity, particle size, shape and bulk powder flow properties. It was demonstrated that spray congealing could be used to produce cocrystals. The thermal analysis and X-ray results of the spray-congealed products were different from the pure components or physical mixtures and were aligned with those reported for the same cocrystals systems produced by other techniques. Cocrystal particles were compact and spherical consisting of aggregates of individual cocrystals entangled or adhered with each other. From the design of experiments, the results demonstrated that varying the process parameters did not influence cocrystal formation, but had an impact on cocrystal purity. Moreover, it was demonstrated that cocrystal particle properties can be adjusted, in situ, by varying atomization and cooling efficiency, in order to produce particles more suited for incorporation in final dosage forms such as tablets.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; R&D Drug Product Development, Hovione Farmaciência SA, Loures, Portugal.
authors.forename: Íris
authors.initials: Í
authors.lastname: Duarte
authors.affiliation: R&D Drug Product Development, Hovione Farmaciência SA, Loures, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Andrade
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: João F
authors.initials: JF
authors.lastname: Pinto
authors.affiliation: R&D Drug Product Development, Hovione Farmaciência SA, Loures, Portugal. Electronic address: mtemtem@hovione.com.
authors.forename: Márcio
authors.initials: M
authors.lastname: Temtem
mesh_terms: D003460:Crystallization / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013607:Tablets / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D012997:Solvents; D013607:Tablets
keywords: Green technology; Particle engineering; Pharmaceutical cocrystals; Spray congealing