title: A PAT approach for the on-line monitoring of pharmaceutical co-crystals formation with near infrared spectroscopy.
abstract: Cocrystals represent a class of crystalline solids consisting of two or more molecular species usually held together by non-covalent bonds. Pharmaceutical cocrystals can alter the physicochemical properties of the active pharmaceutical ingredient to improve solubility, dissolution rate, particle properties and stability. This work presents a process analytical technology (PAT) approach to monitor on-line the cocrystallization of furosemide and adenine by solvent evaporation using near infrared spectroscopy (NIRS). Furosemide and adenine were added to a small volume of methanol in a beaker and stirred on an orbital stirring table during 8h at room temperature. The on-line monitoring was performed with a FT-NIR spectrometer fitted with a reflectance fiber optic probe. Monitoring was performed with the probe tip placed 1cm above the cocrystallization medium to avoid interference with the cocrystallization process. Cocrystals were vacuum dried to remove residual solvent and characterized off-line by NIRS, MIRS, DSC and XRPD. Results demonstrate that it was possible to follow the main cocrystallization events on-line.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Mafalda C
authors.initials: MC
authors.lastname: Sarraguça
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Paulo R S
authors.initials: PR
authors.lastname: Ribeiro
authors.affiliation: Centro de Ciências Sociais, Saúde e Tecnologia, Universidade Federal do Maranhão, Imperatriz, MA, Brazil.
authors.forename: Adenilson O
authors.initials: AO
authors.lastname: Santos
authors.affiliation: Centro de Ciências Sociais, Saúde e Tecnologia, Universidade Federal do Maranhão, Imperatriz, MA, Brazil.
authors.forename: Marta C D
authors.initials: MC
authors.lastname: Silva
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lisbon, Portugal. Electronic address: jlopes@ff.ul.pt.
authors.forename: João A
authors.initials: JA
authors.lastname: Lopes
mesh_terms: D000225:Adenine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods*; D005665:Furosemide / Q000737:chemistry*; D006860:Hydrogen Bonding; D008962:Models, Theoretical; D033362:Powder Diffraction; D012997:Solvents / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared
chemical_list: D012997:Solvents; D005665:Furosemide; D000225:Adenine
keywords: Cocrystallization; Cocrystals; Near infrared spectroscopy; On-line monitoring; Process analytical technology