title: Batch Statistical Process Monitoring Approach to a Cocrystallization Process.
abstract: Cocrystals are defined as crystalline structures composed of two or more compounds that are solid at room temperature held together by noncovalent bonds. Their main advantages are the increase of solubility, bioavailability, permeability, stability, and at the same time retaining active pharmaceutical ingredient bioactivity. The cocrystallization between furosemide and nicotinamide by solvent evaporation was monitored on-line using near-infrared spectroscopy (NIRS) as a process analytical technology tool. The near-infrared spectra were analyzed using principal component analysis. Batch statistical process monitoring was used to create control charts to perceive the process trajectory and define control limits. Normal and non-normal operating condition batches were performed and monitored with NIRS. The use of NIRS associated with batch statistical process models allowed the detection of abnormal variations in critical process parameters, like the amount of solvent or amount of initial components present in the cocrystallization.
authors: LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto Rua Jorge Viterbo Ferreira, 228, 4050-313, Portugal.
authors: Mafalda C
authors: MC
authors: Sarraguça
authors: LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto Rua Jorge Viterbo Ferreira, 228, 4050-313, Portugal; NUPFARQ, Centro de Ciências Sociais, Saúde e Tecnologia, Universidade Federal do Maranhão (UFMA), Imperatriz CP:65.900-410, MA, Brazil.
authors: Paulo R S
authors: PRS
authors: Ribeiro
authors: Centro de Ciências Sociais, Sa úde e Tecnologia, Universidade Federal do Maranhão (UFMA), Imperatriz CP:65.900-410, MA, Brazil.
authors: Adenilson O
authors: AO
authors: Dos Santos
authors: iMed, Departamento de Farmácia Galénica e Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa 1649-003, Portugal. Electronic address: jlopes@ff.ulisboa.pt.
authors: João A
authors: JA
authors: Lopes
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D005665:Furosemide / Q000737:chemistry; D015233:Models, Statistical; D009536:Niacinamide / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D025341:Principal Component Analysis / Q000379:methods; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D009536:Niacinamide; D005665:Furosemide
keywords: co-crystals; cocrystallization; furosemide; near-infrared spectroscopy; nicotinamide; polymorphism; process analytical technology; quality by design; statistical process monitoring