title: Polymorph transformation in paracetamol monitored by in-line NIR spectroscopy during a cooling crystallization process.
abstract: The reliable in-line monitoring of pharmaceutical processes has been regarded as a key tool toward the full implementation of process analytical technology. In this study, near-infrared (NIR) spectroscopy was examined for use as an in-line monitoring method of the paracetamol cooling crystallization process. The drug powder was dissolved in ethanol-based cosolvent at 60°C and was cooled by 1°C/min for crystallization. NIR spectra acquired by in-line measurement were interpreted by principal component analysis combined with off-line characterizations via X-ray diffraction, optical microscopy, and transmission electron microscopy. The whole crystallization process appeared to take place in three steps. A metastable form II polymorph of paracetamol was formed and transformed into the stable form I polymorph on the way to the growth of pure form I by cooling crystallization. These observations are consistent with a previous focused beam reflectance method-based study (Barthe et al., Cryst Growth Des 8:3316-3322, 2008).
authors.affiliation: Department of Smart Foods & Drugs, Inje University, Gimhae, Gyeongnam, South Korea.
authors.forename: In-Chun
authors.initials: IC
authors.lastname: Wang
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Da-Young
authors.initials: DY
authors.lastname: Seo
authors.forename: Hea-Eun
authors.initials: HE
authors.lastname: Lee
authors.forename: Yongsun
authors.initials: Y
authors.lastname: Choi
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Kim
authors.forename: Chang-Sam
authors.initials: CS
authors.lastname: Kim
authors.forename: Myung-Yung
authors.initials: MY
authors.lastname: Jeong
authors.forename: Guang Jin
authors.initials: GJ
authors.lastname: Choi
mesh_terms: D000082:Acetaminophen / Q000737:chemistry* / Q000592:standards; D003080:Cold Temperature; D003460:Crystallization / Q000379:methods* / Q000592:standards; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared / Q000379:methods* / Q000592:standards; D014961:X-Ray Diffraction / Q000379:methods / Q000592:standards
chemical_list: D000082:Acetaminophen