title: In-line monitoring and interpretation of an indomethacin anti-solvent crystallization process by near-infrared spectroscopy (NIRS).
abstract: PAT (process analytical technology) has been emphasized as one of key elements for the full implementation of QbD (quality-by-design) in the pharmaceutical area. NIRS (near-infrared spectroscopy) has been studied intensively as an in-line/on-line monitoring tool in chemical and biomedical industries. A precise and reliable monitoring of the particle characteristics during crystallization along with a suitable control strategy should be highly encouraged for the conformance to new quality system of pharmaceutical products. In this study, the anti-solvent crystallization process of indomethacin (IMC) was monitored using an in-line NIRS. IMC powders were produced via anti-solvent crystallization using two schemes; 'S-to-A' (solvent-to-antisolvent) and 'A-to-S' (antisolvent-to-solvent). In-line NIR spectra were analyzed by a PCA (principal component analysis) method. Although pure α-form IMC powder was resulted under A-to-S scheme, a mixture of the α-form and γ-form was produced for S-to-A case. By integrating the PCA results with off-line characterization (SEM, XRD, DSC) data, the crystallization process under each scheme was elucidated by three distinct consecutive steps. It was demonstrated that in-line NIRS, combined with PCA, can be very useful to monitor in real time and interpret the anti-solvent crystallization process with respect to the polymorphism and particle size.
authors: Department of Pharmaceutical Engg., Inje University, Gimhae, Gyeungnam 621-749, Republic of Korea.
authors: Hea-Eun
authors: HE
authors: Lee
authors: Min-Jeong
authors: MJ
authors: Lee
authors: Woo-Sik
authors: WS
authors: Kim
authors: Myung-Yung
authors: MY
authors: Jeong
authors: Young-Sang
authors: YS
authors: Cho
authors: Guang Jin
authors: GJ
authors: Choi
mesh_terms: D000096:Acetone / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011208:Powders; D025341:Principal Component Analysis; D012997:Solvents / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000893:Anti-Inflammatory Agents; D011208:Powders; D012997:Solvents; D014867:Water; D000096:Acetone; D007213:Indomethacin