Lee, Hea-Eun Lee, Min-Jeong Kim, Woo-Sik Jeong, Myung-Yung Cho, Young-Sang Choi, Guang Jin 2024-01-20T16:01:35Z 2024-01-20T16:01:35Z 2021-09-05 2011-11-28 0378-5173 https://pubs.kist.re.kr/handle/201004/129795 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 alpha-form IMC powder was resulted under A-to-S scheme, a mixture of the alpha-form and gamma-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. (c) 2011 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV BENZOIC-ACID CRYSTALS TRANSFORMATION PRECIPITATION POLYMORPHISM MORPHOLOGY KINETICS FORMS SIZE In-line monitoring and interpretation of an indomethacin anti-solvent crystallization process by near-infrared spectroscopy (NIRS) Article 10.1016/j.ijpharm.2011.08.044 1 INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.420, no.2, pp.274 - 281 INTERNATIONAL JOURNAL OF PHARMACEUTICS 420 2 274 281 scie scopus 000303423800011 2-s2.0-80054678656 Pharmacology & Pharmacy Pharmacology & Pharmacy Article BENZOIC-ACID CRYSTALS TRANSFORMATION PRECIPITATION POLYMORPHISM MORPHOLOGY KINETICS FORMS SIZE Indomethacin (IMC) Polymorphism Anti-solvent crystallization Near-infrared spectroscopy (NIRS) Principal component analysis (PCA)