In-line monitoring and interpretation of an indomethacin anti-solvent crystallization process by near-infrared spectroscopy (NIRS).
Int J Pharm
; 420(2): 274-81, 2011 Nov 28.
Article
em En
| MEDLINE
| ID: mdl-21907779
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Indometacina
/
Espectroscopia de Luz Próxima ao Infravermelho
/
Anti-Inflamatórios
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2011
Tipo de documento:
Article