Laser Raman spectroscopic analysis of polymorphic forms in microliter fluid volumes

✍ Scribed by Patrick A. Anquetil; Colin J. H. Brenan; Claudia Marcolli; Ian W. Hunter

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 305 KB
• Volume: 92
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10267

✦ Synopsis

Knowledge and control of the polymorphic phase of chemical compounds are important aspects of drug development in the pharmaceutical industry. We report herein in situ and real-time Raman spectroscopic polymorphic analysis of optically trapped microcrystals in a microliter volume format. The system studied in particular was the recrystallization of carbamazepine (CBZ) in methanol. Raman spectrometry enabled noninvasive measurement of the amount of dissolved CBZ in a sample as well as polymorphic characterization, whereas exclusive recrystallization of either CBZ form I or CBZ form III from saturated solutions was achieved by specific selection of sample cell cooling profiles. Additionally, using a microcell versus a macroscopic volume gives the advantage of reaching equilibrium much faster while using little compound quantity. We demonstrate that laser Raman spectral polymorphic analysis in a microliter cell is a potentially viable screening platform for polymorphic analysis and could lead to a new high throughput method for polymorph screening.