title: Laser Raman spectroscopic analysis of polymorphic forms in microliter fluid volumes.
abstract: 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.
authors.affiliation: BioInstrumentation Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. pantanq@mit.edu
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Anquetil
authors.forename: Colin J H
authors.initials: CJ
authors.lastname: Brenan
authors.forename: Claudia
authors.initials: C
authors.lastname: Marcolli
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hunter
mesh_terms: D003460:Crystallization; D007834:Lasers; D019999:Pharmaceutical Solutions / Q000032:analysis* / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000295:instrumentation / Q000379:methods; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D019999:Pharmaceutical Solutions