title: Rapid quantification of low level polymorph content in a solid dose form using transmission Raman spectroscopy.
abstract: This proof of concept study demonstrates the application of transmission Raman spectroscopy (TRS) to the non-invasive and non-destructive quantification of low levels (0.62-1.32% w/w) of an active pharmaceutical ingredient's polymorphic forms in a pharmaceutical formulation. Partial least squares calibration models were validated with independent validation samples resulting in prediction RMSEP values of 0.03-0.05% w/w and a limit of detection of 0.1-0.2% w/w. The study further demonstrates the ability of TRS to quantify all tablet constituents in one single measurement. By analysis of degraded stability samples, sole transformation between polymorphic forms was observed while excipient levels remained constant. Additionally, a beam enhancer device was used to enhance laser coupling to the sample, which allowed comparable prediction performance at 60 times faster rates (0.2s) than in standard mode.
authors.affiliation: Cobalt Light Systems Ltd., Milton Park, Abingdon, OX14 4SD, UK. Electronic address: julia.griffen@cobaltlight.com.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Griffen
authors.affiliation: Cobalt Light Systems Ltd., Milton Park, Abingdon, OX14 4SD, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Owen
authors.affiliation: Department of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Burley
authors.affiliation: Department of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Taresco
authors.affiliation: Cobalt Light Systems Ltd., Milton Park, Abingdon, OX14 4SD, UK; Central Laser Facility, STFC Rutherford Appleton Laboratory, Harwell Campus, OX11 0QX, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Matousek
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004304:Dosage Forms; D016018:Least-Squares Analysis; D057230:Limit of Detection; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods
chemical_list: D004304:Dosage Forms; D004364:Pharmaceutical Preparations
keywords: Chemometrics; DoE; High throughput screening; Polymoprh; Stability analysis; Transmission raman