title: Determination of the polymorphic forms of bicifadine hydrochloride by differential scanning calorimetry-thermogravimetric analysis, X-ray powder diffraction, attenuated total reflectance-infrared spectroscopy, and attenuated total reflectance-near-infrared spectroscopy.
abstract: The pharmaceutical compound bicifadine hydrochloride, which has been found to crystallize in two polymorphic forms, has been characterized by thermal analysis, X-ray powder diffraction (XRPD), infrared (IR) spectroscopy, and near-infrared (NIR) spectroscopy. A series of 22 sample mixtures of polymorph 1 and polymorph 2 were prepared and calibration models for the quantitation of these binary mixtures have been developed for each of the XRPD, attenuated total reflectance (ATR)-IR, and ATR-NIR analytical techniques. The quantitative results were obtained using a partial least squares (PLS) algorithm, which predicted the concentration of polymorph 1 from the XRPD spectra with a root mean standard error of prediction (RMSEP) of 4.4%, from the IR spectra with a RMSEP of 3.8%, and from the NIR spectra with a RMSEP of 1.4%. The studies indicate that when analyses are carried out on equivalent sets of spectra, NIR spectroscopy offers significant advantages in quantitative accuracy as a tool for the determination of polymorphs in the solid state and is also more convenient to use than both the ATR-IR and XRPD methods. Density functional theory (DFT) B3LYP calculations and IR spectral simulation have been used to determine the nature of the vibrational modes that are the most sensitive in the analysis.
authors.affiliation: Chemistry Department, National University of Ireland, Galway, Ireland. p.mcardle@nuigalway.ie
authors.forename: Patrick
authors.initials: P
authors.lastname: McArdle
authors.forename: Karen
authors.initials: K
authors.lastname: Gilligan
authors.forename: Desmond
authors.initials: D
authors.lastname: Cunningham
authors.forename: Alan
authors.initials: A
authors.lastname: Ryder
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods*; D003461:Crystallography / Q000379:methods; D007536:Isomerism; D008968:Molecular Conformation; D033362:Powder Diffraction; D013055:Spectrophotometry, Infrared / Q000379:methods*; D013818:Thermogravimetry / Q000379:methods*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C034438:bicifadine