title: A PCA-based chemometrics-assisted ATR-FTIR approach for the classification of polymorphs of cimetidine: application to physical mixtures and tablets.
abstract: The identity of the polymorphic form of an active pharmaceutical ingredient is an important parameter that may affect the performance of the drug formulation. This calls for special techniques, able to classify crystal forms or assign the polymorphic identity to a given solid in a mixture. In order to develop a method to determine which of the relevant polymorphs of Cimetidine (CIM) is present in commercial tablet samples, authentic forms A, B, D and M1 of the drug were prepared, structurally characterized and employed as standards. Thus, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was coupled to Principal Component Analysis (PCA) and used for the classification of physical mixtures of CIM and excipients, as well as laboratory-made and commercial tablets, according to their polymorphic composition. It was demonstrated that two principal components (PCs) suffice to classify the samples of the four forms of CIM into distinct groups, and that method performance is optimum when the second and third PCs are used for the classification process. The application of the method to commercial tablets of CIM also gave good results, confirming they were prepared employing the correct polymorph (form A).
authors: Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
authors: Natalia L
authors: NL
authors: Calvo
authors: Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina. Electronic address: kaufman@iquir-conicet.gov.ar.
authors: Teodoro S
authors: TS
authors: Kaufman
authors: Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina. Electronic address: maggio@iquir-conicet.gov.ar.
authors: Rubén M
authors: RM
authors: Maggio
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002927:Cimetidine / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D025341:Principal Component Analysis / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013607:Tablets / Q000737:chemistry*
chemical_list: D005079:Excipients; D013607:Tablets; D002927:Cimetidine
keywords: ATR-FTIR; Cimetidine; Classification; Crystal polymorphism; Principal Component Analysis