title: Mebendazole crystal forms in tablet formulations. An ATR-FTIR/chemometrics approach to polymorph assignment.
abstract: Structural polymorphism of active pharmaceutical ingredients (API) is a relevant concern for the modern pharmaceutical industry, since different polymorphic forms may display dissimilar properties, critically affecting the performance of the corresponding drug products. Mebendazole (MEB) is a widely used broad spectrum anthelmintic drug of the benzimidazole class, which exhibits structural polymorphism (Forms A-C). Form C, which displays the best pharmaceutical profile, is the recommended one for clinical use. The polymorphs of MEB were prepared and characterized by spectroscopic, calorimetric and microscopic means. The polymorphs were employed to develop a suitable chemometrics-assisted sample display model based on the first two principal components of their ATR-FTIR spectra in the 4000-600 cm(-1) region. The model was internally and externally validated employing the leave-one-out procedure and an external validation set, respectively. Its suitability for revealing the polymorphic identity of MEB in tablets was successfully assessed analyzing commercial tablets under different physical forms (whole, powdered, dried, sieved and aged). It was concluded that the ATR-FTIR/PCA (principal component analysis) association is a fast, efficient and non-destructive technique for assigning the solid-state forms of MEB in its drug products, with minimum sample pre-treatment.
authors.affiliation: Pharmaceutical Analysis, 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.forename: Natalia L
authors.initials: NL
authors.lastname: Calvo
authors.affiliation: Pharmaceutical Analysis, 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.forename: Teodoro S
authors.initials: TS
authors.lastname: Kaufman
authors.affiliation: Pharmaceutical Analysis, 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.forename: Rubén M
authors.initials: RM
authors.lastname: Maggio
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D008463:Mebendazole / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D025341:Principal Component Analysis / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013607:Tablets / Q000737:chemistry*
chemical_list: D011208:Powders; D013607:Tablets; D008463:Mebendazole
keywords: ATR-FTIR/chemometrics; Crystal polymorphism; Form assignment; Mebendazole; Principal component analysis