Mebendazole Crystal Forms in Tablet Formulations. An ATR-FTIR/Chemometrics Approach to Polymorph Assignment

CALVO, NATALIA L; KAUFMAN, T. S.; MAGGIO, R. M.

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 122 p. 157 - 165

0731-7085

tStructural polymorphism of activepharmaceutical ingredients (API) is a relevant concern for themodernpharmaceutical industry, since different polymorphic forms may displaydissimilar properties, criticallyaffecting the performance of the correspondingdrug products. Mebendazole (MEB) is a widely used broadspectrum anthelminticdrug of the benzimidazole class, which exhibits structural polymorphism(FormsA?C). Form C, which displays the best pharmaceutical profile, is therecommended one for clinical use.The polymorphs of MEB were prepared andcharacterized by spectroscopic, calorimetric and microscopicmeans. Thepolymorphs were employed to develop a suitable chemometrics-assisted sampledisplaymodel based on the first two principal components of their ATR-FTIRspectra in the 4000?600 cm−1region. The model was internallyand externally validated employing the leave-one-out procedure andan externalvalidation set, respectively. Its suitability for revealing the polymorphicidentity of MEB intablets was successfully assessed analyzing commercialtablets under different physical forms (whole,powdered, dried, sieved andaged). It was concluded that the ATR-FTIR/PCA (principal component anal-ysis)association is a fast, efficient and non-destructive technique for assigningthe solid-state forms ofMEB in its drug products, with minimum samplepre-treatment.