Mebendazole crystal forms in tablet formulations. An ATR-FTIR/chemometrics approach to polymorph assignment

Abstract

a b s t r a c tStructural 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.

Theoretical study of the geometric and electronic characterization of carbendazim-based drug (Nocodazole)

“…Discrepancies in its anthelmintic potency was reported due to the existence of different polymorphs [18]. Mebendazole can exist in three polymorphic forms -form A, B, and C (Figure 1) [19]. Form A was found to be therapeutically ineffective, while form C was reported as the most effective.…”

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

“…PCA was implemented in order to examine the deformation of pharmaceutical powders during powder compaction (105) and to select the most important variables for developing a solid self-emulsifying drug delivery system for docetaxel (106). A combination of PCA and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) was used to identify the polymorphic forms of mebendazole in tablets (107).…”

Chemometric study of the excipients’ influence on polymorphic-behavior. Mefenamic acid as case of study

“…mebendazole and cimetidine tablets to polymorph assignment. There, PCA allow data compression and visualization, and further statistical analysis using Mahalanobis distance [17,18]. Additionally, NIR spectroscopy was the only vibrational spectroscopy able to successfully predict polymorphic content in commercial tablets of Mefenamic acid, using the obtained polymorphic content to predict the solubility performance [19].…”