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

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Analytical Chemistry

Background:

• Structural polymorphism in active pharmaceutical ingredients (APIs) is critical as different forms affect drug product performance.
• Mebendazole (MEB), a benzimidazole anthelmintic, exists in multiple polymorphic forms (A-C), with Form C being clinically preferred.

Purpose of the Study:

• To develop and validate a chemometrics-assisted model for identifying Mebendazole polymorphic forms.
• To assess the model's efficacy in analyzing commercial Mebendazole drug products.

Main Methods:

• Preparation and characterization of Mebendazole polymorphs using spectroscopic, calorimetric, and microscopic techniques.
• Development of a chemometrics model using principal component analysis (PCA) on ATR-FTIR spectra (4000-600 cm⁻¹).
• Validation of the model using leave-one-out cross-validation and an external validation set.

Main Results:

• The ATR-FTIR/PCA model successfully differentiated Mebendazole polymorphs.
• The model accurately identified polymorphic forms in various commercial tablet preparations (whole, powdered, dried, sieved, aged).
• The technique proved to be fast, efficient, and non-destructive with minimal sample pre-treatment.

Conclusions:

• The ATR-FTIR/PCA approach is a reliable method for determining the solid-state forms of Mebendazole in pharmaceutical products.
• This technique offers a practical solution for quality control and polymorphic identity assessment in drug manufacturing.
• The study highlights the importance of controlling API polymorphism for consistent drug efficacy and safety.