Enantiotropically related albendazole polymorphs

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Albendazole (ABZ) is a widely used anthelmintic drug.
• Understanding the solid-state properties of ABZ is crucial for its formulation and efficacy.
• Polymorphism can significantly impact drug solubility, stability, and bioavailability.

Purpose of the Study:

• To characterize the solid-state properties of albendazole (ABZ) polymorphs.
• To compare re-crystallized ABZ forms with the commercially available form.
• To investigate the thermodynamic parameters and stability of different ABZ crystalline phases.

Main Methods:

• Re-crystallization of ABZ from various solvents (methanol, N,N-dimethylformamide).
• Characterization using thermal analysis (DSC/TGA), X-ray diffractometry (powder and single crystal).
• Solubility studies in methanol and 0.1 N HCl at different temperatures to calculate thermodynamic parameters.

Main Results:

• A new stable polymorph (Form II) was obtained via re-crystallization, enantiotropically related to the commercial metastable form (Form I).
• Form I is metastable at ambient temperature, while Form II is the stable form.
• Both polymorphs demonstrated high physical stability, attributed to a high energy barrier for interconversion.

Conclusions:

• Re-crystallization is an effective method for obtaining different albendazole polymorphs.
• The study identified a new stable polymorph of ABZ, with implications for drug formulation.
• Polymorphism in ABZ involves potential molecular structural differences including tautomerism, conformational variations, molecular disorder, and hydrogen bonding arrangements.