X-ray structural studies and physicochemical properties of cimetidine polymorphism

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Cimetidine is a histamine H2-receptor antagonist.
• Understanding crystalline forms is crucial for drug efficacy and formulation.

Purpose of the Study:

• To characterize four crystalline forms of cimetidine (three anhydrous, one monohydrate).
• To correlate crystalline structure with dissolution rates and biological activity.

Main Methods:

• Infrared spectroscopy
• X-ray powder diffraction
• X-ray diffraction
• Thermal analyses
• Dissolution rate studies

Main Results:

• Form A is the most thermodynamically stable anhydrous form.
• Form C (monohydrate) exhibited significantly higher dissolution rates than anhydrous forms.
• Form C's folded conformation and Form D's spirally curled conformation were elucidated.
• Biological activity correlated with crystalline form, with Form C showing optimal efficacy.

Conclusions:

• Crystalline form significantly impacts cimetidine's dissolution and biological activity.
• The folded conformation of Form C is optimal for histamine H2-receptor binding and clinical efficacy.
• These findings are vital for developing effective cimetidine formulations.