Polymorphism in sulfadimidine/4-aminosalicylic acid cocrystals: solid-state characterization and physicochemical...

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Crystallography

Background:

• Drug polymorphism significantly impacts pharmaceutical properties.
• Polymorphic cocrystals are less explored than individual drug polymorphisms.
• Sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) are key pharmaceutical compounds.

Purpose of the Study:

• To synthesize and characterize a novel polymorphic cocrystal of SD and 4-ASA.
• To investigate the solid-state properties and stability of the new cocrystal form.
• To evaluate the impact of cocrystal formation on drug dissolution rates.

Main Methods:

• Liquid-assisted milling and spray drying for cocrystal synthesis.
• High-resolution X-ray powder diffraction for structure determination.
• Solubility studies across varying pH and dissolution rate assessments.

Main Results:

• A new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was successfully synthesized.
• Form II cocrystal exhibited pH-dependent solubility, predictable by a two amphoteric component model.
• Form I cocrystal demonstrated greater thermodynamic stability than form II.
• Both cocrystal forms enhanced the dissolution rate of SD compared to pure SD and physical mixtures.

Conclusions:

• The discovery of SD:4-ASA polymorphic cocrystals expands the landscape of cocrystal research.
• Cocrystal engineering can be utilized to improve the dissolution profiles of poorly soluble drugs.
• Understanding cocrystal polymorphism is crucial for developing effective drug formulations.