The Complex Solid-State Landscape of Sodium Diatrizoate Hydrates

Area of Science:

• Solid-state chemistry
• Pharmaceutical science
• Crystallography

Background:

• Pharmaceutical sodium salts often exhibit hygroscopicity, absorbing atmospheric moisture.
• This water incorporation can alter the physical and chemical properties of the solid drug form.

Purpose of the Study:

• To investigate the solid-state interaction of diatrizoic acid monosodium salt (a model pharmaceutical sodium salt) with water.
• To characterize the hydrates and solvates formed by this compound.

Main Methods:

• Crystallographic analysis of hydrates and solvates.
• Thermogravimetric analysis to assess water content and release.
• Investigation of interconversion and amorphization behavior.

Main Results:

• Five distinct hydrates were identified, with water content from 0.3 to 8 molar equivalents.
• The hydrates demonstrated significant interconversion, stoichiometric and non-stoichiometric behavior, and potential for amorphization upon dehydration.
• A DMSO/water mixed solvate confirmed the salt's strong affinity for water.
• Incorporated water molecules coordinate to the sodium cation, stabilized by hydrogen bonding.

Conclusions:

• Diatrizoic acid monosodium salt exhibits complex hydration behavior, including interconversion and amorphization.
• Understanding these hydration properties is critical for pharmaceutical applications.
• In-depth investigation of sodium salts is essential for ensuring dose uniformity and formulation stability.