Preparation and solid state characterisation of chlorothiazide sodium intermolecular self-assembly suprastructure

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Crystallography

Background:

• Chlorothiazide (CTZ) is a thiazide diuretic that can form salts, unlike other diuretics in its class.
• An injectable formulation of chlorothiazide sodium exists, but its physicochemical and solid-state properties are unreported.

Purpose of the Study:

• To elucidate the crystal structure of chlorothiazide sodium.
• To characterize its solid-state properties and compare them to chlorothiazide.
• To assess the potential biopharmaceutical advantages of the sodium salt.

Main Methods:

• Single crystal X-ray diffraction
• Nuclear magnetic resonance (NMR) spectroscopy
• Thermal analysis
• Powder X-ray diffraction (PXRD)
• Infrared (IR) spectroscopy
• Dynamic moisture sorption (DMS)
• Solubility analysis

Main Results:

• The crystal structure of chlorothiazide sodium was determined as triclinic (space group P-1).
• It forms a polymeric suprastructure with sodium cations and water bridges: (CTZ)(3)·(H(2)O)·Na(H(2)O)(2)Na·(H(2)O)·(CTZ)(3).
• A stable monosodium dihydrate form (10-90% RH) and an anhydrous form (0-20% RH) were identified.
• Chlorothiazide sodium dihydrate showed approximately 400-fold higher aqueous solubility than chlorothiazide at 37°C.

Conclusions:

• The crystal structure and solid-state characteristics of chlorothiazide sodium have been fully elucidated.
• The salt exists in stable dihydrate and anhydrous forms.
• The significantly enhanced aqueous solubility of chlorothiazide sodium offers potential biopharmaceutical benefits for drug formulation and delivery.