Isoniazid-Saccharin Salts: Synthesis, Structural Aspects, Thermal Properties and Spectroscopic Characterization.

Area of Science:

• Solid-state chemistry
• Crystallography
• Spectroscopy

Background:

• Isoniazid (INH) and saccharin (SAC) are important pharmaceutical compounds.
• Investigating salt forms can improve drug properties and stability.
• Understanding solid-state behavior is crucial for pharmaceutical development.

Purpose of the Study:

• To synthesize and characterize novel isoniazid-saccharin (INH-SAC) salt forms.
• To elucidate the structural and thermal properties of INH-SAC hydrates and anhydrous forms.
• To investigate the solid-state reaction occurring upon heating the INH-SAC salt.

Main Methods:

• Synthesis of monohydrated and anhydrous INH-SAC salts using solvent-assisted methods.
• Spectroscopic characterization using Raman and infrared spectroscopy.
• Thermal analysis by differential scanning calorimetry (DSC).
• X-ray diffraction for crystal structure determination.
• Hirshfeld surface analysis for intermolecular interactions.
• Density functional theory (DFT) calculations.

Main Results:

• Successfully synthesized and characterized one monohydrated (MH) and one anhydrous (A) INH-SAC salt.
• DSC revealed the hydrate converts to the anhydrous form upon heating; the anhydrous form melts at 131.7 °C.
• Melting of the anhydrous form triggers a reaction, forming a new covalent hydrazide-amide derivative (melts at 204.4 °C) via nucleophilic acyl substitution.
• Crystal structures and intermolecular interactions were analyzed for both forms.
• DFT calculations complemented experimental findings.

Conclusions:

• Two distinct solid forms of isoniazid-saccharin salts were successfully prepared and characterized.
• Thermal treatment of the hydrate leads to the anhydrous form, which undergoes a unique decomposition reaction upon melting.
• The study provides comprehensive structural and thermal insights into INH-SAC salts, relevant for pharmaceutical formulation.