Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Physical Chemistry

Background:

• Indapamide (IND) is a widely used diuretic for hypertension.
• Understanding the physicochemical properties of amorphous IND is vital for drug formulation and stability.
• Previous research has not extensively explored the solid-state properties of amorphous IND.

Purpose of the Study:

• To investigate the physicochemical properties of amorphous indapamide (IND) for the first time.
• To assess the purity, molecular mobility, and stability of amorphous IND.
• To evaluate the impact of different preparation methods (vitrification, cryomilling, ball-milling) on IND's properties.

Main Methods:

• X-ray powder diffraction (XRD)
• Mass spectrometry
• Nuclear magnetic resonance (NMR)
• Infrared spectroscopy (FT-IR)
• Differential scanning calorimetry (DSC)
• Broadband dielectric spectroscopy (BDS)
• Density functional theory (DFT) calculations
• Apparent solubility studies

Main Results:

• Confirmed the purity of amorphous IND samples prepared by various methods.
• Characterized molecular mobility in liquid and glassy states, determining glass transition temperature (Tg) and dynamic fragility.
• Demonstrated good chemical and long-term physical stability of amorphous IND under various conditions.
• Apparent solubility was assessed in aqueous buffers and HCl.

Conclusions:

• Amorphous indapamide (IND) possesses favorable physicochemical properties, including good stability.
• The findings support the potential of amorphous IND formulations for improved therapeutic efficacy.
• This comprehensive characterization provides a foundation for future pharmaceutical development of IND.