Long-Term Stabilized and Highly Soluble Bezafibrate-Gliclazide Co-Amorphous Binary System

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Medicinal Chemistry

Background:

• Metabolic syndrome (MS) affects a quarter of the global population, characterized by dyslipidemia, hypertension, and insulin resistance.
• Poor solubility of existing drugs limits their efficacy in treating MS, necessitating novel formulation strategies.
• Amorphous drug formulations can significantly enhance solubility and bioavailability.

Purpose of the Study:

• To develop a novel co-amorphous (CoA) formulation combining Bezafibrate (BZT), a lipid-regulator, and Gliclazide (GZD), a hypoglycemic agent.
• To investigate the solubility enhancement and long-term stability of the BZT-GZD co-amorphous system for potential simultaneous treatment of MS conditions.
• To characterize the intermolecular interactions and thermal properties of the binary co-amorphous system.

Main Methods:

• Construction of a phase diagram to analyze thermal properties and glass transition temperatures.
• Fourier-transform infrared spectroscopy (FTIR) to identify intermolecular interactions (e.g., hydrogen bonds).
• X-ray diffraction (XRD) and differential scanning calorimetry (DSC) to assess structural stability and amorphous state retention.
• Solubility studies to quantify the enhancement of BZT and GZD solubility.

Main Results:

• FTIR analysis confirmed intermolecular interactions, indicated by redshifts in IR bands.
• Co-amorphous formulations significantly increased the solubility of both BZT (up to 4x) and GZD (up to 1.5x).
• XRD and DSC confirmed the amorphous state was retained for over eight years, indicating excellent long-term stability.

Conclusions:

• The developed BZT-GZD co-amorphous system demonstrates enhanced solubility and remarkable long-term physical stability.
• This co-amorphous formulation presents a promising strategy for the simultaneous treatment of lipid dysregulation and hyperglycemia in metabolic syndrome.
• The findings highlight the potential of co-amorphous drug combinations to overcome solubility challenges in treating complex diseases like metabolic syndrome.