Determination of the interaction between glimepiride and hyperbranched polymers in solid dispersions

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Polymer Chemistry

Background:

• Glimepiride, a sulfonylurea antidiabetic drug, suffers from poor water solubility, limiting its therapeutic efficacy.
• Hyperbranched polymers offer unique structural properties for drug delivery applications.
• Developing effective drug delivery systems is crucial for improving oral bioavailability of poorly soluble drugs.

Purpose of the Study:

• To prepare solid dispersions of glimepiride with poly(ester amide) hyperbranched polymers.
• To investigate the potential of these dispersions to enhance glimepiride's water solubility and dissolution rate.
• To elucidate the interaction mechanisms between glimepiride and the hyperbranched polymers.

Main Methods:

• Preparation of glimepiride-hyperbranched polymer solid dispersions.
• Characterization using X-ray powder diffraction (XRPD) for crystallinity.
• Analysis of drug-polymer interactions via Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform-Infrared (FTIR) spectroscopy, and quantum chemical calculations.

Main Results:

• XRPD confirmed the noncrystalline, molecular dispersion of glimepiride within the amorphous hyperbranched polymers.
• Spectroscopic and computational analyses revealed complex formation stabilized by hydrogen bonding between glimepiride and the polymer.
• Hyperbranched polymers with tertiary amino groups showed higher drug loading capacity and significantly improved glimepiride's water solubility and dissolution rate.

Conclusions:

• Solid dispersions of glimepiride in poly(ester amide) hyperbranched polymers effectively improve its solubility and dissolution.
• Complex formation, particularly hydrogen bonding and interactions with tertiary amino groups, is key to enhanced drug performance.
• This approach offers a promising strategy for developing advanced formulations for poorly water-soluble drugs like glimepiride.