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

Abstract

Solid dispersions of glimepiride, belonging to the sulfonylurea group of antidiabetic drugs, and poly(ester amide) hyperbranched polymers of different chemical compositions were prepared in order to improve glimepiride's poor water solubility. X-ray powder diffraction results show that glimepiride is in noncrystalline form, indicating that drug molecules are molecularly dispersed within the amorphous hyperbranched polymers. Nuclear magnetic resonance spectroscopy and Fourier transform-infrared spectroscopy results reveal the complex formation between the glimepiride drug and the particular hyperbranched polymer, which was confirmed also by quantum chemical calculations. The complex is stabilized by a hydrogen-bond interaction between the NH group of the sulfonylurea segment of glimepiride and the carbonyls of the amide and ester bonds of the hyperbranched polymers. The slightly acidic proton of the NH group of the sulfonylurea segment of glimepiride is also involved in an interaction with the tertiary amino functional groups of the hyperbranched polymer. As a consequence, the loading capacity is higher for the hyperbranched polymer with the tertiary amino groups. Owing to a complex formation between glimepiride and a particular hyperbranched polymer, glimepiride's water solubility and its dissolution rate are considerably improved relative to the pure glimepiride drug.