In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier

Abstract

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.

Keywords::

• Repaglinide
• solid dispersion
• polyvinylpyrrolidone
• dissolution
• absorption
• pharmacokinetics

Acknowledgments

We are grateful to Shanghai Colorcon Coating Tech. Ltd. and International Specialty Products Co. for providing hydroxypropyl methylcellulose and polyvinylpyrrolidone, respectively.

Declaration of interest

This study was supported by a grant (NECT-08-0846) from Ministry of Education of the People’s Republic of China, a grant (2009ZX09310-004) from Ministry of Science and Technology of the People’s Republic of China and a grant (2009CB90300) from the National Basic Research Program of China.