Formulation, characterization and in- vitro evaluation of cyclodextrin complexed orodispersible tablets of glimepiride

Abstract

The objective of this research was to improve solubility, and dissolution rate, of poorly water soluble Glimepiride by comlexation with HP-β-Cyclodextrin and impart a fast release in a single formulation. Glimepiride, an oral hypoglycemic agent used in the treatment of non-insulin dependent diabetes mellitus which belongs to Class II of BCS was complexed with HP-β-CD. The complexes of glimepiride with HP-β-CD were prepared by Physical mixing, Co-grinding and kneading methods and were characterized and evaluated to study the effect of complexation on dissolution and solubility profiles. Fourier transform infrared spectroscopy, X-ray diffraction, Differential scanning calorimetry, and Scanning electron microscopy indicated stronger drug amorphization and entrapment in HP-β- CD. Phase solubility studies were performed according to method reported by Higuchi and Connors which was classified as AL type characterized by apparent 1:1 stability constant that had a value of 429.90 in pH 6.8 phosphate buffer. Remarkable improvement was observed in the In-vitro drug release profiles in 0.1N HCl and phosphate buffer pH 6.8 with all complexes. The characterization studies confirmed the inclusion of glimepiride within the nonpolar cavity of HP-β-CD. The glimepiride:HP-β-CD (1:3M) complex prepared by kneading method exhibited higher dissolution rate and dissolution efficiency values in pH 6.8 phosphate buffer than pure drug and physical mixture. The orodispersible tablets were formulated using the kneaded complex with suitable excipients showed 100% release within 5 minutes. Stability studies were carried out as per ICH guidelines indicated that there was no significant change found in physical appearance, disintegration time, and wetting time of the tablets.