A Potential Breakthrough in the Enhancement of Glimepiride Solubility and Dissolution Rate by Binary and Ternary Solid Dispersion Technique and In Vitro Comparison with Marketed Formulation

Abstract

Purpose

Glimepiride, an anti-diabetic and third-generation sulfonylurea drug belonging to class II BCS (Biopharmaceutical Classification System) type, is characterized by its low solubility and high permeability. In order to increase glimepiride’s aqueous solubility and hence increase its dissolution rate, the goal of this study was to formulate the drug as binary and ternary solid dispersion employing water-soluble carriers.

Methods

Three binary solid dispersions of glimepiride were prepared by solvent evaporation technique using β-cyclodextrin with different drug carrier ratios. After optimizing the binary solid dispersion concerning solubility improvement, four different ratios of ternary solid dispersion employing polyvinylpyrrolidone K30 (PVPK30) were fabricated with the optimized solid dispersion to determine solubility and compared with marketed formulation to determine the consequence of the study. Further FTIR, XRD, and DSC studies were performed for a better understanding of the characterization of optimized solid dispersion and to know if there are any significant interactions with water-soluble carriers or with excipients.

Results

The combination of the glimepiride and β-cyclodextrin significantly increases the solubility and in the case of ternary solid dispersion, the solubility is increased even more. The enhancement of the solubility is influenced by the carrier’s concentration.

Conclusions

A total of four tablet formulation batches that were prepared and the explicit in vitro comparisons been carried out with commercially available immediate-release formulation, suggested that formulating glimepiride in ternary solid dispersion has enhanced the solubility and dissolution rate drastically.

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excipients formulation