Preparation and Characterization of Rivaroxaban Nanocrystals Prepared by Combination of Wet Ball Milling and High Pressure Homogenization Methods


Demir H., GÜLSÜN İNAL T. , ŞENER E., ŞAHİN S. , ÖNER L.

LATIN AMERICAN JOURNAL OF PHARMACY, vol.37, no.12, pp.2482-2490, 2018 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 12
  • Publication Date: 2018
  • Title of Journal : LATIN AMERICAN JOURNAL OF PHARMACY
  • Page Numbers: pp.2482-2490

Abstract

The objectives of this study were to develop rivaroxaban (RXB) nanocrystals by combination of wet ball milling and high-pressure homogenization, and to increase the solubility and dissolution rate of RXB. A new nanocrystal formulation was developed, and used to reduce particle size of RXB which is a Biopharmaceutics Classification System Class 2 drug. Particle size of RXB in nanosuspension formulation (551 nm) and nanocrystal formulation (1018 nm) was reduced significantly (p < 0.05) as compared to the particle size of RXB bulk. Dissolution rate of RXB nanocrystals (85% within 15 min) was much faster than that of RXB bulk (12% within 45 min). Also, permeability across Caco-2 cells was enhanced for RXB nanocrystals (10.18 x 10(-5) cm/s) in comparison to the RXB bulk (7.25 x 10(-5) cm/s; p < 0.05). Based on the results, it can be concluded that nanocrystal technology can be employed to improve the solubility and dissolution rate of RXB (hence permeability) with preserving its chemical structure.