Preparation and characterization of rivaroxaban nanocrystals prepared by combination of wet ball milling and high pressure homogenization methods

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

Latin American Journal of Pharmacy, vol.37, no.12, pp.2482-2490, 2018 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 12
  • Publication Date: 2018
  • Journal Name: Latin American Journal of Pharmacy
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2482-2490
  • Keywords: Ball milling, High pressure homogenization, Nanocrystal/nanosuspension, Permeability, Rivaroxaban
  • Ondokuz Mayıs University Affiliated: No

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 × 10 –5 cm/s) in comparison to the RXB bulk (7.25 × 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.