In vitro/in vivo characterization of nanocrystalline formulation of tranilast with improved dissolution and hepatoprotective properties

The present study was undertaken to develop a nanocrystalline formulation of tranilast (NC/TL), an acidic anti-inflammatory agent, with the aim of improving its biopharmaceutical and hepatoprotective properties. NC/TL was prepared by wet-mill technology, and its physicochemical properties were characterized in terms of morphology, crystallinity, particle size distribution, stability and dissolution. Even after the storage of NC/TL for 8 weeks under accelerated conditions, there were no significant transitions in the crystalline form, crystallinity and particle size distribution of wet-milled TL. The nanosized TL particles could be immediately dispersed when the NC/TL was introduced into aqueous medium, and the NC/TL exhibited significant improvement in the dissolution behavior even under acidic conditions, compared with crystalline TL and a physical mixture of TL and polymer (PM/TL). The hepatoprotective effects of orally dosed TL formulations were evaluated in a carbon tetrachloride (CCl4)-treated rat model of acute liver injury. In a rat model of acute liver injury, repeated treatment with NC/TL (2 mg TL/kg) every 12 h led to marked attenuation of hepatic damage as evidenced by decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and total reactive oxygen species levels. However, PM/TL was found to be less effective, and the difference in efficacy between NC/TL and PM/TL should be attributable to the highly enhanced dissolution behavior of NC/TL. Strategic application of NC formulation technology might be an efficacious approach for enhancing the therapeutic potential of TL to treat liver dysfunction.