Tranilast-loaded amorphous solid dispersion prepared with fine droplet drying process for improvement of oral absorption and anti-inflammatory effects on chemically-induced colitis

Abstract

The aim of the present study was to evaluate the applicability of a tranilast (TL)-loaded amorphous solid dispersion prepared with a fine droplet drying (FDD) process for the treatment of inflammatory bowel diseases. The FDD process, a novel powderization technology using an inkjet head, was employed to produce an amorphous solid dispersion of tranilast (ASD/TL). The physicochemical properties of ASD/TL were evaluated in terms of the morphology, particle size, crystallinity, drug-polymer interaction, and dissolution behavior. The oral absorption behavior of TL and anti-inflammatory effect on a chemically-induced colitis model were evaluated after oral administration of TL samples. The particle size of ASD/TL was 4 μm, and the span factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.28. In each ASD/TL particle, TL was dispersed in an amorphous state in the carrier polymer, and ASD/TL showed improved dissolution behavior of TL, as evidenced by a 2-times higher dissolution than the equilibrium solubility of crystalline TL even under acidic conditions. Orally-dosed ASD/TL exhibited rapid and improved oral absorption with 16-fold higher bioavailability than crystalline TL. ASD/TL could significantly attenuate the inflammatory symptoms in the colon tissues of colitis model rats based on the results of histological analyses and measurement of biomarkers. ASD/TL might contribute to the development of effective treatment for inflammatory bowel diseases due to its enhanced biopharmaceutical properties.