Enhanced biopharmaceutical effects of tranilast on experimental colitis model with use of self-micellizing solid dispersion technology

[Display omitted] The present study aimed to clarify the applicability of a self-micellizing solid dispersion of tranilast (SMSD/TL) to the treatment of inflammatory bowel diseases (IBD) using an experimental colitis model. SMSD/TL with several loading amounts ranging from 10 to 50% was prepared using a wet-milling system. The physicochemical properties of SMSD/TL were evaluated in terms of the dissolution behavior, morphology, and particle size distribution. Animal studies were conducted to evaluate oral bioavailability in rats and anti-inflammatory effects in a rat model of chemically induced colitis. SMSD/TL with drug loading of 15% (SMSD/TL15) showed enhanced dissolution behavior at pH 1.2, compared with other tested other formulations. After the dispersion of SMSD/TL15 in deionized water, fine micelles formed with an average diameter of 137 nm. SMSD/TL15 (10 mg-TL/kg) exhibited about 147- and 34-fold greater value for Cmax and the area under the curve of plasma concentration vs. time than crystalline TL, respectively. Although the anti-inflammatory effect on the colitis model was very limited in the crystalline TL (2 mg/kg) group, inflammatory events, such as myeloperoxidase activity and thickening of the submucosa in colon tissues, were significantly suppressed in the SMSD/TL15 (2 mg-TL/kg) group. Based on these findings, SMSD/TL might be a more efficacious dosage option for improved IBD treatment.