title: Novel crystalline solid dispersion of tranilast with high photostability and improved oral bioavailability.
abstract: Tranilast (TL) is an anti-allergic agent and widely used in the clinical treatment of bronchial asthma, atopic rhinitis, atopic dermatitis and keloids. However, therapeutic potential of TL could be partly limited because of its poor solubility, bioavailability, and photostability. To overcome these drawbacks, crystalline solid dispersion of TL (CSD/TL) was prepared by wet-milling technique with aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the formulations prepared were characterized by laser diffraction and dynamic light scattering for particle size analysis, scanning electron microscope for morphological analysis, and powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. TL particles in CSD/TL appeared to be crystalline with diameter of 122 nm, and CSD/TL exhibited marked improvement in the dissolution behavior as compared to crystalline TL. Under irradiation of UVA/B (250 W/m(2)), solution and amorphous solid dispersion of TL were found to be highly photodegradable, whereas high photochemical stability was seen in CSD/TL. After oral administration of CSD/TL, enhanced TL exposure was observed with increase of C(max) and AUC by 60- and 32-fold, respectively, as compared to crystalline TL. According to these observations, taken together with dissolution and pharmacokinetic behaviors, crystalline solid dispersion strategy would be efficacious to enhance bioavailability of TL with high photochemical stability.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Debari
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D012995:Solubility / Q000528:radiation effects; D014466:Ultraviolet Rays; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000528:radiation effects
chemical_list: D062367:ortho-Aminobenzoates; C012293:tranilast