Absorption improvement of tranilast by forming highly soluble nano-size composite structures associated with α-glucosyl rutin via spray drying.
Tranilast (TL) composite particles with α-glucosyl rutin (Rutin-G) were developed to improve the solubility and oral bioavailability of TL. Composite formulation of TL/Rutin-G was prepared using the spray-drying method, and their physicochemical properties were evaluated with respect to the morphology, particle size distribution, solubility and crystallinity. The nanostructure formation of Rutin-G was characterized by dynamic light scattering and transmission electron microscopy when Rutin-G or TL/Rutin-G spray-dried particles (SDPs) were introduced into water. A pharmacokinetic study was also performed to assess the improvement of oral absorption in rats. TL/Rutin-G SDPs were spherical particles with a diameter of 5.5μm. Even in the acidic condition, the remarkable improvement in solubility of TL was achieved, as evidenced by a 32.2-fold increase in solubility compared with untreated TL. The median size of Rutin-G nanostructures in water was 2nm. The formation of Rutin-G nanostructures and their drug inclusion properties may enhance the solubility and dissolution behavior of TL. A drastic increase was found in the exposure of TL in rats, with an increase in Cmax and AUC values of 114- and 36.4-fold, respectively, compared with those of untreated TL. These findings indicated that a TL formulation spray-dried with Rutin-G could enhance its solubility and absorption and thus its therapeutic properties.
Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Hideyuki
H
Sato
Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Miki
M
Fujimori
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Hiroki
H
Suzuki
Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Kazunori
K
Kadota
Department of Chemical Engineering and Material Science, Doshisha University, Kyotanabe, Japan.
Yoshiyuki
Y
Shirakawa
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Satomi
S
Onoue
Osaka University of Pharmaceutical Sciences, Takatsuki, Japan. Electronic address: ytozuka@gly.oups.ac.jp.
Yuichi
Y
Tozuka
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D000067493:Dynamic Light Scattering; D008297:Male; D046529:Microscopy, Electron, Transmission; D053761:Nanocomposites; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D014312:Trisaccharides / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D062367:ortho-Aminobenzoates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D018926:Anti-Allergic Agents; D014312:Trisaccharides; D062367:ortho-Aminobenzoates; D014867:Water; C069037:4(G)-alpha-glucopyranosyl-rutin; D012431:Rutin; C012293:tranilast
Composite; Nanostructure; Oral bioavailability; Spray-drying; Tranilast; α-Glucosyl rutin