title: Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability.
abstract: Considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders, however, the therapeutic potential of curcumin could often be limited by its poor solubility, bioavailability, and photostability. To overcome these drawbacks, efficacious formulations of curcumin, including nanocrystal solid dispersion (CSD-Cur), amorphous solid dispersion (ASD-Cur), and nanoemulsion (NE-Cur), were designed with the aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the prepared formulations were characterized by scanning/transmission electron microscope for morphological analysis, laser diffraction, and dynamic light scattering for particle size analysis, and polarized light microscope, powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. In dissolution tests, all curcumin formulations exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin. Significant improvement in pharmacokinetic behavior was observed in the newly developed formulations, as evidenced by 12- (ASD-Cur), 16- (CSD-Cur), and 9-fold (NE-Cur) increase of oral bioavailability. Upon photochemical characterization, curcumin was found to be photoreactive and photodegradable in the solution state, possibly via type 2 photochemical reaction, whereas high photochemical stability was seen in the solid formulations, especially CSD-Cur. On the basis of these observations, taken together with dissolution and pharmacokinetic behaviors, CSD strategy would be efficacious to enhance bioavailability of curcumin with high photochemical stability.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, Global Center of Excellence Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Haruki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.forename: Junya
authors.initials: J
authors.lastname: Hatanaka
authors.forename: Barbara
authors.initials: B
authors.lastname: Timmermann
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D004655:Emulsions; D008297:Male; D009055:Mouth / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010777:Photochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D003474:Curcumin