title: Amorphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization.
abstract: The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats. The ASD/CsA was obtained in the form of uniform spherical particles, and the span factor was calculated to be ca. 0.4. CsA in the formulation existed in an amorphous state. The ASD/CsA exhibited a higher dissolution behavior of CsA than amorphous CsA, whereas storage of the ASD/CsA under accelerated conditions led to impairment in the dissolution behavior. The constant release of CsA from non-aged ASD/CsA was observed during dissolution testing. After oral administration of CsA samples (10mg-CsA/kg) in rats, the ASD/CsA showed a high and sustained plasma concentration of CsA as evidenced by a 18-fold increase in the oral bioavailability of CsA compared with amorphous CsA. From these findings, the FDD process might be an efficacious option for the ASD formulation of CsA with enhanced biopharmaceutics properties.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Functional Material Development Center, Imaging Engine Development Division, RICOH Company, Ltd., 16-1 Honda-machi, Numazu-shi, Shizuoka 410-1458, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Moritani
authors.affiliation: Functional Material Development Center, Imaging Engine Development Division, RICOH Company, Ltd., 16-1 Honda-machi, Numazu-shi, Shizuoka 410-1458, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Morinaga
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: onoue@u-shizuoka-ken.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016572:Cyclosporine / Q000737:chemistry* / Q000493:pharmacokinetics*; D004146:Dioxanes / Q000737:chemistry; D004355:Drug Stability; D008297:Male; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004146:Dioxanes; D011208:Powders; D016572:Cyclosporine; C025223:1,4-dioxane
keywords: Amorphous solid dispersion; Cyclosporine A; Dissolution; Fine droplet drying process; Oral absorption