title: Long-term studies on the stability and oral bioavailability of cyclosporine A nanoparticle colloid.
abstract: The present study was geared at the long-term stability and the changes in oral bioavailability of CyA Eudragit S100 nanoparticles stabilized by suspending agents. CyA Eudragit S100 nanoparticle colloids were prepared by quasi-emulsion solvent diffusion technique and they were mixed with Xanthan gum to obtain suspended nanoparticle colloids. The suspended nanoparticle colloids were preserved at different temperatures for different period of time, as long as 18 months. During the storage period, the CyA concentration, particle size, pH and viscosity were determined. The results indicated that CyA concentration, particle size and viscosity of the colloids had no obvious change. However, the pH increased slightly from 5.5 to about 6.4. The results of bioavailability and pharmacokinetic study revealed that all formulations of nanoparticles showed higher C(max) and higher AUC(0-24) values than that of reference (Neoral). The relative bioavailability of S-CyA-S100 NP initial compared with Neoral was 162.8%. The C(max) and AUC(0-24) values of nanoparticle formulations at 12 and 18 months were both lower than that of the initial. The bioequivalency was suggested between the tested nanoparticle formulations at the initial and 12 months. It was deduced by surface analysis, TEM observation, in vitro release as well as the characteristics of Eudragit S100 that the decrease in bioavailability might be due to the pH change of the nanoparticle colloid.
authors.affiliation: School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083, PR China.
authors.forename: Xue-qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Jun-dong
authors.initials: JD
authors.lastname: Dai
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Wan-liang
authors.initials: WL
authors.lastname: Lü
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian-cheng
authors.initials: JC
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003102:Colloids; D016572:Cyclosporine / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013696:Temperature; D014783:Viscosity
chemical_list: D003102:Colloids; D011109:Polymethacrylic Acids; D011135:Polysaccharides, Bacterial; C038300:methylmethacrylate-methacrylic acid copolymer; D016572:Cyclosporine; C002563:xanthan gum