title: Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat.
abstract: Sorafenib is slightly absorbed in the gastrointestinal tract due to its poor solubility in water. To improve its absorption, a novel nanoparticulate formulation-nanomatrix was used in the study. The nanomatrix was a system prepared from a porous material Sylysia(®) 350 and a pH sensitive polymer Eudragit(®). The formulations were optimized by orthogonal design (L(9)(3(4))) and their bioavailability were evaluated in rat, comparing to pH-sensitive Eudragit nanoparticles and suspension of sorafenib. In the formulations, the ratio of sorafenib to Eudragit(®) S100 was found to be more important determinant of the sorafenib bioavailability than the ratio of sorafenib to Sylysia(®) 350. As for the bioavailability, the AUC(0-36 h) of sorafenib nanomatrix was 13-33 times to that of sorafenib suspension, but only 16.8% to 40.8% that of Eudragit(®) S100 nanoparticles. This may be resulted from the different drug dispersion degree, release character and bioadhension activity. However, because all the materials used in the nanomatrix formulation are commonly adjuvant, safe, easy to get and cheap, above all, the nanomatrix formulation can solve the stability and scaling up problems in the nanoparticles, it had potential to develop into a product in the future.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xue-qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Jie-ming
authors.initials: JM
authors.lastname: Fan
authors.forename: Ya-ou
authors.initials: YO
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Zeng-rong
authors.initials: ZR
authors.lastname: Jia
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D006863:Hydrogen-Ion Concentration; D008297:Male; D053758:Nanoparticles; D049329:Nanostructures; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011109:Polymethacrylic Acids / Q000737:chemistry; D016062:Porosity; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D000077157:Sorafenib; D013535:Suspensions
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011109:Polymethacrylic Acids; D011725:Pyridines; D013535:Suspensions; C038300:methylmethacrylate-methacrylic acid copolymer; D009536:Niacinamide; D012822:Silicon Dioxide; D000077157:Sorafenib