title: A novel nanomatrix system consisted of colloidal silica and pH-sensitive polymethylacrylate improves the oral bioavailability of fenofibrate.
abstract: A novel solid particle system with a nanomatrix structure and without surfactant for the oral delivery of insoluble drugs was prepared. This used a combination of pH-sensitive polymethylacrylate and nano-porous silica, in order to improve the drug absorption using only pharmaceutical excipients and a relative simple process. The in vitro drug dissolution and in vivo oral bioavailability of this formulation, using fenofibrate as the model drug, were compared with other reference formulations such as a suspension, micronized formulation or self microemulsion drug delivery system (SMEDDS). The supersaturation stabilizing effect of different polymers was evaluated and the physicochemical characterization of the optimal formulation was conducted by SEM, TEM, surface area analysis, DSC, and XRD. The optimized formulation prepared with polymethylacrylate (Eudragit®L100-55) and silica (Sylysia®350) markedly improved the drug dissolution compared with other reference preparations and displayed a comparative oral bioavailability to the SMEDDS. Fenofibrate existed in a molecular or amorphous state in the nanomatrix, and this state was maintained for up to 1year, without obvious changes in drug release and absorption. In conclusion, the nanomatrix formulation described here is a promising system to enhance the oral bioavailability of water-insoluble drugs.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China.
authors.forename: Zengrong
authors.initials: Z
authors.lastname: Jia
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000042:Absorption; D000818:Animals; D001682:Biological Availability; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D011345:Fenofibrate / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D058608:Nanopores; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000378:metabolism
chemical_list: D003102:Colloids; D004655:Emulsions; D005079:Excipients; D000960:Hypolipidemic Agents; D011108:Polymers; D011109:Polymethacrylic Acids; D013501:Surface-Active Agents; C038300:methylmethacrylate-methacrylic acid copolymer; D012822:Silicon Dioxide; D019904:Polymethyl Methacrylate; D011345:Fenofibrate