title: A novel strategy to produce highly stable and transparent aqueous 'nanosolutions' of water-insoluble drug molecules.
abstract: A surprisingly large proportion of new drug candidates emerging from drug discovery programmes are water-insoluble and, as a result, have poor oral bioavailability. To overcome insolubility, the drug particles are usually dispersed in a medium during product formation, but large particles that are formed may affect product performance and safety. Many techniques have been used to produce nanodispersions-dispersions with nanometre-scale dimensions-that have properties similar to solutions. However, making nanodispersions requires complex processing, and it is difficult to achieve stability over long periods. In this paper, we report a generic method for preparing drug nanoparticles with a combination of antisolvent precipitation in the presence of water-soluble matrices and spray-drying. The spray-dried powder composites (solid dispersion) are microspherical, highly stable and thus form transparent nanodispersions or so-called 'nanosolutions' of water-insoluble drug when simply added to water. Aqueous nanodispersions of silybin (a kind of water-insoluble drug for liver protection) with an average size of 25 nm produced with this approach display a 10 times faster dissolution rate than that of raw drug. This has great potential to offer a novel solution for innovative drugs of the future.
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, People's Republic of China.
authors.forename: Jie-Xin
authors.initials: JX
authors.lastname: Wang
authors.forename: Zhi-Bing
authors.initials: ZB
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Le
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Chen
mesh_terms: D016503:Drug Delivery Systems; D055808:Drug Discovery; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D033362:Powder Diffraction; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions; D014867:Water
chemical_list: D012838:Silymarin; D012996:Solutions; D013535:Suspensions; D014867:Water; D000077385:Silybin