title: Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique.
abstract: We developed solid dispersions, using the gas anti-solvent technique (GAS), to improve the oral bioavailability of the poorly water-soluble active component oridonin. The solubility of oridonin in supercritical carbon dioxide was measured under various pressures and temperatures. To prepare oridonin solid dispersions using the GAS technique, ethanol was used as the solvent, CO(2) was used as the anti-solvent and the hydrophilic polymer polyvinylpyrrolidone K17 (PVP K17) was used as the drug carrier matrix. Characterization of the obtained preparations was undertaken using scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses and a drug release study. Oridonin solid dispersions were formed and oridonin was present in an amorphous form in these dispersions. Oridonin solid dispersions significantly increased the drug dissolution rate compared with that of oridonin powder, primarily through drug amorphization. Compared with the physical mixture of oridonin and PVP K17, oridonin solid dispersions gave higher values of AUC and C(max), and the absorption of oridonin from solid dispersions resulted in 26.4-fold improvement in bioavailability. The present study illustrated the feasibility of applying the GAS technique to prepare oridonin solid dispersions, and of using them for the delivery of oridonin via the oral route.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
authors.forename: Songming
authors.initials: S
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhao
authors.forename: Nianping
authors.initials: N
authors.lastname: Feng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D045786:Diterpenes, Kaurane / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D005740:Gases / Q000378:metabolism; D006801:Humans; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011208:Powders / Q000737:chemistry; D055607:Receptors, Natural Killer Cell / Q000037:antagonists & inhibitors; D012995:Solubility; D012997:Solvents / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D004337:Drug Carriers; D005079:Excipients; D005740:Gases; D004364:Pharmaceutical Preparations; D011108:Polymers; D011208:Powders; D055607:Receptors, Natural Killer Cell; D012997:Solvents; C011959:oridonin