title: A novel strategy to design sustained-release poorly water-soluble drug mesoporous silica microparticles based on supercritical fluid technique.
abstract: BACKGROUND
  The organic solvent solution immersion method was often used to achieve the loading of the drugs into mesoporous silica, but the drugs that have loaded into the pores of the mesoporous silica would inevitable migrate from the inside to the external surface or near the outside surface during the process of drying. Hence, it often leads to the pores of mesoporous materials not be fully utilized, and results in a low drug loading efficiency and a fast releasing rate.
  
  
  OBJECTIVE
  The purpose of this study was to develop a novel drug loading strategy to avoid soluble component migration during the process of drying, then, to prepare poorly water-soluble drug mesoporous silica microparticles with higher drug loading efficiency and longer sustained-release time.
  
  
  METHODS
  Ibuprofen was used as model drug. The microparticles were prepared by a novel method based on mesoporous silica and supercritical fluid (SCF) technique. The drug-loaded mesoporous silica microparticles prepared by SCF technique were analyzed by thermogravimetric analysis (TGA), N2 adsorption/desorption, scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). In vitro releasing study was used to evaluate the sustained-release effect of the drug-loaded microparticles.
  
  
  RESULTS
  By virtue of the high diffusibility and the high dissolving capacity of the supercritical carbon dioxide (SCF-CO2), the poorly water-soluble drugs, ibuprofen, entered the pores of the mesoporous silica. The amount and the depth of ibuprofen entered the pores of the mesoporous silica by SCF technique were both larger than those by the solution immersion method. It was found that ibuprofen loaded into the mesoporous silica by SCF technique was amorphous and the largest amount of the ibuprofen loaded into the mesoporous silica by SCF technique could reach 386 mg/g (w/w, ibuprofen/SiO2), it was more than that by the solution immersion method. In vitro releasing study showed that the sustained-release effect of ibuprofen in the samples prepared by SCF technique was 50% in 15 min and 90% in 60 min. It was longer than that prepared by the solution immersion method.
  
  
  CONCLUSIONS
  Present study showed that sustained-release poorly water-soluble drug mesoporous silica microparticle based on SCF technique has twofold advantages. One is the larger drug loading amount in internal pores of the mesoporous silica, the other is the longer drug releasing time.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li-Hong
authors.forename: Che
authors.initials: C
authors.lastname: Xin
authors.forename: Xu
authors.initials: X
authors.lastname: Hui
authors.forename: Zhou
authors.initials: Z
authors.lastname: Li-Li
authors.forename: Han
authors.initials: H
authors.lastname: Jing
authors.forename: Zou
authors.initials: Z
authors.lastname: Mei-Juan
authors.forename: Liu
authors.initials: L
authors.lastname: Jie
authors.forename: Liu
authors.initials: L
authors.lastname: Yi
authors.forename: Liu
authors.initials: L
authors.lastname: Jin-Wen
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wei
authors.forename: Cheng
authors.initials: C
authors.lastname: Gang
mesh_terms: D000327:Adsorption; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D016062:Porosity; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012997:Solvents; D014867:Water; D012822:Silicon Dioxide; D007052:Ibuprofen
keywords: Ibuprofen; Loading capacity; Mesoporous silica; Supercritical CO(2) fluid; Sustained-release