title: Seventy-two-hour release formulation of the poorly soluble drug silybin based on porous silica nanoparticles: in vitro release kinetics and in vitro/in vivo correlations in beagle dogs.
abstract: The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, 301 Xuefu Road, Jingkou District, Zhenjiang 212001, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
authors.forename: Wenwen
authors.initials: W
authors.lastname: Deng
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hongfei
authors.initials: H
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wei
authors.forename: Ximing
authors.initials: X
authors.lastname: Xu
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D005750:Gastric Juice / Q000737:chemistry; D007419:Intestinal Secretions / Q000737:chemistry; D007700:Kinetics; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D017693:Sodium Bicarbonate / Q000737:chemistry; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D012838:Silymarin; D000077385:Silybin; D012822:Silicon Dioxide; D017693:Sodium Bicarbonate