title: A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation.
abstract: In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na2CO3 at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12 h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Shujuan
authors: S
authors: Li
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Xiaoyu
authors: X
authors: Wang
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Yingying
authors: Y
authors: Wang
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Qianqian
authors: Q
authors: Zhao
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Lina
authors: L
authors: Zhang
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Xinggang
authors: X
authors: Yang
authors: b School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology , Benxi , PR China.
authors: Dandan
authors: D
authors: Liu
authors: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China and.
authors: Weisan
authors: W
authors: Pan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005480:Flurbiprofen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007260:Infusion Pumps; D008297:Male; D009995:Osmosis / Q000187:drug effects / Q000502:physiology; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen
keywords: Alkalizer; central composite design; flurbiprofen; oral bioavailability; osmotic pump capsule; solid dispersions