title: A pH-independent instantaneous release of flurbiprofen: a study of the preparation of complexes, their characterization and in vitro/in vivo evaluation.
abstract: In this study, furbiprofen/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes were prepared to improve the drug dissolution and facilitate its application in hydrophilic gels. Inclusion complexes were prepared using a supercritical fluid processing and a conventional optimized co-lypholization method was employed as a reference. The entrapment efficacy and drug loading of both methods were investigated. Evaluation of drug dissolution enhancement was conducted in deionized water as well as buffer solutions of different pH. Carbopol 940 gels of both flurbiprofen and flurbiprofen/HPβCD inclusion complexes, with or without penetration enhancers, were prepared and percutaneous permeation studies were performed using rat abdominal skin samples. Formation of flurbiprofen/HPβCD inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The results obtained showed that SCF processing produced a higher EE (81.91 ± 1.54%) and DL (6.96 ± 0.17%) compared with OCL with values of 69.11 ± 2.23% and 4.00 ± 1.01%, respectively. A marked instantaneous release of flurbiprofen/HPβCD inclusion complexes prepared by SCF processing (103.04 ± 2.66% cumulative release within 5 min, a 10-fold increase in comparison with flurbiprofen alone) was observed. In addition, this improvement in dissolution was shown to be pH-independent (the percentage cumulative release at pH 1.2, 4.5, 6.8 and 7.4 at 5 min was 95.19 ± 1.71, 101.75 ± 1.44, 105.37 ± 4.58 and 96.84 ± 0.56, respectively). Percutaneous permeability of flurbiprofen-in-HPβCD-in-gels could be significantly accelerated by turpentine oil and was related to the water content in the system. An in vivo pharmacokinetic study showed a 2-fold increase in Cmaxand a shortened Tmaxas well as a comparable relative bioavailability when compared with the commercial flurbiprofen Cataplasms (Zepolas®). With their superior dissolution, these flurbiprofen/HPβCD inclusion complexes prepared by SCF processing could provide improved applications for flurbiprofen.
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Yang
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Gai
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Bing-Chao
authors.initials: BC
authors.lastname: Cheng
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Li
authors.affiliation: b College of Pharmacy , Liaoning University , Liaoning , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Xing-Gang
authors.initials: XG
authors.lastname: Yang
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Liaoning , China.
authors.forename: Wei-San
authors.initials: WS
authors.lastname: Pan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D005480:Flurbiprofen / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005480:Flurbiprofen
keywords: flurbiprofen; instantaneous; pH-Independent; supercritical fluid process