title: Preparation and in vitro/in vivo evaluation of esomeprazole magnesium-modified release pellets.
abstract: To reduce the drug plasma concentration fluctuation without being destroyed by gastric fluid, novel Esomeprazole magnesium modified-release pellets (EMZ-MRPs) with suitable in vitro release profiles and good in vitro and in vivo correlation (IVIVC) were developed. Fluid-bed was used to obtain EMZ-loaded pellets by spraying drug suspension onto blank sugar pellets. The drug-loaded pellets were subsequently coated with Eudragit® RS30D/RL30D (ERS/ERL) aqueous dispersion to achieve sustained-release (SR) characteristics. Furthermore, the SR pellets were coated with Eudragit® L30D-55 (EL-55) aqueous dispersion to achieve enteric properties. Besides, isolated coating film was necessary between drug layer and SR layer, as well as SR and enteric-coated layer to protect from their possible reaction. The resulting pellets were filled into the hard gelatin capsules for in vitro release processing and single-dose pharmacokinetic study in rats. The optimal formulation achieved good SR feature both in vitro and in vivo with a relative bioavailability of 103.50%. A good IVIVC was characterized by a high coefficient of determination (r = 0.9945) by deconvolution method. Compared to those of EMZ enteric-coated pellets (EMZ-ECPs, trade name NEXIUM), the in vivo study make known that the EMZ-MRPs with decreased maximum plasma concentration (Cmax), prolonged peak concentration time (Tmax) and mean residence time (MRT), and similar values both area under concentration-time curve from 0 to t (AUC0-t) and 0 to infinity (AUC0-∞). Collectively, these results manifested EMZ-MRPs had a satisfactory sustained-release behavior, a desired pharmacokinetic property, improved in vivo retention and decreased plasma drug concentration fluctuation.
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Kan
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004343:Drug Implants / Q000737:chemistry* / Q000493:pharmacokinetics; D064098:Esomeprazole / Q000737:chemistry* / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; C477852:Eudragit L 30 D-55; D005079:Excipients; D008689:Methacrylates; D011108:Polymers; D064098:Esomeprazole
keywords: Enteric-coated; esomeprazole magnesium; fluid-bed coating; relative bioavailability; sustained-release pellets