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 (C_max), prolonged peak concentration time (T_max) and mean residence time (MRT), and similar values both area under concentration–time curve from 0 to t (AUC_0–t) and 0 to infinity (AUC_0–∞). 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.

• Enteric-coated
• esomeprazole magnesium
• fluid-bed coating
• relative bioavailability
• sustained-release pellets

Acknowledgements

Thanks to FMC, Meggle GmbH, ISP and Evonik Industries for providing the excipients and coating materials.

Declaration of interest

This article is submitted to be considered for publication as an “Original Article” in your journal. Neither the entire article nor any part of its content has been published or accepted elsewhere. This study is financially supported by the major project of National College Students Innovation Project for the R&D of Novel Drugs (No. J1030830).