Development of an osmotically-driven pellet coated with acrylic copolymers (Eudragit® RS 30 D) for the sustained release of oxymatrine, a freely water soluble drug used to treat stress ulcers (I): in vitro and in vivo evaluation in rabbits

Abstract

Purpose: To develop an osmotically-driven pellet coated with polymeric film for sustained release of oxymatrine (OMT), a freely water soluble drug.

Methods: Pellet containing OMT and sodium chloride (NaCl), an osmotically active agent, were prepared by extrusion/spheronization and then coated with acrylic copolymers (Eudragit^® RS 30 D) by the fluidized bed coating process. In vitro release and swelling behavior studies were employed to optimize and to evaluate the sustained-release behavior from the osmotically-driven pellets with film coated. Finally, in vivo evaluation in rabbits was employed to investigate the sustained plasma level of OMT and its active metabolite matrine.

Results: It was found that the F3 formulation, prepared with 20% NaCl and an 8% coating level, showed a continuous NaCl-induced water influx into the pellets providing a gradual sustained release of OMT for over 12 h. Finally, we confirmed that oral OMT with sustained release led to a gradual sustained plasma profile of both OMT, with a reduction in its bioavailability, and MT with an increase in the bioavailability compared with that of oral OMT with immediate release. Conclusions: The pharmaceutical parameters obtained suggested the potential usefulness of oral OMT with sustained release for the treatment of stress ulcers, as well as reducing the risk of MT-induced side effects.

Keywords::

• Oxymatrine
• matrine
• sustained-release
• osmotically-driven
• pellets

Acknowledgments

We also thank Dr. Meijuan Zou for helpful advises in in vivo study.

Declaration of interest

This work was supported in part by a grant from Shenyang Pharmaceutical University.