Novel ethylcellulose-coated pellets for controlled release of metoprolol succinate without lag phase: characterization, optimization and in vivo evaluation

Abstract

The objective of this study was to develop a novel ethylcellulose (EC)-coated pellet with partial active dose as a pore former for the controlled release of water-soluble metoprolol succinate (MS) without an initial lag phase (slow/non-drug release phase). MS-layered cores with a high drug-loading efficiency (97%, w/w), a smooth surface, and an acceptable level of resistance to abrasion were first obtained by spraying a concentrated drug solution (60% w/w at 70 °C) on non-pareils in the absence of other binders. The presence of the drug in an EC coating solution significantly improved the coating process by reducing pellet stickiness. Central composite design and response surface methodology was employed to optimize and explore the effect of pore former MS level (X₁) and EC coating level (X₂) on the drug release. The pore former level had a positive effect on the MS release and the coating level had a negative effect. The level of X₁ and X₂ of the optimization were 17% and 23%, respectively, and the cumulative percent of MS released within 1 h was up to 9.2%. Accordingly, the initial lag phase associated with in vitro drug release from EC-coated pellets was absent when MS drug was used as a pore former, which was further confirmed by in vivo drug release in beagle dogs. Thus, a novel approach for the controlled release of MS from coated pellets without lag phase has been successfully developed, which is valuable for the advancement of sustained-release pellets.

• Coated pellets
• in vivo evaluation
• lag phase
• metoprolol succinate
• pore former
• response surface methodology

Declaration of interest

The study was supported by the Important National Science & Technology Specific Projects (Grant No. 2012ZX09301003-001-009) and the State Key Laboratory of Antitoxic Drugs and Toxicology for their financial support. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.