Water insoluble polymers as efficient binder in fluid bed granulation of metoprolol for preparation hydrophilic matrix extendedrelease tablets

Abstract

Objectives. The objective of this study was to investigate the possibility of developing metoprolol extended-release tablets by using hydroxypropyl methylcellulose (HPMC) in order to obtain the hydrophilic matrix and Eudragit NE 40D, Kollicoat SR 30D and Surelease E7 as binders during the granulation process. Material and methods. The extended-release tablets were prepared via fluid bed granulation of metoprolol powder using Eudragit NE 40D / Kollicoat SR 30D / Surelease E7 as binders, followed by compression. The influence of three formulation factors (the type of granulation polymers, the ratio of granulation polymers and the HPMC ratio) on the kinetic metoprolol tartrate release was investigated through a full factorial experimental design. Outcomes. The kinetic release of all 26 formulations was best fitted with Peppas model. According to n values of Peppas equation, the release mechanism of drug consists in water diffusion into the matrix, followed by matrix swelling and erosion. The results also indicated that the formulations containing an increased amount of Eudragit NE (10% or more) as binder in the granulation process presented a satisfactory release rate of metoprolol over 12 hours from the granules incorporated in the hydrophilic matrix. Conclusions. This study demonstrated the possibility of lowering of the burst effect from hydrophilic matrix extendedrelease dosage forms incorporating a freely soluble drug, by granulating the drug with a high amount of Eudragit NE 40D and processing the obtained granules in a hydrophilic matrix by tableting.

Keywords

• metoprolol
• hydrophilic matrix
• extended-release
• eudragit ne
• kollicoat
• surelease
• hpmc