ABSTRACT:
This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol succinate (50 mg) sufficiently sensitive to manufacturing variables and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR). Natural polymer of Xanthan gum with different concentration, cellulose derivatives, fillers and binders were studied. Three granulation processes were evaluated; direct compression, dry granulation and wet granulation by planetary mixer, RMG, FBP. Lubrication was performed in a V-blender and tablets were compressed on an instrumented rotary tablet press. Direct compression and dry granulation formulations exhibited poor flow, picking and sticking problems during tableting. Wet granulation resulted in the formation of hard granules that were difficult to mill but yielded good tablets. Fluid-bed granulations were made and appeared to be satisfactory in terms of flow and tableting performance. In vitro drug release testing was performed in pH 6.8 phosphate buffer using USP apparatus 2 (paddle) at 50 rpm. At a different polymer level, drug release from Xanthan gum was slower Increase in polymer level from 30 to 60% and adding of extra granulating HPMC 5–10% decrease in the amount of metoprolol succinate release 4-20hr. The results of this study led to the choice of Xanthan gum as the hydrophilic matrix polymer and fluid-bed granulation as the process of choice for further evaluation of critical and non-critical formulation and processing variables.