Effects of Processing on a Sustained Release Formulation Prepared by Twin-Screw Dry Granulation

Dry granulation is an indispensable process used to improve the flow property of moisture-sensitive materials. Considering the limitations of currently available dry granulation techniques, it is necessary to develop a novel technique. In this study, a twin-screw dry granulation (TSDG) technology was successfully applied to produce a sustained-release dry granule formulation, which was subsequently compressed into sustained-release tablets. Based on a preliminary study, theophylline was selected as model drug, Klucel^™ EF, Ethocel^™, and magnesium stearate were selected as excipients. A Resolution V Irregular Fraction Design was applied to determine the effect of different processing parameters (screw speed, feeding rate, barrel temperature, and screw configuration) on product properties (flow properties, particle size distribution, and dissolution time). A reliable model was achieved by combining the data obtained, and processing parameters were automatically optimized to attain the setting goal. In general, TSDG was demonstrated to be an alternative method for the preparation of dry granules. The continuous processing nature, simplicity of operation, and ease of optimization made TSDG competitive compared with other conventional dry granulation techniques.