(431e) Identifying Optimum Liquid-to-Solid Ratio Range for Microcrystalline Cellulose Based Formulations in Twin Screw Wet Granulation

Twin screw wet granulation (TSWG) is gaining increasing interest in the pharmaceutical industry as an effective continuous manufacturing process for solid oral dosage forms. Although multiple variables have been shown to impact various characteristics of granules produced by this technique, liquid-to-solid ratio is known to be one of the primary factors affecting granule attributes. Hence, identifying an optimum range of liquid-to-solid ratio can help streamline formulation development and minimize material requirements for TSWG process development. Here we present the results of TSWG studies conducted with microcrystalline cellulose-based (MCC) formulations of varying drug loads, using micronized acetaminophen as a model active compound. The blends were granulated using a GEA ConSigma-1 25 mm twin screw wet granulator with a standard kneading element screw configuration at a wide range of liquid-to-solid ratios until pasting was visually determined. It was observed that the paste points for different granulations were dependent on the level of MCC in the formulation. We couple this process-focused analysis with a lab-scale approach to establish viable ranges of liquid-to-solid ratios in advance of actual process development. Comparisons of lab-scale mechanical properties of wet granular material, various process parameters, and material and granule characteristics will be discussed, with guidelines for optimizing liquid addition levels proposed.