A scaled down method for identifying the optimum range of L/S ratio in twin screw wet granulation using a regime map approach.

Twin screw wet granulation (TSWG) has gained momentum in the pharmaceutical industry for effective continuous granulation of solid dosage products. Liquid-to-solid (L/S) ratio is a key process parameter affecting granule properties. Identifying an optimum range of L/S ratio while reducing the number of full scale experiments can minimize material requirements and streamline formulation and process development. In this work, microcrystalline cellulose-based (MCC) formulations of varying drug loads were granulated using a kneading element screw configuration at a wide range of L/S ratios until pasting was visually determined. Quantitative criteria based on process relevant granule size and mass % of fines were established to identify undesirable granulation conditions. Key mechanical properties of wet compacts measured using a small scale approach are discussed. The stress-strain behavior is used to predict pasting, and natural strain at peak yield stress and total work of deformation are used to identify undergranulation and overgranulation respectively. The small scale method is used to establish viable ranges of L/S ratios in advance of at-scale experiments. A quantitative predictive growth regime map is proposed based fully on small scale experiments and input process parameters. Strategies for establishing a generalized growth regime map for various systems of interest are discussed.