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710b

Optimization and Scale-up of High Shear Wet Granulation Processes Using Lasentec Fbrm and Pvm In-Situ Particle Characterization

Zane Arp1, Benjamin Smith2, and Des O'Grady2. (1) Pd-Most-Puc, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, (2) Particle Systems Characterization - Process Analytical Technology, Mettler Toledo, Redmond, WA 98052

High shear wet granulation is a common unit operation in solid dosage formulation, yet a mechanistic understanding of high shear wet granulation is not well known. One goal of high shear granulation is to yield a repeatable particle size and shape distribution at the batch endpoint. One measure of a successful granulation process is a repeatable endpoint particle distribution that achieves repeatable downstream drying, milling, flow properties, and content uniformity. However, inconsistencies often occur during granulation scale up due to changing raw materials or changing process dynamics such as segregation, agglomeration, or breakage. By designing a robust granulation process one can ensure consistent downstream processing from granulation through tablet dissolution. FBRM and PVM allow a user to directly link process control parameters to the particle distribution and the product quality. In this work bottom driven high shear wet granulation experiments at several volumes are compared with various formulation conditions and excipients. The application of in-situ particle size monitoring techniques, Lasentec FBRM and PVM is demonstrated to track a series of granulation batch process in the laboratory while varying the batch volume, raw materials, shear, and liquid addition. Target particle distributions are achieved by using FBRM and PVM to understand the critical process parameters and predict the effect during granulation scale up. FBRM and PVM are ultimately used to target a specific growth profile and endpoint particle size and shape distribution at the various scales and vessel configurations.