(417c) Determination of Structure, Porosity and API Distribution in Granules By the Computed Micro-Tomography

A mechanistic understanding of the correlation between the properties of the primary powder and granules can lead to enhanced and efficient process development in tablet manufacturing via high-shear wet granulation (HSWG), which is currently the most common route undertaken. Moreover, Quality-by-Design (QbD) in pharmaceutical manufacturing desires the identification of an optimal design space of critical quality attributes (CQAs) as a function of critical process variables and material properties. This work deals with the application of micro-tomography (CT) technique and image analysis to study granules prepared by the high shear granulator. The influence of granulation process parameters (binder content, wet massing time and vessel RPM) on particle structure (porosity, API distribution) has been investigated. The formulation comprises of acetaminophen and microcrystalline cellulose (30% APAP, w/w). Water is used as a binder. CT measurement allows us to study localization of the API (acetaminophen) in the matrix of granule (cellulose) and evaluate the diffusion mechanism of API from granules into surroundings for different process variables. This approach could be very beneficial in optimization of granulation process and properties of the final product.