Investigation of the solid-state, powder flow and tabletability properties of comminuted active pharmaceutical ingredients

Abstract

An understanding of the effect of processing on the solid-state properties of active pharmaceutical ingredients (APIs) is essential for product manufacturing success. During product development it is possible to induce physical changes in the API, for example amorphisation (transformation from crystalline state to amorphous state) or polymorphic transformations. The rate and extent of such phase transitions within the API will depend on physicochemical characteristics of the API. The presence of even a small amount of amorphous component(s) in a crystalline product may have a considerable impact on the stability, processability and bioavailability of the material, and its performance during product manufacture and use. The main focus of this thesis was to determine the impact of a milling, or comminution, process on the physiochemical properties of a range of sulfonamide (sulfa) materials, and to evaluate how these changes affected the material’s ability to flow as well as the impact of these changes on the properties of tablets produced using the comminuted powders.