Towards a continuous manufacturing strategy for complex oral health formulations

Abstract

The conversion of traditional batch operations into continuous processes represents an important goal towards process intensification. The rigorous design of continuous manufacturing operations poses several challenges, especially for processes involving complex fluids, whose rheological properties change during processing. The scope of this thesis is to provide a new approach for the development of a continuous process aimed at the production of a non-aqueous Carbopol gel used in oral health formulations. The dissertation addresses two main challenges related to the process: (i) in-line mixing of complex liquids and (ii) control over the Carbopol gelation. First, the impact of complex rheological properties on the mixing stage was investigated experimentally and numerically. Concentrations maps, obtained at different mixers lengths via Planar Laser Induced Fluorescence experiments, revealed that mixing of viscoelastic fluids reduces when the elastic rheological response becomes significant. To prevent these effects and better control the evolution of the rheological properties over the entire process, the kinetics of the gelation process was investigated via time-resolved rheometry and UV-Vis spectroscopy. This study yielded insights into the mechanism of gelation, leading to a kinetic relation to describe the time-evolution of the linear elastic properties of the Carbopol matrix. To further link the kinetic findings with the evolution of the flow properties, the rheological properties of Carbopol dispersions and the impact of different solvents on the swollen configuration of the microgels were investigated. In the presence of co-solvents, the kinetic aspect of the swelling process is critical in determining the final swollen state. Once the final particle dimension has been determined, a generalized scaling behaviour of the flow properties can be retrieved as function of the particle volume fraction. Finally, the scaling laws and the kinetic model were implemented in a computational fluid dynamic model to enable simulations of the gelating flow in different operating conditions

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