Quantitative investigation of particle formation of a model pharmaceutical formulation using single droplet evaporation experiments and X-ray tomography

Doerr, Frederik J.S. and Oswald, Iain D.H. and Florence, Alastair J. (2018) Quantitative investigation of particle formation of a model pharmaceutical formulation using single droplet evaporation experiments and X-ray tomography. Advanced Powder Technology, 29 (12). pp. 2996-3006. ISSN 1568-5527 (https://doi.org/10.1016/j.apt.2018.09.027)

[thumbnail of Doerr-etal-APT-2018-Quantitative-investigation-of-particle-formation-of-a-model-pharmaceutical-formulation]
Preview
Text. Filename: Doerr_etal_APT_2018_Quantitative_investigation_of_particle_formation_of_a_model_pharmaceutical_formulation.pdf
Accepted Author Manuscript
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo

Download (8MB)| Preview

Abstract

The implementation of a particle design platform that can be applied to novel pharmaceutical systems using acoustic levitation (SAL) and X-ray tomography (XRT) is discussed. Acoustic levitation was employed to provide a container-less particle design environment for single droplet evaporation experiments. Dried particles were subject to further visual and quantitative structural analysis using X-ray tomography to assess the three-dimensional volume space. The workflow of the combined SAL-XRT platform has been applied to investigate the impact of increasing HPMC K100LV concentrations on the evaporation, drying and final particle morphology of particles from a model pharmaceutical formulation containing metformin and D-mannitol. The morphology and internal structure of the formulated particles after drying are dominated by a crystalline core of D-mannitol partially suppressed with increasing HPMC K100LV additions. The final structure can be correlated to the observed evaporation kinetics. The characterisation and its influence on the final particle morphology can enable the selection of process conditions that deliver the desired particle structure and consequent performance by design.