(56a) A Rational Single Particle Design Approach Using an Acoustic Levitation System and X-Ray Tomography
World Congress on Particle Technology
Tuesday, April 24, 2018 - 1:30pm to 2:00pm
An acoustic levitator was employed to provide a container-less particle design environment for single droplet drying experiments with starting droplet volumes between 10 ul â 80 ul. The temperature and humidity was controlled by an enclosure. The system gave access to characterise the particle formation and subsequent drying process using thermal and high speed imaging techniques. The dried particles were subject to visual and quantitative analysis using nano-focused x-ray tomography to allow a three-dimensional structural description. Extracted morphological descriptors of each particle have been related to solid phase nucleation and growth kinetics. Special emphasis of this study is the evaluation of the solid phase porosity, structural thickness and crystallinity influenced by the solidification from solution and with an impact on key particle performance attributes such as mechanical stability, manufacturability, solubility and solid state stability. Formulations of an active pharmaceutical ingredient with polymeric excipients have been developed to address challenges of a highly crystalline solid with large elongated primary particles. The formulated particles exhibited significantly improved structural modifications leading to an increased mechanical stability, (partially) suppressed crystallinity and tailored dissolution rates. The overall observed diversity of particle properties obtained from single droplet experiments for changing compound systems expressed the importance of an in-depth characterisation of the solidification process prior to process implementation.
In summary this study combined the capabilities of an acoustic levitation system and a nano-focused x-ray tomograph to provide a platform to investigate the particle formation and allows a morphological characterisation on a single droplet scale. A comprehensive study enables the development of a mechanistic understanding for a rational particle design approach of novel compound systems targeting critical particle properties influencing particle performance. The fundamental knowledge gained from this method can then be transferred to develop a design space for process applications involving particle formation and drying such as spray drying.