Quality by Design Approach to Advanced Particle Engineering, Process Optimisation and Upscaling of Electrohydrodynamic Atomisation Technology

Particle engineering for drug delivery (DD) has gained enormous research interests in recent years, with continuous development of new technological platforms and improvement of existing ones. Unlike most other technologies, the electrohydrodynamic atomisation (EHDA), has been shown to have more advantages in the fabrication of nano- and micro-sized drug particulates. With the advent of the recent pandemic and huge demand for large scale industrial application of nanotechnology, there is now more emphasis on the need for further advancement and upscaling of the EHDA technology. The research presented in this thesis employed the use of EHDA technologies in the engineering of drug particles and application of QbD technique in its optimisation and subsequent upscaling of the process. The work presented in this research is a proof-of-concept; demonstrating the capacity for upscaling of this promising technology. This was first achieved by the utilisation of the EHDA technique in the nanofabrication of indomethacin (INDO) crystal, with the intention of achieving nanocrystals with sustained or improved particle properties for DD. QbD technique was used in the optimisation of the process with an experimental model engendered using 23 full factorial screening design. This design of experiment (DoE) was achieved by carrying out a risk assessment (RA) of the critical quality attributes (CQAs) and critical process parameters (CPP) and using these to establish a quality target product profile (QTPP) yielding nanocrystals of desired particle properties with 395nm size. The nanonisation of crystal particles using this technology opens a new frontier in crystal engineering. Further modification and remodelling lead to the design of a quadrant nozzle system and 8-nozzle system with capabilities of large scale electrospraying of drug particles. Studies on the droplet dynamics showed the impact of the electric field from each nozzle on the spray pattern altering the spray projection of INDO in ethanol (EtOH). The voltage utility graph also demonstrated a higher energy requirement in the formation of stable cone-jets in the upscaled system. Hereafter, based on the result obtained from this work, QbD was subsequently employed in the optimisation of cone-jet formation of chloramphenicol (CAM) and polyvinyl pyrrolidone (PVP) using single nozzle, as well as spraying head designed for improved formulation flow such as multi-tip emitter (MTE) device and flute spraying head. Characterisation of the particles formed from the INDO in EtOH formulation showed stable, nano-sized particles while retaining the physico-chemical properties of INDO. Consequently, characterisation of the fabricated particulates yielded stable polymeric nanoparticles (NPs) which demonstrated a proper incorporation of the CAM in PVP with a steady release profile. This analysis shows a promising potential for the use of this novel upscaling designs in the pharmaceutical industries for the fabrication of both micro- and nano-sized composites, whilst requiring an in-depth exploration of the design functionality in different particle engineering remit