Spray drying assembly of uniform microparticles for microencapsulation and controlled release

A micro-fluidic jet spray drying (MFJSD) technique, which can produce highly monodispersed microparticles from a variety of precursors, has been developed at Monash University. This facility enables a better control over properties of spray-dried microparticles, since every atomized droplet is dried to individual particles. In addition, the method is scalable, waste-free,and eliminates the need of organic solvents in the formulation. This thesis developed the protocol for particle design and assembly via MFJSD, by elucidating the mechanisms of particle formation. The relationship between synthesis conditions and physicochemical properties and functionalities of particles was investigated, focusing on their applications for microencapsulation and controlled release. Among the model systems used to investigate effects of different process parameters on properties of microparticles was chitosan, with the emphasis on tuning the particle size, morphology, and surface feature by adjusting drying temperature and properties of chitosan solution. Spray drying of precursors containing alginate and silica nanoparticles demonstrated that silica nanoparticles were first aligned into structured clusters with alginate in the solution. Subsequently, the evaporation induced self-assembly during spray drying induced further aggregation into sub-micron spherical aggregates that closely packed the internalstructure of uniform microparticles, while the shell was mainly formedby silica nanoparticles. The effects of formulation (pH, concentration, dopants, solvents) and process parameters (drying time) on microstructural properties and controlled release functionalities were elucidated for both silica-based and polymer-based microencapsulates. The ability to tailor drug release kinetics of polymeric microparticles by manipulating their microstructures was demonstrated using polymeric aqueous dispersions Eudragit® RS and Eudragit® NE as matrix materials. The microstructures of particles and their corresponding drug release mechanisms could be tuned by different blending strategies, such as the incorporation of highly hydrophilic ingredients to accelerate release, or acid-hydrolysed tetraethyl orthosilicate (TEOS) to generate interpenetrating networksupon drying that served as an additional barrier for release. The method can also be used to assemble microencapsulates with defined core-shell structures using a Eudragit® RS / silica system. Uniform core-shell microencapsulates with different shell thickness could be assembled in a single step from a homogenous precursor, illustrating the ability to tailor particle structures and release rates of the active ingredient. The ability to produce highly uniform particles with this unique approach has thus contributed to the understanding of how particles with different microstructures are formed, and how the physicochemical properties are related to their functionality. The underlying principles of particle formation mechanisms can be applied for other functional particles, with the strategy useful for designing spray-dried particles of tailored properties in a scalable manner.