A single step assembly of uniform microparticles for controlled release applications

Microparticles with homogeneous properties are crucial for pharmaceutical applications where the prior knowledge of exact drug loading and release behaviour is essential to achieve targeted therapeutic goals. Various methods such as membrane microemulsion or templating to assemble uniform particles often involve multiple steps, including post-processing for purification and recovery, with additional chemical reactivity is often required to form solid particles, rendering less flexibility in the procedure. Spray drying is a common method to produce pharmaceutical particles, although control over the particle properties poses a challenge. Here we used a specially designed dryer utilising a micro-fluidic-aerosol-nozzle to atomize monodisperse droplets from a range of precursors, to generate uniform microparticles for controlled release applications. The versatility of the device enabled microparticles with easily tunable drug release kinetics to be assembled by adjusting the drying conditions or the composition of the precursors, including the use of dopants or different solvents. Significant adjustment of the release profiles could be realized by manipulating the microstructure of the microparticles. Due to the homogeneity of the particles, a direct correlation between the microstructural properties and release mechanisms could be obtained, the knowledge of which is crucial for the design of spray-dried polymeric-based pharmaceutical particles

On spray drying of uniform silica-based microencapsulates for controlled release

Although spray drying is a scalable route for particle formation with easy product recovery, a typical spray drier produces broad distributions of particles with various morphologies in a single batch, due to the non-uniform formation of droplets, wide spray trajectories, and various residence times experienced by the droplets during drying. Thus any attempt to interpret the resulting particle functionality directly in relation to their physico-chemical properties is difficult. Here, uniform silica-based microencapsulates encapsulating vitamin B(12) homogenously distributed within their matrix were synthesised in a single step via a micro-fluidic-jet-spray-dryer (MFJSD), utilising a micro-fluidic-aerosol-nozzle (MFAN) for continuous generation of monodisperse droplets. We investigated the effects of lactose and Na-alginate to the properties of the silica matrix, as well as the overall particle shapes. The uniform nature of the particles allowed direct correlations between the matrix properties and the release behaviour of vitamin B(12) to be observed without the complications of wide size distribution or variety of shapes. Spherical particles with relatively smooth surface were obtained with lactose addition, while incorporation of Na-alginate resulted in increasing surface roughness. Lactose accelerated the release of the encapsulated vitamin B(12) (VB12), due to the relatively fast lactose dissolution that allowed buffer to penetrate deep into the matrix to facilitate diffusion and silica erosion. On the contrary, Na-alginate slowed down the release considerably by serving as an additional barrier to decelerate the matrix erosion, as well as due to ionic attraction to the VB12 molecules. Release kinetics data indicated diffusion as the main release mechanism independent of the microencapsulate composition. The release profiles from different compositions of the synthesized particles demonstrated good agreements with the computational predictions, highlighting the ability to modulate the release behaviour directly from the precursor compositions.Australian Research Council (ARC)[DP0773688

Facile Spray-Drying Assembly of Uniform Microencapsulates with Tunable Core-Shell Structures and Controlled Release Properties

Microencapsulates with defined core shell structures are of interest for applications, such as controlled release and encapsulation, because of the feasibility of fine-tuning individual functionalities of different parts. Here, we report a new approach for efficient and scalable production of such particles. Eudragit RS (a co-polymer of ethyl acrylate, methyl methacrylate, and a low content of methacrylic acid ester with quaternary ammonium groups) was used as the main shell component, with silica as the core component, formed upon a single-step spray-drying assembly. The method is capable of forming uniform core shell particles from homogeneous precursors without the use of any organic solvents. Evaporation-induced self-assembly attained the phase separation among different components during drying, resulting in the core shell spatial configuration, while precise control over particle uniformity was accomplished via a microfluidic jet spray dryer. Direct control over shell thickness can be achieved from the ratio of the core and shell ingredients in the precursors. A fluorescent compound, rhodamine B, is used as a highly water-soluble model component to investigate the controlled release properties of these microencapsulates, with the release behaviors shown to be significantly dependent upon their architectures.Monash University; China Scholarship Counci

Assembly of Uniform Photoluminescent Microcomposites Using a Novel Micro-Fluidic-Jet-Spray-Dryer

Generation of uniform micro-particles containing (i) pure lactose; (ii) silica nanoparticles and lactose; (iii) silica nanoparticlesllactose doped with Eu(III) have been successfully achieved using a novel spray dryer with a uniquely designed microfluidic aerosol nozzle as the monodisperse droplet generator. Here we investigate the impacts of precursor compositions and concentrations, as well as the drying temperature profile on particle size, morphology, and surface element distribution. Distinct morphologies are observed with different precursor compositions, ranging from smooth spherical lactose microparticles to the buckled shape for composites containing silica nanoparticles. The formation of such morphology is qualitatively interpreted by using Peclet number, indicating that the presence of the suspended silica nanoparticles facilitates shell formation at the early stage of the drying process. As the drying continue, such shell is subject to buckling, induced by the capillary force due to the lower mechanical integrity inside the droplet. Post calcination, transmission electron micrographs of Eu(III)Isilica nanoparticlesllactose microcomposites confirm the formation of nano-sized Eu,03 homogeneously embedded on the silica shell. Photoluminescence spectra of these particles indicate that enhancement of photoluminescence intensity is directly related to the europium loading, which could be adjusted from the precursor composition. This work demonstrates a scalable route to assemble relatively complex composites with uniform properties, without extensive conjugation or purification steps commonly required in wet chemistry-based processes. (C) 2011 American Institute of Chemical Engineers AIChE J, 57: 2726-2737, 2011Australian Research Council; Monash Research Graduate School and Department of Chemical Engineering, Monash Universit

Microfluidic spray drying as a versatile assembly route of functional particles

Microfluidic spray drying is a versatile route to synthesize functional particles, as the technique is scalable with sufficient yields for practical use and easy product recovery, whilst allowing for subsequent processing as necessary. Here a microfluidic jet spray drier producing single trajectory droplets with identical thermal history was used to obtain monodisperse particles with precise morphology. The method employed a moderate temperature range (< 300 degrees C), and was able to handle multi-component precursors to form solid particles in a single step. Spray drying of a stable colloidal suspension containing iron chloride, lactose, and silica nanoparticles produced microcomposites with platelet-like morphology due to the nanoparticles in the precursor. Subsequent calcination caused the formation of iron oxide crystals of 10 nm-1 mu m on the surface of the particles. Both calcination period and post-drying conditions affected the magnetic properties of the composites, with the increase in magnetization correlating well with the proportion of magnetite phase in the iron oxide crystals. The reaction pathways pertaining to the formation of different iron oxide phases are discussed. (C) 2011 Elsevier Ltd. All rights reserved.Australia Postgraduate Award (APA