Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

Self-assembly of Tween 80 micelles as nanocargos for oregano and trans-cinnamaldehyde plant-derived compounds

The self-assembly of Tween 80 (T80) micelles loaded with plant-based oregano essential oil (OR) and trans-cinnamaldehyde (TCA) was studied. The effect of different factors, including the surfactant to oil ratio, the presence of sodium chloride, thermal treatment, and dilution on their formation and physicochemical stability was evaluated. The creation of nano-cargos was confirmed by TEM. The self-associated structures had z-average droplet diameters of 92 to 337 nm without any energy input. Whereas addition of 10% (w/v) NaCl prevented the formation of oregano essential oil nano-assemblies of T80, swollen micelles containing TCA were successfully produced. Moreover, the OR or TCA loaded-micelles had only a slight droplet size variation upon thermal treatment. Ultimately, their antibacterial activity analysis against some food pathogens revealed that the encapsulation of OR and TCA within micelles crucially improved their antibacterial activity. These straightforward and cost-effective designed systems can be applicable in different products, including foods and agrochemicals

DNA-coated Functional Oil Droplets

Many industrial soft materials often include oil-in-water (O/W) emulsions at the core of their formulations. By using tuneable interface stabilizing agents, such emulsions can self-assemble into complex structures. DNA has been used for decades as a thermoresponsive highly specific binding agent between hard and, recently, soft colloids. Up until now, emulsion droplets functionalized with DNA had relatively low coating densities and were expensive to scale up. Here a general O/W DNA-coating method using functional non-ionic amphiphilic block copolymers, both diblock and triblock, is presented. The hydrophilic polyethylene glycol ends of the surfactants are functionalized with azides, allowing for efficient, dense and controlled coupling of dibenzocyclooctane functionalized DNA to the polymers through a strain-promoted alkyne-azide click reaction. The protocol is readily scalable due to the triblock's commercial availability. Different production methods (ultrasonication, microfluidics and membrane emulsification) are used with different oils (hexadecane and silicone oil) to produce functional droplets in various size ranges (sub-micron, $\sim 20\,\mathrm{\mu m}$ and $> 50\,\mathrm{\mu m}$), showcasing the generality of the protocol. Thermoreversible sub-micron emulsion gels, hierarchical "raspberry" droplets and controlled droplet release from a flat DNA-coated surface are demonstrated. The emulsion stability and polydispersity is evaluated using dynamic light scattering and optical microscopy. The generality and simplicity of the method opens up new applications in soft matter and biotechnological research and industrial advances.Comment: 7 pages, 2 figures, 1 tabl

Stability of water-in-oil-in-water emulsions formed by membrane emulsification : a thesis presented in partial fulfilment of the requirements for the degree of Master of Technology in Food Technology at Massey University, Palmerston North, New Zealand

The main objectives of this study were to determine i. The effectiveness of encapsulating whey protein concentrates (WPC) within water-in-oil-in-water multiple emulsions produced by membrane emulsification. ii. The effect of the primary and secondary emulsification conditions and membrane operating parameters on the multiple emulsion properties; of particular concern were the yield and physical stability of the emulsions. The multiple emulsions were prepared by a two-stage emulsification process. The emulsification conditions were varied widely to determine the optimum conditions for the production of multiple emulsions. Ultra-Turrax, ultrasound and valve homogenisation were tried for the preparation of the primary emulsion; an Ultra-Turrax and Shirazu porous glass (SPG) membrane emulsification were used for secondary emulsification. The standard primary emulsions (water-in-oil) were prepared with 10% of the WPC and 6.4% glucose (as a marker) in the water phase with a water-in-oil volume fraction of 0.25. The oil phase (soybean oil) consisted of 10% hydrophobic emulsifier (Polyglycerol polyricinoleate [PGPR] or Span 80). Typically pre-emulsification was carried out in an Ultra-Turrax at 20500 rpm and the primary emulsification was done in a homogeniser at a pressure of 500/100 bars in the two stages; secondary emulsions were prepared with an SPG membrane of pore size 2μm or 3.8µm with the dispersed phase (water-in-oil) being pushed through the pores of the membrane at a specific transmembrane pressure (125-150 kPa) and dispersed phase flux into a continuous phase (water with a hydrophilic emulsifier concentration, usually Tween 80, of 1%) flowing through the inside of the membrane at a particular velocity (standard of 1 m/s). The yield of the multiple emulsions formed was estimated by measuring glucose release using an Advantage Glucose meter. Unlike Span 80, PGPR was able to form stable o/w emulsions and hence the initial yield of the multiple emulsions varied from 80% at 2.5% to 100% at 10% PGPR. The higher the concentration of water in the inner phase the lower the yield of the multiple emulsions and the higher the droplet size of the primary emulsions. A valve homogeniser gave the best results for primary emulsification. Of the 3 homogenisation pressures (250 bar, 500 bar, 1000 bar) tried, the w/o emulsion produced with 500 bar and 10% PGPR was taken as the standard as this was found to be stable for 6 months without physical damage. A 30% maximum loading of the WPC in the inner water phase was also determined. A further increase may destabilise the process by causing blockage to the membrane pores. The yield as well as the droplet size of the multiple emulsions was found to increase as the membrane pore-size was increased from 1.4 µm to 3.8 µm. Transmembrane pressure and continuous phase velocity did not have much influence on the yield of the multiple emulsions. However an increase in continuous phase velocity increased the opacity of the serum layer formed indicating that an increased amount of smaller droplets were formed. The dispersed phase flux was increased by increases in any of the transmembrane pressure, PGPR concentration and membrane pore-size. Hydrophilic emulsifiers (whey protein isolate, soy protein isolate and sodium caseinate) did not influence the yield; however the Tween 80 stabilised multiple emulsions showed a smaller droplet size. An increase in temperature from 20 - 50°C resulted in a lower yield as well as a higher droplet size. The osmotic gradient set up by glucose and WPC in the inner phase of the emulsion resulting in an influx of water from the outer phase causing bulging of the droplets. Sorbitol added at 1.7% in the outer phase gave a high initial yield (100%) as well as a low droplet size (2-3 µm). The cream layer formed as a result of storage was found to decrease with increase in sorbitol concentration (to 5.9%) due to the lower size ot the droplets formed. The key issues identified were to find an alternative to PGPR with lower Accepted Daily Intake (ADI) value without compromising the emulsification properties and to standardise ways to analyse droplet size of w/o emulsions. Overall the study proved that functional ingredients can be encapsulated using stable w/o/w multiple emulsions prepared using SPG membranes under standardised conditions and hence appears to offer promise for manufacture of commercial products

Emulsification in binary liquids containing colloidal particles: a structure-factor analysis

We present a quantitative confocal-microscopy study of the transient and final microstructure of particle-stabilised emulsions formed via demixing in a binary liquid. To this end, we have developed an image-analysis method that relies on structure factors obtained from discrete Fourier transforms of individual frames in confocal image sequences. Radially averaging the squared modulus of these Fourier transforms before peak fitting allows extraction of dominant length scales over the entire temperature range of the quench. Our procedure even yields information just after droplet nucleation, when the (fluorescence) contrast between the two separating phases is scarcely discernable in the images. We find that our emulsions are stabilised on experimental time scales by interfacial particles and that they are likely to have bimodal droplet-size distributions. We attribute the latter to coalescence together with creaming being the main coarsening mechanism during the late stages of emulsification and we support this claim with (direct) confocal-microscopy observations. In addition, our results imply that the observed droplets emerge from particle-promoted nucleation, possibly followed by a free-growth regime. Finally, we argue that creaming strongly affects droplet growth during the early stages of emulsification. Future investigations could clarify the link between quench conditions and resulting microstructure, paving the way for tailor-made particle-stabilised emulsions from binary liquids.Comment: http://iopscience.iop.org/0953-8984/22/45/455102

Optimization of Oil-in-Water Emulsion Stability: Experimental Design, Multiple Light Scattering, and Acoustic Attenuation Spectroscopy

To find an optimal formulation of oil-in-water (O/W) emulsions (o = 0.05), the effect of emulsifier nature and concentration, agitation speed, emulsifying time, storage temperature and their mutual interactions on the properties and behavior of these dispersions is evaluated by means of an experimental design (Nemrodw software). Long-term emulsion stability is monitored by multiple light scattering (Turbiscan ags) and acoustic attenuation spectroscopy (Ultrasizer). After matching surfactant HLB and oil required HLB, a model giving the Sauter diameter as a function of emulsifier concentration, agitation speed and emulsification time is proposed. The highest stability of C12E4-stabilized O/W emulsions is observed with 1% emulsifier

Effect of viscosities of dispersed and continuous phases in microchannel oil-in-water emulsification

Although many aspects of microchannel emulsification have been covered in literature, one major uncharted area is the effect of viscosity of both phases on droplet size in the stable droplet generation regime. It is expected that for droplet formation to take place, the inflow of the continuous phase should be sufficiently fast compared to the outflow of the liquid that is forming the droplet. The ratio of the viscosities was therefore varied by using a range of continuous and dispersed phases, both experimentally and computationally. At high viscosity ratio (eta (d)/eta (c)), the droplet size is constant; the inflow of the continuous phase is fast compared to the outflow of the dispersed phase. At lower ratios, the droplet diameter increases, until a viscosity ratio is reached at which droplet formation is no longer possible (the minimal ratio). This was confirmed and elucidated through CFD simulations. The limiting value is shown to be a function of the microchannel design, and this should be adapted to the viscosity of the two fluids that need to be emulsified

Comparison between three static mixers for emulsification in turbulent flow

This paper deals with comparing performances of three different static mixers in terms of pressure drop generated by both single-phase flow and liquid–liquid flow in turbulent flow regime and in terms of emulsification performances. The three motionless mixers compared are the well-known SMX™ and SMV™ and the new version of the SMX called SMXPlus™. This experimental study aims at highlighting the influence of the dispersed phase concentration and some of the geometrical parameters such as number of elements and design of the motionless mixer on droplets size distributions characteristics. Finally, experimental results are correlated in terms of Sauter mean diameter as a function of hydrodynamic dimensionless numbers

Transposition from a batch to a continuous process for microencapsulation by interfacial polycondensation

A novel continuous process is proposed and investigated to produce microcapsules by interfacial polycondensation. Polymeric microcapsules are obtained via a two-step process including an initial emulsification of two immiscible fluids in static mixers and a subsequent interfacial polycondensation reaction performed in two different continuous reactors, the Deanhex heat exchanger/reactor or a classical coiledtube. This study is carried out through a step by step approach. A model system involving polyurea as the polymeric membrane and cyclohexane as the encapsulated species is chosen. A semi-batch reaction kinetic study is first performed in order to obtain kinetics data of the polycondensation reaction and to highlight hydrodynamic issues that can happen when running the encapsulation reaction in classical stirred tank. Parameters influencing droplets size obtained when carrying out emulsification in static mixers are then investigated. The hydrodynamic of the Deanhex reactor used is also characterized in terms of mixing time and residence time distribution. To validate the innovative continuous process, the emulsion droplets obtained at the static mixer outlet are encapsulated firstly in the Deanhex reactor and secondly in the coiled-tube. The apparent reaction kinetics and microcapsules characteristics corresponding to different operating conditions are discussed