Recent developments in manufacturing multiple emulsions using membrane and micro fluidic devices

Membrane and microfluidic devices are new routes for controllable production of multiple emulsions with uniformly sized drops and accurate control of the internal drop structure. Membrane emulsification involves injecting single emulsion through a porous membrane into continuous phase in a stirred cell or cross-flow membrane module. In this work an alternative method to generate shear at the membrane surface was applied, based on the low frequency oscillation of the membrane at 10-90 Hz in a direction perpendicular to the flow of the injected phase. The advantage of oscillating membrane technique is that the risk of the drop breakage in the continuous phase is minimal, because the shear is generated only at the membrane surface. The oscillation signal was provided by an audio generator which fed a power amplifier driving the electro-mechanical oscillator on which the inlet manifold was mounted. The membrane was a microsieve-type membrane with regular pore spacing formed by Ni electroforming. At the constant maximal shear stress at the membrane surface the mean size of oil globules in W/O/W emulsions decreased with increasing the amplitude of oscillation. The most narrow drop size distribution with a span of 0.36 was obtained at 70 Hz and the peak amplitude of about 0.4 mm. A disadvantage of membrane emulsification is that the internal drop structure cannot be accurately controlled. Microfluidic devices with co-axial glass microcapillaries developed in Weitz Lab have been found convenient for controllable generation of both core-shell drops and multiple emulsion drops with a controlled number of inner drops in the outer drop. In this work core-shell drops with a size between 50 and 150 μm have been produced at the production rate ranging from 1,000 to 10,000 drops/s. The shell thickness was accurately controlled by adjusting the ratio of the middle fluid flow rate to the inner fluid flow rate and the drop size decreased with increasing the outer fluid flow rate

Emulsion templating of poly(lactic acid) particles: droplet formation behavior

Monodisperse poly(dl-lactic acid) (PLA) particles of diameters between 11 and 121 ?m were fabricated in flow focusing glass microcapillary devices by evaporation of dichloromethane (DCM) from emulsion droplets at room temperature. The dispersed phase was 5% (w/w) PLA in DCM containing 0.1−2 mM Nile red and the continuous phase was 5% (w/w) poly(vinyl alcohol) in reverse osmosis water. Particle diameter was 2.7 times smaller than the diameter of the emulsion droplet template indicating very low particle porosity. Monodisperse droplets have only been produced under dripping regime using a wide range of dispersed phase flow rates (0.002−7.2 cm3h-1), continuous phase flow rates (0.3−30 cm3h-1) and orifice diameters (50−237 ?m). In the dripping regime, the ratio of droplet diameter to orifice diameter was inversely proportional to the 0.39 power of the ratio of the continuous phase flow rate to dispersed phase flow rate. Highly uniform droplets with a coefficient of variation (CV) below 2 % and a ratio of the droplet diameter to orifice diameter of 0.5−1 were obtained at flow rate ratios of 4−25. Under jetting regime, polydisperse droplets (CV > 6 %) were formed by detachment from relatively long jets (between 4 and 10 times longer than droplet diameter) and a ratio of the droplet size to orifice size was 2−5

Fabrication of biodegradable poly(lactic acid) particles in flow focusing glass capillary devices

Fabrication of biodegradable poly(lactic acid) particles in flow focusing glass capillary device

Fabrication of monodisperse poly(dl- lactic acid) microparticles using drop microfluidics

Monodisperse poly(dl-lactic acid) particles with a diameter between 11 and 121 μm were fabricated by drop microfluidics/solvent evaporation method using flow focusing glass capillary device. In the dripping regime, the ratio of droplet diameter to orifice diameter was in the range of 0.37−1.34 and was inversely proportional to the 0.39 power of the ratio of the continuous phase flow rate to dispersed phase flow rate

Fabrication of biodegradable poly(lactic acid) particles in flow-focusing glass capillary devices

Monodisperse poly(dl-lactic acid) (PLA) particles with a diameter in the range from 12 to 100 9m were fabricated in flow focusing glass capillary devices by evaporation of dichloromethane (DCM) from emulsions at room temperature. The dispersed phase was 5% (w/w) PLA in DCM containing a small amount of Nile red and the continuous phase was 5% (w/w) poly(vinyl alcohol) in reverse osmosis water. Particle diameter was 2.7 times smaller than the size of the emulsion droplet template indicating that the particle porosity was very low. SEM images revealed that the majority of particle pores are in the sub-micron region but in some instances these pores can reach 3 9m in diameter. Droplet diameter was influenced by the flow rates of the two phases and the entry diameter of the collection capillary tube; droplet diameters decreased with increasing values of the flow rate ratio of the dispersed to continuous phase to reach constant minimum values at 40-60 % orifice diameter. At flow rate ratios less than 5, jetting can occur, giving rise to large droplets formed by detachment from relatively long jets (~10 times longer than droplet diameter)

Polymer Phase Separation in a Microcapsule Shell

Phase separation has been used for engineering microscale fluids and particles with designed structures. But it is challenging to use phase separation to create complicated microcapsules because phase separation in the shell correlates with applied osmotic pressure and affects capsule stability significantly. Here we employ two biodegradable polymers to study the phase separation in microcapsule shells and its effect on the mechanical stability. The dynamic process reveals that phase separation creates a patchy shell with distinct regions transiently, then transports the discrete domains across the shell, and coalesces them at the surface. The equilibrium structure with balanced osmotic pressure is a Janus shell, where one component forms the shell and the other component dewets on the surface. Under slight osmotic pressure to the shell, phase separation reaches a different Janus shape, which consists of two partial shells of each component. We can in further take advantage of phase separation and osmotic pressure to rupture microcapsules at specific locations. Phase separation in the shell provides a facile approach to create versatile capsule structures and affords a reliable strategy to harness the shell mechanics

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Monodisperse core/shell drops with aqueous core and poly(dimethylsiloxane) (PDMS) shell of controllable thickness have been produced using a glass microcapillary device that combines co-flow and flow-focusing geometries. The throughput of the droplet generation was high, with droplet generation frequency in the range from 1,000 to 10,000 Hz. The size of the droplets can be tuned by changing the flow rate of the continuous phase. The technique enables control over the shell thickness through adjusting the flow rate ratio of the middle to inner phase. As the flow rate of the middle and inner phase increases, the droplet breakup occurs in the dripping-to-jetting transition regime, with each double emulsion droplet containing two monodisperse internal aqueous droplets. The resultant drops can be used subsequently as templates for monodisperse polymer capsules with a single or multiple inner compartments, as well as functional vesicles such as liposomes, polymersomes and colloidosomes

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Control over the shell thickness of core/shell drops in three-phase glass capillary device

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Monodisperse core/shell drops with aqueous core and poly(dimethylsiloxane) (PDMS) shell of controllable thickness have been produced using a glass microcapillary device that combines co-flow and flow-focusing geometries. The throughput of the droplet generation was high, with droplet generation frequency in the range from 1,000 to 10,000 Hz. The size of the droplets can be tuned by changing the flow rate of the continuous phase. The technique enables control over the shell thickness through adjusting the flow rate ratio of the middle to inner phase. As the flow rate of the middle and inner phase increases, the droplet breakup occurs in the dripping-to-jetting transition regime, with each double emulsion droplet containing two monodisperse internal aqueous droplets. The resultant drops can be used subsequently as templates for monodisperse polymer capsules with a single or multiple inner compartments, as well as functional vesicles such as liposomes, polymersomes and colloidosomes

Stabilization of the Amorphous Structure of Spray-Dried Drug Nanoparticles

The bioavailability of hydrophobic drugs strongly increases if they are formulated as amorphous materials because the solubility of the amorphous phase is much higher than that of the crystal. Moreover, the stability of these particles against crystallization during storage increases with decreasing particle size. Hence, it is advantageous to formulate poorly water soluble drugs as amorphous nanoparticles. The formulation of an amorphous structure is often difficult because many of these drugs have a high propensity to crystallize. This difficulty can be overcome if drugs are spray-dried using a microfluidic nebulator we recently developed. However, these nanoparticles agglomerate when they come in contact with each other, and this compromises the stability of their amorphous structure through crystallization. To improve their stability, we coat the nanoparticles with a sterically stabilizing polymer layer; this can be accomplished by co-spraying them with an excipient. However, this excipient must meet strict solubility limits, which severely limit the choice of polymers. Alternatively, the nanoparticles can be sterically stabilized by spraying them directly into a polymeric matrix; this enables a much wider choice of stabilizing polymers