This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu ...Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100 l h
−1
.
•Uniform POPC and Lipoid® E80 liposomes were produced using microengineered membrane.•Three different methods of generating shear stress on the membrane surface were used.•POPC vesicles with 80nm ...size were made using a ring membrane oscillating at 40Hz.•The mean vesicle size increased with increasing the pore size and injection time.•The mean vesicle size of 80–86nm and a CV of 26–36% was suitable for drug delivery.
A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid® E80 liposomes at different production scales. A stirred cell device was used to produce 73ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140lm−2h−1), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5μm and pore spacing of 200μm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80–86nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations.
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•Novel azimuthally oscillating membrane emulsification system has been used for the production of highly uniform W1/O/W2 emulsions.•Emulsion dilution promoted the solvent removal ...allowing the polymer solidification.•Uniform solid multi-core poly-caprolactone particles were produced.•Particle morphology and encapsulation efficiency were controlled by the solidification step.•Encapsulation efficiency of both copper ions and α-tocopherol was achieved.
Co-encapsulation of drugs in the same carrier, as well as the development of microencapsulation processes for biomolecules using mild operating conditions, and the production of particles with tailored size and uniformity are major challenges for encapsulation technologies. In the present work, a suitable method consisting of the combination of membrane emulsification with solvent diffusion is reported for the production of multi-core matrix particles with tailored size and potential application in multi-therapies. In the emulsification step, the production of a W/O/W emulsion was carried out using a batch Dispersion Cell for formulation testing and subsequently a continuous azimuthally oscillating membrane emulsification system for the scaling-up of the process to higher capacities. In both cases precise and gentle control of droplet size and uniformity of the W/O/W emulsion was achieved, preserving the encapsulation of the drug model within the droplet. Multi-core matrix particles were produced in a post emulsification step using solvent diffusion. The compartmentalized structure of the multicore-matrix particle combined with the different chemical properties of polycaprolactone (matrix material) and fish gelatin (core material) was tested for the simultaneous encapsulation of hydrophilic (copper ions) and hydrophobic (α-tocopherol) test components. The best operating conditions for the solidification of the particles to achieve the highest encapsulation efficiency of copper ions and α-tocopherol of 99 (±4)% and 93(±6)% respectively were found. The multi-core matrix particle produced in this work demonstrates good potential as a co-loaded delivery system.
Liposomes with a mean size of 59-308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of ...540 mm and a pore spacing of 80 or 200 mm. An ethanolic phase containing 20-50 mg ml(-1) phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or Lipoid (R) E80), 5-12.5 mg ml(-1) stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg m(-1) vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142-355 l m(-2) h(-1) and a shear stress on the membrane surface of 0.80-16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of the prepared liposomes increased with an increase in the pore size of the membrane and decreased with an increase in the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. The reproducibility of the developed fabrication method was high.
Raw depectinized apple juice was clarified in a laboratory scale ultrafiltration system using ceramic tubular membranes (Tech-Sep Carbosep) with a molecular weight cut-off of 300,000, 50,000, and ...30,000 Da. The experiments have been carried out over a wide range of transmembrane pressures (100–400 kPa), temperatures (20–55 °C), and feed flow rates (100–900 ml/min). Permeate flux significantly decreased with time until a steady-state was established. The steady-state permeate flux reached a maximum at a transmembrane pressure of about 200 kPa. Higher permeate flux was obtained at higher temperatures due to lower permeate viscosity. The steady-state permeate flux was proportional to the feed flow rate raised to powers ranging between 0.22 and 0.31. All the membranes studied produced the clarified juice with a satisfactory clarity and color intensity value.
Membrane emulsification (ME) is a relatively new technique for the highly controlled production of particulates. This review focuses on the recent developments in this area, ranging from the ...production of simple oil-in-water (O/W) or water-in-oil (W/O) emulsions to multiple emulsions of different types, solid-in-oil-in-water (S/O/W) dispersions, coherent solids (silica particles, solid lipid microspheres, solder metal powder) and structured solids (solid lipid microcarriers, gel microbeads, polymeric microspheres, core-shell microcapsules and hollow polymeric microparticles). Other emerging technologies that extend the capabilities into different membrane materials and operation methods (such as rotating membranes, repeated membrane extrusion of coarsely pre-emulsified feeds) are introduced. The results of experimental work carried out by cited researchers in the field together with those of the current authors are presented in a tabular form in a rigorous and systematic manner. These demonstrate a wide range of products that can be manufactured using different membrane approaches. Opportunities for creation of new and novel entities are highlighted for low throughput applications (medical diagnostics, healthcare) and for large-scale productions (consumer and personal products).
Purpose
Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl cellulose/ gelatine (NaCMC/GEL) hydrogel and a ‘poke and patch’ microneedle delivery method was used to enhance ...permeation flux of LidH.
Methods
The microparticles were formed by electrostatic interactions between NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean particle size and morphology. Subsequent
in vitro
skin permeation studies were performed via passive diffusion and microneedle assisted permeation of LidH NaCMC/GEL to determine the maximum permeation rate through full thickness skin.
Results
LidH 2.4% w/w NaCMC/GEL 1:1.6 and 1:2.3 respectively, possessed optimum zeta potential. LidH 2.4% w/w NaCMC/GEL 1:2.3 and 1:2.7 demonstrate higher pseudoplastic behaviour. Encapsulation efficiency (14.9–17.2%) was similar for LidH 2.4% w/w NaCMC/GEL 1:1.6–1:2.3. Microneedle assisted permeation flux was optimum for LidH 2.4% w/w NaCMC/GEL 1:2.3 at 6.1 μg/ml/h.
Conclusion
LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum therapeutic drug threshold with microneedle skin permeation in less than 70 min.
SPG membranes were used to prepare monodispersed O/W and W/O/W emulsions over a wide range of membrane wall shear stress (0.37–40
Pa), dispersed phase content (1–20
vol.%) and transmembrane pressure. ...Although the most uniform droplets were prepared at the membrane wall shear stress of 30
Pa, a monodispersed O/W emulsion can be even obtained at the wall shear stress of 0.37
Pa, corresponding to laminar flow regime of continuous phase inside the membrane tube. The minimum droplet size somewhat decreased with time, probably due to gradual activation of smaller pores. There was no significant difference in the size distribution curve of pure oil droplets of O/W emulsions and W/O drops of W/O/W emulsions, if they were both prepared under the same conditions. No significant change in droplet size distribution of prepared O/W emulsions was observed during the storage time of up to 159 days.
The influence of various emulsifier types (anionic, nonionic, and zwitterionic) on the mean particle size, transmembrane flux, and membrane fouling in repeated membrane homogenization using a Shirasu ...porous glass (SPG) membrane has been investigated. Oil-in-water (O/W) emulsions (40 wt % corn oil stabilized by 0.06−2 wt % sodium dodecyl sulfate (SDS) or 0.1−2 wt % Tween 20 at pH 3 or 0.5−2 wt % β-lactoglobulin (β-Lg) at pH 7) were prepared by passing coarsely emulsified feed mixtures five times through the membrane with a mean pore size of 8.0 μm under the transmembrane pressure of 100 kPa. The flux increased as the number of passes increased, tending to a maximum limiting value. The maximum flux for the Tween 20-stabilized emulsions (5−47 m3·m-2·h-1) was smaller than that for the SDS-stabilized emulsions (29−60 m3·m-2·h-1) because less energy was needed for the disruption of a SDS-stabilized droplet due to the lower interfacial tension. The mean particle size after five passes was 4.1−6.8 and 6.4−8.7 μm for 0.1−2 wt % SDS and Tween 20, respectively. The flux in the presence of β-Lg was much smaller than that in the presence of SDS and Tween 20, which was a consequence of more pronounced membrane fouling, due to the protein adsorption to the membrane surface. After five passes through the membrane, the fouling resistance in the presence of 2 wt % β-Lg (1.1 × 1010 1/m) was 2 orders of magnitude higher than that for 0.5 wt % Tween 20 and an order of magnitude higher than the membrane resistance. If a clean membrane was used in the fifth pass, a 2-fold reduction of the fouling resistance was observed.
Shirasu-porous-glass (SPG) membranes with a mean pore size from 0.4–6.6 μm were used to produce O/W emulsions consisting of vegetable (rape seed) oil as the dispersed phase and Span 80 dissolved in ...demineralized water as the continuous phase. The emulsion droplets with a mean droplet size 3.5 times larger than the mean pore size and the span of the droplet size distribution between 0.26 and 0.45 were produced using 2% emulsifier at a transmembrane pressure slightly exceeding the capillary pressure. Under these conditions the dispersed phase flux through the membrane was in the range of 0.7–7 1·m
−2·h
−1 and only about 2% of the pores were active. However, if the transmembrane pressure was considerably higher than the capillary pressure, the dispersed phase flux strongly increased and droplets with a broad droplet size distribution were produced. The hydraulic resistance of the SPG membrane was inversely proportional to the square of the mean pore size, which is in agreement with the Hagen-Poiseuille law. The membrane porosity is independent on the pore size and ranged from 53–60%.
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