Re-coalescence of emulsion droplets during high-energy emulsification

Production of sub-micron emulsions by ultrasound and microfluidization techniques

The purpose of this study was to produce an oil-in-water nano-emulsion with different compositions of the continuous and dispersed phases through microfluidization. The aqueous phase was a solution of maltodextrin with five different emulsifying ingredients including modified starch (Capsul and Hi-Cap), sodium caseinate (SC), whey protein hydrolysate (WPH), or whey protein concentrate (WPC), while the oil phase consisted of d-limonene or fish oil. Results showed that micofluidizer was capable of producing nano-emulsions (D32 as small as 150 nm) with a narrow size distribution. Generally, moderate microfluidization pressures (42–63 MPa) and cycles (1–2) were the optimum conditions beyond which, there were adverse changes in the emulsion size. For the two oils tested as the dispersed phase, fish oil emulsions had lower Sauter mean diameters (D32) but with wider size distributions than d-limonene. When different emulsifying ingredients were compared, Hi-Cap produced nano-emulsions with the narrowest distribution but highest D32 (about 600 nm). Nano-emulsions with WPC had the smallest D32 (about 200 nm) but the widest size distribution. It was found that a d-limonene volume fraction of 0.10 was the optimum dispersed-phase concentration in terms of emulsion droplet size (D32). Also, adding a surfactant (Tween 20) helped to reduce the emulsion size significantly during microfluidization, but it lead to extensive flocculation of emulsion droplets because of surfactant–biopolymer interactions and emulsifier displacement.

Optimization of nano-emulsions production by microfluidization

Rheological behavior and stability of d-limonene emulsions made by a novel hydrocolloid (Angum gum) compared with Arabic gum

In this study we investigated the effect of droplet size on the antimicrobial activity of emulsions containing two essential oil compounds that are known for their antimicrobial effectiveness: carvacrol and eugenol. Coarse emulsions were prepared by blending a triacylglyceride (Miglyol 812N) containing various concentrations of carvacrol or eugenol (5, 15, 30, 50 wt%) at an oil droplet mass fraction of 10 wt% with an aqueous phase containing 2 wt% Tween 80®. Premixes were then further dispersed using a high shear blender, a high pressure homogenizer at different pressures or an ultrasonicator to produce droplets with a variety of mean diameters. Microscopy and light scattering storage stability studies over 10 days indicated that manufactured emulsions were stable, i.e. that no aggregation, creaming or other destabilization mechanisms occurred and droplet size distributions remained unchanged. The antimicrobial activity of emulsions was assessed against two model microorganisms, the Gram negative Escherichia coli C 600 and the Gram positive Listeria innocua, by determining growth over time behavior. The analysis yielded the unexpected result that emulsions with larger droplet sizes were more effective at inhibiting growth and inactivating cells than smaller ones. For example, emulsions with a mean oil droplet size of 3000 nm at a concentration of 800 ppm carvacrol completely inhibited L. innocua, while for 80 nm emulsions, only a delay of growth could be observed. Measurements of the concentration of the antimicrobial compounds in the aqueous phase indicated that concentrations of eugenol and carvacrol decreased with decreasing oil droplet sizes. Determination of interfacial tension further showed that eugenol and carvacrol are preferentially located in the oil–water interfaces. Theoretical calculations of Tween 80® concentrations needed to saturate interfaces suggested that in small emulsions for the given formulation less Tween 80® micelles are present in the aqueous phase. We therefore attribute the fact that antimicrobial nanoemulsions are less active than macroemulsions due to an increased sequestering of antimicrobials in emulsion interfaces and a decreased solubilization in excess Tween 80® micelles.

Influence of droplet size on the efficacy of oil-in-water emulsions loaded with phenolic antimicrobials

Emulsification plays an important role in the formulation of lipophilic pharmaceutical agents. These substances are often included in the disperse phase of an oil-in-water emulsion. To reach a high bioavailability and a good long-term stability, drop sizes much less than 1 micron are required. For the generation of such emulsions, energy densities of a quality which can only be reached in high-pressure systems, are necessary. Actually available apparatus, such as high-pressure homogenizers fitted with valves, microfluidizer or jet disperser, reach particle sizes of about 0.2 micron in continuous processes. It is indispensable to produce emulsions with smaller globules in order to receive a maximum of diversity in application. Therefore, dispersion units with a higher efficiency in drop breakup are needed. Especially in the case of parenterally administered medicament formulations an average particle size between 0.04 and 0.1 microns is requested which is up to now not reachable by continuous emulsification. In this study the drop breakup behavior of a new high-pressure nozzle is investigated with the example of oil-in-water emulsions and compared to the breakup behavior of a state-of-the-art nozzle and to available data published.

Evaluation of a New High-Pressure Dispersion Unit (HPN) for Emulsification

Untersuchungen zum Aufbruch von Einzeltropfen in Dispergiereinheiten zur Emulsionsherstellung

A process for mixing or dispersing liquids is provided that includes introducing liquids to be mixed or dispersed into a mixing device having a cylindrical support. The cylindrical support includes an inlet nozzle having a bore which is in fluid communication through a turbulence chamber with a bore of an outlet nozzle, wherein the bores of the nozzles are axially spaced apart relative to one another. The liquids are then allowed to enter the turbulence chamber through the bore of the inlet nozzle where the liquids are mixed or dispersed. The mixed or dispersed liquid is then recovered from the outlet nozzle. Various devices for mixing or dispersing liquids are also provided.

Preparation of liquid dispersions

A method for mixing or dispersing liquids in which the liquids to be mixed or to be dispersed are pumped at temperatures of about 20°C to about 250°C, preferably of about 20°C to about 200°C, and pressures of about 50 bar to about 2500 bar, preferably of about 100 bar to about 800 bar, through a mixing device which consists of one or more inlet nozzles (6), one or more turbulence chambers (7) and one or more outlet nozzles (8), with the inlet nozzle(s), turbulence chamber(s) and outlet nozzle(s) being pressed in sequence in a cylindrical support and the axes of the bores of the inlet nozzle and the outlet nozzle being arranged axially to one another, as well as mixing devices for performing this method.

Gudrun Kolb

Papers

Evaluation of a New High-Pressure Dispersion Unit (HPN) for Emulsification

Untersuchungen zum Aufbruch von Einzeltropfen in Dispergiereinheiten zur Emulsionsherstellung

Preparation of liquid dispersions

Process and apparatus for mixing or dispersing liquids

Zur Herstellung von Feinemulsionen mittels Hochdruckdispergiereinheiten