Premix Membrane Emulsification Research Articles

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Production and characterization of a blood analogue based on alginate microparticles

This work addresses the need for a universal blood substitute by focusing on developing alginate-based microparticles engineered to replicate the mechanical properties of red blood cells (RBCs). Alginate, known for its biocompatibility and tunable mechanical properties, is used to create microparticles that closely resemble RBCs in size and shape. These alginate microparticles are produced through premix membrane emulsification (PME), ensuring a uniform size distribution. The viscosity ratio and the size of the filter pores influence the final size of the microparticles. Filters with pores of 20 µm were used to produce 5 wt% alginate microparticles with a diameter of 7.81 µm ± 0.77, and filters with pores of 30 µm were used to produce 0.5 wt% alginate microparticles with a diameter of 8.69 µm ± 3.30. The Deformability Index (DI) of the alginate microparticles follows the correlation that microparticles with higher elastic modulus exhibit lower DI values. The DI found for 0.5 wt% alginate microparticles solution is higher than the DI found for 5 wt% alginate microparticles. The DI of RBCs is higher than the ones found for the alginate microparticles, however the value is in the range of the experimental error. Rheological studies reveal that suspensions of 25–30 wt% alginate microparticles exhibit a shear-thinning behavior similar to human blood. The DI of the alginate microparticles shows little influence on the rheology of the suspensions. Furthermore, the Cell-Free Layer (CFL) of alginate microparticles is close to that of RBCs, reinforcing the potential of alginate as a suitable material for blood substitute development. The alginate microparticles produced in this work show a great potential to contribute to creating a blood-mimicking fluid for applications in medical treatments and research.

Fabrication of an injectable hydrogel scaffold embedding kartogenin-encapsulated PLGA microsphere with long-term drug release to promote chondrogenesis

To address the long-lasting challenges on repair of articular cartilage defects in clinic, cartilage tissue engineering (CTE) strategy aims to develop favorable scaffolds to undertake mechanical support and simulate the cellular microenvironment for remodeling or replacing the defective cartilage tissues. Wherein, facile operation, favorable mechanical strength, excellent biocompatibility, suitable biodegradability, and innate chondrogenic ability are crucially adjective in CTE. Herein, we fabricated an injectable tetra-PEG hydrogel scaffold embedding kartogenin-encapsulated poly (lactic-co-glycolic acid) (PLGA@KGN) microspheres by means of the premix membrane emulsification (PME) method and quick sol-gel transformation. The unform tetra-PEG network endowed this composite hydrogel (tetra-PEG/PLGA@KGN) with favorable pores, easy injectability, mechanical strength and lower swelling ratio, while the internal small KGN drugs with the unique differentiation ability into chondrocytes could be slowly released for a long period of time, thus capably allowing the maintenance of the drug's effective concentration and long-lasting sustained release up to >28 days and persistently enhancing its chondrogenic efficiency. In vitro results indicated its satisfactory compatibility for supporting the cell activity, proliferation, and differentiation. Overall, due to improved mechanical property and sustainable KGN release behavior, this designable hydrogel scaffold may provide an option with clinical translational potential for cartilage repair.

Characterization of β-lactoglobulin adsorption on silica membrane pore surfaces and its impact on membrane emulsification processes

Protein adsorption plays a key role in membrane fouling in liquid processing, but the specific underlying molecular mechanisms of β-lactoglobulin adsorption on ceramic silica surfaces in premix membrane emulsification have not been investigated yet.In this study, we aimed to elucidate the β-lactoglobulin adsorption and its effect on the premix membrane emulsification of β-lactoglobulin-stabilized oil-in-water emulsions. In particular, the conformation, molecular interactions, layer thickness, surface energy of the adsorbed β-lactoglobulin and resulting droplet size distribution are investigated in relation to the solvent properties (aggregation state of β-lactoglobulin) and the treatment of the silica surface (hydrophilization).The β-lactoglobulin adsorption is driven by attractive electrostatic interactions between positively charged amino acid residues, i.e., lysin and negatively charged silanol groups, and is stabilized by hydrophobic interactions. The strong negative charges of the treated silica surfaces result in a high apparent layer thickness of β-lactoglobulin. Although the conformation of the adsorbed β-lactoglobulin layer varies with membrane treatment and the solvent properties, the β-lactoglobulin adsorption offsets the effect of hydrophilization of the membrane so that the surface energies after β-lactoglobulin adsorption are comparable. The resulting droplet size distribution of oil-in-water emulsions produced by premix membrane emulsification are similar for treated and untreated silica surfaces.

Development of tetracycline-modified nanoparticles for bone-targeted delivery of anti-tubercular drug.

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs). Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice. Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC-PLGA-PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094μg/mL, whereas this of free rifapentine was 0.25μg/mL. Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.

Lipase adsorption during premix-membrane emulsification affects membrane surface properties and structural conformation of lipase

Fouling during membrane emulsification due to biomolecule adsorption is still a drawback for broader applicability and a better holistic understanding is needed. This study aimed to investigate the fouling effect on the membrane and the enzyme being modified due to adsorption. Therefore, a lipase solution with varying concentrations and pH was filtered through a silica-based membrane. The degree of adsorption, membrane properties (microstructure and phase wetting), and enzymatic characteristics (conformation and activity) were evaluated. For insights on the molecular level, molecular dynamic simulations of the conformational changes of lipase caused by adsorption were performed. Regarding the membrane, an increase in lipase concentration increased the adsorption leading to higher fouling and decreased wetting implying a higher hydrophobicity of the membrane. Additionally, SEM showed that the pH of the lipase solution modified the microstructure of the foulant layer. Regarding the impact on the lipase, molecular dynamic simulations revealed an increase in the hydrophobic surface area, a rearrangement of the C-alpha atoms of the protein backbone, and an increase in the radius of gyration. Despite leading to enzyme mass loss, both the secondary structure and the activity showed no significant differences after processing, which might be due to the reversible adsorption.

Membranes with surficial spherical nanoarchitecture – Material importance in emulsion formulation by premix membrane emulsification

Premix membrane emulsification (PME), commonly utilized for the high-throughput manufacturing of sized-controlled emulsion droplets and microparticles with low energy inputs, was applied to the formulation of the emulsion with potential use in cosmetics. It was revealed that membrane material significantly impacts the quality and stability of the emulsion. Membrane materials with spherical (3D) architecture were generated by the chemical attachment of chitosan to the activated and silanized PVDF matrix. Hydrophobic (HB) and hydrophilic (HL) PVDF were used as starting materials. For the first time, hydrophilic PVDF was applied for such functionalization. The systematical study of wettability, surface charge, and physicochemistry was performed and referred to the quality and stability of the emulsion. It was found, that hybrid membranes HB-chitosan were the most effective, joining hydrophobic surface with hydrophilic domains. Owing to the unique structure, the mentioned material was the most promising, considering the transport features, stability, and physicochemical properties. Due to the production of highly stable emulsions their potential in the formulation of cosmetic products is pointed out. The collected results allow to fill the scientific gap identified in the literature on the lack of research focusing on the droplet break-up in PME and the correlation between membrane features and emulsion formulation effectiveness. Such correlation was deliberated and supported with the comprehensive experimental study.

New Approach in the Determination of a Suitable Directionally Coarsened Microstructure for the Fabrication of Nanoporous Superalloy Membranes Based on CMSX-4.

The pore size of nanoporous superalloy membranes produced by directional coarsening is directly related to the γ-channel width after creep deformation, since the γ-phase is removed subsequently by selective phase extraction. The continuous network of the γ'-phase thus remaining is based on complete crosslinking of the γ'-phase in the directionally coarsened state forming the subsequent membrane. In order to be able to achieve the smallest possible droplet size in the later application in premix membrane emulsification, a central aspect of this investigation is to minimize the γ-channel width. For this purpose, we use the 3w0-criterion as a starting point and gradually increase the creep duration at constant stress and temperature. Stepped specimens with three different stress levels are used as creep specimens. Subsequently, the relevant characteristic values of the directionally coarsened microstructure are determined and evaluated using the line intersection method. We show that the approximation of an optimal creep duration via the 3w0-criterion is reasonable and that coarsening occurs at different rates in dendritic and interdendritic regions. The use of staged creep specimens shows significant material and time savings in determining the optimal microstructure. Optimization of the creep parameters results in a γ-channel width of 119 ± 43 nm in dendritic and 150 ± 66 nm in interdendritic regions while maintaining complete crosslinking. Furthermore, our investigations show that unfavorable stress and temperature combinations favor undirectional coarsening before the rafting process is completed.

Effect of Continuous and Discontinuous Droplet-Size Distributions on the Viscosity of Concentrated Emulsions in Premix Membrane Emulsification

The dispersed phase volume fraction of concentrated emulsions can be substantially increased without a considerable increase in viscosity by optimizing the droplet-size distribution (DSD) of emulsion mixtures. However, due to the limitations of the traditional methods to control the DSD, the study of its effect on the viscosity of emulsion mixtures is usually limited. The premix membrane emulsification method was used to prepare a droplet-size-controlled concentrated emulsion, and the DSD’s effect on the viscous behavior of emulsion mixtures was investigated. It was observed that widening the DSD led to a decrease of the viscosity at lower shear rates, while at higher shear rates, a shear-thickening behavior was observed. In a discontinuous DSD, there was a tendency for the viscosity to decrease to a minimum value at about 75% mixing fraction of larger-droplet-size emulsions beyond which the viscosity increased until the monomodal packing limit. The viscosity could be decreased by more than 20-fold in bimodal emulsions depending on the droplet-size ratio. Mixing emulsions of different DSDs enabled attaining a viscosity lower than that of the monodispersed parent emulsions.

A review of recent research and development on GLP-1 receptor agonists-sustained-release microspheres.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.

Protein conformational changes at the oil/water-interface induced by premix membrane emulsification

We present combined experimental and modelling evidence that β-lactoglobulin proteins employed as stabilizers of oil/water emulsions undergo minor but significant conformational changes during premix membrane emulsification processes. Circular Dichroism spectroscopy and Molecular Dynamics simulations reveal that the native protein structure is preserved as a metastable state after adsorption at stress-free oil/water interfaces. However, the shear stress applied to the oil droplets during their fragmentation in narrow membrane pores causes a transition into a more stable, partially unfolded interfacial state. The protein’s β-sheet content is reduced by up to 8% in a way that is largely independent of the pressure applied during emulsification, and is driven by an increase of contacts between the oil and hydrophobic residues at the expense of structural order within the protein core.

Encapsulation of curcumin within oil-in-water emulsions prepared by premix membrane emulsification: Impact of droplet size and carrier oil on the chemical stability of curcumin

Oil-in-water emulsions containing curcumin with different droplet sizes were produced by premix membrane emulsification with different carrier oils: tributyrin (short chain triglycerides, SCT), medium chain triglycerides (MCT) and corn oil (long chain triglycerides, LCT). The influence of carrier oil type and droplet size on the physical stability, chemical stability of curcumin and lipid oxidation stability of emulsions were investigated. Turbiscan results indicated that the physical stability of emulsions was related to both carrier oils and emulsion droplet sizes. The oil type and droplet size of emulsions stored at 25 °C showed limited effect on the stability of curcumin, but significantly affected the stability of curcumin at 55 °C. Chemical stability of curcumin decreased with the decrease of emulsion droplet sizes. For each droplet size emulsions, the stability of curcumin decreased in the order SCT > MCT > LCT. Moreover, the lipid oxidation in LCT-based emulsions resulted in lower zeta potential of droplets, which was independent of emulsion droplet sizes. The presence of curcumin improved the oxidative stability of emulsions.

Ultrafiltration for Homogenization of Wheat Germ Oil:Water System: Droplet Size Distribution and Stability of Emulsion

Wheat germ oil (WGO) in water emulsion is increasingly being used in a variety of fields due to its outstanding nutritional and health benefits. To enhance WGO composability, emulsification should be performed to allow them to dissolve more easily in food matrix or active packaging. Membrane emulsification is a promising advanced homogenization technology that has recently been developed. This research focused on application of membrane emulsification for homogenization of WGO-in-water emulsion by polyether sulfone (PESU) membrane with 0.45 µm of pore size, operating pressure from 5 to 9 bar, WGO fraction in range 10–20% w/w, and lecithin ratio in range 0–0.2% w/v were evaluated on the mean of particle diameters, distribution of particle diameter, stability of emulsion, and permeate flux. Higher operating pressure led to smaller mean particle diameters and higher homogenization efficiency and permeate flux. However, increasing the WGO fraction showed the opposite trend. Notably, increasing lecithin ratio from 0 to 0.2%, the mean particle diameters increased from 3.36 to 7.72 µm, homogenization efficiency decreased from 98.54 to 97.68%, and permeate flux decreased from 105.95 to 77.45 L h−1 m−2. The results showed the advantage of using PESU membrane in WGO-in-water homogenization, that produce emulsions with small particle size (50% of particle volume was less than 5 µm), high emulsion stability (greater than 95%), and lower emulsifier usage. Results imply premix membrane emulsification is potential to apply homogenization WGO-in-water emulsion.

Relationship between the continuous phase viscosity and the membrane permeation rate in premix membrane emulsification using Shirasu porous glass membranes

Emulsion viscosity and membrane permeation rate (MPR) are the major factors influencing the wall shear stresses in the membrane pores. However, the effect of the discrete phase viscosities and their relationship with the MPR is not well elaborated. The relationship between droplet size and the continuous phase viscosity at different MPRs was investigated. At higher MPR, the emulsion droplet size was observed to decrease with continuous phase viscosity due to the increase in the wall shear stress in the pores, as the thickness of the lubrication layer between the droplets and the pore walls increases with viscosity. While at low MPR, the droplet size increased with viscosity due to coalescing as the rate of surfactant diffusion onto the interface of the new droplets reduced. The MPR was observed to complement or contrast the effects of the continuous phase viscosity on droplet formation in the membrane pores, depending on its relative magnitude.

Premix membrane emulsification for the preparation of curcumin-loaded nanoemulsions

In order to overcome limitations of conventional methods, premix membrane emulsification (ME) using Shirasu porous glass (SPG) membranes was investigated for the preparation of O/W food-grade nanoemulsions. In this study, the effects of major emulsification process variables, formulation and membrane parameters on the mean droplet diameter and polydispersity (PDI) were systematically investigated. Stability of curcumin-loaded nanoemulsions with different size was also investigated during 28 days storage period. The results revealed that surfactant type and concentration, and medium-chain triglyceride (MCT) concentration played an important role on droplet size and PDI values, while premix quality, flow rate and cycle number had a minor effect on the droplet size. Moreover, there was a linear relationship between the membrane pore size and mean droplets size of nanoemulsions. Curcumin-loaded nanoemulsions with high encapsulation efficiency (>94%) had a good stability (>96% retention rate) after 28 days of storage at 4 °C. Also, there were no major differences on the retention rate of curcumin for nanoemulsions with different droplet size when they were stored at 4 °C, 25 °C and 37 °C under both pH 3 and pH 7. These results indicated that premix ME can be successfully used for the preparation of food-grade nanoemulsions with controlled droplet sizes and narrow droplet size distributions. • Premix ME using SPG membranes was used for the nanoemulsions preparation. • The influence of formulation, operating and membrane parameters were investigated. • Curcumin concentration had no effect on the droplet size and PDI values of nanoemulsions. • Curcumin-loaded nanoemulsions had high encapsulation efficiency. • Premix ME could be successfully used for the preparation of food-grade nanoemulsions.

Reducing the γ'-Particle Size in CMSX-4 for Membrane Development.

Colloidal emulsions for lipophilic drugs can be fabricated using premix membrane emulsification. The state of the art is the application of membranes made from, for example, polycarbonate or polyester, which, however, are prone to fouling and cause waste, due to the low number of cycles. With the use of metallic membranes made from the nickel based single crystalline superalloy CMSX-4, these key disadvantages are eliminated. However, instead, the pore size and the resulting droplet size distribution need to be adjusted and improved. This can be realized by tailoring the size of the γ′-particles, which is controllable by the time and temperature used during precipitation heat treatment and the quenching method after homogenization heat treatment. Therefore, we utilized different heat treatment protocols, varying the cooling rate (water quenching and air cooling) after homogenization heat treatment and the holding time and temperature during precipitation heat treatment. Then, we investigated the γ/γ′-microstructure, including the γ′-morphology and γ′-particle size. We show that water quenching has a significant impact on the γ/γ′-microstructure and often leads to irregular-shaped and poorly aligned γ′-particles after precipitation heat treatment. In comparison, air cooling, followed by a subsequent precipitation heat treatment, results in well-aligned and cubic shaped γ′-particles and is, therefore, favorable for membrane fabrication. A reduction in precipitation temperature leads to morphology changes to the γ′-particles. A reduction of the holding time during precipitation heat treatment diminishes the γ′-particle growth, resulting in smaller γ′-particles. Additionally, a suitable heat treatment protocol for membrane fabrication was identified with a γ′-edge length of 224 ± 52 nm and well-aligned, cubic shaped γ′-particles.

Preparation, characterization and in vivo efficacy evaluation of ropivacaine O/W emulsion by premix membrane emulsification

Ropivacaine (ROP), a new type of amide local anesthetic (LA) with low cardiac and neurotoxicity, is used to treat postoperative pain. However, ROP has a short half-life (t1/2 = 1.8 h) and the analgesic duration of a single-dose injection last only 3–4 h, which cannot meet clinical needs. In order to solve the problem, we combined an O/W emulsion method with a premix membrane emulsion technique to prepare sustained-release ropivacaine-loaded emulsion (ROP-E) with narrow droplets size distribution. As a result, the ROP-E about 8.385 µm with a span value of 0.737 was obtained. Moreover, the sciatic nerve block model and the cutaneous trunci pinprick model were established to evaluate the efficacy of ROP-E in vivo. The results of the sciatic nerve model showed that the sensory nerve block duration (4.27 h) of ROP-E was significantly prolonged, which was 2.15 and 1.42 folds of ROP injection and Exparel® formulation, respectively. Similarly, the motor nerve block duration (3.62 h) was 1.8 and 1.46 folds of ROP injection and Exparel® formulation, respectively. Effective analgesia duration of ROP-E was about 18 h, 2.25 folds longer than that of ROP injection in the cutaneous trunci pinprick model. Besides, the ROP-E displayed excellent stability according to the droplet size, drug loading concentration, in vivo and in vitro release. H&E and blood biochemistry showed an insignificant difference between the ROP-E and the ROP injection, which further indicated the safety of ROP-E. These results suggested that ROP-E may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity.

Encapsulation of curcumin within oil-in-water emulsions prepared by premix membrane emulsification: Impact of droplet size and carrier oil type on physicochemical stability and in vitro bioaccessibility

Oil-in-water emulsions containing curcumin with different droplet size (small ≈ 0.5 µm, medium ≈ 0.8 µm, large ≈ 3.7 µm and premix ≈ 60 µm) were prepared through premix membrane emulsification using different carrier oils: tributyrin (short chain triglycerides, SCT), medium chain triglycerides (MCT) and corn oil (long chain triglycerides, LCT). An in vitro gastrointestinal model was used to evaluate the impact of oil and droplet size on lipid digestion and curcumin bioaccessibility. Lipid digestion and bioaccessibility decreased with the increase of droplet size for LCT-based emulsions, whereas there was no significant difference for small, medium and large emulsions in SCT and MCT-based emulsions. In addition, encapsulation efficiency played an important role in determining bioaccessibility. Bioaccessibility in MCT premix was significantly lower than that in other size MCT-based emulsions because of its low encapsulation efficiency. The bioaccessibility decreased in the order MCT > SCT > LCT in each size of emulsions..

Preparation of monodispersed emulsions by premix membrane emulsification without repetitive permeation: Influence of membrane permeation rate (flux) and emulsion viscosity

A method for preparing emulsions with a narrow droplet size distribution (span) without repetitive membrane permeation, by controlling the premix emulsion viscosity and membrane permeation rate (MPR), flux, was provided. The mean emulsion viscosity and the MPR are some of the main factors that control the wall shear stresses responsible for droplet break up in premix membrane emulsification (PME). Hence, striking a balance between these two factors is important for preparing monodispersed emulsions.

Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm.

Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc™) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc™ membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase.