Process optimization for microfluidic preparation of liposomes using food-grade components.

This study explores the potential for optimizing a sustainable manufacturing process that maintains the essential characteristics of conventional liposomes using food-grade solvents and components. The focus was comparing the physicochemical, morphological, and interfacial properties of liposomes produced with these food-grade ingredients to those made by conventional methods. It was found that there was no significant difference in particle size (195.87 ± 1.40 nm) and ζ-potential (-45.13 ± 0.65 mV) between liposomes made from food-grade and conventional materials. The manufacturing process for liposomes, utilizing food-grade solvents and components, was optimized through the application of Plackett-Burman design and response surface methodology. This approach helped identify key parameters (soy lecithin, ß-sitosterol, W/O ratio) and their optimal values (3.17 g, 0.25 g, 1:2.59). These findings suggest that it is possible to enhance the use of liposomes as an effective and safe delivery system in the food industry, adhering to the strict guidelines set by regulatory agencies.

Clofazimine nanoclusters show high efficacy in experimental TB with amelioration in paradoxical lung inflammation.

The rise of tuberculosis (TB) superbugs has impeded efforts to control this infectious ailment, and new treatment options are few. Paradoxical Inflammation (PI) is another major problem associated with current anti-TB therapy, which can complicate the treatment and leads to clinical worsening of disease despite a decrease in bacterial burden in the lungs. TB infection is generally accompanied by an intense local inflammatory response which may be critical to TB pathogenesis. Clofazimine (CLF), a second-line anti-TB drug, delineated potential anti-mycobacterial effects in-vitro and in-vivo and also demonstrated anti-inflammatory potential in in-vitro experiments. However, clinical implications may be restricted owing to poor solubility and low bioavailability rendering a suboptimal drug concentration in the target organ. To unravel these issues, nanocrystals of CLF (CLF-NC) were prepared using a microfluidizer® technology, which was further processed into micro-sized CLF nano-clusters (CLF-NCLs) by spray drying technique. This particle engineering offers combined advantages of micron- and nano-scale particles where micron-size (∼5 µm) promise optimum aerodynamic parameters for the finest lung deposition, and nano-scale dimensions (∼600 nm) improve the dissolution profile of apparently insoluble clofazimine. An inhalable formulation was evaluated against virulent mycobacterium tuberculosis in in-vitro studies and in mice infected with aerosol TB infection. CLF-NCLs resulted in the significant killing of virulent TB bacteria with a MIC value of ∼0.62 µg/mL, as demonstrated by Resazurin microtiter assay (REMA). In TB-infected mice, inhaled doses of CLF-NCLs equivalent to ∼300 µg and âˆ¼ 600 µg of CLF administered on every alternate day over 30 days significantly reduced the number of bacteria in the lung. With an inhaled dose of ∼600 µg/mice, reduction of mycobacterial colony forming units (CFU) was achieved by ∼1.95 Log10CFU times compared to CLF administered via oral gavage (∼1.18 Log10CFU). Lung histology scoring showed improved pathogenesis and inflammation in infected animals after 30 days of inhalation dosing of CLF-NCLs. The levels of pro-inflammatory mediators, including cytokines, TNF-α & IL-6, and MMP-2 in bronchoalveolar lavage fluid (BAL-F) and lung tissue homogenates, were attenuated after inhalation treatment. These pre-clinical data suggest inhalable CLF-NCLs are well tolerated, show significant anti-TB activity and apparently able to tackle the challenge of paradoxical chronic lung inflammation in murine TB model.

Effect of Dynamic High-Pressure Microfluidizer on Physicochemical and Microstructural Properties of Whole-Grain Oat Pulp.

By avoiding the filtration step and utilizing the whole components of oats, the highest utilization rate of raw materials, improving the nutritional value of products and reducing environmental pollution, can be achieved in the production of whole-grain oat drinks. This study innovatively introduced a dynamic high-pressure microfluidizer (DHPM) into the processing of whole-grain oat pulp, which aimed to achieve the efficient crushing, homogenizing and emulsification of starch, dietary fiber and other substances. Due to DHPM processing, the instability index and slope value were reduced, whereas the ß-glucan content, soluble protein content and soluble dietary fiber content were increased. In the samples treated with a pressure of 120 MPa and 150 MPa, 59% and 67% more ß-glucan content was released, respectively. The soluble dietary fiber content in the samples treated with a pressure of 120 MPa and 150 MPa was increased by 44.8% and 43.2%, respectively, compared with the sample treated with a pressure of 0 MPa. From the perspective of the relative stability of the sample and nutrient enhancement, the processing pressure of 120 MPa was a good choice. In addition, DHPM processing effectively reduced the average particle size and the relaxation time of the water molecules of whole-grain oat pulp, whereas it increased the apparent viscosity of whole-grain oat pulp; all of the above changes alleviated the gravitational subsidence of particles to a certain extent, and thus the overall stability of the system was improved. Furthermore, CLSM and AFM showed that the samples OM-120 and OM-150 had a more uniform and stable structural system as a whole. This study could provide theoretical guidance for the development of a whole-grain oat drink with improved quality and consistency.

One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique.

The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells. Moreover, HPH allowed for modification of polyethylene glycol (PEG)-conjugated lipids onto RAW-Exos, as well as encapsulation of the anti-cancer agent doxorubicin. Importantly, the doxorubicin encapsulation efficiency became higher upon increasing the process pressure and simultaneous HPH with PEG-lipids. Moreover, treatment with PEG-modified RAW-Exos encapsulating doxorubicin significantly suppressed tumor growth in colon-26-bearing mice. Taken together, these results suggest that HPH using a microfluidizer could be useful to prepare PEG-modified Exos encapsulating anti-cancer drugs via a one-step pharmaceutical process, and that the prepared functional Exos could be applied for the treatment of cancer in vivo.

Exploring the Potential of a Herbal Nanoemulsion as an Antimicrobial Mouthwash.

The study aimed to formulate a nanoemulsion, combine it with aqueous extracts of herbal powders, and test its efficiency as caries-preventing mouthwash. Formulation of nanoemulsion using microfluidizer, characterization of nanoemulsion, minimum inhibitory concentration, adherence test, biofilm assay, and artificial mouth assay was carried out. The biofilms of Streptococcus mutans, Lactobacillus casei, Actinomyces viscosus, and a combination of the three cultures were developed and treated with formulations to study the inhibitory effect of the samples. In artificial mouth assay, human tooth samples were used as surfaces to grow the biofilm of S. mutans, and daily, the teeth were treated with the formulations to test their real-time efficiency. The nanoemulsion was characterized using dynamic light scattering and the size of the particles was within the 100-300 nm range. Above 50 °C, the nanoemulsion combined with plant extract lost its emulsified state within 2 h of incubation, while the nanoemulsion was stable. Nanoemulsion with plant extract inhibited the adherence of L. casei (73%) and biofilm of L. casei (66%). In artificial mouth assay, after 10 days of nanoemulsion, nanoemulsion with plant extract showed DIAGNOdent pen values 3.5 and 2 respectively whereas the negative control value was 14.4 indicating caries initiation. The nanoemulsion with plant extract showed anti-adherence and anti-biofilm activity and hence can be used as a potent anticariogenic mouthwash.

A New Control Strategy for High-Pressure Homogenization to Improve the Safety of Injectable Lipid Emulsions.

Intravenous lipid emulsions are biocompatible formulations used as clinical nutrition products and lipid-based delivery systems for sparingly soluble drugs. However, the particle-size distribution is associated with risks of embolism. Accordingly, the mean particle diameter (MPD) and particle-distribution tailing (characterized as the pFAT5 value) are critical quality attributes that ensure patient safety. Compliance with the limits stated in the United States Pharmacopoeia is ensured by high-pressure homogenization, the final step of the manufacturing process. The US Food and Drug Administration's Quality-by-Design approach requires a control strategy based on deep process understanding to ensure that products have a consistent and predefined quality. Here we investigated the process parameters of a jet-valve high-pressure homogenizer, specifically their effect on the MPD, pFAT5 value and droplet count (determined by microscopy) during the production of a Lipofundin MCT/LCT 20% formulation. We provide deep insight into droplet breakup and coalescence behavior when varying the process pressure, emulsion temperature and number of homogenization cycles. We found that high shear forces are not required to reduce the pFAT5 value of the particle distribution. Finally, we derived a control strategy for a rapid and cost-efficient two-cycle process that ensures patient safety over a large control space.

Whole tomato juice produced by a novel industrial-scale microfluidizer: Effect on physical properties and in vitro lycopene bioaccessibility.

Whole tomato juice (WTJ) was prepared using a novel "industrial-scale microfluidizer system" (ISMS). The impacts of ISMS processing pressure (0-120 MPa) on the physicochemical properties and bioaccessibility of tomato juice were investigated. Increasing the processing pressure reduced the mean particle diameter (D[4,3]) of the tomato juice from 151 to 30 µm, which was mainly attributed to degradation of the tomato plant cell structures by the strong disruptive forces generated by microfluidizer. Pulp sedimentation rate, precipitation weight ratio, and turbidity measurements showed that the physical stability of the tomato juice increased with increasing pressure. Indeed, ISMS-treated tomato juice remained stable for 28 days without evidence of visible layering. The lycopene concentration in the tomato juice increased from 25.0 to 28.2 µg/mL and the lycopene bioaccessibility increased from 9.0% to 14.1% after ISMS treatment. These results suggest that ISMS can improve the physical stability and nutritive value of commercial tomato juice products.

Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach.

The aim of this research was to develop a nanosuspension of aprepitant (APT) using the Nano-by-Design approach. A novel microfluidization technology was used for processing the formulation. A 32 full factorial design was used for the optimization of dependent variables, which included critical quality attributes like particle size and polydispersity index. Subsequently, the design space was generated and the optimum formulation was located using desirability constraints followed by its validation.The prepared nanosuspension had a particle size of 721 nm ± 5%, a polydispersity index of 0.106 ± 3%, and a zeta potential of - 8.06 ± 5 mV. Its surface morphology was studied using SEM, DSC, and XRD. It revealed that the prepared nanosuspension had a nano-crystalline nature. The process parameters did not lead to any physicochemical interaction between the drug and excipients. This was confirmed using FTIR analysis. In vitro dissolution studies revealed 100% cumulative drug release over 60 min, showing better results in comparison with pure APT. Thus, it has been shown that microfluidization can be an industrially feasible, novel, green technology for the preparation of a stable APT nanosuspension for improving the dissolution profile of the drug.

Disintegrating the Structure and Improving the Functionalities of Pea Fiber by Industry-Scale Microfluidizer System.

In the food industry, the most prominent and concerned points in the application of dietary fiber are hydration properties and oil absorption capacity. The target of this work was to investigate the impact of a novel industry-scale microfluidizer system (ISMS) on the changing structures and functionalities of pea fiber. Different ISMS treatment intensity (0-120 MPa for one pass and 120 MPa for two passes) was applied to treat pea fiber. ISMS treatment induced the reduction in particle size and the transformation of big compact blocks to loose flakes, and the destruction of the original ordered cellulose structure caused the decline of crystallinity. Meanwhile, the hydration properties of pea fiber were improved, and pre-pulverizer and industry-scale microfluidizer treatment together increased the swelling capacity and water retention capacity of fiber. The oil holding capacity of ISMS-treated fiber was increased to more than double the original one. The elevated functionalities of pea fiber by ISMS treatment could be attributed to loosening structure, exposing more surface area, and disordering the crystalline structure, which increased the sites of water binding and oil adsorption. These findings suggested that ISMS could be applied as an effective industrial technique to the disintegrate structure and improve the functionalities of pea fiber, so as to widen the application of pea fibers in foods.

Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.

One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., "pilot-scale" production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer-a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts.

Stable W/O/W multiple nanoemulsion encapsulating natural tocotrienols and caffeic acid with cisplatin synergistically treated cancer cell lines (A549 and HEP G2) and reduced toxicity on normal cell line (HEK 293).

This work aimed to evaluate the effects of encapsulated tocotrienols (TRF) and caffeic acid (CA) in water-in-oil-in-water (W/O/W) multiple nanoemulsion with cisplatin towards cancer cells. This work is important considering the limited efficacy of cisplatin due to tumour resistance, as well as its severe side effects. A549 and HEP G2 cancer cell lines were utilised for evaluating the efficacy of the encapsulated W/O/W while HEK 293 normal cell line was used for evaluating the toxicity. TRF, CA and CIS synergistically improved apoptosis in the late apoptotic phase in A549 and HEP G2 by 23.1% and 24.9%, respectively. The generation of ROS was enhanced using TRF:CA:CIS by 16.9% and 30.2% for A549 and HEP G2, respectively. Cell cycle analysis showed an enhanced cell arrest in the G0/G1 phase for both A549 and HEP G2. TRF, CA and CIS led to cell death in A549 and HEP G2. For HEK 293, ~33% cell viability was found when only CIS was used while >95% cell viability was observed when TRF, CA and CIS were used. This study demonstrates that the encapsulated TRF and CA in W/O/W with CIS synergistically improved therapeutic efficacy towards cancer cells, as well as lowered the toxicity effects towards normal cells.

Characteristics of an Emulsion Obtained Using Hydrophobic Hydroxypropyl Methylcellulose as an Emulsifier and a High-Pressure Homogenizer.

Hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a polymer in which a small amount of HPMC is stearoxyl substituted, was used as an emulsifier of emulsion-type lotion. A high-pressure homogenizer (microfluidizer) was used. The viscosity of the 1% HM-HPMC aqueous gel decreased after passing through the microfluidizer from 5.5 to 2.7 Pa·s. When liquid paraffin (LP) was used as the oil phase, a stable emulsion was obtained with an LP ratio of 1-40%. The apparent viscosity decreased with LP ratios up to 20%, and then increased with increasing LP concentration. The emulsions with an LP ratio <20% presented a pseudo-viscous flow, similar to that of the diluted polymer solution. HM-HPMC likely adsorbed onto the oil with a stearoxyl group; thus, the interaction between the stearoxyl group, which explained the high viscosity of HM-HPMC, decreased, reducing the viscosity of the emulsion. The LP ratio was 40%, and the emulsion presented a plastic flow, which is typical of concentrated emulsions. The size of the droplet in the emulsion was approximately 1 µm regardless of the LP ratio. When low-viscosity LPs or monoester-type oils such as isopropyl myristate were used, some of the emulsions presented creaming. An emulsion using HM-HPMC as an emulsifier and an appropriate oil homogenized with a microfluidizer is stable, has low viscosity, and can be easily spread on skin.

Comparison of media milling and microfluidization methods for engineering of nanocrystals: a case study.

OBJECTIVE: The article focuses on exploring and comparing two top-down methods, i.e. media milling and microfluidization for the fabrication of nanocrystals of rifampicin (RIF), a poorly water-soluble drug in terms of their potential for generation of stable and efficacious nanocrystals. SIGNIFICANCE: Nanocrystals are often the system of choice for the formulation of poorly water-soluble drugs. The characteristic benefit of nanocrystals lies in their ability to boost the bioavailability of such drugs by enhancing their saturation solubility and dissolution velocity. Nanocrystals can be prepared by either bottom-up or top-down approach. The latter is often preferred due to the feasibility of scale-up and economical nature. Hence, the emphasis is on these methods. METHODS: Stable RIF nanocrystals (RIF NCs) were developed and optimized using media milling and microfluidizer method by incorporating a suitable surfactant/stabilizer. The developed nanocrystals were evaluated for their saturation solubility, in vitro dissolution, solid-state characteristics, morphology, intrinsic dissolution rate, and short-term physical stability. RESULTS: Both the methods were found to be equally efficient in terms of development of stable RIF NCs, while in terms of processing time and efficacy, microfluidization was found to be advantageous. Amorphization and polymorphic conversion were evident based on the results of solid-state characterization. Furthermore, both formulations exhibited an enhanced solubility and faster dissolution velocity. CONCLUSION: Based on the characterization outcomes, it can be concluded that both the top-down technologies could be successfully applied to develop nanocrystals of poorly water-soluble drugs. However, microfluidization was found to outplay media milling in terms of processing time and drug loading.

Ultrasound-assisted production of palm oil-based isotonic W/O/W multiple nanoemulsion encapsulating both hydrophobic tocotrienols and hydrophilic caffeic acid with enhanced stability using oil-based Sucragel.

In this work, the effects of thickeners and tonicity towards producing stable palm oil-based water-in-oil-in-water (W/O/W) multiple nanoemulsion using ultrasound and microfluidizer were investigated. Palm oil, Sucragel, polyglycerol polyricinoleate, Tween 80, Xanthan gum, and NaCl were used. W/O/W was formed under the optimized conditions of ultrasound at 40% amplitude and for 180 s of irradiation time, whereas for the microfluidizer, the optimized conditions were 350 bar and 8 cycles. This is the first work that successfully utilized Sucragel (oil-based thickener) in imparting enhanced stability in W/O/W. W/O/W with isotonic stabilization produced the lowest change in the mean droplet diameter (MDD), NaCl concentration, and water content by 1.5%, 2.6%, and 0.4%, respectively, due to reduced water movement. The final optimized W/O/W possessed MDD and dispersity index of 175.5 ± 9.8 and 0.232 ± 0.012, respectively. The future direction of formulating stable W/O/W would be by employing oil phase thickeners and isotonicity. The observed ~12 times lesser energy consumed by ultrasound than microfluidizer to generate a comparable droplet size of ~235 nm, further confirms its potential in generating the droplets energy-efficiently.

Development of Atovaquone Nanosuspension: Quality by Design Approach.

OBJECTIVE: The present study reports the use of MicrofluidizerTM technology to form a stable nanosuspension of atovaquone (ATQ) using quality by design (QbD) approach. METHODS: The patient-centric quality target product profile and critical quality attributes (CQAs) were identified. A Box-Behnken design was employed for the optimization of dependent variables, while CQAs like particle size and PDI were evaluated as response variables. Effective optimization of ATQ nanosuspension preparation using Microfluidizer processor as a novel green technology was achieved using QbD approach. RESULT: The prepared nanosuspension had a mean particle size of 865 nm ± 5%, PDI of 0.261 ± 3%, and zeta potential of -1.79 ± 5 mV. The characterization of the prepared nanosuspension by SEM, DSC, and XRD revealed its nano-crystalline nature whereas FTIR spectroscopic analysis confirmed the absence of any physicochemical interaction because of process parameters between the drug and excipients. CONCLUSION: In vitro dissolution studies of the nanosuspension using USP-IV exhibited a 100% cumulative drug release over 90 minutes, which is significantly better than that of ATQ pure API. In vivo pharmacokinetic studies revealed bioequivalence of ATQ nanosuspensions by Microfluidizer homogenization process to the marketed formulation1.

Scalable Manufacturing Processes for Solid Lipid Nanoparticles.

BACKGROUND: Solid lipid nanoparticles offer a range of advantages as delivery systems but they are limited by effective manufacturing processes. OBJECTIVE: In this study, we outline a high-throughput and scalable manufacturing process for solid lipid nanoparticles. METHODS: The solid lipid nanoparticles were formulated from a combination of tristearin and 1,2-Distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjugate-2000 and manufactured using the M-110P Microfluidizer processor (Microfluidics Inc, Westwood, Massachusetts, US). RESULTS: The manufacturing process was optimized in terms of the number of process cycles (1 to 5) and operating pressure (20,000 to 30,000 psi). The solid lipid nanoparticles were purified using tangential flow filtration and they were characterized in terms of their size, PDI, Z-potential and protein loading. At-line particle size monitoring was also incorporated within the process. Our results demonstrate that solid lipid nanoparticles can be effectively manufactured using this process at pressures of 20,000 psi with as little as 2 process passes, with purification and removal of non-entrapped protein achieved after 12 diafiltration cycles. Furthermore, the size could be effectively monitored at-line to allow rapid process control monitoring and product validation. CONCLUSION: Using this method, protein-loaded solid lipid nanoparticles containing a low (1%) and high (16%) Pegylation were manufactured, purified and monitored for particle size using an at-line system demonstrating a scalable process for the manufacture of these nanoparticles.

Lytic polysaccharide monooxygenases (LPMOs) facilitate cellulose nanofibrils production.

BACKGROUND: Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that cleave polysaccharides through an oxidative mechanism. These enzymes are major contributors to the recycling of carbon in nature and are currently used in the biorefinery industry. LPMOs are commonly used in synergy with cellulases to enhance biomass deconstruction. However, there are few examples of the use of monocomponent LPMOs as a tool for cellulose fibrillation. In this work, we took advantage of the LPMO action to facilitate disruption of wood cellulose fibers as a strategy to produce nanofibrillated cellulose (NFC). RESULTS: The fungal LPMO from AA9 family (PaLPMO9E) was used in this study as it displays high specificity toward cellulose and its recombinant production in bioreactor is easily upscalable. The treatment of birchwood fibers with PaLPMO9E resulted in the release of a mixture of C1-oxidized oligosaccharides without any apparent modification in fiber morphology and dimensions. The subsequent mechanical shearing disintegrated the LPMO-pretreated samples yielding nanoscale cellulose elements. Their gel-like aspect and nanometric dimensions demonstrated that LPMOs disrupt the cellulose structure and facilitate the production of NFC. CONCLUSIONS: This study demonstrates the potential use of LPMOs as a pretreatment in the NFC production process. LPMOs weaken fiber cohesion and facilitate fiber disruption while maintaining the crystallinity of cellulose.

Continuous production of core-shell protein nanoparticles by antisolvent precipitation using dual-channel microfluidization: Caseinate-coated zein nanoparticles.

Antisolvent precipitation is commonly used to fabricate protein nanoparticles using a simple batch method that involves injecting a protein-solvent mixture into an antisolvent. In this study, the potential of producing core-shell protein nanoparticles by antisolvent precipitation using a continuous dual-channel microfluidization method was investigated. The solvent phase (zein in ethanol) and antisolvent phase (casein in water) were made to impinge on each other at high velocity, which generates intense shear, turbulent, and cavitation forces that ensure thorough mixing and breakup of the phases. Relatively small core-shell protein nanoparticles (d<125nm) could be produced using this method when the conditions were optimized. The mean particle diameter decreased with increasing antisolvent-to-solvent ratio, increasing homogenization pressure, increasing ethanol content in the solvent phase, and decreasing zein content in the solvent phase. Depending on the processing conditions employed, zein particles in the range of about 120nm to over 1000nm could be produced. The operating conditions were further optimized to increase the final zein concentration and decrease the organic solvent content while still obtaining small particles. The surface potential of the core-shell protein nanoparticles went from positive at low pH to negative at high pH, with a point of zero charge around pH5. Electron microscopy indicated that the protein particles formed had a roughly spherical shape. The results suggest that the dual-channel microfluidizer could be used to continuously form protein nanoparticles by antisolvent precipitation. Nevertheless, when the microfluidization method was compared with the simple batch method the size of the particles produced under similar conditions were fairly similar.

Fabrication of Concentrated Fish Oil Emulsions Using Dual-Channel Microfluidization: Impact of Droplet Concentration on Physical Properties and Lipid Oxidation.

Chemically unstable lipophilic bioactives, such as polyunsaturated lipids, often have to be encapsulated in emulsion-based delivery systems before they can be incorporated into foods, supplements, and pharmaceuticals. The objective of this study was to develop highly concentrated emulsion-based fish oil delivery systems using natural emulsifiers. Fish oil-in-water emulsions were fabricated using a highly efficient dual-channel high-pressure microfluidizer. The impact of oil concentration on the formation, physical properties, and oxidative stability of fish oil emulsions prepared using two natural emulsifiers (quillaja saponins and rhamnolipids) and one synthetic emulsifier (Tween-80) was examined. The mean droplet size, polydispersity, and apparent viscosity of the fish oil emulsions increased with increasing oil content. However, physically stable emulsions with high fish oil levels (30 or 40 wt %) could be produced using all three emulsifiers, with rhamnolipids giving the smallest droplet size (d < 160 nm). The stability of the emulsions to lipid oxidation increased as the oil content increased. The oxidative stability of the emulsions also depended on the nature of the emulsifier coating the lipid droplets, with the oxidative stability decreasing in the following order: rhamnolipids > saponins ≈ Tween-80. These results suggest that rhamnolipids may be particularly effective at producing emulsions containing high concentrations of ω-3 polyunsaturated fatty acids-rich fish oil.

Development of microfluidization methods for efficient production of concentrated nanoemulsions: Comparison of single- and dual-channel microfluidizers.

Nanoemulsions are being increasingly utilized within the pharmaceutical, food, personal care, and chemical industries because of their unique physicochemical properties and functional performances: high optical clarity; prolonged stability; enhanced bioavailability; and novel rheology. For commercial applications, it is important to be able to produce nanoemulsions containing small droplets using efficient homogenization processes. In this study, we compared two microfluidization methods for fabricating nanoemulsions: (i) single-channel microfluidization and (ii) dual-channel microfluidization. The influence of emulsifier concentration, homogenization pressure, disperse phase volume fraction, and initial emulsifier location (oil versus water phase) on particle size was examined. For both devices, the mean particle diameter decreased with increasing emulsifier concentration and homogenization pressure, and there was a linear log-log relationship between mean particle diameter and homogenization pressure. At a similar emulsifier level and homogenization pressure, dual-channel microfluidization produced smaller droplets and narrower distributions than single-channel microfluidization. This effect was attributed to a higher droplet disruption efficiency and/or lower droplet recoalescence rate for the dual-channel system. The dual-channel method could successfully produce nanoemulsions even at high oil concentrations (50%), whereas the single-channel method was only effective at producing nanoemulsions at relatively low oil concentrations (10%). This study demonstrates that dual-channel microfluidization is an efficient means of producing fine nanoemulsions with high oil loading levels, which may be advantageous for many commercial applications.