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1.
In the present study, response surface methodology (RSM) based on central composite design (CCD) was employed to investigate the influence of main emulsion composition variables, namely drug loading, oil content, emulsifier content as well as the effect of the ultrasonic operating parameters such as pre-mixing time, ultrasonic amplitude, and irradiation time on the properties of aspirin-loaded nanoemulsions. The two main emulsion properties studied as response variables were: mean droplet size and polydispersity index. The ultimate goal of the present work was to determine the optimum level of the six independent variables in which an optimal aspirin nanoemulsion with desirable properties could be produced. The response surface analysis results clearly showed that the variability of two responses could be depicted as a linear function of the content of main emulsion compositions and ultrasonic processing variables. In the present investigation, it is evidently shown that ultrasound cavitation is a powerful yet promising approach in the controlled production of aspirin nanoemulsions with smaller average droplet size in a range of 200-300 nm and with a polydispersity index (PDI) of about 0.30. This study proved that the use of low frequency ultrasound is of considerable importance in the controlled production of pharmaceutical nanoemulsions in the drug delivery system.  相似文献   

2.
An ultrasonic microreactor with rough microchannels is presented in this study for oil-in-water (O/W) emulsion generation. Previous accounts have shown that surface pits or imperfections localize and enhance cavitation activity. In this study cavitation bubbles are localized on the rough microchannels of a borosilicate glass microreactor. The cavitation bubbles in the microchannel are primarily responsible for emulsification in the ultrasonic microreactor. We investigate the emulsification mechanism in the rough microchannels employing high-speed imaging to reveal the different emulsification modes influenced by the size and oscillation intensity of the cavitation bubbles. The effect of emulsification modes on the O/W emulsion droplet size distribution for different surface roughness and frequency is demonstrated. The positive effect of the frequency on minimizing the droplet size utilizing a reactor with large pits is presented. We also demonstrate microreactor systems for a successful generation of miniemulsions with high dispersed phase volume fractions up to 20%. The observed emulsification mechanism in the rough microchannel offers new insights into the utility and scale-up of ultrasonic microreactors for emulsification.  相似文献   

3.
In the present investigation, the operating efficiency of a bench-top air-driven microfluidizer has been compared to that of a bench-top high power ultrasound horn in the production of pharmaceutical grade nanoemulsions using aspirin as a model drug. The influence of important process variables as well as the pre-homogenization and drug loading on the resultant mean droplet diameter and size distribution of emulsion droplets was studied in an oil-in-water nanoemulsion incorporated with a model drug aspirin. Results obtained show that both the emulsification methods were capable of producing very fine nanoemulsions containing aspirin with the minimum droplet size ranging from 150 to 170 nm. In case of using the microfluidizer, it has been observed that the size of the emulsion droplets obtained was almost independent of the applied microfluidization pressure (200–600 bar) and the number of passes (up to 10 passes) while the pre-homogenization and drug loading had a marginal effect in increasing the droplet size. Whereas, in the case of ultrasound emulsification, the droplet size was generally decreased with an increase in sonication amplitude (50–70%) and period of sonication but the resultant emulsion was found to be dependent on the pre-homogenization and drug loading. The STEM microscopic observations illustrated that the optimized formulations obtained using ultrasound cavitation technique are comparable to microfluidized emulsions. These comparative results demonstrated that ultrasound cavitation is a relatively energy-efficient yet promising method of pharmaceutical nanoemulsions as compared to microfluidizer although the means used to generate the nanoemulsions are different.  相似文献   

4.
《Ultrasonics sonochemistry》2014,21(6):2069-2083
Novel nanoemulsion-based drug delivery systems (DDS) have been proposed as alternative and effective approach for the delivery of various types of poorly water-soluble drugs in the last decade. This nanoformulation strategy significantly improves the cell uptake and bioavailability of numerous hydrophobic drugs by increasing their solubility and dissolution rate, maintaining drug concentration within the therapeutic range by controlling the drug release rate, and reducing systemic side effects by targeting to specific disease site, thus offering a better patient compliance. To date, cavitation technology has emerged to be an energy-efficient and promising technique to generate such nanoscale emulsions encapsulating a variety of highly potent pharmaceutical agents that are water-insoluble. The micro-turbulent implosions of cavitation bubbles tear-off primary giant oily emulsion droplets to nano-scale, spontaneously leading to the formation of highly uniform drug contained nanodroplets. A substantial body of recent literatures in the field of nanoemulsions suggests that cavitation is a facile, cost-reducing yet safer generation tool, remarkably highlighting its industrial commercial viability in the development of designing novel nanocarriers or enhancing the properties of existing pharmaceutical products. In this review, the fundamentals of nanoemulsion and the principles involved in their formation are presented. The underlying mechanisms in the generation of pharmaceutical nanoemulsion under acoustic field as well as the advantages of using cavitation compared to the conventional techniques are also highlighted. This review focuses on recent nanoemulsion-based DDS development and how cavitation through ultrasound and hydrodynamic means is useful to generate the pharmaceutical grade nanoemulsions including the complex double or submicron multiple emulsions.  相似文献   

5.
In this study, nanoemulsions for skincare products were continuously produced using a hydrodynamic cavitation reactor (HCR) designed with a rotor and stator. The key component of this research is the utilization of a 3D-printed rotor in a HCR for the production of an oil-in-water nanoemulsion. Response surface methodology was used to determine the process conditions, such as speed of the rotor, flow rate, as well as, Span60, Tween60, and mineral oil concentrations, for generating the optimal droplet size in the nanoemulsion. The results showed that a droplet size of 366.4 nm was achieved under the recommended conditions of rotor speed of 3500 rpm, flow rate of 3.3 L/h, Span60 concentration of 2.36 wt%, Tween60 concentration of 3.00 wt%, and mineral oil concentration of 1.76 wt%. Moreover, the important characteristics for consideration in skincare products, such as polydispersity index, pH, zeta potential, viscosity, stability, and niacin released from formulations, were also assessed. For the niacin release profile of emulsion and nanoemulsion formulations, different methods, such as magnetic stirring, ultrasound, and hydrodynamic cavitation, were compared. The nanoemulsion formulations provided a greater cumulative release from the formulation than the emulsion. Particularly, the nanoemulsion generated using the HCR provided the largest cumulative release from the formulation after 12 h. Therefore, the present study suggests that nanoemulsions can be created by means of hydrodynamic cavitation, which reduces the droplet size, as compared to that generated using other techniques. The satisfactory results of this study indicate that the rotor-stator-type HCR is a potentially cost-effective technology for nanoemulsion production.  相似文献   

6.
The optimum formulation and ultrasonic condition for fabrication of cinnamon essential oil (CEO) nanoemulsion were determined using Response Surface Methodology (RSM). The CEO nanoemulsions were formed using an ultrasonic bath (43 kHz at power output of 210 W) and an ultrasonic probe (24 kHz at power of 400 W). Probe ultrasonication outperformed bath ultrasonication since it produced nanoemulsions with smaller droplet size, narrower size distribution as measured using polydispersity index (PDI), and higher viscosity. The influences of sonication time of 180.23–351.77 s, temperature of 4.82–45.18 °C, and Tween® 80 concentration of 1–3% w/w on the droplet size, PDI, and viscosity were investigated using RSM based on Box-Behnken design (BBD). The RSM revealed that the sonication time of 266 s, temperature of 4.82 °C, and Tween® 80 of 3% w/w produced the optimum CEO nanoemulsion with droplet size of 65.98 nm, PDI of 0.15, and viscosity of 1.67 mPa.s. Moreover, the optimum nanoemulsion had good stability in terms of droplet size and PDI when storing at 4, 30, and 45 °C for 90 days. The antifungal activity of the optimum CEO nanoemulsion was then investigated against Aspergillus niger, Rhizopus arrhizus, Penicillium sp., and Colletotrichum gloeosporioides in comparison to CEO coarse emulsion. The results showed that the CEO nanoemulsion had better antifungal activity than coarse emulsion of CEO.  相似文献   

7.
Nanoemulsions can be used for transporting pharmaceutical phytochemicals in skin-care products because of their stability and rapid permeation properties. However, droplet size may be a critical factor aiding permeation through skin and transdermal delivery efficiency. We prepared d-limonene nanoemulsions with various droplet sizes by ultrasonic emulsification using mixed surfactants of sorbitane trioleate and polyoxyethylene (20) oleyl ether under different hydrophilic–lipophilic balance (HLB) values. Droplet size decreased with increasing HLB value. With HLB 12, the droplet size was 23 nm, and the encapsulated ratio peaked at 92.3%. Transmission electron microscopy revealed spherical droplets and the gray parts were d-limonene precipitation incorporated in spherical droplets of the emulsion system. Franz diffusion cell was used to evaluate the permeation of d-limonene nanoemulsion through rat abdominal skin; the permeation rate depended on droplet size. The emulsion with the lowest droplet size (54 nm) achieved the maximum permeation rate. The concentration of d-limonene in the skin was 40.11 μL/cm2 at the end of 360 min. Histopathology revealed no distinct voids or empty spaces in the epidermal region of permeated rat skin, so the d-limonene nanoemulsion may be a safe carrier for transdermal drug delivery.  相似文献   

8.
Ultrasound is an emerging and promising method for demulsification, which is highly affected by acoustic parameters and emulsion properties. Herein, a series of microscopic and dehydration experiments are carried out to investigate the parameter optimization of ultrasonic separation. The results show that the optimal acoustic parameters highly depend on the emulsion properties. For low frequency ultrasonic standing waves (USWs), mechanical vibrations not only facilitate droplet collision and coalescence, but also disperse the surfactant absorbed on the interface to decrease the interfacial strength. Therefore, low frequency ultrasound is suitable for separating emulsions with high viscosity and high interfacial strength. Increasing the energy density to produce moderate cavitation can increase demulsification efficiency. However, excessive cavitation results in secondary emulsification. In high frequency USWs, the droplets migrate directionally and form bandings, thereby promoting droplet coalescence. Therefore, high frequency ultrasound is favorable for separating emulsions with low dispersed phase content and small droplet size. Increasing the energy density can accelerate the aggregation of droplets, however, excessive energy density causes acoustic streaming that disturbs the aggregated droplets, resulting in reduced demulsification efficiency. This work presents rules for acoustic parameter optimization, further advancing industrial applications of ultrasonic separation.  相似文献   

9.
Ultrasonically-induced nanoemulsions have been widely investigated for the development of functional food, cosmetics, and pharmaceuticals due to ideal droplet sizes (DS), low polydispersity index (PDI), and superior physical stability. However, a series of frequently-used ultrasonic set-ups mainly suffered from a low ultrasonic energy efficiency caused by the large acoustic impedance and energy consumption, subordinately confronted with a low throughput, complicated fabrication with complex structure and weak ultrasonic cavitation. Herein, we employed a typical ultrasonic microreactor (USMR) that ensured the high-efficient energy input and generated intense cavitation behavior for efficient breakage of droplets and continuous production of unified oil-in-water (O/W) nanoemulsions in a single cycle and without any pre-emulsification treatment. The emulsification was optimized by tuning the formula indexes, technological parameters, and numerical analysis using Response Surface Methodology (RSM), followed by a comparison with the emulsification by a traditional ultrasonic probe. The USMR exhibited superior emulsification efficiency and easy scale-up with remarkable uniformity by series mode. In addition, concurrent and uniform nanoemulsions with high throughput could also be achieved by a larger USMR with high ultrasonic power. Based on RSM analysis, uniform DS and PDI of 96.4 nm and 0.195 were observed under the optimal conditions, respectively, well consistent with the predicted values. Impressively, the optimal nanoemulsions have a uniform spherical morphology and exhibited superior stability, which held well in 45 days at 4℃ and 25℃. The results in the present work may provide a typical paradigm for the preparation of functional nanomaterials based on the novel and efficient emulsification tools.  相似文献   

10.
Polysaccharides of β-d-glucan configuration have well-known antioxidant activity against reactive free radicals generated from the oxidation of metabolic processes. In this study, β-d-glucan-polysaccharides extracted from Ganoderma lucidum were incorporated in palm olein based nanoemulsions which act as carrier systems to enhance the delivery and bioactivity of these polysaccharides and could be potentially useful for skin care applications. Initially response surface statistical design (Central Composite Design – CCD) was subjected to optimize the formulation variables of oil-in-water (O/W) nanoemulsions induced by ultrasound. The optimal formulation variables as predicted by CCD resulted in considerably improving the physical characteristics of ultrasonically formulated nanoemulsions by minimizing their droplet size, polydispersity index and viscosity. Moreover, the β-d-glucan-loaded nanoemulsions exhibited good stability over 90 days under different storage conditions (4 °C and 25 °C). The studies using palm olein based β-d-glucan-loaded nanoemulsion generated using ultrasound confirm higher antioxidant activity as compared to free β-d-glucan.  相似文献   

11.
Fang JY  Hung CF  Hua SC  Hwang TL 《Ultrasonics》2009,49(1):39-14347
Camptothecin is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. However, its clinical application is limited by its insolubility, instability, and toxicity. The aim of the present study was to develop acoustically active nanoemulsions for camptothecin encapsulation to circumvent these delivery problems. The nanoemulsions were prepared using liquid perfluorocarbons and coconut oil as the cores of the inner phase. These nanoemulsions were stabilized by phospholipids and/or Pluronic F68 (PF68). The nanoemulsions were prepared at high drug loading of ∼100% with a mean droplet diameter of 220-420 nm. Camptothecin in these systems showed retarded drug release. Camptothecin in nanoemulsions with a lower oil concentration exhibited cytotoxicity against melanomas and ovarian cancer cells. Confocal laser scanning microscopy confirmed nanoemulsion uptake into cells. Hemolysis caused by the interaction between erythrocytes and the nanoemulsions was investigated. Formulations with phosphatidylethanolamine as the emulsifier showed less hemolysis than those with phosphatidylcholine. Using a 1 MHz ultrasound, an increased release of camptothecin from the system with lower oil concentration could be established, illustrating a drug-targeting effect.  相似文献   

12.
Aiming at elucidating ultrasonic emulsification mechanisms, the interaction between a single or multiple acoustic cavitation bubbles and gallium droplet interface was investigated using an high-speed imaging technique. To our best knowledge, the moment of emulsification and formation of fine droplets during ultrasound irradiation were observed for the first time. It was found that the detachment of fine gallium droplets occurs from the water-gallium interface during collapse of big cavitation bubbles. The results suggest that the maximum size of cavitation bubble before collapsing is of prime importance for emulsification phenomena. Previous numerical simulation revealed that the collapse of big cavitation bubble is followed by generation of high-velocity liquid jet directed toward the water-gallium interface. Such a jet is assumed to be the prime cause of liquid emulsification. The distance between cavitation bubbles and water-gallium interface was found to slightly affect the emulsification onset. The droplet fragmentation conditions are also discussed in terms of the balance between (1) interfacial and kinetic energies and (2) dynamic and Laplace pressure during droplet formation.  相似文献   

13.
Preparation of pea protein isolate-xylan (PPI-X) conjugate-stabilized nanoemulsions using ultrasonic homogenization and the corresponding structure and environmental stability were investigated in this study. Conditions used to prepare nanoemulsions were optimized using a response surface methodology as follows: protein concentration 8.86 mg/mL, ultrasound amplitudes 57 % (370.5 W), and ultrasound time 16 min. PPI-X conjugate-stabilized nanoemulsions formed under these conditions exhibited less mean droplet size (189.4 ± 0.45 nm), more uniform droplet distribution, greater absolute value of zeta-potential (44.8 ± 0.22 mV), and higher protein adsorption content compared with PPI-stabilized nanoemulsions. PPI-X conjugate-stabilized nanoemulsions also exhibited even particle distribution and dense network structure, which might be reasons for the observed high interfacial protein adsorption content of conjugate-stabilized nanoemulsions. Moreover, better stability against environmental stresses, such as thermal treatment, freeze–thaw treatment, ionic strength and type, and storage time was also observed for the conjugate-stabilized nanoemulsions, indicating that this type of nanoemulsions possess a potential to endure harsh food processing conditions. Therefore, results provide a novel approach for the preparation of protein-polysaccharide conjugate-stabilized nanoemulsions to be applied as novel ingredients to meet special requirements of processed foods.  相似文献   

14.
The removal of the adsorbed oil droplet is critical to deoiling treatment of oil-bearing solid waste. Ultrasonic cavitation is regarded as an extremely useful method to assist the oil droplets desorption in the deoiling treatment. In this paper, the effects of cavitation micro-jets on the oil droplets desorption were studied. The adsorbed states of oil droplets in the oil-contaminated sand were investigated using a microscope. Three representative absorbed states of the oil droplets can be summarized as: (1) the individual oil droplet adsorbed on the particle surface (2) the clustered oil droplets adsorbed on the particle surface; (3) the oil droplet adsorbed in a gap between particles. The micro-jet generation during the bubble collapse near a rigid wall under different acoustic pressure amplitudes at an ultrasonic frequency of 20 kHz was investigated numerically. The desorption processes of the oil droplets at the three representative absorbed states under micro-jets were also simulated subsequently. The results showed that the acoustic pressure has a great influence on the velocity of micro-jet, and the initial diameter of cavitation bubbles is significant for the cross-sectional area of micro-jets. The wall jet caused by a micro-jet impacting on the solid wall is the most important factor for the removal of the absorbed oil droplets. The oil droplet is broken by the jet impinging, and then it breaks away from the solid wall due to the shear force generated by the wall jet. In addition to a higher sound pressure, the cavitation bubble at a larger initial diameter is more important for the desorption of the clustered oil droplets. Conversely, the micro-jet generated by the cavitation bubble at a smaller initial diameter (0.1 mm) is more appropriate for the desorption of the oil droplet in a narrow or sharp-angled gap.  相似文献   

15.
《Ultrasonics sonochemistry》2014,21(4):1265-1274
This study reports on the process optimization of ultrasound-assisted, food-grade oil–water nanoemulsions stabilized by modified starches. In this work, effects of major emulsification process variables including applied power in terms of power density and sonication time, and formulation parameters, that is, surfactant type and concentration, bioactive concentration and dispersed-phase volume fraction were investigated on the mean droplet diameter, polydispersity index and charge on the emulsion droplets. Emulsifying properties of octenyl succinic anhydride modified starches, that is, Purity Gum 2000, Hi-Cap 100 and Purity Gum Ultra, and the size stability of corresponding emulsion droplets during the 1 month storage period were also investigated. Results revealed that the smallest and more stable nanoemulsion droplets were obtained when coarse emulsions treated at 40% of applied power (power density: 1.36 W/mL) for 7 min, stabilized by 1.5% (w/v) Purity Gum Ultra. Optimum volume fraction of oil (medium chain triglycerides) and the concentration of bioactive compound (curcumin) dispersed were 0.05 and 6 mg/mL oil, respectively. These results indicated that the ultrasound-assisted emulsification could be successfully used for the preparation of starch-stabilized nanoemulsions at lower temperatures (40–45 °C) and reduced energy consumption.  相似文献   

16.
Using time-resolved small angle neutron scattering, we have measured the wave-number-dependent structure factor S(q) of monodisperse nanoemulsions that aggregate and gel after we suddenly turn on a strong, short-range, slippery attraction between the droplets. At high q, peaks in S(q) appear as dense clusters of droplets form, and S(q) increases strongly toward low q, as these dense clusters become locked into a rigid gel network, despite the fluidity of the films between the droplets. The long-time high-q structure of nanoemulsion gels formed by slippery diffusion-limited cluster aggregation is universal in shape and remarkably independent of the droplet volume fraction, phi.  相似文献   

17.
Recently, nanoemulsions have been employed for different applications including food and drug industries for efficient nutrient delivery system. In this study, vitamin D (a lipophilic molecule) was encapsulated in fish oil for higher oral bioavailability. The oil-in-water nanoemulsion was formulated by ultrasonication technique with a droplet size range of 300–450 nm and a shelf life of more than 90 days. The influence of oil, water and surfactant concentration was investigated by phase diagram. The formulated nanoemulsion had encapsulation efficiency in the range of 95.7–98.2%. Further, nanoemulsion passed through simulated gastro-intestinal tract revealed an increased bioavailability than non-encapsulated vitamin. Thus, the formulation can be used as a drug delivery vehicle for various lipophilic compounds. Till date, no one have fabricated an efficient nano-vehicle for the delivery of vitamin D as well as analyzed the efficient delivery system in simulated GI-tract, this is first of its kind study in this regard. This can be scaled up further after analyzing the safety aspects.  相似文献   

18.
The effect of aggregation of dispersed water droplets on secondary atomization of emulsified fuel droplets in a heating process was investigated. Secondary atomization was observed using a single droplet experiment in which a water-in-oil (W/O) emulsified fuel droplet prepared using colored water was heated by a halogen heater. The initial diameter of dispersed water droplets before heating was controlled, and the change in the diameter of dispersed water droplets was measured by image analysis. As a result, the aggregation process of dispersed water droplets in the heating process was successfully visualized. The dispersed water droplet diameter increased with an increase in W/O emulsified fuel droplet temperature. The occurrence probability of micro-explosion increased with an increase in the dispersed water droplet diameter in emulsified fuel droplets. It is suggested that the occurrence probability of micro-explosion can be increased by accelerating the aggregation and coalescence of dispersed water droplets below 430 K, which is the average temperature of the starting point of puffing.  相似文献   

19.
Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21 ± 0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood–brain barrier in the treatment of epilepsy.  相似文献   

20.
Ultrasonic emulsification of oil and water was carried out and the effect of irradiation time, irradiation power and physicochemical properties of oil on the dispersed phase volume and dispersed phase droplet size has been studied. The increase in the irradiation time increases the dispersed phase volume while decreases the dispersed phase droplets size. With an increase in the ultrasonic irradiation power, there is an increase in the fraction of volume of the dispersed phase while the droplet size of the dispersed phase decreases. The fractional volume of the dispersed phase increases for the case of groundnut oil-water system while it is low for paraffin (heavy) oil-water system. The droplet size of soyabean oil dispersed in water is found to be small while that of paraffin (heavy) oil is found to be large. These variations could be explained on the basis of varying physicochemical properties of the system, i.e., viscosity of oil and the interfacial tension. During the ultrasonic emulsification, coalescence phenomenon which is only marginal, has been observed, which can be attributed to the collision of small droplets when the droplet concentration increases beyond a certain number and the acoustic streaming strength increases.  相似文献   

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