Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation

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.     

Response surface methodology for optimization of cinnamon essential oil nanoemulsion with improved stability and antifungal activity

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.     

Emulsification mechanism in an ultrasonic microreactor: Influence of surface roughness and ultrasound frequency

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.     

Preparation of biodiesel with the help of ultrasonic and hydrodynamic cavitation

An alkali-catalyzed biodiesel production method with power ultrasonic (19.7 kHz) has been developed that allows a short reaction time and high yield because of emulsification and cavitation of the liquid-liquid immiscible system. Orthogonality experiments were employed to evaluate the effects of synthesis parameters. Furthermore, hydrodynamic cavitation was used for biodiesel production in comparison to ultrasonic method. Both methods were proved to be efficient, and time and energy saving for the preparation of biodiesel by transesterification of soybean oil.     

Optimization of acoustic parameters for ultrasonic separation of emulsions with different physical properties

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.     

Impact of process parameters in the generation of novel aspirin nanoemulsions – Comparative studies between ultrasound cavitation and microfluidizer

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.     

Structure and stability characterization of pea protein isolate-xylan conjugate-stabilized nanoemulsions prepared using ultrasound homogenization

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.     

碟形超声变幅杆的设计

优化超声变幅杆的形状结构可有效地提高水域声场分布和空化区域,提升对水域超声空化效果。通过模拟分析发现传统超声变幅杆在水域中具有声场分布均匀性差、变幅杆端部声压高等特征,不利于声波在水域中传播。基于此,提出并优化设计了一种具有碟形结构的变幅杆,位于变幅杆的最大振幅处的碟形结构,有更大的振动位移;模拟表明其水域声场和声压均衡度显著优于传统变幅杆,铝箔空化腐蚀实验进一步证实了其水域中的声压分布均匀性。同时,实验通过铝箔的空化腐蚀、KI剂量测定及工件表面油渍去除对比了传统变幅杆和碟形变幅杆,分析表明碟形变幅杆所在水域中有较大的空化腐蚀区域,腐蚀速率明显提升,声化学反应速率提高,油渍去除程度增强,说明了设计的碟形变幅杆能够促进空化泡的产生,增加水域空化区域。     

High-speed imaging of ultrasonic emulsification using a water-gallium system

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.     

A study on the emulsification of oil by power ultrasound

A commercial ultrasonic probe was used to study emulsification of an o/w system (5 wt% soybean oil stabilised with 1 wt% Tween 80 in water). Two different sets of experiments were performed.

Firstly, we investigated the effect of power, duty cycle and ultrasound time on the production of an oil-in-water emulsion from a coarse pre-emulsion mix. The droplets reached a stable size (0.7 μm) within 5 min independent of the power and duty cycle used.

Secondly, the mechanism of emulsification was studied by observing the emulsification process at an oil–water interface (no pre-mix) with a high-speed camera. Transient cavitation is thought to be responsible for acoustic emulsification; however there have been no measurements to relate the transient cavitation zone to the production of an emulsion. It has already been shown that the transient cavitation in probe systems is directly under the probe tip. High-speed observations showed that an emulsion could only be obtained if the interface was within a few millimetres of the probe tip. These results strongly suggest that the transient cavitation zone is responsible for the acoustic emulsification of oil.     

A theoretical study of hydrodynamic cavitation

The optimization of hydrodynamic cavitation as an AOP requires identifying the key parameters and studying their effects on the process. Specific simulations of hydrodynamic bubbles reveal that time scales play a major role on the process. Rarefaction/compression periods generate a number of opposing effects which have demonstrated to be quantitatively different from those found in ultrasonic cavitation. Hydrodynamic cavitation can be upscaled and offers an energy efficient way of generating cavitation. On the other hand, the large characteristic time scales hinder bubble collapse and generate a low number of cavitation cycles per unit time. By controlling the pressure pulse through a flexible cavitation chamber design these limitations can be partially compensated. The chemical processes promoted by this technique are also different from those found in ultrasonic cavitation. Properties such as volatility or hydrophobicity determine the potential applicability of HC and therefore have to be taken into account.     

超声清洗装置空化噪声谱分析法空化噪声级测量

空化强度是用以衡量液体介质中空化活动的剧烈程度,同时空化效应在超声清洗中起关键作用,因此,测量超声清洗槽中的空化强度便可了解其中空化活动的情况.当发生空化时,液体介质中会产生成分复杂空化噪声,对空化噪声谱进行分析和计算得到空化噪声级,据此可判断空化强度.实验测得结果表明:超声清洗装置内稳态空化分布广泛、均匀,瞬态空化分...     

Effect of ultrasonic power on the stability of low-molecular-weight oyster peptides functional-nutrition W1/O/W2 double emulsion

Ultrasonic-assisted treatment is an eco-friendly and cost-effective emulsification method, and the acoustic cavitation effect produced by ultrasonic equipment is conducive to the formation of stable emulsion. However, its effect on the underlying stability of low-molecular-weight oyster peptides (LOPs) functional-nutrition W₁/O/W₂ double emulsion has not been reported. The effects of different ultrasonic power (50, 75, 100, 125, and 150 W) on the stability of double emulsions and the ability to mask the fishy odor of LOPs were investigated. Low ultrasonic power (50 W and 75 W) treatment failed to form a well-stabilized double emulsion, and excessive ultrasound treatment (150 W) destroyed its structure. At an ultrasonic power of 125 W, smaller particle-sized double emulsion was formed with more uniform distribution, more whiteness, and a lower viscosity coefficient. Meanwhile, the cavitation effect generated by 125 W ultrasonic power improved storage, and oxidative stabilities, emulsifying properties of double emulsion by reducing the droplet size and improved sensorial acceptability by masking the undesirable flavor of LOPs. The structure of the double emulsion was further confirmed by optical microscopy and confocal laser scanning microscopy. The ultrasonic-assisted treatment is of potential value for the industrial application of double emulsion in functional-nutrition foods.     

Cavitation bubble dynamics studied by high speed photography and holography: part one

Bubble dynamics has been recognized as being responsible for many effects in ultrasonic fields, for example cleaning and destruction of surfaces, and emulsification. To improve the performance of ultrasonic devices which make use of these effects some knowledge of the dynamics of cavitation bubbles is needed. One of the main means of studying bubble dynamics is high speed photography in conjunction with some suitable bubble production mechanism to get rid of the statistical appearance of bubbles encountered in ultrasonic cavitation. Results of jet and vortex ring formation obtained mainly with spark-and laser-produced bubbles are reported and demonstrated in a series of frames.     

Characterization of cavitation under ultrasonic horn tip – Proposition of an acoustic cavitation parameter

Acoustic cavitation, generated by a piezo-driven transducer, is a commonly used technique in a variety of processes, from homogenization, emulsification, and intensification of chemical reactions to surface cleaning and wastewater treatment. An ultrasonic horn, the most commonly used acoustic cavitation device, creates unique cavitation conditions under the horn tip that depend on various parameters such as the tip diameter, the driving frequency of the horn, its amplitude, and fluid properties. Unlike for hydrodynamic cavitation, the scaling laws for acoustic cavitation are poorly understood. Empirical relationships between cavitation dynamics, ultrasonic horn operating conditions, and fluid properties were found through systematic characterization of cavitation under the tip. Experiments were conducted in distilled water with various sodium chloride salt concentrations under different horn amplitudes, tip geometries, and ambient pressures. Cavitation characteristics were monitored by high-speed (200,000 fps) imaging, and numerous relations were found between operating conditions and cavitation dynamics. The compared results are discussed along with a proposal of a novel acoustic cavitation parameter and its relationship to the size of the cavitation cloud under the horn tip. Similar to the classical hydrodynamic cavitation number, the authors propose for the first time an acoustic cavitation parameter based on experimental results.     

Influence of hydrostatic pressure and gas content on continuous ultrasound emulsification.

Ultrasound is one means among others of producing emulsions mechanically. Droplet disruption in sonicated liquid-liquid systems is considered to be controlled by cavitation. Both hydrostatic pressure and gas content of the liquids influence the probability and intensity of cavitation. Continuous ultrasound emulsification experiments were carried out to elucidate the effect of these parameters on the result of droplet disruption. Maximum energy density in the apparatus decreases with increasing hydrostatic pressure, probably due to partial suppression of cavitation which is the main mechanism of power dissipation. At constant energy density there is no significant influence of hydrostatic pressure on the emulsification result, however. Corresponding results were obtained for the influence of the gas content. Gas saturation or partial degassing prior to emulsification lead to a shift in maximum energy density. But, again, at constant energy density no clear effect on the droplet size of the emulsion is observed.     

Cavitation technology – A greener processing technique for the generation of pharmaceutical nanoemulsions

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.     

Investigations on the generation of oil-in-water (O/W) nanoemulsions through the combination of ultrasound and microchannel

O/W nanoemulsions are isotropic colloidal systems constituted of oil droplets dispersed in continuous aqueous media and stabilised by surfactant molecules. Nanoemulsions hold applications in more widespread technological domains, more crucially in the pharmaceutical industry. Innovative nanoemulsion-based drug delivery system has been suggested as a powerful alternative strategy through the useful means of encapsulating, protecting, and delivering the poorly water-soluble bioactive components. Consequently, there is a need to generate an emulsion with small and consistent droplets. Diverse studies acknowledged that ultrasonic cavitation is a feasible and energy-efficient method in making pharmaceutical-grade nanoemulsions. This method offers more notable improvements in terms of stability with a lower Ostwald ripening rate. Meanwhile, a microstructured reactor, for instance, microchannel, has further been realised as an innovative technology that facilitates combinatorial approaches with the acceleration of reaction, analysis, and measurement. The recent breakthrough that has been achieved is the controlled generation of fine and monodispersed multiple emulsions through microstructured reactors. The small inner dimensions of microchannel display properties such as short diffusion paths and high specific interfacial areas, which increase the mass and heat transfer rates. Hence, the combination of ultrasonic cavitation with microstructures (microchannel) provides process intensification of creating a smaller monodispersed nanoemulsion system. This investigation is vital as it will then facilitate the creation of new nanoemulsion based drug delivery system continuously. Following this, the fabrication of microchannel and setup of its combination with ultrasound was conducted in the generation of O/W nanoemulsion, as well as optimisation to analyse the effect of varied operating parameters on the mean droplet diameter and dispersity of the nanoemulsion generated, besides monitoring the stability of the nanoemulsion. Scanning transmission electron microscopy (STEM) images were also carried out for the droplet size measurements. In short, the outcomes of this study are encouraging, which necessitates further investigations to be carried out to advance a better understanding of coupling microchannel with ultrasound to produce pharmaceutical-grade nanoemulsions.     

High intensity ultrasonic equipment for teaching and research

Colleges now need equipment to demonstrate ultrasonic effects such as cavitation and emulsification to students. The author uses his equipment to do this and also to carry out fundamental research into the applications of high intensity ultrasound     

Sonochemical and hydrodynamic cavitation reactors for laccase/hydrogen peroxide cotton bleaching

The main goal of this work is to develop a novel and environmental-friendly technology for cotton bleaching with reduced processing costs. This work exploits a combined laccase–hydrogen peroxide process assisted by ultrasound. For this purpose, specific reactors were studied, namely ultrasonic power generator type K8 (850 kHz) and ultrasonic bath equipment Ultrasonic cleaner USC600TH (45 kHz). The optimal operating conditions for bleaching were chosen considering the highest levels of hydroxyl radical production and the lowest energy input. The capacity to produce hydroxyl radicals by hydrodynamic cavitation was also assessed in two homogenizers, EmulsiFlex®-C3 and APV-2000. Laccase nanoemulsions were produced by high pressure homogenization using BSA (bovine serum albumin) as emulsifier. The bleaching efficiency of these formulations was tested and the results showed higher whiteness values when compared to free laccase. The combination of laccase–hydrogen peroxide process with ultrasound energy produced higher whiteness levels than those obtained by conventional methods. The amount of hydrogen peroxide was reduced 50% as well as the energy consumption in terms of temperature (reduction of 40 °C) and operating time (reduction of 90 min).