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.
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.
The crystallographic plane of the ZnO nanocrystals photocatalyst is considered as a key parameter for an effective photocatalysis, photoelectrochemical reaction and photosensitivity. In this paper, we report a simple method for the synthesis of a new (101) high-energy plane bounded ZnO nanocubes photocatalyst directly on the FTO surface, using a seed-mediated ultrasonic assisted hydrolysis process. In the typical procedure, high-density nanocubes and quasi-nanocubes can be grown on the substrate surface from a solution containing equimolar (0.04 M) zinc nitrate hydrate and hexamine. ZnO nanocubes, with average edge-length of ca. 50 nm, can be obtained on the surface in as quickly as 10 min. The heterogeneous photocatalytic property of the sample has been examined in the photodegradation of methyl orange (MO) by UV light irradiation. It was found that the ZnO nanocubes exhibit excellent catalytic and photocatalytic properties and demonstrate the photodegradation efficiency as high as 5.7 percent/μg mW. This is 200 times higher than those reported results using a relatively low-powered polychromatic UV light source (4 mW). The mechanism of ZnO nanocube formation using the present approach is discussed. The new-synthesized ZnO nanocubes with a unique (101) basal plane also find potential application in photoelectrochemical devices and sensing.
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.
Techniques to improve solder joint reliability have been the recent research focus in the electronic packaging industry. In this study, Cu/SAC305/Cu solder joints were fabricated using a low-power high-frequency ultrasonic-assisted reflow soldering approach where non-ultrasonic-treated samples were served as control sample. The effect of ultrasonic vibration (USV) time (within 6s) on the solder joint properties was characterized systematically. Results showed that the solder matrix microstructure was refined at 1.5s of USV, but coarsen when the USV time reached 3s and above. The solder matrix hardness increased when the solder matrix was refined, but decreased when the solder matrix coarsened. The interfacial intermetallic compound (IMC) layer thickness was found to decrease with increasing USV time, except for the USV-treated sample with 1.5s. This is attributed to the insufficient USV time during the reflow stage and consequently accelerated the Cu dissolution at the joint interface during the post-ultrasonic reflow stage. All the USV-treated samples possessed higher shear strength than the control sample due to the USV-induced-degassing effect. The shear strength of the USV-treated sample with 6s was the lowest among the USV-treated samples due to the formation of plate-like Ag3Sn that may act as the crack initiation site.
This paper presents the successful application of ultrasound-assisted packed-bed (UAE-PB) method for the extraction of hypericin from the Hypericum perfuratum L. The Soxhlet system was utilized for the determination of suitable solvent from ethanol, methanol or from the mixture of different proportions of ethanol-methanol. The mixture of 50:50 v/v ethanol-methanol was obtained to be the most suitable solvent since it led to the highest extraction amount of hypericin. The extraction amount of hypericin increased by 13.6% and 21.4% when the solvent changed from pure methanol to the mixture of 50:50 v/v ethanol-methanol for the extraction time of 3 and 8 h, respectively. Subsequently, the extraction was conducted through the UAE-PB, and the effects of temperature, time, and the ratio of solvent to the dried plant were studied. The response surface method (RSM) was used to investigate the effect of parameters on the extraction in the UAE-PB system. At the temperature of 60 °C, extraction time of 105 min, and the solvent to plant ratio of 15.3, the maximum extraction yield of hypericin was achieved. In the optimal conditions, the amount of extraction was 0.112 mg hypericin/g dried plant, which was in accordance with the optimized predicted value (0.111 mg hypericin/g dried plant) from Design-Expert software.
The use of water in subcritical conditions for extraction has several drawbacks. These include the safety features, higher production costs and possible degradation of the bioactive compounds. To overcome these problems, sonic energy and an entrainer were used as external interventions to decrease the polarity of water at milder operating conditions. The effect of low (28kHz) and high (800kHz) frequencies of sonication in the extraction of the main ginger bioactive compound (6-gingerol) were compared. Six parameters were studied: mean particle size (MPS, mm), time of extraction, applied power, sample to solvent ratio (w/v), temperature of extraction, and the percentage of entrainer. The optimum conditions for high frequency SAWE prototype were MPS 0.89-1.77mm, 45min, 40W applied power, 1:30 (w/v), 45°C, and 15% of ethanol as entrainer. Two-way analysis of variance (ANOVA) gave the most significant parameter, which was power with F (1, 45.07), p<2.50×10-9. Although the effect of low frequency was stronger than high frequency, at the optimum conditions of the sample to solvent ratio 1:30 (w/v) with 700mL solvent and temperature 45°C, the concentration and recovery of 6-gingerol from high frequency of SAWE prototype was 2.69 times higher than at low frequency of SAWE. It was found that although the effects of high frequency (800kHz) were negligible in other studies, it could extract suitable compounds, such as 6-gingerol, at lower temperature. Therefore, the effects of sonication, which cause an enlargement in the cell wall of the ginger plant matrix, were observed using a Scanning Electron Microscope (SEM). It was found that the applied power of sonication was the most significant parameter compared to the other parameters.
Phenolic acids of oak gall were extracted using ultrasonic-probe assisted extraction (UPAE) method in the presence of ionic liquid. It was compared with classical ultrasonic-bath assisted extraction (CUBAE) and conventional aqueous extraction (CAE) method, with and without the presence of ionic liquid. Remarkably, the UPAE method yielded two-fold higher extraction yield with the presence of ionic liquid, resulting 481.04 mg/g for gallic acids (GA) and 2287.90 mg/g for tannic acids (TA), while a decreased value of 130.36 mg/g for GA and 1556.26 mg/g for TA were resulted with the absence of ionic liquid. Intensification process resulted the highest yield of 497.34 mg/g and 2430.48 mg/g for GA and TA, respectively, extracted at temperature 50 °C with sonication intensity of 8.66 W/cm2 and 10% duty cycle, diluted in ionic liquid, 1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [Bmim][Tf2N] at concentration of 0.10 M with sample-to-solvent ratio 1:10 for 8 h. Peleg's model successfully predicted the UPAE process confirming that extraction capacity is the controlling factor in extracting phenolic acids. Hence, it can be concluded that UPAE method and ionic liquid have synergistic effect as it effectively enhanced the extraction efficiency to increase the bioactive constituents yield.
A non-seeded method of incorporating superparamagnetic iron oxide nanoparticles (SPION) into silica nanoparticles is presented. Mixture of both SPION and silica nanoparticles was ultrasonically irradiated. The collapsed bubbles and shockwave generated from the ultrasonic irradiation produce tremendous force that caused inelastic collision and incorporation of SPION into the silica. Physicochemical analyses using transmission electron microscope (TEM), electronic spectroscopic imaging (ESI), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy demonstrated the formation of SPION/silica composite nanoparticles. The prepared composite nanoparticles exhibited superparamagnetic behaviour and nearly 70% of the initial saturation magnetization (Ms) of the SPION was retained. The presence and reactivity of the silica were demonstrated via assembling decanethiol monolayer on the composite nanoparticles. The silanol group of the silica provided the binding site for the alkyl group in the decanethiol molecules. Therefore, the thiol moiety became the terminal and functional group on the magnetic composite nanoparticles.
Optimization of sonochemical method of functionalizing a Silane coupling agent, Amino-Silane on Superparamagnetic Iron Oxide Nanoparticles (SPION) using Central Composite Design is reported. The Amino-Silane is grafted on the SPION in an iced bath environment using a Vibra-Cell 20 kHz ultrasonic irradiator with 13 mm diameter horn. Throughout the experiment amplitude of the ultrasonic device is maintained at 47%. The percentage atomic compositions of various APTES elements which bind to the SPION due to the ultrasonic irradiation were determined using X-ray photoelectron spectrometer (XPS). The influence of ultrasonic irradiation time and amount of APTES required for facile, rapid and effective functionalization of Organo-metallic compound on SPION are optimized. The optimized sonication time and amount of APTES are 8.49 min and 3.40 ml, respectively. The predicted results were validated with experimental data. Using the optimized values APTES were functionalized on the SPION experimentally and the results were compared. The experimental results validate the predicted data. Results show that very minimum sonication time is required for effective grafting of APTES on SPION.
Superparamagnetic iron oxide nanoparticles (SPION) are material of interest for biomedical research and related applications. Recently, several works have reported facile sonochemical method of functionalizing nanoparticles with organic coupling agents. Herein, we present the influence of ultrasonic irradiation on the rate of functionalization of 3-amino propyl triethoxyl silane (APTES) on SPION. The effect of sonication on the process is investigated by varying the sonication period between 1 and 20min. Grafting of the organo-metallic molecules on SPION is demonstrated through FTIR and XPS. The results show that in one minute, organo-silane compound can be functionalized onto SPION through unique conditions generated from ultrasonic irradiation. The XPS survey spectra of the as-synthesized APTES-SPION at different sonication periods revealed that absorbed energy due to silanization reactions in all the samples appeared at same peaks. The percentage atomic concentrations of all the elements present in the as-synthesized APTES-SPION are determined by the software CASAXPS. The result demonstrated that highest percentage atomic concentration is observed at the one minute sonication period.
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.
The dynamics of droplet breakup during emulsification is a complicated process due to the interplay between multiple physico-chemical and hydrodynamic factors, especially in an energy-intensive ultrasound-assisted emulsification process. In this work, by mapping the physical processing parameters of ultrasound emulsification into a reduced domain that is governed by the power density and the initial average droplet diameter, a dimensionless parameter that resembles the dynamic breakup potential (η) was established via dimensional analysis. In addition to shedding important insights into the emulsification process, η further facilitates the establishment of a transient scaling relationship that is a function of the characteristic value (a) of the emulsion system. Experimental case study on a cellulose nanocrystals (CNC)-based olein-in-water emulsion system prepared via ultrasound cavitation confirmed the validity of the scaling relationship and sub-universal self-similarity was observed. Using the proposed model, good predictions of the transient of droplet size evolution were attained where the value of η, i.e. the proportionality constant, can be conveniently computed using data from a single time point. Application on other emulsion systems further suggested that the value of a possibly indicates the relative minimum size limit of a particular fluids-emulsifier system. Our approach is general, which encourages widespread adoption for emulsification related studies.
Recent advances in ultrasound (US) have shown its great potential in biomedical applications as diagnostic and therapeutic tools. The coupling of US-assisted drug delivery systems with nanobiomaterials possessing tailor-made functions has been shown to remove the limitations of conventional drug delivery systems. The low-frequency US has significantly enhanced the targeted drug delivery effect and efficacy, reducing limitations posed by conventional treatments such as a limited therapeutic window. The acoustic cavitation effect induced by the US-mediated microbubbles (MBs) has been reported to replace drugs in certain acute diseases such as ischemic stroke. This review briefly discusses the US principles, with particular attention to the recent advancements in drug delivery applications. Furthermore, US-assisted drug delivery coupled with nanobiomaterials to treat different diseases (cancer, neurodegenerative disease, diabetes, thrombosis, and COVID-19) are discussed in detail. Finally, this review covers the future perspectives and challenges on the applications of US-mediated nanobiomaterials.
The aim of this study was ultrasound assisted removal of Ceftriaxone sodium (CS) based on CCD model. Using sonochemical synthesized Bi2WO6 implanted on graphitic carbon nitride/Multiwall carbon nanotube (g-C3N4/MWCNT/Bi2WO6). For this purpose g-C3N4/MWCNT/Bi2WO6 was synthesized and characterized using diverse approaches including XRD, FE-SEM, XPS, EDS, HRTEM, FT-IR. Then, the contribution of conventional variables including pH, CS concentration, adsorbent dosage and ultrasound contact time were studied by central composite design (CCD) under response surface methodology (RSM). ANOVA was employed to the variable factors, and the most desirable operational conditions mass provided. Drug adsorption yield of 98.85% obtained under these defined conditions. Through conducting five experiments, the proper prediction of the optimum point were examined. The respective results showed that RSD% was lower than 5% while the t-test confirmed the high quality of fitting. Langmuir isotherm equation fits the experimental data best and the removal followed pseudo-second order kinetics. The estimation of the experimentally obtained maximum adsorption capacities was 19.57 mg.g- of g-C3N4/MWCNT/Bi2WO6 for CS. Boundary layer diffusion explained the mechanism of removal via intraparticle diffusion.
The effect of ultrasound treatment on molecular mobility and organization of the main components in raw goat milk was studied by EPR and NMR spectroscopies. NMR relaxation studies showed an increase in the spin-lattice T1 and spin-spin T2 relaxation times in goat milk products (cream, anhydrous fat) and change in the diffusion of proton-containing molecules during ultrasound treatment. The diffusion became more uniform and could be rather accurately approximated by one effective diffusion coefficient Deff, which indicates homogenization of goat milk components, dispersion of globular and supermicellar formations under sonication. EPR studies have shown that molecular mobility and organization of hydrophobic regions in goat milk are similar to those observed in micellar formations of surfactants with a hydrocarbon chain length C12-C16. Ultrasound treatment did not affect submicellar and protein globule organization. Free radicals arising under ultrasound impact of milk reacted quickly with components of goat milk (triglycerides, proteins, fatty acids) and were not observed by spin trapping method.
Methods of NMR relaxation and differential scanning calorimetry (DSC) were used to study the crystallization of anhydrous milk fat (AMF) obtained from milk and subjected to ultrasonic (US) processing. Amongst the changes in the crystallization nature under the influence of ultrasound are the decrease in the crystallization temperature and the increase in the melting enthalpy of the anhydrous milk fat samples. The increase is ∼30% at 20 min of isothermal crystallization and is presumably explained by the additional formation of β'-form crystals from the melt. The parameters of the Avrami equation applied to the description of experimental data show an increase in the crystallization rate in samples with ultrasonic treatment and a change in the dimension of crystallization with a change in melting temperature.
5-Hydroxymethylfurfural (HMF) has been identified as a promising biomass-derived platform chemical. In this study, one pot production of HMF was studied in ionic liquid (IL) under probe sonication technique. Compared with the conventional heating technique, the use of probe ultrasonic irradiation reduced the reaction time from hours to minutes. Glucose, cellulose and local bamboo, treated with ultrasonic, produced HMF in the yields of 43%, 31% and 13% respectively, within less than 10min. The influence of various parameters such as acoustic power, reaction time, catalysts and glucose loading were studied. About 40% HMF yield at glucose conversion above 90% could be obtained with 2% of catalyst in 3min. Negligible amount of soluble by-product was detected, and humin formation could be controlled by adjusting the different process parameters. Upon extraction of HMF, the mixture of ionic liquid and catalyst could be reused and exhibited no significant reduction of HMF yield over five successive runs. The purity of regenerated [C4C1im]Cl and HMF was confirmed by NMR spectroscopy, indicating neither changes in the chemical structure nor presence of any major contaminants during the conversion under ultrasonic treatment. 13C NMR suggests that [C4C1im]Cl/CrCl3 catalyses mutarotation of α-glucopyranose to β-glucopyranose leading to isomerization and finally conversion to HMF. The experimental results demonstrate that the use of probe sonication technique for conversion to HMF provides a positive process benefit.
Ultrasonic treatment is an emerging food processing technology that has growing interest among health-conscious consumers. Freshly squeezed Chokanan mango juice was thermally treated (at 90 °C for 30 and 60s) and sonicated (for 15, 30 and 60 min at 25 °C, 40 kHz frequency, 130 W) to compare the effect on microbial inactivation, physicochemical properties, antioxidant activities and other quality parameters. After sonication and thermal treatment, no significant changes occurred in pH, total soluble solids and titratable acidity. Sonication for 15 and 30 min showed significant improvement in selected quality parameters except color and ascorbic acid content, when compared to freshly squeezed juice (control). A significant increase in extractability of carotenoids (4-9%) and polyphenols (30-35%) was observed for juice subjected to ultrasonic treatment for 15 and 30 min, when compared to the control. In addition, enhancement of radical scavenging activity and reducing power was observed in all sonicated juice samples regardless of treatment time. Thermal and ultrasonic treatment exhibited significant reduction in microbial count of the juice. The results obtained support the use of sonication to improve the quality of Chokanan mango juice along with safety standard as an alternative to thermal treatment.
In this study, a simple sugaring-out supported by liquid biphasic flotation technique combined with ultrasonication was introduced for the extraction of proteins from microalgae. Sugaring-out as a phase separation method is novel and has been used in the extraction of metal ions, biomolecules and drugs. But, its functioning in protein separation from microalgae is still unknown. In this work, the feasibility of sugaring-out coupled with ultrasound for the extraction of protein was investigated. Primary studies were carried out to examine the effect of sonication on the microalgae cell as well as the separation efficiency of the integrated method. Effect of various operating parameters such as the concentration of microalgae biomass, the location of sonication probe, sonication time, ultrasonic pulse mode (includes varying ON and OFF duration of sonication), concentration of glucose, types of sugar, concentration of acetonitrile and the flow rate in the flotation system for achieving a higher separation efficiency and yield of protein were assessed. Besides, a large-scale study of the integration method was conducted to verify the consistency of the followed technique. A maximum efficiency (86.38%) and yield (93.33%) were attained at the following optimized conditions: 0.6% biomass concentration, 200 g/L of glucose concentration, 100% acetonitrile concentration with 5 min of 5 s ON/10 s OFF pulse mode and at a flow rate of 100 cc/min. The results obtained for large scale were 85.25% and 92.24% for efficiency and yield respectively. The proposed liquid biphasic flotation assisted with ultrasound for protein separation employing sugaring-out demonstrates a high production and separation efficiency and is a cost-effective solution. More importantly, this method provides the possibility of extending its application for the extraction of other important biomolecules.