Conventional atomizers used on spray drying.
\r\n\tInitially, macroecology includes the study of food and space of species of particular area but now it encompasses the relationships between organisms and environment characterized by their distribution, diversity and patterns of abundance. The spatial macroecological investigations are important and being carried out on the dynamics of functional ecosystem and climate change, biodiversity and fisheries.
\r\n\t
\r\n\tThis book covers the findings and reviews of various aspects of freshwater ecosystems which highlight not only the underlying challenge of macroecological processes but also the emerging traits of functional diversity including micro-organisms, algae, macrophytes, invertebrates, fish and other vertebrates.
\r\n\t
\r\n\tThe book will be useful for those who are working in the field of freshwater ecosystems. Each chapter of the book focuses on the basic and current status of the knowledge based on the concerned topics in the field of freshwater ecology. Hopefully the book will be beneficial not only for academicians but also for
\r\n\tindustrialists and professionals.
Spray drying is a well-known method of particle production which consists on the transformation of a fluid material into dried particles, taking advantage of a gaseous hot drying medium [1]. Its first observation is dated 1860 and a primitive spray dryer device was patented by Samuel Percy in United States in 1872 [1, 2, 3].
Ever since it was first discovered, the spray-drying technique has been improved concerning its operational design and applications. In fact, the primordial spray dryer devices lacked process efficiency and safety. After overcoming these issues, spray drying became an attractive method for food industry purposes, ending up to be used in milk powder production in the 1920s, remaining one of the most important applications until the current days. Spray-drying evolution was directly influenced by World War II, where there was an imperative need to reduce the weight and volume of food and other materials to be carried [3, 4]. As a result, spray drying has become an industry benchmark, namely in the dairy products’ fabrication. In the post-war period, the spray-drying method continued progressing, reaching the pharmaceutical, chemical, ceramic and polymer industries [3, 5].
Even after more than a century of research, spray drying is still a target of study and innovation due to the increasing demand for complex particles with specific characteristics. This is considered a powerful technological process since it brings feasibility to the production of free-flowing particles with well-defined particle size. Besides, bearing in mind the ability to use different feedstocks as well as its high productivity and broad applications, makes this technique more and more attractive to the scientific community [2, 3].
Spray-drying mechanism is based on moisture elimination using for that a heated atmosphere to which the feed product is subjected. The process may be described by three major phases (atomization, droplet-to-particle conversion and particle collection), although some authors use four or five minor steps to describe it in more detail [2, 4, 6]. As shown in Figure 1, a solution is pumped to an atomizer, breaking up the liquid feed into a spray of fine droplets. Then, the droplets are ejected into a drying gas chamber where the moisture vaporization occurs, resulting in the formation of dry particles. Finally, using an appropriate device, the dried particles are separated from the drying medium, being then collected in a tank.
Schematic representation of spray-drying mechanism. (1) Atomization. (2) Droplet-to-particle conversion. (3) Particle collection. Adapted from [
All of these stages, conjointly with the conditions, in which they are processed, play a crucial impact in the yield of spray-drying mechanism as well as in the final particle properties [1, 3]. Thus, every step of this mechanism will be meticulously described below.
The spray-drying process is initiated with the feed solution atomization in small droplets due to a decrease of surface tension. This is considered a crucial step for the subsequent phases, namely during the drying chamber exposition. In fact, breaking up the initial solution into many droplets increases their surface area, optimizing therefore the heat and mass transfers between the heated drying gas and the liquid particles. In other words, this gathers the ideal conditions for evaporation process, which will be preponderant for the formation of dried particles [1, 6, 8].
The physical principle behind the atomization transformation process is based on the liquid disintegration phenomenon. Several authors have addressed different interpretations and analytical models to explain such event [2].
In 1873, Joseph Plateau was a pioneer in this issue, realizing that a liquid jet of constant radius, falling due to gravity, experiences a progressive increase of its length [2]. As soon as a critical value is reached, the cylindrical shape of the jet is disintegrated into small spherical droplets, which essentially takes place due to a decrease in surface tension (Figure 2A). Later, Lord Rayleigh (1878) [2] validated Plateau’s work and postulated the “Liquid jet theory”. In broad terms, he described the existence of perturbations waves in a simple laminar jet. For certain wavelengths, the optimum wavelength (λopt = 4.51d, where d is the initial jet diameter), such perturbations grow larger in time, causing the droplet formation (Figure 2B) [2].
Schematic representation of droplet formation mechanism showing the optimum wavelength introduced by Rayleigh [
Weber (1931) [2] and Ohnesorge (1936) [2] built a more complete model to describe the liquid instability. Besides the surface tension and inertial forces underlying the previous works, they described the impact of other factors in the system, namely feed viscosity, the surrounding air and the atomization gas. Weber proved that the frictional forces of the surrounding air cause a decrease in the λopt for drop formation. Moreover, the increase of the relative velocity between the liquid jet and the surrounding air also provokes a decrease in the λopt, and consequently a reduction in the final droplet size. Regarding Ohnesorge’s contribution, he reported the propensity of a liquid jet to breakup into droplets through a relationship (Eq. (1)) between its viscosity, density, surface tension and jet size [2].
The atomization process into droplet form may be accomplished by pressure, centrifugal, electrostatic or ultrasonic energy, using specific devices called atomizers [6, 8]. There are different atomizers (Figure 3), which are used according the desired product characteristics (shape, structure and size) as well as depending on the nature of the feed solution. The most common devices used in the majority of atomization processes are explained below and summarized in Table 1 [1, 2]. In fact, there is a mathematical equation (Eq. (2)) which expresses the relation between the droplet diameter (
Schematic representation of conventional atomizers used on spray drying. (A) Rotary atomizer with respective disc atomizer in detail. (B) Hydraulic nozzle atomizer, (C) pneumatic nozzle atomizer—internal and external two-fluid nozzles. Adapted from [
Rotary atomizer | Hydraulic nozzle atomizer | Pneumatic nozzle atomizer | |
---|---|---|---|
Atomization energy | Centrifugal | Pressure | Kinetic |
Atomization parameters | Disc speed 10,000–30,000 rotations per minute (rpm) | Nozzle pressure 250–10,000 PSI | Nozzle pressure 250–10,000 PSI |
Type of spray | Fine, medium, coarse | Coarse, less homogeneous | Medium coarseness, poor homogeneity |
Mean droplet size | 30–120 μm [2] 10–200 μm [11] | 120–250 μm [2] 30–350 μm [11] 20–600 μm [4] | 30–150 μm [2] 5–100 μm [11] 10–200 μm [4] |
Relation between | |||
Relation between | |||
Advantages | Handle high feed rates without clogging; formation of uniform size particles; low pressure operation; high efficiency | Low price; formation of particles with little occluded air (i.e. particle production of higher density); enables the use of narrow drying chambers | Better control over particle size than in the hydraulic nozzle; useful for feeds of high viscosity; ideal to laboratory scale since it requires small drying chamber; good efficiency |
Drawbacks | High price; not suitable to viscous feed; Inability to use a horizontal and small spray dryer chambers | Not suitable to high viscous feed; high feed rates cause coarse and less homogeneous sprays (i.e. broad particle size distribution) | High operation costs due to the need of high amounts of compressed gas for atomization; production of particles with high occluded air; Downstream turbulence |
The rotary atomizers have a horizontal wheel or disc, and the feedstock solution is driven to its center. There, a centrifugal force is applied which accelerates the feed solution to the periphery, forming a spray of droplets. It is common to find grooves in the atomizer disc, since these structures maximize the control over the solution dispersion caused by the rotary high velocities [1, 2].
Also known as one-fluid nozzles, the operation principle of the hydraulic nozzles consists on the conduction of the feed solution, under pressure, through a pipe with gradually decreasing diameter. The fluid emerges from a small nozzle orifice (usually ranging from 0.4 to 4 mm in diameter) at high velocity with a simultaneous loss in its pressure, undergoing atomization, and thus it is disintegrated in the form of droplets [1, 2].
Pneumatic nozzles are also called multi-fluid nozzles. The most common configuration of these devices is based on a two-fluid nozzle atomizer, where two phases are fed into the nozzle, namely the feedstock solution and the compressed gaseous atomizing medium. The gas flows separately from the feed solution, meeting it whether within or outside the nozzle. Due to the high frictional forces over the liquid surface caused by the high gas velocity, atomization takes place and the feedstock solution is broken down into a cloud of droplets, as stated by Weber. Similarly to the previous atomizers, atomization is influenced by feed properties. Herein, gas velocity and density, as well as its direction and the ratio liquid/gas, also have an important effect in the atomization process [1, 2, 3].
After atomization, the spray-drying mechanism proceeds with the particle formation phase, a crucial stage marked by two events: spray-air contact and droplet drying step, resulting, as a whole, in the removal of the droplets’ solvent content and consequently on their transformation into dried particles [4, 6].
Atomized droplets are exposed to a hot gas within the drying chamber, resulting on first rapid moisture evaporation. Usually, this drying gas is heated (and filtered) atmospheric air, although in some cases there is a need to use other inert gases to avoid eventual instabilities between the gas and the droplets [2]. In what concerns drying chamber’s size and shape, it should be consistent with the spray dryer setup, that is, it should be chosen according the used atomizer and the pretended particle properties. Thus, there are different sized drying chambers (smaller or taller), though they should be big enough to guarantee that particles have the necessary time to dry before reaching the chamber’s walls (otherwise they would deposit in the chamber walls, which is undesirable). The majority of vertical chambers are cylindrical, ending with an inverted cone on its base, as depicted in Figure 4 [1].
Air-droplet flow patterns within the drying chamber. An exemplificative temperature profile is also represented. (A) Co-current flow. (B) Counter-current flow. (C) Mixed flow [
There are different drying chamber configurations, in which the flow pattern between the hot gas and the spray of droplets is distinct: co-current flow, counter-current flow and mixed flow [1].
In the co-current flow (Figure 4A), both the atomized spray and the heated gas enter at the top of the drying chamber, flowing through it in the same direction. The dried particles are dropped at the bottom of the chamber, where they are released together with the gas. In such configuration, there is no time for the drying gas to exchange some of its heat with the surroundings, and thus the atomized droplets meet the highest temperatures inside the drying chamber. However, this implies an instantaneous high rate of solvent evaporation (thermal energy of hot air is utilized for evaporation, cooling it), enabling the dried particles to contact with moderate temperatures which avoid undesirable thermal degradation [1, 2, 8].
In the counter-current design (Figure 4B), spray and hot gas are introduced at opposite ends of the chamber, being the atomizer positioned at its top and the air supplied from the bottom. This flow pattern is considered the most efficient use of the chamber’s heat since the upward streamline of the hot gas will reduce the downward flow velocity of the atomized spray, subjecting it to a longer period of time inside the chamber [3]. However, in contrast with what happens in the co-current flow, during the upward flow of the hot gas some of its heat is released to the surroundings. Thus, atomized droplets with high amounts of solvent will hit the gas at lower temperatures, whereas the driest particles will contact with the highest temperatures of the drying medium at the bottom of the chamber, limiting the application of this process to heat resistant materials. The dried particles are released at the bottom of the chamber while the gas leaves it through its upper part [1].
Mixed flow dryer construction (Figure 4C) combines both co-current flow and counter-current flow, that is, atomized droplets are fed from the bottom of the chamber in counter-current relative to the downward streamline of the drying gas which is supplied from the top. The dried particles as well as the drying gas are then released at the bottom of the chamber. First, the atomized spray experiences an upward flow, and due to the impact of the downward flow of the drying medium, there is a reversion on its path, ultimately falling in the bottom of the chamber. Hence, the residence time of spray inside the chamber is maximized, being this method preferential to dry coarse droplets, even in small chambers [3]. This arrangement is also appropriated only for heat resistant materials.
As introduced above, as soon as the aerosol droplets contact with the drying medium within the chamber, they undergo evaporation and solute condensation, resulting in solvent removal. This phenomenon reflects a heat and mass balance problem driven by the difference between the solvent’s vapor pressure and its partial pressure toward a gas phase. Thus, the hot gas temperature triggers a heat exchange from it to the droplets, whereas the vapor pressure difference causes a moisture transfer in the opposite direction. As a result, dried particles are obtained [5, 8].
Drying kinetics of the spray-drying process comprise several steps with different durations and specific events, as shown in Figure 5 [2, 12].
Temperature evolution during drying kinetics of a sprayed liquid droplet. Adapted from [
Immediately upon gas-droplet contact, heat transfer from the gas to the droplet causes an increase of droplet’s temperature, from its initial temperature (
Schematic representation of droplet morphological changes during spray drying. Adapted from [
During the constant drying rate period, the evaporation of a liquid droplet with a given diameter
Moisture evaporation occurs at a constant rate until a critical value of the droplet water content is reached. In other words, when the solute dissolved in the liquid reaches almost its saturation, a thin shell (also known as crust) is formed at the droplet surface (Figure 6—step 2), and, as a result, evaporation slows down and becomes dependent on the water diffusion rate through such surface shell [2, 3]. This marks the beginning of the drying kinetics’ falling rate period, being immediately noticeable an increasing particle temperature (Figure 5CD). When droplet temperature reaches the moisture boiling point, vaporization takes places, a transition which requires a large amount of energy (Figure 5DE). This means there is no longer a sensible heating of the particles and thus, the drying process proceeds driven by external heat transfer from the air to the particle. Once again, there is an increase of particle temperature until it becomes equal to that of the surrounding gas, marking the end of the drying process (Figure 5EF) [12]. Along the falling rate period, when the partial pressure of moisture vapor at the droplet core overcomes the ambient pressure, bubble formation inside the droplets may occur (Figure 6—step 3) [2].
In order to achieve a successful droplet-to-particle conversion, an optimization of the process conditions is required. Regarding the drying mechanism, two major aspects have a huge impact in the final products: the minimum temperature (
Regarding
Once the droplet-to-particle conversion is concluded, it is necessary to collect the dried particles. This implies a separation procedure, in which the dried particles are disassociated from the drying gas. Such separation occurs in general in two phases, called primary and second separation. In the primary separation, the most dense particles are recovered at the conical bottom of the drying chamber, as they settle on it [2, 8]. On the second separation, the finest or smallest particles are transferred to external devices, where they are separated from the humid air. The most common dry collectors include the cyclone separator, the bag filter and the electrostatic precipitator (Figure 7); equipment with different efficiencies and which are used according to the size of particles exhausted with the humid gas and the desired characteristics of the final product [6]. Moreover, it is also common to use wet scrubbers after the dry collectors in order to perform an extra gas cleaning step, as it will be explained below [2].
Typical collectors used on spray drying. (A) Cyclone separator. (B) Bag filter. (C) Electrostatic precipitator. (D) Venturi wet scrubber. Adapted from [
The separation mechanism of the cyclone separator is based on centrifugal force. This device presents a cylindrical upper part, the barrel, and a conical part on its bottom, the cone (Figure 7A). The streamline of air containing the dried particles coming from the drying chamber is supplied into the cyclone at its top, namely tangentially to the barrel. Then, this streamline follows a downward flow, creating an outer vortex. The high velocities of the outer vortex create a centrifugal force on the particles, allowing the particles-gas stream separation. As soon as the gas reaches the cone, an inner vortex is created in the opposite direction. Thus, the gas is expelled from the cyclone at its top, whereas the particles settle into a collection chamber placed on its bottom [2].
Filtration based on bags is extensively used in the spray-drying process. Herein, the air streamline containing the dry particles enters the bag filter under pressure or suction by its hopper and is passed through a fabric, which halts the particles path (Figure 7B). This means that the dry particles are retained on the bag surface while the clean air passes through it, being expelled from the device. The accumulated particles on the bag surface are then collected due to pulses of compressed air injected in counter-current flow inside the bags [2, 18]. Bag filters present high operation efficiency, especially when they are arranged in filtering units with decreasing fabric pores diameter [1].
Electrostatic precipitation is a method of particle collection whose principle is based on electrostatic forces. A high voltage is applied to discharged wires, forming an electric field between them and the collecting plates that constitute the precipitator (Figure 7C). As a result, the gas around these wires is ionized, being capable of charging the particle content of the drying air flowing around this area. Due to Columbic forces, the charged particles converge to the collecting plates and thus the air becomes devoid of dust [2]. Electrostatic precipitators are also very efficient but seldom used taking into account the high equipment costs [1].
In a spray-drying process, it is usual to find some particles escaping in the air stream after the dry collection. Owing to this, it is quite common to install an additional collecting system after the dry collectors, the wet scrubbers. These devices are economical and effective alternatives which perform a final gas cleaning step, being thus capable of minimizing the particle content or even some odor intensity before releasing the gas streamline to the atmosphere [2, 18].
Venturi wet scrubbers (Figure 7D) are well studied devices of easy cleaning or maintenance, being therefore one of the most used equipment in the spray-drying process. They present a converging section, a throat (narrowest part) and a divergent section (diffuser). The inlet air carrying fine particles enters the scrubber and is mixed up with the scrubbing liquid (usually water). This mixture flows throughout the converging section, reaching the throat at high velocity. As a result, a spray of droplets is formed with the dust particles entrapped inside them (scrubbing liquid could also be injected at the throat level). Lastly, the fluid content is separated from the clean gas, being the former discharged and the latter released into the atmosphere [16, 18].
As it could be noted above, the final properties of the dried products are directly influenced by a set of equipment parameters, such as the atomization devices, the drying chamber configuration and the collector type choice. Additionally, a variety of feedstock specificities and process parameters also play a crucial role in the final particle characteristics, conferring different morphologies, sizes or residual moisture amounts. It is thus fundamental to realize how these variables influence the spray-drying mechanism in order to achieve an optimized operation [2].
Atomization stage is carried under pressure, namely when nozzle atomizers are used. The pressure involved during this process has an impact on droplet size. For a given atomizer device and feed solution, droplet size decreases with increasing pressure, as expressed in the following mathematical correlation (Eq. (8)) [1, 2]:
In the particular case of rotary atomizers, droplet size exhibits an inverse relationship with wheel rotation speed and wheel diameter [2].
Feedstock solution is pumped into the atomizer at a controllable rate. Keeping the atomization pressure constant, there is an increase in the droplet size with increasing feed flow rates. This is easily understandable bearing in mind that the nozzle would have the same energy amount to spend in the atomization process of higher feeding volumes. Thus, the droplet fissions are minimized, provoking a small reduction of its size [2].
When feed viscosity is increased, a great percentage of atomization energy supplied to the nozzle is used to overcome the large viscous forces of the solution. Hence, a small amount of energy is left for the droplet fission, resulting in larger droplet sizes. This mechanism follows (Eq. (9)).
As stated above, atomization occurs due to the disruption of the feed surface tension. This means that a feedstock solution with higher surface tension hinders the atomization process. In that sense, before starting the spray-drying process, feedstocks are usually emulsified and homogenized in order to reduce their surface tension [2].
The inlet temperature refers to the heated drying gas temperature, measured right before its entry into the drying chamber. The thermal charge of inlet drying gas reflects its capacity to dry the humid atomized droplets and, thereby, higher inlet temperatures enable higher solvent evaporation rates. Nevertheless, the inlet temperature should not just be increased to achieve better drying performances because it also has an impact in the wet-bulb temperature of the surrounding air. In fact, lower inlet temperatures lead to lower surrounding air wet-bulb temperature, preventing therefore thermal degradation of the final product. Hence, a wise choice of inlet temperature, balanced on these factors, should be done according the feedstock properties [1, 2].
Drying gas flow rate is the volume of drying gas which is supplied to the drying chamber per unit time. High gas flow rates will increase particle movements inside the chamber, minimizing air-droplet interaction time. Besides, it is also reported that the higher the drying gas flow rate, the greater efficiency will be obtained during cyclone separation. This means that the drying gas flow rate should be low enough to ensure a complete particle moisture removal, but on the other hand, it should be suitable for the subsequent separation procedure [1].
Outlet temperature is the temperature of the air containing the dried particles just before such content to be piped into the collection devices. Theoretically, the outlet temperature is the highest temperature to which the dried powder can be heated, although in the counter-current dryers the final product may present a higher temperature than the outlet air (Figure 4B) [1, 2].
Outlet temperature results from all heat and mass exchanges inside the drying chamber, and thus is not directly regulated by the operator. However, this is a function of parameters like the inlet temperature, the drying gas flow rate, as well as the feed properties (solvent evaporation enthalpy and droplet solid concentration) [1].
Residence time refers to the exposition period of the atomized droplets inside the drying chamber, being another important factor with a direct influence on the final product quality. Residence time should be long enough to guarantee that the main goal of the drying stage is accomplished, that is, to obtain dried particles. On the other hand, it is fundamental to keep the product characteristics and when the dried particles are subjected to longer residence times, thermal degradation may occur, especially upon heat-sensitive materials. It is hard to experimentally predict the minimum residence time to be used, although it could be approximately calculated using the (Eq. (6)), defined above. Notwithstanding, it should be remarked that the residence time is usually in the order of a few seconds (e.g. in general, fine particles should not stay more than 10–15 s inside the drying chamber) [2, 19].
Glass transition temperature is an important thermophysical property of amorphous polymers. Above
Summing up, the importance of processing parameters on the spray-drying efficiency is clear. Therefore, the advantages and drawbacks of each parameter should be weighed in order to produce products with desirable characteristics. The trade-off between some of the spray-drying parameters is summarized inTable 2.
Throughout this review, the importance of the spray-drying technique is evidenced. It enables the production of particles with high yield and made up of several raw materials on an industrial scale, thus proving to be a cost-effective process. Spray drying is preferred over conventional particle production approaches, such as emulsion/solvent evaporation method, due to its unique properties: rapid, continuous and single-step method that displays great versatility and reproducibility [22]. Additionally, spray drying does not require a final drying step, as is the case of the majority of conventional methods, and allows to deal with heat-sensitive materials. Considering these ideas, the use of the spray drying in the production of several drug particles or polymeric carriers with well-defined particle size and good flowability (in opposition to the conventional methods) comes as no surprise. Some examples are detailed below [22].
However, spray drying presents some challenges as it was being explained in the previous sections. It is worth highlighting issues like product loss associated to particle deposition inside the walls of the drying chamber, as well as due to the inability of the separation devices to collect the smallest particles. As a result the process yield tend to decrease, while in optimal conditions would be close to 100%. Moreover, it is important to note that it is very challenging to obtain very small particles (nanometer scale) by spray drying, not only due to the inefficiency of the collecting devices but also due to the inherent difficulty of disintegrating the feedstock solution (atomization step) into submicron droplets [22].
Spray-drying mechanism can be carried out in a pilot-spray dryer developed on a laboratory scale or performed in commercially available instruments. The best spray dryer configuration depends on the purpose for which the instrument is used, that is, the equipment must be compatible with the feedstock solution and meet the processing conditions, which lead to the desirable particle specificities.
Büchi (Switzerland) have been developing reliable and versatile spray dryers, which have been used for various intents [22, 23, 24, 25, 26, 27]. Mini Spray Dryer B-290 and Nano Spray Dryer B-90 HP are two of those instruments and thus, their major characteristics and benefits are organized in Table 3 [22].
Spray drying medical applications are mainly focused on the production of microparticles designed for encapsulation purposes and drug delivery systems, which can be then administered orally, pulmonary, ophthalmologically, parenterally, nasally or even vaginally [22]. The fact that this technological process enables to dry heat-sensitive components, like enzymes or proteins, without compromising their biological activity makes the production of such systems possible [32, 33]. As a result, within the biomedical field, spray drying is primarily used to produce dry powder aerosols and to tune active pharmaceutical compounds, making them useful and suitable for drug delivery [11, 32]. In that sense, different strategies have been used to tailor the sprayed products according to the desired goals.
Regarding the spray-drying approach aiming drug encapsulation and delivery systems, it usually takes advantage of a complex initial system containing the active drug substance and an aqueous/organic phase (solution, emulsion or suspension) to produce either microspheres or microcapsules [11, 32].
The fabrication of biodegradable microspheres filled with an active drug is one of the most common strategies of spray drying. Polyesters gather important requirements, such as good biocompatibility, biodegradability and easiness to process, and thus they are usually chosen for the manufacturing of such products. As a result, it is possible to control the drug release over time as the polymer fraction is gradually degraded toward the physiological environment [32, 34]. There are several studies which have reported the production of a wide variety of polymeric microspheres using spray drying. Exemplificative findings involve the use of co-poly (d,l-lactic/glycolic acid) (PLGA) encapsulating a drug designed to fight solid tumors [34], polylactide (PLA) and poly(lactide-co-glycolide) (PLG) entrapping antigens [35], and a mix of PLGA and poly(ε-caprolactone) (PCL) incorporating a specific chemotherapy agents used in the treatment of ovarian and breast cancer [36].
The incorporation of hydrophilic domains in the spray-dried particles is an alternative way of controlling the drug release behavior. In fact, the hydrophilicity of the polymers used to encapsulate the drug has a direct impact on the behavior it, as a more hydrophilic polymer enables fast gelation, consequently slowing the drug release rate. On the other hand, a low concentration of hydrophilic polymeric coating can enhance the drug release rate of poorly water soluble drugs, since it will improve the wettability of the surrounding fluids. Derivative cellulose polymers such as sodium carboxymethyl cellulose, hydroxypropylmethyl cellulose and methylcellulose are just three examples of hydrophilic polymers which have been purposed for these endings [11, 32, 37].
A singular method focused on the encapsulation of sensitive bioactive compounds (e.g. peptides, proteins) or other drugs can be also achieved through spray-drying technology associated to sol-gel polymerization process. In other words, sol-gel process is carried under soft conditions, and when combined with spray drying can deal with the production of microspheres with sensitive molecules entrapped on them [32, 38]. Spray-dried silica gel microspheres are reported in the literature as a promising system to be administered in the form of a drug injectable [38, 39].
Some literature findings are assembled in the following subsections, which have reported the use of spray drying for different applications within the medical area.
Pulmonary drug delivery route is considered an interesting alternative to the oral drug delivery system, as the lung presents a high surface area covered by a rich blood supply. Thus, a targeted delivery to the lungs enables the use of reduced doses, consequently minimizing the side effects associated with systemic drug administration [24, 40]. Notwithstanding, this strategy implies the use of aerosol drugs, whose production is indeed feasible through the spray-drying technology. As reported in the literature, spray drying has revealed to be a powerful tool in fabricating an inhalable powder suitable for lung delivery, since it allows the production of dried, stable and well-defined solid particles within the “respirable size range for pulmonary delivery” [25, 26, 41, 42].
Adi et al. [43] used spray-drying method to produce dry powders for inhalation-containing doxycycline or ciprofloxacin or even a combination of these two chemicals. The cospray formulation of doxycycline and ciprofloxacin (1:1 ratio) has proved to be more efficient for lung delivery than each one of the single spray-dried antibiotic since it exhibited improved physical stability which favored the drug deposition profile.
Beck-Broichsitter et al. [24] investigated the release profile of phosphodiesterase V (PDE-5) (a drug prescribed in the treatment of severe pulmonary hypertension) encapsulated within spray-dried polymeric particles. In that sense, they produced particles from organic PLGA solutions and also composite particles obtained from aqueous PLGA nanosuspensions. They concluded that both spray-dried products were aerodynamically suitable for deep lung deposition but the particles produced from the organic solution are preferred over the composite ones to work as pulmonary drug delivery vehicles as they exhibited an extended drug releasing profile.
Grenha et al. [44] developed microencapsulated protein (insulin)-loaded chitosan/tripolyphosphate nanoparticles by spray drying. In particular, by taking advantage of the ionotropic gelation of chitosan with the tripolyphosphate, they prepared the nanoparticles and then incorporated the protein content within such particles using aerosol excipients (mannitol and lactose). As a result, suitable microspheres for lung protein delivery were produced. In fact, the microspheres presented a good protein loading capacity, being released in a matter of a few minutes toward the lung environment. Nevertheless, the authors realized that the mannitol/protein ratio impacts the microspheres morphology, namely spherical shapes are obtained in the presence of higher amounts of nanoparticles.
Similarly to the pulmonary drug delivery, nasal drug delivery present some remarkable advantages when compared to drug delivery using the central nervous system, standing out the rapid onset action. Nasal surface presents a large surface area with rich porous vascularized epithelium, favoring the drug adsorption. Dry powder-based mucoadhesive products are ideal for nasal administration and thus, spray-drying technique has been used for such purposes [26, 45, 46].
Tadwee et al. [46] prepared, by spray drying, hydoxypropyl methylcellulose microspheres loading carbamazepine, an antiepileptic drug which is used in epileptic seizures. Along this study, they found in this system a promising strategy to allow the drug absorption by the mucosal membrane. This is of extreme importance considering that carbamazepine has a poor aqueous solubility which hinders its use by oral administration.
Alhalaweh et al. [45] developed zolmitriptan-chitosan microparticles by spray drying. Zolmitriptan is a drug prescribed to fight the migraine symptoms (pain, nausea, photophobia and phonophobia). In the present days, it already exist a tablet and a nasal spray (based on zolmitriptan drug) solutions used to treat such health condition. Nevertheless, in both alternatives, the absolute bioavailability of this drug does not exceed 40% [47]. In that sense, Alhalaweh et al. intended to use chitosan in the preparation of a zolmitriptan powder, considering that the mucoadhesive property of chitosan may have an important impact on increasing the bioavailability of the drug in the nose. Some important notes can be drawn from this study, such as: spray drying allowed the production of chitosan spherical particles entrapping good amounts of zolmitriptan; zolmitriptan dispersion around the chitosan matrix is dependent on the chitosan quantity; zolmitriptan release is also affected by proportion and molecular weight of chitosan.
Recently, Zadeh et al. [48] used spray drying to produce insulin loaded microspheres for intranasal delivery application, which is indeed an alternative route of insulin administration that has been tested in the treatment of diabetic mellitus. For that purpose, Zadeh et al. used spray drying to produce microspheres of chitosan and polyvinyl alcohol (PVA) working as the carrier vehicle of insulin. As expected, the properties of the microspheres varied upon different material ratios. In what concerns the rate and drug release from the microspheres, it is important to highlight that chitosan microspheres led to an initial fast insulin release, followed by a slower release rate, but with effective insulin absorption, while the microspheres made up of chitosan and PVA allowed rapid insulin release but without absorption effectiveness.
Spray-drying mechanism can also be used in the materials production focused in the orthopedic field, as it will be hereafter explained. Aiming bone repair purposes, Quinlan et al. [27] proposed the development of a collagen-hydroxyapatite scaffold enhanced with spray-dried alginate particles loading vascular endothelial growth factor (VEGF). In other words, VEGF was primarily encapsulated in the alginate particles which were then incorporated within the collagen-hydroxyapatite matrix. Upon this biomaterial implantation in a bone damage site, it was registered VEGF release for 35 days. As a result, there was an effective vessel formation with consequent improved bone regeneration outcomes, which did not happen at all in the presence of a scaffold without the growth factor.
Sequeira et al. [49] pointed the use of two inorganic oxides, zirconia and alumina, as potential candidates to be used in the orthopedic implantology field. A biocompatible material for such purpose may be obtained combining these two materials, since the stiffness and long-term stability of alumina is merged to the chemical stability and mechanical strength of zirconia. Herein, different zirconia-toughened alumina and alumina-toughened zirconia composite granules were produced by spray drying. Both composites exhibited good mechanical properties as well as allowed osteoblastic cytocompatibility.
Ceramic powders are of major importance in bone tissue engineering. Innovative approaches like 3-D printing makes use of calcium phosphate ceramic powders to shape complex and precise products aiming the regeneration of bone defects. Nevertheless, conventional powder fabrication procedures are far from being ideal for the subsequent 3-D printing usage, as they lack flowability and dispersity which cause agglomeration and irregular morphology issues [50]. Following along with this idea, spray drying has proved to be a credible method to overcome those problems, and thus being suitable in the production of such powders. Ben et al. [50] used spray drying to fabricate monodispersed and spherical β-tricalcium phosphate (β-TCP) powders to be used in 3-D printing. They obtained ceramic materials with good dispersity and flowability, satisfying a high density and uniform porous architecture, meeting therefore important requirements for bone regeneration.
Cholas et al. [51] embedded spray-dried hydroxyapatite (HA) microspheres within a collagen matrix. HA microspheres presented a mesoporous structure which in combination with the collagen matrix formed a good composite scaffold for human bone tissue engineering. Moreover, the authors realized that promising outcomes may be obtained using a simple modification of this system. These HA microspheres could be loaded for drug delivery purposes or even to control the pore structure of the ceramic particle.
Due to the increasing interest of spray-drying technology as well as the numerous applications that spray-dried products can hit, specially within the medical field, several patents were issued until these days. Table 4 compiles some of those patents of the past 10 years.
Title and number of the patent | Technical field | Brief description/main goal | Publication year | Ref. |
---|---|---|---|---|
Thermostable spray-dried rotavirus vaccine formulation and process thereof (US20170173145) | Vaccine development (pharmaceutical) | Provide an enhanced spray-drying process to obtain said rotavirus vaccine formulation. In particular, it was obtained a vaccine with improved heat-stability, ease-of-use, ease-of-transportation and affordability features | 2017 | [52] |
Inhalable epinephrine (US20170119699) | Inhalable drug delivery | Development of particles for delivery of epinephrine to the respiratory system. It was intended to spray-dry particles exhibiting aerodynamic characteristics that enable targeted delivery of epinephrine to the site of action | 2017 | [53] |
Pharmaceutical composition with improved bioavailability (US20170000764) | Solubility and bioavailability enhancement | It was intended to use spray drying to get improved bioavailability (good solubility/dissolution rate), safety and tolerability of a compound for therapeutic endings | 2017 | [54] |
Method for improving the pharmaceutical properties of microparticles comprising diketopiperazine and active agent (US20160101049) | Pharmaceutical formulations for pulmonary delivery | Spray drying was used to fabricate diketopiperazine-insulin particles, improving the aerodynamic performance, active agent stability and efficiency delivery, when compared to diketopiperazine-insulin particles obtained by lyophilization | 2016 | [55] |
Spray drying vancomycin (US20150231197) | Injectable antibiotic (pharmaceutical) | As an alternative to lyophilization, spray-dried vancomycin (an injectable antibiotic to fight bacterial infections in the body) was proposed. Spray-dried antibiotic demonstrated favorable reconstitution times and water content | 2015 | [56] |
Spray drying of high molecular weight hyaluronic acid (US20140155347) | Spray drying of polysaccharides | Hyaluronic acid is commonly used in several medical applications due to its single physical and biological properties. This invention allows a minimal molecular weight loss of the spray-dried polysaccharide | 2014 | [57] |
Liposomal formulations of lipophilic compounds (US20130259922) | Liposomal preparation for drug delivery | Liposomes have been used in the pharmaceutical industry for drug delivery purposes, being usually administrated by injection. Long-term stability and preparation procedures of liposomes involve dehydration and rehydration steps, which can be accomplished by spray drying | 2013 | [58] |
Adhesive containing microparticles (WO2012158483) | Medical devices for skin delivery | A liquid containing active agents was spray dried, resulting in microparticles which can be subsequently incorporated in an adhesive | 2012 | [59] |
Nanoparticle carriers for drug administration and process for producing same (US20110033550) | Nanoparticle carriers for oral administration | Herein, a double emulsion of water-oil-water emulsion was spray dried to form spherical nanometric particles loaded with a specific drug. It is worth mentioning that the nanoparticle carrier itself is made up of polymeric material, the drug is delivered into one of the emulsion phases and the oil-phase or the outer-water phase was doped with a carbohydrate | 2011 | [60] |
Method of producing porous microparticles (US20100092453) | Production of porous microparticles | The production of porous particles is feasible using spray drying under specific conditions. In particular, combining desirable organic compounds with a volatile solvent system. | 2010 | [61] |
Pulmonary delivery of polyene antifungal agents (US20090081302) | Spray-dried polyene compositions | Polyenes (e.g. amphotericin) are efficient antifungal compounds, but lack solubility, either in water or organic solvents. In that sense, the current invention deals with complex issues to get a chemical stable and dispersible powder polyene antibiotic. Nevertheless, the obtained particles are good candidates to be administered by inhalation to the lung to fight pulmonary fungal infections | 2009 | [62] |
Inhalable powders comprising protein, phenylalanine, and other protein stabilizers (US20080089849) | Production of phenylalanine-containing powders | This invention deals with the production of spray-dried powders containing a phenylalanine fraction and other active substance to serve as an inhalative pharmaceutical composition. The resulting powders revealed good aerodynamic characteristics and stabilization of the extra active agent | 2008 | [63] |
Spray drying is considered a powerful technological process since it brings feasibility to the production of free-flowing particles with well-defined particle size. This is indeed a cost-effective manufacturing process capable of producing dried particles in submicron-to-micron range [2, 3]. Moreover, the ability to use different feedstocks and the high productivity and broad applications of this technique makes it more and more attractive to the scientific community [2, 3]. It was noticed that the spray-drying conditions form a network of mutual relationships which have a direct influence on the spray-drying efficiency. The advantages and drawbacks of each parameter should be weighed in order to produce products with desirable characteristics. Such parameters should not be analyzed separately, but rather looked as a complex model, which as a whole contributes to the success of the spray-drying process [2, 64]. The scalability and the cost-effectiveness of this manufacturing process in obtaining dried particles in submicron-to-micron scale favors an increasing variety of applications within the food, chemical, polymeric, pharmaceutical, biotechnology and medical industries.
Olive oil is one of a great interest in the vegetable oils world market. It is produced from the fruit of olive (
Publication trends of olive oil composition (based on data retrieved from Scopus database).
Olive oil is made from fresh olives, which are extracted by mechanical processes [3]. Olive oil extraction technologies are summarized in Figure 2. There are two main olive oil extraction processes: traditional oil mills, and a relatively new extraction process known also by continuous mills and characterized by two or three phases [4, 5] Figure 2. All the above processes aim at separating the liquid oil phase from the other constituents of the fruit [6]. Likewise, olives should be processed as rapidly as possible after harvesting to reduce oxidation and preserve their quality [7].
Scheme of discontinuous and continuous extraction systems. OMWW = olive mill wastewater.
Concerning the traditional press method, olive fruits liberated from leaves are washed, crushed using mill stones, and malaxed into a paste containing solid matter (core debris, epidermis, cell walls, etc.) and fluids (oil and vegetation water contained in the cells of olives). This is then spread on spherical mats [6]. Pressure with a hydraulic piston press is exerted then to obtain, firstly, a solid fraction (known as pomace) and, secondly, the mixture of oil and water is filled into a container and, eventually, the oil and water are then separated by gravity and collected through decantation [5]. The pressing process is the oldest method of obtaining olive oil [8]. Owing to lower production efficiency and high labor costs, during the last decade, the discontinuous pressing systems have widely been substituted by continuous systems, along with the development of centrifuge technology [4, 9]. After the steps of washing, crushing, and mixing, the mechanical extraction of the oil occurs mainly by a continuous process based on centrifugation using a decanter. The decanter centrifuge is equipped with a rotary bowl as well as a screw conveyor, which allows the processing of great quantities of olives in a short time [7]. Continuous separation systems can be divided into two-phase and three-phase systems, based on the decanter type used and the level of the phase of separation [9]. In the three-phase process, an additional amount of hot water is added to wash the oil, and then the three-phase decanter (insoluble solids, oil phase, and an aqueous phase), are separated following their density [7, 10]. Firstly, the solid wastes (insoluble solids), are separated from the remaining two phases in the decanter, and the liquid phases (oil phase as well as aqueous phase), are then subjected to vertical centrifugation to separate the olive oil from the olive mill wastewater [7].
Owing to the significant issue of wastewater produced, this three-phase system is preferred over the two-phase system since it is more eco-friendly [11]. This latest uses only a semi-liquid slurry (vegetation water along with insoluble solids) phase and the oil phase, a semi-liquid slurry, which is also known as two-phase olive mill waste [7]. This process has a reduced environmental impact owing to the reduced requirement of water as well as the amount of waste produced [7].
Olive oil glyceridic fraction consists of triacylglycerols, diacylglycerols, monoacylglycerols and free fatty acids (FFA). Among them, 80% of them are unsaturated fatty acids. It is particularly rich in essential monounsaturated fatty acids (55–83% of oleic acid) and polyunsaturated fatty acids (2.5–21% of linoleic acid) [12]. The remaining fatty acids, apart from C16: 1, display an average value ranging from 0.3 to 3.5% (Table 1 and Figure 3). Nevertheless, linolenic acid is a minority and its concentration is lower than 1% [12]. A low level of linolenic acid can be used to detect adulteration via some vegetable oils such as rapeseed and soybean oils [13]. Small quantities of saturated fatty acids also compose the triglycerides of olive oil: stearic acid (about 0.5–5%) and palmitic acid (about 7.5–20%). The remaining fatty acids (C17: 0, C17: 1, C20: 0, C20: 1, and C22: 0) are found to be of lower magnitudes. Since their concentrations are below 0.5% (Table 1). The unsaponified matter (about 1–2%) contains sterols, triterpene alcohols, tocopherol (mainly α-tocopherol), tocotrienol polyphenols, and squalene. The oil also contains a non-negligible proportion of volatile compounds. The total phytosterols content of VOO ranges between 100 and 200 mg/100 g. Also, 100 mg/100 g represents the inferior limit set by the international olive council [12]. Apparent beta-sitosterol, (beta-sitosterol + delta-5-avenasterol + delta-5-23-stigmastadienol + clerosterol + sitostanol + delta 5–24-stigmastadienol) are the main compounds in the sterol fraction with a value more than 93% while β-sitosterol has the greatest relative percentage [14, 15] (Figure 4). VOO content also includes up to 4.5 g/100 g of total phytosterols [12]. The erythrodiol (5α-olean-12-ene-3β, 28-diol, homo-olestranol) in free and esterified forms and are the major triterpene di-alcohols found in olive oil [14], and their percentage reached up to 4.5% of the total content of sterols [12]. Moreover, four isoforms of tocopherols (α, β, γ, and δ-tocopherol) (Figure 5) and four tocotrienols (α, β, γ and δ- Tocotrienol) are present in olive oil. α-tocopherol is the main tocopherol found in olive oil, constituting more than 90% of the total tocopherol fraction [14]. Cunha et al. [16] reported that the proportions of tocopherols and tocotrienols ranged from 100 to 270 mg/kg in Portuguese olive oils [16]. Gharby et al. [47] found that the values of tocopherols varied from 150 to 250 mg/kg in three varieties (‘Arbequina’, ‘Moroccan Picholine’, and ‘Picual’) of olive oil [17]. Moreover, another study, based on the comparison of the tocopherol contents of olive oils from 4 different varieties harvested at different ripening periods found that the α-tocopherol (major tocopherol) in oils obtained from olives composed of 130.54–180.43 mg/kg [18]. In general, tocopherol and tocotrienol levels in oil fluctuate with several factors such as harvest year, climatic conditions, storage time, extraction method, soil properties and spacing between olive trees [19]. Tocopherols possess a strong antioxidant power [20]. Together with tocopherols and tocotrienols, olive oil contains other antioxidant molecules such as polyphenolic compounds.
Fatty acid [g/100 g] | Norm [12] | Physicochemical parameters | |
---|---|---|---|
Myristic acid [C14: 0] | ≤ 0.2 | Density [20°C] | 0.906–0.919 |
Palmitic acid [C16: 0] | 11.5–15 | Refraction index [20°C] | 1.463–1.472 |
Stearic acid [C18: 0] | 4.3–7.2 | Saponification value [mg of KOH/g] | 184–196 |
Arachidic acid [C20: 0] | ≤ 0.5 | Iodine value [g (I2)/100 g] | 75 to 94 |
Behenic acid [C22: 0] | ≤ 0.2 | Phytosterol [g/100 g] | (IOC 2021) |
15.8–23.1 | Cholesterol | ≤ 0.5 | |
Palmitoleic acid [C16: 1] | ≤ 0,2 | Brassicasterol | ≤ 0.1 |
Oleic acid [C18: 1] | 43,0–49,1 | Campesterol | ≤ 4 |
Eicosenoic acid [C20: 1] | ≤ 0.5 | Stigmasterol | < Campesterol |
43–49.8 | Delta-7-stigmastenol | ≤ 0.5 | |
Linoleic acid [C18: 2] | 29.3–36,0 | Apparent beta-sitosterol | > 93 |
Linolenic acid [C18: 3] | ≤ 0.3 | Total sterol [mg/100 g] | ≤ 220 |
29–36.3 | Erythrodiol & Uvaol (% total sterols) | ≤ 4.5 |
Physicochemical parameters, fatty acids, phytosterols, and tocopherols composition of olive oil.
SFA-Saturated Fatty acids, MUFA-Monounsaturated fatty acids, PUFA-Polyunsaturated fatty acids: Apparent beta-sitosterol: beta-sitosterol +delta-5-avenasterol +delta-5-23-stigmastadienol +clerosterol + sitostanol +delta 5–24-stigmastadienol.
Chromatogram of fatty acids.
Chromatogram of sterols.
Tocopherols chemical structure.
Many research works have demonstrated that the content of tocopherols in VOO is lower than that of argan oil [21, 22, 23].
The phenolic compounds are endowed to have a large scale of biological functions including stability to auto-oxidation, beneficial effects on human health [24]. About their well-known activities, olive oil polyphenols have been proven to possess an effective role in maintaining the organoleptic properties and the stability of olive oils [25].
Such bioactive compounds are extensively studied for their anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antidiabetic, antimicrobial, and anticancer properties [26, 27, 28, 29].
Franco et al. reported that phenolic compounds have a considerable increase during olive fruit growth. However, they are reduced when the fruits reach the maturation stage [30]. Khalatbary documented that the total phenolic content (TPC) in olive oils varies from 190 to 500 mg/kg [31]. In addition, in extra virgin olive oil, TPC commonly varies from 250 to 925 mg/kg [32]. Other factors including climatic conditions, variety, storage time, extraction conditions, soil properties, and analysis of polyphenolic compounds can lead to important variations in TPC [33]. Likewise, several classes of polyphenols are found in olive oils. These are presented as a separate class, to better understand the antioxidant phenolic chemistry of olive oil [33]. Finicelli et al. classify olive oil polyphenols following their chemical structure as follows [34]:
Phenolic alcohols with a hydroxyl group are linked to an aromatic hydrocarbon group. The main constituents of this class are oleocanthal, hydroxytyrosol, and tyrosol (Figure 6) [26].
Secoiridoids are phenolic compounds present in high amounts in olive oil in comparison to other plant species. The bitterness of extra virgin olive oil is a result of the content of secoiridoids [35].
Lignans are chemically characterized by the aggregation of aromatic aldehydes. The pulp of the olives as well as the woody part of the seed contains lignans. These molecules are liberated into the oil during the process of extraction without biochemical changes [36].
Flavonoids are chemically structured with two benzene rings attached via three linear carbon chains. The first flavonoids identified in VOO were flavones; their free forms, apigenin, and luteolin. They are the more abundant compounds [36].
Hydroxyisocromans are the only two molecules characterized in commercial VOO. These compounds are produced via the HydroxyTyrosol reaction with benzaldehyde and vanillin [37].
Phenolic acids are divided into two main classes: hydroxycinnamic acid along hydroxybenzoic acid [26].
Some phenolic alcohols present in olive oil.
The volatile fraction of VOOs has been reported to have about 280 different compounds [38]. The majority of volatile compounds are quickly developed during olive milling as a result of the disturbance of olive cells [39]. Although, Nardella et al. reported that most of the volatile compounds typical of olive oils are generated during malaxation due to the activation of particular pathways, in which the lipoxygenase (LOX) enzyme plays an essential role in producing a large quantity of C6 aldehydes, esters, and alcohols. These constitute almost all of the positive sensory marks in olive oils [40]. Such changes are initiated when olive tissues are affected, thereby enhancing the liberation of endogenous enzymes like hydroperoxide lyase and lipoxygenase [40].
Besides, several analytical techniques have been used to determine volatiles composition in olive oil. The main important are: GC (gas chromatography), HPLC (high-performance liquid chromatography), HPLC/MS (high-performance liquid chromatography/mass spectroscopy), IRMS (isotope ratio mass spectroscopy), ICP (inductively coupled plasma spectroscopy), NMR (nuclear magnetic resonance), SPME-GC/MS (solid-phase microextraction followed by gas chromatography/mass spectrometry, SNIF/NMR (specific natural isotopic fractionation nuclear magnetic resonance), SCIRA (stable carbon isotope ratio analysis), PTR/MS (proton transfer mass spectrometry) [41]. Fregapane et al. reported that the composition of volatiles may be affected significantly according to many factors such as cropping season, olive variety, harvest time, technological parameters, and agronomic conditions among other factors [42]. Ghanbari et al. reported that several chemical factors such as hydrophobicity, volatility, position, and functional groups type are reported to be directly linked to the odor degree of a given volatile component more than its content [38]. Theodosi et al. investigated correlations between the composition of volatiles of olive oil and altitude variation. The findings demonstrate that the total volatile compounds of ‘Koroneiki’ olive oil samples and altitude levels are negatively associated. The most important volatile compounds are alcohols, aldehydes, esters, and hydrocarbons [43].
Parameters routinely used to evaluate physicochemical properties of olive oil include density, iodine value, refractive index, saponification value along with unsaponifiable matter. For vegetable oils including olive oil, both density and refraction index depend on the temperature [44]. Table 1 shows the ranges of the main physicochemical parameters of olive oil. The refractive index at 20°C varies in the range 1.463–1.472. At this same temperature, its density relative to water is between 0.906 and 0.919 [12]. The iodine value is a measure of the total number of double bonds found in an oil sample [1]. Olive oil displays an iodine value between 75 and 94 mg/100 g [17] (Table 1). This value is lower than that of argan oil (91–110 g I2/100 g), and cactus seed oil (131.5 ± 0.5 g (I2)/100 g) but higher than that of coconut oil (6.3–10.6 g (I2)/100 g) [13]. High iodine value is associated with the greater number of double bonds and reduced oxidative stability [45]. The saponification value is a measure of the average chain lengths of fatty acids. An oil sample with shorter fatty acids has a high saponification value. Moreover, according to CODEX STAN 33, the saponification value of olive oil varies between 184 and 196 mg (KOH)/g.
Olive oil is subject to enormous analytical and sensory controls to assess its overall quality. These analyses evaluate the freshness of the oil regarding hydrolytic and oxidative alterations to ensure the conformity of products to their labels. For example, extra VOO by simple routine analyses (free fatty acids, peroxide value, specific extinction (E270 along with E232) and/or purity blending with other oils and contaminants. These criteria require detailed analyses (triglycerides contents, fatty acids, sterols, tocopherols, etc. …). Organoleptic characteristics (taste, odor, color, etc. …) also have to be taken into account.
As for other vegetable oils, the olive oil oxidation leads to natural phenomena alteration [46, 47]. This can be controlled since fruit harvest until oil storage. Because of oxidation, physicochemical parameters such as acidity, peroxide value and extinction specific at wavelength 270 (λ270 or λ270) have been selected as the backbone of olive oil quality determination by the International Olive Council [12]. Also, acidity of olive oil is classified into four grades: extra-virgin (Acidity < 0.8 g/100 g), fine-virgin (0.8 < Acidity < 2 g/100 g), ordinary virgin (2 < acidity < 3.3 g/100 g), and lampante olive oil (Acidity > 3.3) (Table 2) [12].
Category olive oil | Acidity (g/100 g) | Peroxide index mEq O2/Kg | Extinction specific at K232 | Extinction specific at K270 |
---|---|---|---|---|
1. Extra virgin olive oil | ≤ 0.8 | ≤ 20 | ≤ 2.50 | ≤ 0.22 |
2. Fine Virgin olive oil | ≤ 2.0 | ≤ 20 | ≤ 2.60 | ≤ 0.25 |
3. Ordinary Virgin olive oil | ≤ 3.3 | ≤ 20 | no limit | ≤ 0.30 |
4. Lampante olive oil | > 3.3 | no limit | no limit | no limit |
Limits established for acidity, peroxide index and extinction specific (K232 and K270) for each olive oil category.
The variability of the extra VOO, acid value according to various parameters has been studied [47]. Oil oxidative state is examined from peroxide value and specific extinction coefficients (K232 or K270). These indicate the presence of primary and secondary oxidation products [1, 48]. The peroxide value of extra VOO oil must be below 20 mEq O2/kg and specific extinction K232 < 2.5. The other two main indices used to evaluate the secondary oxidation products are the following: p-anisidine value and specific extinction K270 [1, 49]. The International Olive Council (IOC) has set 0.22 and 0.25 as a limit value for both the extra VOO and VOO, respectively [12].
Furthermore, along with oxidation and acidity concerns, the quantification of major compounds such as fatty acids (Figure 3), and minor compounds, like sterols (Figure 4), polyphenols, tocopherols, minerals elements, and other bioactive molecules, are also of great importance for the purity and for detection of olive oil adulteration, which is a complex problem. Owing to its high cost and demand, fraudsters blend VOO with cheaper edible oils (most often with sunflower and soybean oils) and sometimes with low-quality olive oil. Today, the problem exceeds the borders of the main producer countries and it tackles the international level market. In addition to known risks of commercializing a mixture of vegetable oils. There is another type of adulteration resulting from the mixing of relatively low and high-quality olive oil, and the outcome is a product, which is sold as “high quality extra VOO”. The control of adulteration, and authentication is of a crucial importance for the olive oil quality control. Codex Alimentarius (fats and oils), International Olive Council, and European Union Commission are dealing with the monitoring along with the regulation of VOO [50]. These international organizations have described the official control methods and have specified olive oil quality limits. Generally, all analytical techniques (chromatography, spectrophotometry, voltametric, differential scanning calorimetry), as well as several analytical methods, have been used to detect the adulteration of olive oil. Gas chromatography (GC), which analyzes oil fatty acids profile, can be used to detect virgin oil purity by distinguishing it from other vegetable oils such as sunflower, soybean, walnut, rapeseed, and canola oils [51]. Moreover, HPLC-technique can be used, to calculate, the difference between the theoretical and experimental equivalent carbon number (ΔECN42th). Likewise, the determination of phytosterols composition (namely campesterol Δ7-stigmasterol) using gas chromatography can be used to detect olive oil adulteration with low levels of cotton, corn, sunflower, soybean, and rapeseed oils [51]. In addition, Vietina et al. reported that the polymerase chain reaction (PCR) technique was demonstrated to be an efficient technique to detect VOO adulteration with cheaper vegetable oils by comparing their DNA melting profiles [52]. MS has also been used to detect the fraudulent presence of vegetable oils. Also, a lot of different techniques involving MS have been significantly developed, such as LC–MS, GC–MS, and MALDI-TOF/MS, which are of highly accurate identification [51]. Indeed, many other studies have also outlined the application of fluorescence spectroscopy, UV–Vis spectroscopy, [50] Fourier transform infrared spectroscopy [53] mid-infrared (MID) or near-infrared spectroscopy (NIR) [54] and Raman spectroscopy [55] for authentication and detection of adulteration of vegetables oil present in VOO [50]. Otherwise, differential scanning calorimetry (DSC) has also been used to detect argan oil purity by discriminating it from sunflower, high oleic sunflower as well as refined hazelnut oil [50]. Apetrei and Apetrei have investigated the use of the voltametric method based on modified EO carbon paste-based sensors to determine the adulteration of VOO with soybean and sunflower oils [56].
On the other hand, identification of contaminants is one of the multiple checks that must be performed on oils. Vegetable oils have limited values for aromatic hydrocarbons polycyclics (PAHs), heavy metals, mycotoxins, phthalates, and pesticides. Although, the physicochemical characterization of olive oil is an essential step, it is not sufficient and organoleptic characteristics along with the above-mentioned supplementary analyses are required for a full picture of olive oil quality [1].
To satisfy consumers, organoleptic characteristics (color, taste, smell, etc.) must be taken into account. This is particularly important for olive oil. The organoleptic analysis is an essential step for successful food marketing. It is an integral part of evaluating olive oil. IOC has established a procedure to evaluate the organoleptic characteristics of VOO according to COI/T.20/Doc. [12] No 15/Rev. 102,018. It has classified such characteristics into positive and negative attributes as highlighted in Tables 2 and 3.
Fusty/muddy sediment | The characteristic flavor of oil obtained from olives stocked in such a way that they have developed an enhanced stage of anaerobic fermentation, |
Musty-humid-earthy | Flavor characteristic of oils from fruits in which a lot of fungi and yeasts have been developed or from olives picked up with mud or earth and not been previously cleaned. |
Winey- vinegary | The flavor characteristic of some oils reminiscent of vinegar or wine. |
Acid-sour | The flavor is primarily caused by the formation of ethyl acetate, ethanol, and acetic acid. |
Rancid | Flavor of oils that have been submitted to an intense oxidation process |
Frostbitten olives (wet wood) | Flavor characteristic of oils obtained from olives that have been damaged by frost on the tree. |
Fruity | Characteristic of the oil that varies according to the variety and is obtained from fresh olives, ripe or not. |
Bitter | Primary taste characteristic of oil extracted from green olives or olives that are becoming colored. |
Pungent | Characteristic of oils obtained at the beginning of the crop year, mostly from olives that are not ripe yet. |
1. Extra virgin oil | Md = 0 | Mf > 0 |
2. Virgin olive oil | Md ≤ 3.5 | Mf > 0 |
3. Lampante oil | Md > 3.5 | __ |
Organoleptic attributes of olive oil.
Oxidation of lipids including oils is a major concern to food industries [57, 58]. While, vegetable oils are endowed with a wide variety of endogenous antioxidants (pigments, vitamins, tocols, phenols, etc.), the use of exogenous antioxidants is widely practiced to enhance oxidative stability. In this regard, synthetic antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), as well propyl gallate are commercially used to extend oils’ shelf life by delaying or even hindering lipids degradation. These molecules are considered as Generally Recognized as Safe (GRAS) preservatives with a concentration limit of 0.02% in oils and fats [59]. In contrast, some reports associated these molecules with health risks because of carcinogenesis, leading to a restriction of the use of the GRAS list and a reduction of their utilization in different countries [59]. For this reason, natural antioxidants are a good alternative to replace the synthetic ones in preserving vegetable oils including olive oil [59, 60, 61]. An overview of factors involved in the balance of antioxidants and pro-oxidants as well as synthetic and natural antioxidants are summarized in Figure 7.
An overview of factors involved in olive oil oxidative stability as well as natural and synthetic antioxidants. BHA, butylated hydroxyanisole; BHT, butylated hydrolxytoluene; TBHQ, tertiary butylhydroquinone; MUFA, monounsaturated fatty acids, and PUFA, polyunsaturated fatty acids.
Natural extracts sourced from various plant parts (peel, fruit, leaf, flower, and root) from different aromatic and medicinal herbs, agri-food residues and by-products were investigated for their antioxidant power as well as their use for the enrichment of olive oil with an emphasis on improving oxidative stability. Such natural extracts were proved to have a wide range of bioactive compounds were identified. These are mainly carotenoids and phenols [62, 63]. Promising results were obtained regarding the improvement of oxidative stability and shelf life of olive oil. Regarding the antioxidant activity of synthetic and natural additives, several mechanisms are involved. They act as free radical scavengers, inactivators of peroxides as well as other reactive oxygen species (ROS), singlet oxygen quenchers, metal ion chelators, quenchers of secondary oxidation products, and inhibitors of pro-oxidative enzymes, among other compounds [64]. Following these authors, antioxidants can be classified, based on their mode of action, into primary antioxidants. These break the oxidation chain reaction through scavenging free radical intermediates, however secondary antioxidants delay or even prevent oxidation through suppression of oxidation initiator, accelerators or regeneration of primary antioxidants.
Olive oil is an important food in the Mediterranean diet. Its importance and nutritional value arise from chemical composition. Its richness in essential fatty acids is behind their health-promoting properties. A set of other minor compounds such as polyphenols and tocopherols act as antioxidants which are directly associated with oxidative stability and shelf life of olive oil on one hand as well as human health on the other hand. Along with these endogenous antioxidants, olive oil quality can be enhanced through natural antioxidants extracted from herbs and agri-food residues.
This work has no acknowledgments.
The authors declare no conflict of interest.
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\\n\\nBut, one thing we have in common is -- we are all scientists at heart!
\\n\\nSara Uhac, COO
\\n\\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\\n\\nAdrian Assad De Marco
\\n\\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\\n\\nDr Alex Lazinica
\\n\\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
\n\nCo-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\n\nAdrian Assad De Marco
\n\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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