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Extraction of Natural Compounds From Plants
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59
2.3. EXTRACTION
In the process chain, the next step after harvesting is the desired substance
extraction. However, we need to consider several regulations. In the use
of solvents (appropriate one), there are regulations if the products are used
with foods. According to governmental regulations and European Union,
the allowed solvents are given below (Chemat et al., 2012; Dreisewerd et
al., 2015):
• Water (with acids or base admixture);
• Foodstuffs having solvent properties;
• Solvents like ethyl acetate, propane, N
and ethanol.
It is assumed that with foodstuffs and water, the residue of inevitable
solvent is not harmful. As shown in Table 2.4, maximum residues with
industrial solvents are dened for a specic purpose. From natural resources,
the limits when the aroma is extracted are shown in Table 2.5. In any case,
the maximum content of lead or arsenic for all these solvents is 1 mg. The
use of ethyl methyl ketone and hexane mixture is forbidden (Vitha et al.,
1996; Rombaut et al., 2014).
O, CO 2, acetone, butane,
2
In the food industry, liqueed gases, water, organic solvents, and
solvents from natural sources (such as limonene) are used. The market is
strongly dominated by liqueed CO
. It is used for decaffeination of tea or
2
coffee beans, extraction of essential oils, spices, pungent constituents, herbs,
antioxidants, and natural colorants, production of highly valued fatty oils,
and preparation of leaf extracts (Lack and Simandi, 2001). Solvents with
maximal residue content and foodstuffs are shown in Table 2.4.
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Natural Compounds: An Introduction
Table 2.4: Solvents with Maximal Residue Content and Foodstuffs
Solvent Purpose Max. Residue
Hexane Fractionating of cacao but-
ter, oils, or fats
Protein defatting of prod-
ucts such as our
Corn seed defatting 5 mg/kg in seed (defatted one)
Methyl acetate Extraction of caffeine or
other constituents from coffee or tea
Sugar production from
molasses
Ethylmethylketone Fat and oil fractionating 5 mg/kg in fat or oil
Extraction of caffeine or
other constituents from coffee or tea
Dichloromethane Extraction of caffeine or
other constituents from cof-
fee or tea
Methanol For every product 10 mg/kg
Propane-2-ol For every product 10 mg/kg
1 mg/kg in cacao butter, oil, or fat
30 mg/kg in defatted soy products,
while in others it is 10 mg/kg
20 mg/kg in coffee or tea
1 mg/kg sugar
20 mg/kg in coffee or tea
5 mg/kg in tea and 2 mg/kg in
roasted coffee
Table 2.5: Residues Present in Articially Flavored Products
Solvent The Maximum Residue (mg kg
Cyclohexane 1
Hexane 1
Butane-1-ol 1
Methyl acetate 1
Ethylmethylketone 1
Butane-2-ol 1
Propane-1-ol 1
Dichloromethane 0.02
1,1,1,2-Tetra uoroethane 0.02
Diethyl ether 2
−1
)
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In pharmaceuticals, similar guidelines regarding acceptable amounts for
residual solvents are also recommended by the European Medicines Agency
(Humfrey, 2007). Unacceptable toxicities are caused by solvents (class 1, e.g.,
benzene, carbon tetrachloride, 1,1-dichloroethane, 1,1,1-trichloroethane).
These solvents should not be used in the production of drug products,
excipients, or drug substances (unless there is a strong need and their use is
necessary). The solvent having less severe toxicity (class 2) can be used, but
their use has to be limited. The “permitted daily exposure” (PDE) is given
in Table 2.6. It guides the acceptable intake quantity of the residual solvents
(in terms of mg/day). Table 2.7 shows fewer toxic solvents (class 3). They
can be used where practical. There remain solvents, as shown in Table 2.8,
may also be of interest in manufacturing drug products, drug substances, or
excipients. In pharmaceutical products, justication for the used residual
levels of these solvents should be provided by manufacturers (Fedors, 1974;
Chemat et al., 2019a, b).
However, other exotic solvents, such as ionic liquids or surfactant-rich
phases are applied for the extraction of plants. A new solvents class (the latter
one) has almost zero vapor pressure, and extraction of large biomolecules is
enabled by the surfactant-rich phases.
Table 2.6: Solvents (Class 2) in Pharmaceutical Products
Solvent PDE (mg/day)
Acetonitrile 4.1
Cyclohexane 38.8
Chloroform 0.6
Dichloromethane 6.0
1,2-Dichloroethene 18.7
N,N-Dimethylacetamide 10.9
1,2-Dimethoxyethane 1.0
1,4-Dioxane 3.8
N,N-Dimethylformamide 8.8
Ethylene glycol 6.2
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Natural Compounds: An Introduction
2-Ethoxyethanol 1.6
Hexane 2.9
Formamide 2.2
2-Methoxyethanol 0.5
Methanol 30.0
Methylcyclohexane 11.8
Methylbutylketone 0.5
Nitromethane 0.5
N-Methylpyrrolidone 48.4
Sulfolane 1.6
Pyridine 2.0
1,1,2-Trichloroethene 0.8
Tetraline 1.0
Xylene
Toluene 8.9
Chlorobenzene 3.6
(a)
usually 60% m-xylene, 14% p-xylene, 9% o-xylene with 17% ethylbenzene.
(a)
21.7
In any solvent other than water, they would degenerate, as they like an
aqueous environment. However, water usage is ambiguous. Water extraction
was used in preparing traditional medicines, but for conventional isolation
methods (e.g., crystallization or chromatography), impurities (water-soluble)
present challenges. Preferentially, polar compounds (for example, tannins
and plant pigments) are extracted by water, and for further purication, they
require special post-treatment (such as caustic wash or ion exchange). The
crude extract, in many cases, is evaporated, while the remains (its residue)
are dissolved in solvent (appropriate one) to purify it further. In contrast to
organic solvent, water is more difcult to remove and possesses the highest
heat of evaporation (McKenzie et al., 2004; Jones and Kinghorn, 2012).
Extraction of Natural Compounds From Plants
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Table 2.7: Solvents (Class 3) That Should be Limited
Acetic Acid Heptane
Ethyl formate Propyl acetate
Anisole Isopropyl acetate
Butyl acetate Methyl ethyl ketone
2-Butanol 3-Methyl-1-butanol
Cumene 2-Methyl-1-propanol
Tetra-butyl methyl ether Methyl isobutyl ketone
Ethanol 1-Pentanol
Dimethylsulfoxide Pentane
Ethyl ether 2-Propanol
Ethyl acetate 1-Propanol
Formic acid Tetrahydrofuran
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1-Butanol Methyl acetate
Acetone Isobutyl acetate
Table 2.8: Solvents That Have no Adequate Toxicological Data
1,1-Diethoxypropane Methylisopropylketone
Isooctane Trichloroacetic acid
2,2-Dimethoxypropane Petroleum ether
1,1-Dimethoxymethane Methyltetrahydrofuran
Isopropyl Ether Triuoroacetic acid
The “like dissolves like” principle is followed by the choice of the
solvent. One will come up with a solubility parameters concept that follows
the concept of regular solution theory. This was initially developed by van
Laar for indicating the choice of any solvent (Blanco et al., 199). Nonetheless,
strong dependence was shown by the results on the applied mixing rules,
and later, Hildebrand and Scott (1964) improved them.
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Natural Compounds: An Introduction
Though solubility serves as an important factor in obtaining a crude
extract, there are other criteria for solvent selection that are similar to the
ones in liquid-liquid extraction:
• Selectivity: Fewer stages are used if the selectivity is high.
Group selectivity become important when the feed is in the form
of a complex mixture and there is a need of extracting multiple
components.
• Recoverability of Solvent: The solvent phase recovery should
be convenient. If distillation or evaporation is used, it should not
form azeotropes but should possess a low heat of evaporation,
and cooling water should easily condense it. With subcritical
uids or liquid CO
, only a ash is needed. The product has to be
2
volatile, as it is not possible to evaporate ionic liquids. However,
in acidic media (such as HCl), if alkylated tertiary amines, such
as trioctylamine, are used, the ionic liquid forms spontaneously
(for example, trioctylamine). Alkali can reverse this reaction and
then, the free amine might be distilled.
• Viscosity and Melting Point: The mass transfer efciency is
reduced by high viscosities, and they also lead to difculties
with dispersion and pumping. The solvent’s melting temperature
should be less than the ambient (it provides ease in handling).
• Surface Tension: Wetting of the solids is promoted by low surface
tension. The wetting ability is extremely important as the solvent
should necessarily penetrate the matrix (capillaries, pores, etc.).
• Toxicity and Flammability: Only non-toxic solvents are taken
into consideration for food processing. Generally, any solventrelated hazard requires extra safety measures. Due to this fact,
aliphatic diluents should be preferably halogenated or aromatic
ones.
• Corrosivity: The equipment cost is increased by the corrosive
solvents. They also require expensive post- and pre-treatment of
streams.
• Chemical and Thermal Stability: For solvent, it is necessary
that it is chemically and thermally stable as it has to be recycled.
Especially during the solvent recovery, it should resist breakdown
in an evaporator.
Extraction of Natural Compounds From Plants
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• Availability and Costs: As compared to the price, the annual
cost of the solvent is important, it is because of the inevitable
operation losses. The solvent has to be readily available.
• Environmental Impact: The solvent should be compatible
with the environment and with downstream process steps. By
environment, we mean that there should be minimal losses due
to entrainment, solubility, and evaporation. From spent solids
and residual plant material, removal of solvents can cause many
problems. For reducing the residue level, post-treatment might be
required. It is due to mechanical pressing, as it is not economic
to use other solvents for further treatment (Van Krevelen and Te
Nijenhuis, 2009; Hernandez et al., 2010).
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2.4. EXTRACTION TECHNIQUES
Solid-liquid extraction or leaching is such a separation process in which
we cannot define any sharp interface for mass transfer. In several natural
product extraction processes, a liquid phase impregnates or is contained by
the solid. In the sucrose extraction from beet, high molecular and undesired
constituents are prevented from being extracted by the cell walls. Thus, in
long strips, the beet is prepared for minimizing the damages caused to cell
walls. The solute, in actuality, is a liquid but for those fatty oils needs to
be extracted; hence, it will diffuse easily. This results in a faster transfer of
mass. If the solute is liquid or solid, adsorbed upon, chemically combined
with, incorporated within, or in a structure of the insoluble material, it affects
the latter remarkably (Taft, 1983; Mason et al., 2011).
In that regard, it is generally recommended to use a pretreatment for
changing the initial matrix structure. Classically, the grinding approach (bead
milling) was used for gaining smaller particles that the solvent can penetrate
more easily. Alternatively, enzymatic treatments, pure water swelling
process, or freezing and thawing, give an improvement. At 3, 7, and 12 pH,
as depicted in Figure 2.10, leaves (ground ones) of S. lavendulifolia were
soaked, and after four hours, in an alcohol extract, the maximum yield was
with pure water (Dyakowski et al., 2000). Nevertheless, soaking of fresh
plant material is recommended with organic solvents (methanol, ethanol),
the solute will be preserved undamaged (as the enzymes will be denatured).
Cooking or hot steam is used by more drastic approaches (Bart and Schmidt,
2007; Tiwari, 2015).
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Figure 2.10: Pre-treatment at 298 K (pH = 7, pH = 3, and pH = 12).
Source: https://onlinelibrary.wiley.com/toc/15222640/79/5.
Natural Compounds: An Introduction
Materials that are specically used for producing oil are a huge source
of proteins (e.g., sesame seeds, cottonseeds, peanuts, ax seeds, soya
beans), these materials must be cooked so that before oil extraction, the
protein can be coagulated. From any pressurized apparatus, the porosity is
increased by the expanding vapors, this is due to the explosion (the solid
cells evaporation). Alternatively, pulsed electric elds or ultrasound can
be used for destroying the cell walls and facilitating extraction (Tzia and
Liadakis, 2003; Savova et al., 2005). Usually, it is preferred in bench-scale
equipment, as it gets difcult to adjust energy efciency and penetration
depth at larger scales (Martin et al., 1987; Heron et al., 1994).
One has to differentiate between continuous and batch operations in terms
of extraction procedures. The latter are applied frequently in combination
with slurries or suspensions, though, continuous solid extraction is also
used widely (Chhabra and Gurappa, 2019). Maceration is mostly used
with thermal or volatile unstable products. In any solvent, it serves as a
“cold” extraction of pulverized material. During the fermentation process,
the extraction of aroma, tannin, and color through alcohol is a well-known
example. Enzymatic processes support this process (Knez Hrnčič et al., 2019).
At higher temperatures, this process is called digestion (tea preparation is an
example from daily life). Sometimes, the major disadvantage is the solvent
consumption (when present in a batch stirred tank) and long duration (hours).
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67
Percolation is a technique, widely used when the feed material’s mean
diameter increases. On the top of the material (solid), the solvent is poured
and allowed to percolate by the means of the bed. However, the percolator
may be clogged by the swelling of plants and ne powders (e.g., containing
mucilages). The apparatus side has sliding cells, baskets, carousels, etc.
An example of it from life is lter coffee preparation (Ganeva et al., 2004;
Cseke et al., 2016).
As discussed earlier by Chhabra and Gurappa (2019); Soxhlet (1879)
extraction is a very efcient form of obtaining compounds from complex
substances. It was originally designed to extract lipids from solid materials.
The solid material is percolated, as the solvent is heated to condense (reux).
It has a disadvantage that it may cause damage to the thermolabile compounds
because the solute is at the solvent’s boiling temperature. Distillation is an
alternative to this. Distillation can be used only with volatile compounds.
From steam distillation, the vapors are condensed and the obtained distillate
is in two-phase (water and oil). This practically immiscible water-oil mixture
has a boiling point beneath 100° C. As both of this constituent exerts their
vapor pressure independently, hence, this helps in preparing high boiling
thermosensitive oils (such as lavender oil and fragrances).
The mathematical treatment of counter-, co-current, and mass transfer
apparatus balances is also found under “leaching.” Right-angled triangular
diagrams conveniently represent this process. Figure 2.11 depicts a countercurrent process. The apparatus balance (overall) in a multistage operation is
(Fadel et al., 1999):
P = F – E
= Ri – E
1
i
or
F + E
= Ri + E
i
1
where; Ei represents fresh; E1 represents the loaded solvent; F represents
the feed; and R
is the raffinate (at the end of ith stage). Ri is present on
i
the pseudo-equilibrium curve and needs to be determined experimentally.
Determining the true equilibria with the extraction of solids is difficult. This
is because of very slow extraction kinetics. The processing of the stage is
somewhere similar to the concept given by Hunter-Nash for liquid-liquid
extraction. Figure 2.11 depicts the four stages of extraction (Barton et al.,
2010; Bezazi et al., 2014).
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Figure 2.11: For counter-current solid extraction, a right-angled triangular diagram.
Source: https://pubs.acs.org/doi/pdf/10.1021/ie50307a022.
Natural Compounds: An Introduction
2.5. PURIFICATION
The purification methods depend on chromatography. Then, crystallization
helps in obtaining the final product. In applications with fragrances,
cosmetics, and nutraceuticals, there is no need of having ultrapure products.
Chromatographic methods are flexible because of their separation principles.
These principles are discussed in the following sections (Zeković et al.,
2017; Li et al., 2019).
2.5.1. Chromatography
2.5.1.1. Adsorption Chromatography
The oldest form of chromatography is liquid-solid chromatography or
adsorption chromatography. On the adsorbent’s surface, the sample
components are adsorbed. Here, they displace the loosely adsorbed molecules
of solvent. This form provides the best results for organic-soluble, non-ionic
samples of molecules having intermediate weights. It can also separate
water-soluble substances. The adsorbent, also called the stationary phase,
is mostly a polar solid (usually alumina or silica), commonly used with a
non-polar liquid. The adsorbent surface easily attracts the functional (polar)
groups of the components and then it displaces solute (non-polar) molecules.
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