Journal of Materials Science and Chemical Engineering, 2013, 1, 1-6 Published Online October 2013 (
Copyright © 2013 SciRes. MSCE
Application of Sub-Critical Water E xtraction in
Pharmaceutical Industry
Xiaoxia Liang, Qiaojia Fan
Department of Pharmacy, College of Veterinary, Sichuan Agricultural University, Ya’an, Sichuan, China
Received June 2013
Sub-critical water extraction is a brand-new separation technology. This paper mainly discussed the principle, advan-
tages of sub-critical water extraction, and its applicatio ns ranging from the medicinal plants tradition ally used in Europe
and Asia to produce pharmaceutical extracts (such as volatile oil, tannins, flavonoids, anthraquinone, lactone, etc.).
Meanwhile, the prospect of sub-critical water extraction in plant extractives is also explored. It will be widely used in
the field of medical plants, bringing huge economic benefits, environmental benefits and social benefits.
Keywords: Sub-Critical Water Extraction; Pharmaceutical Extracts; Application
1. Introduction
At present, plant medicine, which mainly comes from
plant extraction, has occupied nearly 30 percent to 40
percent among the thousands of worldwide used phar-
maceutical products. As a natural healthy protection
product, it has incomparable natural advantages, com-
pared with the relative chemical drugs. Extraction and
separation of effective pharmaceuticals, looking for
leading compounds, is the first and most important step
in the new drug development. However, chemical com-
position of various medicinal plants is very complex,
usually containing many kinds of effective ingredients.
Numerous methods, including conventional solvent ex-
traction, steam distillation, and sublimation, etc., are
known for extracting phytochemicals from plant materi-
als, most based on sequential extraction processes incor-
porating one or more organic solvents in combination
with washing steps. Phytochemical extracts produced by
such methods must be further processed to remove all
trace of the organic solvents, to remove impurities, and to
separate and purify individual phytochemicals. While
such methods are useful for extraction and purification of
small quantities of phytochemicals for research purposes,
they are difficult to scale to commercial through-put vo-
lumes because of the problems associated with cost -ef-
fectively, safely and completely removing and recov-
ering the organic solvents from the extracts and spent
plant materials. Furthermore, the types and concentra-
tions of organic solvents must be carefully selected in
order to avoid structural changes to the target phyto-
chemicals during extraction that may adversely affect
one or more of their desirable physical, chemical and
biological properties.
In recent years, many new technologies and methods,
such as ultrasonic extraction, microwave extraction,
membrane separation technology, molecular distillation,
macroporous resin adsorption and supercritical CO2 ex-
traction technology, are introduced to the extraction
and separation of effective components in medicinal
plants, promoting the development of plant extracts in-
dustry. Among those new technologies, supercritical flu-
id extraction (referred to as SFE) [1,2], is the most com-
pelling one, which is especially feasible for heat-sensi-
tive material with its own unique advantages, including
non-toxic, no solvent residue, high extraction rate, and
free of environmental pollution. However, as every coin
has two sides, SFE has less capacity, mainly for the ex-
traction of high value-added products. Its application has
been limited [3,4], due to the high extraction pressure
and equipment costs. Finally, with the development of
SFE, a new extraction technique, subcritical water ex-
traction”, emerged. Its principle, advantages, and appli-
cations of the extraction to a range of medicinal plants,
traditionally used in Europe or Asia to produce pharma-
ceutical extracts (such as volatile oil, tan nins, flavonoids,
anthraquinone, lactone, etc.), will be introduced in this
2. Principle of Sub-Critical Water
Water, an inexpensive and environmentally friendly sol-
vent is an ideal solvent for the industrial extraction of
Copyright © 2013 SciRes. MSCE
medical plants, but its use is limited due to poor extrac-
tion efficiency for most organic compounds such as po-
lychlorinated biphenyls (PCBs), polycyclic aromatic hy-
drocarbons (PAHs) and most pesticides at ambient tem-
perature. However, it has gained an increasing amount of
attention due to its unique solvation properties, which
can be altered by changing the temperature [5]. It is
known that the physical and chemical properties of water
within sealed systems can be manipulated by concur-
rently controlling the temperature and pressure, where by
the water remains in a liquid state even though its tem-
perature is significantly increased above its atmospheric
boiling point of 100˚C. The polarity, viscosity, surface
tension, and disassociation constant of sub-critical water
are significantly lowered compared to water at ambient
temperature and pressure conditions, thereby signifi-
cantly altering its chemical properties to approximate
those of organic solvents. Consequently, pressurized low-
polarity water under sub-critical conditions can easily
solubilize organic compounds from polar (at lower tem-
peratures) to nonpolar (at higher temperatures), such as
phytochemicals which are normally insoluble in ambient
water [6]. In this condition, it is known as sub-critical”
or “hot/liquid” water. Sub-critical water can be main-
tained in the liquid form until a temperature of 374˚C and
a pressure of 221 bars are reached after which, it be-
comes supercritical water [7,8]. Sub-critical Water Ex-
traction (SBWE), also known as hot water extraction,
pressurized (hot) water extraction, pressurized low polar-
ity water extraction, high-temperature water extraction,
superheated water extraction or hot liquid water extrac-
tion, is such a promising green technique based on the
use of water at a sub-critical state as the sole extraction
solvent [6,9]. A further advantage of sub-critical water
extraction is that the high temperature and pressure pro-
duce high diffusion rates which promote very efficient
extraction of the r aw material. In addition, that rates vary
according to different chemical structures [10,11 ] of or-
ganic compounds. Therefore, extraction with subcritical
water can be both selective and rapid.
3. Advantages of Sub-Critical Water
As we mentioned above, from water-solubility to lipo-
soluble substances were successively extracted with
SBW. Its ability to dissolve nonpolar organics is similar
to that of organic solvents, which are expensive, poten-
tially harmful to the operator, and need to be disposed of.
Using SBWE instead is highly desirable from environ-
mental and health perspectives. It shows lower handling
time and solvent consumption, reducing the loss of heat-
sensitive compounds, and totally eliminates the use of
toxic organic solvent, with no organic solvent remain,
with no waste produced at the same extraction efficiency.
The technique could achieve selectively extraction of
polar, moderately polar, and nonpolar organics by alter-
ing extraction parameter, such as temperature, pressure
and co-solvent. Meanwhile, compared with supercritical
extraction (SFE) (CO2 used particularly), SBW can be
used in the extraction of substances from moderately
polar to heavy molecular weight in medical plants. This
just compensates for the drawback of SFE (CO2 used
particularly, which can ju st extract nonpolar or light mo-
lecular weight substance and will not extract the com-
pounds most readily soluble in methanol or aqueous
ethanol, including the important classes of flavonoids,
lignans and other related polyphenolic compounds.) Re-
cently, SBEW has been applied largely abroad. Most of
these reports focused on the determination of organic
pollutants [12-14] in soils, sludges and sediments, and
the extraction of spice components from plants. Its ap-
plication in the field of pharmaceutical industry is also
encouraging [15].
4. Application in Pharmaceutical Industry
Sub-critical water extraction has been extracted the most
active compounds from herbs, such as Rosmarinus offi-
cinalis (rosemary), Matricaria recutita (German chamo-
mile), Cassia angustifolia (senna), Valeriana officinalis
(valerian), Scutellaria baicalensis (Baikal skullcap),
Schisandra chinensis (Wuweizu), Zingiber officinale
(ginger), Astragalus Membranaceus, etc. [16]. Those ex-
tracts were demonstrated to exhibit a composition es-
sentially similar to that of the corresponding methanol or
aqueous alcohol, which would show comparable phar-
macological activities.
4.1. Extraction of Volatile Oils
Volatile oil, also known as essential oil, is present in a
class of plants with aromatic smell, which is water in-
soluble and can be distilled with steam. As an important
class of active ingredients, essential oils are volatile oil-
like components of the general, with a variety of phar-
macological activities and applications in medicine and
food industry. Traditional methods include steam distil-
lation and organic solvent extract, indicating much more
shortcomings, such as volatile components loss, low ex-
traction efficiency, heating for a long time, organic sol-
vent residual and so on. In 1998, Basile et al [17] first
confirmed that the sub-critical water extraction was a
practical method for the essential oil. In their research,
the extracts from rosemary was compared with that from
steam distillation, the fo rmer showed pleasantly surprised
advantages, including short extraction time, high yield of
oxygenated compounds, good quality and lower energy
consumption. From that brand-new start, sub-critical
Copyright © 2013 SciRes. MSCE
water extraction has been applied on essential oils of
different kinds of herbs, including Fructus Foeniculi [18],
Thymbra spicata [19], Marjoram [20], Peppermint [21,22],
Laural [23], Eucalyptus [24], and clove buds [25], etc.,
which were compared with hydro-distillation, supercriti-
cal carbon dioxide and extraction. The effects of experi-
mental parameters (extraction temperature, extraction
pressure, time and entrainer on essential oil) were also
analyzed. All of the further evidences supported the
sub-critical water extraction as a powerful alternative of
the extraction of essential oil from herbs with higher oil
yield and shorter extraction time.
4.2. Extraction of Plant Phenols
As a kind of widespread active ingredients of many me-
dicinal plants in nature, plant phenolic compounds main-
ly exist in plants, roots, leaves the skin, shell and pulp,
including tannins, flavonoids, anthraquinones, lignin and
some simple phenols. In recent years, as the research
[26,27] showed that some polyphenols could inhibit tu-
mor development in animals and humans, prevent cardi-
ovascular disease, as well as anti-mutation, anti-virus and
anti-oxidation, the study of polyphenols has been at-
tracted more and more attention. Sub-critical water has
been proved good to extract plant phenolic compounds
according to many results of researches. Some examples
will be given be low.
4.2.1. Extraction of Tannins
G. M. Matilde [28] extracted grape seed extract in batch
and continuous Manners at different temperatures (50˚C,
100˚C, 150˚C), the result showed that a continuous ex-
traction of material is conducive to the dissolution of
tannin. In the research of Antuon [29], when the extrac-
tion time fixed to 20 min, the total polyphenol content of
grape seed by sub-critical water extraction is 2 times
higher than that of 70% ethanol extraction.
4.2.2. E xtraction of Flavonodis
Flavonoids are a subgroup of plant polyphenols, widely
found in fruits, vegetables, beans, tea and many medical
plants. As a type of phytochemicals, they have been ex-
tensively applied to treat and inhabit disease and medi-
cally functional disorders as healers, antimicrobial agen ts,
as well as antioxidants. However, the poor water solubil-
ity and lipid solubility limit their application. With the
rise of sub-critical water extraction, a study, focused on
the influence of different pressures, temperatures and
flow rates in the water extraction of five isoflavones from
defatted soybeans, was started by Chang et al [30]. The
results exhibited the best extraction yield of total isofla-
vones up to 99.7%. Then Charlotta Turner et al. [31]
demonstrated that sub-critical water extraction following
by β-glucosidase-catalyzed hydrolysis was a rapid me-
thod to determine the content of quercetin and isorham-
netin in onion samples, and environmentally sustainable
as the only use of water. In another research, Zhi-hong
Xu et al. [32] has fig ured out the influence of temperature,
pressure, time, particle size, solvent ratio on the extrac-
tion of baicalin from Scutellariae Radix by sub-critical
water and compared with the organic solvent extraction
method. The result turned out that while maintaining the
same extraction effect, the former had greatly reduced
the extraction time and avoided the organic solvent pol-
lution. Furthermore, flavonoids were extracted by sub-
critical water from Oregano leaves [33].
4.2.3. E xtraction of Anthraquinones
As another subtype of plant polyphenols, anthraquinones
present various biologically activities, which make the
potential usefulness in several medical applications. A
study [34] of the extraction anthraquinones from dried
roots of Morinda citrifolia (Noni)., which possesses sev-
eral therapeutic proper ties, such as antiviral, antibacterial,
and anticancer, determined their solubility in sub-critical
water and indicated the increase of extraction yield with
the rise of temperature, while almost unaffected by pres-
sure. In the extraction of damnacanthal, which is the
most valuable anthraquinone compound in the roots of
Morinda citrifolia (Noni)., Anekpankul et al [35] inves-
tigated the extraction yield at different temperatures and
flow rates, and suggested that the sub-critical water ex-
traction would be a promising method. In addition, the
extraction of anthraquinones by sub-critical water from
the roots of mulberry was also reported [36-38].
4.2.4. E xtraction of Lignins and Others
Researches on the sub-critical water extraction in other
subtypes of nutraceutical phenolic compounds, such as
lignins [39,40], phenolic acids [41-46], and some simple
phenols [47], were reported, besides the examination of
parameters affecting extraction. For example, in the study
of the water extraction of polyphenol compounds in bit-
ter melon, Budrat [41] reported that as the extraction
temperature increased, the total polyphenol content could
increase, while the extracts at lower temperature showed
higher antioxidant activity. Furthermore, their antioxi-
dant activity was about three times higher than methanol
extraction or ultrasonic extraction in boiling water.
4.3. Extraction of Lactones
Kavalactones, active ingredients from the roots and rhi-
zomes of piper methysticum forst, are widely used as
medicine and soft drink in Europe and America. Kuba-
tova et al. [48] compared its sub-critical water extraction
with that of soxhlet extraction, ultrasonic extraction in
boiling water and acetone extraction. The result turned
out that the extraction rate of the first method, sub-criti-
Copyright © 2013 SciRes. MSCE
cal water extraction, was much higher than the others,
whether the peper was crushed or not.
4.4. Extraction of Others
Baek et al [49] examined the influence of different tem-
peratures and time on the sub-critical water extraction
yield of antioxidant nutrients from Glycyrrhiza. The re-
sult showed that the antioxidant activity and nutrient
content of the extract by sub-critical water has been en-
hanced, and significantly affected by the temperature and
time. Besides, in a further research, Isabella D’Antuono
[29] have confirmed the feasibility and advantages of
sub-critical water as available extraction solvent for the
recovery of natural antioxidants from by-products of the
food industry.
5. Conclusion
In conclusion, the use of sub-critical water as available
alternative solvent for the extraction of phytochemicals
from medical plants has been shown to be feasible. In
particular, the process, not involving any use of organic
solvents, does not originate pollution problems, associ-
ated either with the desolventization step of the extracts,
or to inevitable losses of the organic solvent during the
process. Hence, as the improved living standards and
social progress, the use of sub-critical water could repre-
sent a way for realizing a true green process. Currently,
sub-critical water extraction technology has been applied
to the essential oil, tannins, flavonoids, lactones, anthra-
quinone, glycosides, lignans, protein, pectin, polysaccha-
rides and organic acids. However, due to the complexity
and similarity of plant active ingredients, sub-critical
water extraction technique alone often can not meet the
requirements of purity, its development, coupled with
other separation means, such as sub-critical water extrac-
tion—Membrane Separation and Purification, sub-critical
water extraction—Molecular distillation, sub-critical wa-
ter extraction—Large Macropor ous resin adsorp tion, e tc.,
is of great significance. Further studies are being carried
out in order to investigate more deeply the composition
of the pharmaceutical extracts and sub-critical water ex-
traction in the field of medical plants w ill b e wid ely u s ed,
bringing huge economic benefits, environmental benefits
and Social benefits.
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