Chemical Engineering Research and Design 183 (2022) 382–397

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Chemical Engineering Research and Design

journal homepage: www.elsevier.com/locate/cherd

Enrichment of phenolic compounds from grape

(Vitis vinifera L.) pomace extract using a
]]
]]]]]]
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macroporous resin and response surface

methodology
⁎
Sarvenaz Heravi a, Masoud Rahimi a,b, , Mahshad Shahriari a,
Samad Nejad Ebrahimi a
a
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University,
Tehran, Iran
b
Department of Pharmaceutical Engineering, Medicinal Plants and Drugs Research Institute, Shahid Beheshti
University, Tehran, Iran

a r t i c l e i n f o a b s t r a c t

Article history: A green protocol was proposed for the extraction and separation of high-value phenolic
Received 21 January 2022 compounds (PCs) from grape (Vitis vinifera L.) pomace. The most important variables for scale-
Received in revised form 30 April up purposes including extraction time (4–16 h), temperature (40–80 ℃), and solvent-to-feed
2022 ratio (8–40 mL.g−1) on the extraction efficiency and yield of PCs were scrutinized by experi­
Accepted 10 May 2022 mental design using Response Surface Methodology (RSM). The yield of PCs was quantified by
Available online 13 May 2022 monitoring the content of gallic acid (GA) and procyanidin B using the HPLC-UV analysis. To
obtain an enriched extract, the optimized extract was loaded on a new designed multi-stage
Keywords: continuous flow adsorption column filled with a nonionic acrylic polymeric resin (LXA-10)
Grape pomace adsorbent. The adsorption properties, including the adsorption isotherms and kinetics as
Phenolic compounds well as dynamic test in term of breakthrough curve analysis have also been investigated. The
Response surface methodology optimal extraction condition was attained at 80 °C, 10 h and 20 mL.g−1, and extraction effi­
Adsorption ciency of 10.67% w/w. After enrichment process, the purity of PCs in the resulting product
Pilot scale was reached to 99%, and the yield of product respect to initial grape pomace powdered was
1.91%. These findings may have implications in the development of adjuvant supplement
manufacturing with potential effect on improving immune system.
Data Availability: The authors confirm that the data used to support the findings of this
study are included within the article and its Supplementary material.
© 2022 Institution of Chemical Engineers. Published by Elsevier Ltd. All rights reserved.

(Food and Agriculture Orgaization of the United Nations,

1. Introduction
2019, July 12). The red skins, seeds, and stems of grapes as
by-products of the winery and soft drink production, are rich
Grapes, with an annual production of around 77 million
sources of polyphenols (Teixeira et al., 2014). They have been
metric tons, are one of the world’s largest crops by weight
obtained great attention regarding their positive potential in

Abbreviation: BC, Bed capacity; EBTC, Empty bed contact time; PCs, Phenolic compounds; GPE, Grape pomace extract; OFAT, One-
factor-at-a-time; TPCs, Total phenolic compounds; RSM, Response surface methodology; BBD, Box-Behnken design; GA, Gallic acid;
HPLC, High-Performance Liquid Chromatography; BV, Bed volume; IBC, Ideal breakthrough curve
⁎
Correspondence to: Shahid Beheshti University, Evin, Tehran, Iran.
E-mail addresses: ma_rahimi@sbu.ac.ir, ma_rahimi@sbu.ac.ir (M. Rahimi).
https://doi.org/10.1016/j.cherd.2022.05.011
0263-8762/© 2022 Institution of Chemical Engineers. Published by Elsevier Ltd. All rights reserved.
 Chemical Engineering Research and Design 183 (2022) 382–397
biological properties including anti-cancer, antimicrobial,
antiviral, anti-inflammatory, neuroprotective, cardioprotec­
tive, and hepatoprotective activities (Gupta et al., 2020),
which could be utilized as nutritional adjuvants and func­
tional foods for strengthen body’s immune system against
SARS-CoV-2 pandemic (El‐Missiry et al., 2021; Hamid
et al., 2021).
On the other hand, recently global attention on agri­
cultural wastes has been considerably increased (Muhlack
et al., 2018). This leads to an increase in the production of
value-added products from agricultural wastes, and it also
provides an opportunity for the development of related spin-
off industries in terms of human health as well as environ­
mental pollution issues (Beres et al., 2017). In Iran, grape
production is around 3.2 million tons, which comprised
15.2% of all crops and made it the second-highest produced
crop by weight (Ministry of Jahad in Agriculture, 2017).
Therefore, considering the massive volume of grapes and
their by-products, attempting to recovery beneficial com­
pounds for human health is essential.
Various solid-liquid extraction systems such as conven­
tional maceration, ultrasounds assisted and microwave-as­
sisted extraction are usually opted for obtaining maximum
PCs from grapes (Drosou et al., 2015). Metabolite extraction
efficiency may be significantly affected by numerous factors,
such as type of solvent and composition, extraction time,
temperature, and the solvent-to-feed ratio (Jiménez-Moreno
et al., 2019; Zhang and Lee, 2021). However, most of the
studies have been performed using the traditional approach
one-factor-at-a-time (OFAT) manner to optimize the extrac­
tion process (Spigno et al., 2007). The actual response of the
effective extraction process is the interactive influence of
various variables. Therefore, recently the effects of multiple
factors on the extraction efficiency of many plants have been
widely studied through new statistical methods which take
into account the interaction of variables (Drevelegka and
Goula, 2020; Garrido et al., 2019; Ghafoor et al., 2009; Karvela
et al., 2009). Methods of extraction PCs from plant materials
are non-selective and usually yield a bunch of byproducts
including sugars, organic acids, sugar alcohols, amino acids,
and proteins (Câmara et al., 2021). The presence of some of
these impurities leads to hindering the concentration of PCs
as well as intensifying challenges in downstream process
steps such as storing and drying (Liu et al., 2004).
Adsorption resins have been considered as an expedient
option to adsorb polar compounds like PCs (Wang et al.,
2021). Generally, there are two main aspects regarding using
adsorbent resin, which influence on the adsorption process
(Lv et al., 2008; Xiong et al., 2014); chemical features which
related to the extent of resin polarity and the adsorbate
structure, the macroporous resin tends to adsorb more alike
substances ‘polar like polar’, and physical properties of re­
sins associated with their average pore diameters, pore vo­
lume and surface areas by which some possible interaction
such as electrostatic, hydrogen-bonding, van der Waals
might be happened between adsorbent and adsorbate
(Kammerer et al., 2005; Zagklis and Paraskeva, 2015). For in­
stance, styrene–divinylbenzene copolymer (Kammerer et al.,
2005), non-ionic XAD4, XAD16, and XAD7HP resins (Zagklis
and Paraskeva, 2015), nine sorbing materials in adsorption/
desorption system (Trikas et al., 2017), were executed to
concentrate and purify the target PCs from different grape
pomace extract. Also, on the other hand, various mathema­
tical models were employed to screen characteristics of
383
adsorption/desorption systems such as kinetic, isotherm and
dynamic tests (Che Zain et al., 2021; Chen et al., 2022). De­
spite its simplicity, high capacity, easily regenerable and low
price, only a few number of adsorption/desorption systems
have been implemented for the purification of specific com­
pounds from natural sources especially on a large scale
(Kammerer et al., 2010; Seeram et al., 2005). There is no re­
port considering the analysis and optimization of whole as­
pects of process towards enriched end product especially for
this type of grape pomace (i.e., Vitis vinifera L.).
The objective of this study in the first stage was to opti­
mize an efficient green technique to extract the maximum
amount of desirable PCs from grape pomace, in both lab and
pilot-scale. In the next stage, enrichment of PCs of GPE was
achieved by using a non-ionic acrylic adsorption resin (LXA-
10) followed by determining adsorption properties in terms
of static and dynamic tests. Ultimately, the multistage con­
tinuous flow larger-scale column was designed, and different
aspect of operating condition for the enrichment of PCs was
evaluated.
2. Materials and methods
2.1. Materials and reagents
Grape (Vitis vinifera L.) pomace was provided as a by-product
of juice factories, by Vasha Herbal Pharmaceutical Company
(Qom, Iran). The moisture content of the grape pomace was
determined based on forced draft oven method (Nielsen,
2010). 3 g of ground sample was placed in the pan and
weighed accurately. Then, it was put in a forced draft oven at
98–100 °C for 24 h, stored in a desiccator until sample is
weighed. The percentage moisture (wt/wt) was calculated as
described below:
Moisture content (%)
(weight of wet sample + pan) (weight of dried sample + pan) (1)
= *100
weight of wet sample
The vacuum-oven dried grape pomace has a wet basis
moisture content of approximately 5.51%. Folin-Ciocalteu
and sodium carbonate (Na2CO3) were acquired from Merck
(Darmstadt, Hesse, Germany). Methanol (HPLC Gradient
grade) was provided from Biochem (Cosne-Cours-sur-Loire,
France). Gallic acid (GA), catechin and procyanidin B from
Biopurify (Chengdu, Sichuan, China) were utilized in this
experiment. The HPLC grade water was provided through a
water purification system (model Direct-Q3 UV Millipore,
Molsheim, France).
2.2. Instruments
An Eppendorf centrifuge model 5702 R (Hamburg, Germany)
was used to precipitate suspended particles in GPEs. A
spectrophotometer (Shimadzu UV/Vis 2501 PC, Kyoto, Japan),
and a microplate reader (EPOCH2 Bio Tek, Santa Clara,
California, USA) were employed for spectroscopic analyses.
Analyses of quantity and quality of target PCs present in the
samples was investigated at wavelength of 280 nm. The PCs
and proanthocyanidins were separated from GPEs using
Waters high-performance liquid chromatography (Milford,
Massachusetts, USA) coupled with a photodiode array (PDA)
detector, and equipped with SunFire C18 column (150 mm ×
5.0 mm × 3.5 µm).
384 Chemical Engineering Research and Design 183 (2022) 382–397

Table 1 – The experimental plan of the extraction process, the raw results, and predicted responses.
Runs Factors Response-1 Response-2

Temperature Time Solvent/ Efficiency of Predicted Yield of PCs (mg GA Predicted yield of PCs (mg
(°C), X1 (h), X2 Feed extraction (%) efficiency of plus Procyanidins /g of GA plus Procyanidins /g of
(mL.g−1), X3 extraction (%) dried grape pomace) dried grape pomace)

1 80 4 24 9.87 9.71 3.68 6.33

2 40 16 24 5.12 5.28 2.20 0.45
3 80 10 40 11.74 11.23 9.53 8.30
4 60 10 24 8.26 8.15 4.98 4.68
5 60 10 24 8.22 8.15 4.11 4.68
6 60 10 24 7.95 8.15 4.29 4.68
7 40 10 40 7.04 7.07 0.36 2.77
8 40 4 24 8.12 7.42 3.00 2.00
9 60 10 24 8.19 8.15 4.99 4.68
10 60 16 40 9.32 9.13 1.99 2.22
11 60 10 24 8.13 8.15 5.01 4.68
12 80 10 8 10.38 10.35 14.55 12.14
13 60 4 8 7.97 8.16 3.35 3.12
14 40 10 8 5.31 5.82 1.18 2.41
15 60 16 8 9.12 8.45 1.78 3.19
16 80 16 24 10.98 11.68 9.48 10.48
17 60 4 40 8.95 9.61 2.02 0.61

2.3. Experimental set-up and procedure
The extraction and purification studies were performed in
two different stages, bench and pilot scales. At the bench-
scale study, operating conditions to increase product yields
and purity were optimized. Then to manufacture of larger
product quantities and to predict the behavior of the la­
boratory-scale data at an industrial scale, the processes were
investigated at a larger scale.
2.3.1. Extraction process
2.3.1.1. Bench-scale. The dried powdered pomace of grapes
(2 g) were extracted by maceration in Florence flasks of
250 mL and 29 mm diameter, which were shaken at the
constant rotation of 500 rpm in an oil bath on a heating
magnetic stirrer. Extracts were then filtered by centrifugation
for 45 min at 2500 rpm and concentrated to dryness by
vacuum rotary evaporation, which is located in a water
bath at 35 °C. The extracts were stored at 3 °C for the next
examinations.
2.3.1.2. Pilot scale. 40 kg of grinded GP were fed into
extraction vessel filled with 800 L water (Fig. S6A in
supporting information). The vessel was surrounded by a
constant flow of water to keep the extraction temperature at
80 °C. The extraction has been processed for 10 h under
constant rotation. In the last step, the enriched extract was
passed through the filters with various mesh sizes to remove
suspended solids. The filtered extract was stored in cool dry
place for the next enrichment process.
extraction efficiency in bench-scale operation. The efficiency
of extraction (%) and yield of PCs (mg GA plus Procyanidins /g
of dried grape pomace) as two dependent responses were
evaluated. The yield of PCs was quantified based on cali­
bration with respective standards and peak-areas measure­
ment (external standard method) (Massart et al., 1998), and
efficiency of extraction was calculated according to the fol­
lowing equation:
Efficiency of extraction(%)
weight of the extract residue obtained after
(2)
solvent removal(g)
= × 100
weight of dried grape pomace(g)
The suitable ranges which have been determined based
on the preliminary experiments, and the central point value
of all the three process variables are as followed:
Temperature 40, 60, 80 °C, Time 4, 10, 16 h and Solvent-to-
Feed ratio, S , 8, 24, 40 mL.g−1. Based on the BBD, 17 experi­
F
ments including five replicates of the central runs (Table 1)
were conducted to obtain a reasonable estimation of the
experimental error. It is important to note that each experi­
mental test was repeated triplicate and the mean value of
three measurements was reported.
The extraction process optimization was numerically
exploited to maximize the yield of PCs corresponding to the
regression analysis and the 3D surface plots of the in­
dependent variables. The target responses were determined
under the suggested extraction conditions. Finally, to check
out the validity of the proposed model the predicted values
were compared with the experimental values.

2.3.2. Optimization of extraction process
Response surface methodology (RSM) as a statistical tech­
nique has been employed to study and analyze the inter­
active effects of different variables (Khodaei et al., 2018). The
Box-Behnken design (BBD) as a subset of RSM was selected to
correlate the most appropriate equations corresponding to
the experimental data (Rahimi et al., 2017). The incubation
temperature (X1), time (X2), and solvent-to-feed ratio (X3)
were chosen as the most effective variables to investigate the
2.3.3. Enrichment by resin adsorbent in bench-scale process
A polymeric adsorbent (LXA-10) which was supplied from
Sunresin (Xi'an, Shaanxi, China) is a type of non-ionic mac­
roporous acrylic adsorption resin (milk-white opaque sphere
appearance) with a special pore structure, particle diameter
(dp) 0.3–1.25 mm, density 1000–1100 g. L−1, moisture content
60–70%, pore size 8.14 nm, pore volume 0.94 cm3.g−1 and large
surface area, ≥ 400 m2.g−1, which is capable of adsorbing
water-soluble polyphenols from herbals. Before every
 Chemical Engineering Research and Design 183 (2022) 382–397 385

experiment, the resin pretreating was performed as de­ 1

RL = (9)
scribed by the supplier (Pretreatment of Ion Exchange Resin). 1+ C0 KL
After pretreating the resin, the adsorption process of the where RL specifies the nature of adsorption. The value of RL
optimized GPE on the resin was investigated by kinetic, iso­ between 0 and 1 indicates the adsorption is favorable
therm, and dynamic models. whereas the adsorption is unfavorable when the RL value is
greater than 1, and RL is equal to 1 means linear adsorption.
2.3.3.1. Static adsorption tests Freundlich model:
2.3.3.1.1. Kinetic study. For kinetic analysis, 20 mL
1
optimized GPE was mixed with 2 g pretreated adsorbent at Ln qe = Ln Kf + Ln Ce (10)
n
450 rpm for 3 h. Aliquots of the sample solution were taken at
special time intervals until equilibrium was reached, and where Kf ((mg. g−1)(L. mg)1/n) indicates the Freundlich con­
then the TPCs content was measured. The adsorption stant representing adsorption capacity, and 1 specifies the
n
capacity at equilibrium (qe, mg. g−1 resin) was calculated adsorption intensity. The value of 1
presents the nature of
n
according to the following equation: adsorption at which 0 < 1
< 1 indicates favorable, 1
> 1 is
n n
qe = (C0 Ce) × V/
i w (3) unfavorable adsorption, and 1
= 1 shows adsorption is irre­
n
where C0 and Ce denote TPCs content at initial and versible.
equilibrium (mg. L−1), the Vi represents the volume of GPE Temkin model:
(L), and w represents the mass of the resin (g). qe = BLn KT + BLn Ce (11)
To investigate the adsorption kinetic, the pseudo-first-
−1
order, pseudo-second-order, fractional power, and intra- KT (L. mg ) denotes the Temkin isotherm constant and is
b
particle diffusion kinetic models were studied. The equations related to the binding energy, and B = RT which b is the
were expressed as follows (Hassani et al., 2014): Temkin constant related to heat of adsorption (J. mol−1), R is
The pseudo-first-order model: the gas constant (8.314 J. mol−1. K−1) and T is the absolute
temperature (K).
Ln(qe qt) = Lnqe k1t (4) Being exothermic or endothermic of adsorption is de­
The pseudo-second-order model: termined by the B value. If B > 0, it indicates that during the
adsorption, the heat is released indicating the exothermic
t t 1
= + (5) process, and if B < 0, it implies that, heat is absorbed during
qt qe k2 qe2
the adsorption process, and the process is endothermic.
The fractional power kinetic model:
Log qt = Log K3 + vLogt (6) 2.3.3.2. Dynamic adsorption and desorption tests. Dynamic
adsorption experiments were performed on a lab-scale
The intra-particle diffusion equation:
glass column (3 cm × 30 cm) wet-packed with the LXA-10
qt = Ki t0.5 + C (7) resin. The BV of the wet resin was 170 mL which is equal to
156 g dry resin. The concentrations of PCs in the effluent's
where qe (mg. g ) and qt (mg. g ) are the amount of ad­
−1 −1
fractions (4 mL) were collected at various residence times
sorbed TPCs at equilibrium and at time “t”; k1 (min−1), k2 (g.
(0.02–55 h), which were determined by UV-Spectrometric
mg−1. min−1), K3 (mg. g−1), v (min−1), and Ki (mg. g−1. min−0.5)
analysis. It is also known as breakthrough curve test
are the constant rate of pseudo-first-order, pseudo-second- C
( C vs time ), which is essential for scaling up the results.
order, fractional power, the rate constant of fractional power, 0
When the absorbance of the eluent reaches one-tenth of
and intra-particle diffusion rate constant, respectively; and
the loading extract, it indicates the PCs has leaked out (He
also, C is a constant.
and Xia, 2008), and/or the resin is near saturation point,
2.3.3.1.2. Isotherm study. The adsorption characterization
which is called the breakpoint (tBP ). After the breakpoint time
of TPCs on LXA-10 resin was investigated according to the
the concentration rises up to exhaustion point time (tEP ),
adsorption isotherms. The adsorption isotherm was evaluated
where the bed is considered ineffective. In our experiments
by shaking 10 mL optimized GPE at 450 rpm with variant
the loading of the extract was stopped after reaching about
amounts of pretreated resin (0.3–1 g) at room temperature.
90% of absorbance of the loading extract, and the adsorption
Langmuir, Freundlich, and Temkin isotherm models have
capacity of the resin was calculated. The area above the
been studied for their fitness to represent measured data. In
breakthrough curve signifies the bed capacity (BC) in mg
all isotherm models, the linear form of equations was applied.
(McCabe et al., 1993), and is calculated by
These models are expressed as follows (Ayawei et al., 2017;
Li et al., 2018): C0 tEP Cf
BC = 1 dt (12)
Langmuir model: V 0 C0
1 1 1
= + (8) where V is the volume flow rate (mL. min−1), C0 and Cf are the
qe Ce KL qm qm
inlet and outlet concentration (mg. mL−1) at time t,
The terms qe (mg. g−1) and Ce (mg. mL−1) denote ad­ respectively, and tEP is the actual time required for full bed
sorption capacity and TPCs concentration at equilibrium. exhaustion.
qm (mg. g−1) indicates the maximum adsorption capacity, Ideal breakthrough curve (IBC) is a condition in which
and KL (mL. mg−1) is the Langmuir constant which is related rapid mass transfer rate between solution and adsorbent is
to the free energy or net enthalpy of adsorption. Based on the happened. It is assumed that the breakthrough curve be a
initial TPCs content (C0 ) and Langmuir constant (KL ), di­ vertical line at tIBC , which is the time required for full bed
mensionless equilibrium parameter RL can be evaluated exhaustion under ideal conditions. This means that the area
using the expression: below the curve between tBP and tIBC is equal to the area above
386 Chemical Engineering Research and Design 183 (2022) 382–397
Fig. 1 – HPLC-UV chromatograms of grape pomace crude extract in 280 nm for different solvents.
the curve between tIBC and tEP . The length of unused bed HUNB
(cm) which represents the mass-transfer zone is essentially
independent of total length of the column and determined
Eq. (13).
tBP
HUNB = H 1 (13)
tIBC
where H (cm) is the bed height.
The adsorbate-laden column was firstly washed with
deionized water to eliminate water-soluble impurities and
then desorbed with aqueous methanol solution until PCs
were no longer detected in the eluents.
2.4. Measurement of total phenolic compounds (TPCs)
content
The total phenolic content of the extracts was determined
using Folin–Ciocalteu reagent (FCR) (Bayati et al., 2021).
Briefly, to 25 µL of diluted each extract (1000 ppm), 125 µL of
FCR diluted (1:9 in water) was added, followed by 100 µL of
7.5% (w/w) Na2CO3 solution. The mixtures were put into a 96-
multiwell insert system (Greiner Bio-one, Germany) in dark­
ness for 2 h. The absorbance of solutions was measured at a
wavelength of 760 nm by a multifunctional microplate
reader. Calibration curve was created using GA standard
solutions (10–300 ppm). The results were expressed in mg
PCs equivalent per gram of grape pomace, on a dry weight
basis.
2.5. High-Performance Liquid Chromatography (HPLC)
Stock solutions of GA, catechin, and procyanidin were pre­
pared in dimethyl sulfoxide (DMSO) from the standard sub­
stance: concentration 1 mg. mL−1. Then working solutions of
different concentrations 7.81, 15.62, 31.25, 62.5, 125, 250, and
500 µg. mL−1 were prepared in HPLC grade DMSO, stored at
− 20 ◦C, and brought to room temperature before usage. Each
standard solution was filtered via a 0.2 µm-membrane filter
and then subjected to HPLC analysis to obtain a peak height
at a static retention time. A calibration curve was plotted for
 Chemical Engineering Research and Design 183 (2022) 382–397 387

Fig. 2 – HPLC-UV chromatograms of grape pomace crude extract (A), standard Gallic acid (B), and standard Procyanidin B (C)
in 280 nm.

concentration (µg. mL−1) versus peak area. The plots (Fig. S1
in Supporting Information) were further used to determine
the concentration of GA, catechin, and procyanidin B in test
samples. 15 mg of various GPEs were weighed and dissolved
in HPLC grade water to make a final concentration of
15000 µg. mL−1. The solution was then filtered through a 0.2-
µm membrane filter and 30 µL of the obtained solution was
prepared for HPLC analysis and the concentrations of major
constituents, GA, catechin and procyanidin B in the extracts
were then calculated based on the equations for the cali­
bration curves. Linear gradient elution system was used with
acidic water (0.02% TFA) as eluent (A) and methanol con­
taining 0.02% TFA as eluent (B) as follows: 0–10 min, 3–20% B;
10–30 min, 20–40% B; 30–40 min, 40–80% B; 40–45 min,
80–100% B, 45–47 min, 100% B, 47–50 min, 3% B. The mobile
phase flow rate was fixed at 0.5 mL. min−1. Separation was
carried out at 25 °C. The chromatograms were monitored at
wavelength 280 nm. Peak assignment was performed by
comparison of the retention time and spectra with those
obtained from the corresponding standards.
3. Results and discussion
3.1. Optimization of extraction
3.1.1. Effect of the solvent type on the extraction process
Extraction was performed at completely similar conditions,
with different solvents such as pure ethanol, ethanol-water
(50:50), and distilled water. The extraction efficiency reaches
20.33%, 10.77%, and 15.49% w/w for each solvent,
388 Chemical Engineering Research and Design 183 (2022) 382–397

Fig. 3 – Evaluation of RSM proposed model between predicted and experimental values; A) Predicted versus actual values
plot, B) Normal plot of residuals, and C) Residual versus predicted plot.

respectively. The HPLC profiles of GPE at different solvents
were shown in Fig. 1A-C. As can be observed in Fig. 1, in­
creasing the water proportion in extraction solvent cause
growth in the area below the peaks and therefore was con­
cluded more effective for extraction of PCs in comparison
with hydroalcoholic solvent systems (the final concentration
of PCs in the extracts of ethanol, water-ethanol, and water is
650, 860 and 876 ppm, respectively). This observation can be
ascribed to the fact that, by adding water to organic solvents
usually more polar medium will be created, which expedite
the extraction of polyphenols (Spigno et al., 2007). Taking
into consideration that by using water as the extraction
solvent there would be no need for evaporation of solvent for
the next step of adsorption on resin, and consequently
saving more energy and time for industrial production, water
was selected as the appropriate green solvent for extraction
of PCs from grape pomace.
3.1.2. Identification and quantification of PCs
GA and Procyanidin B as the PCs in grape pomace were
identified by matching retention times and UV spectra of GPE
peaks with GA and Procyanidin B standards. From Fig. 2,
these two compounds were in remarkable amounts in the
extracts. Due to the lack of standards, the other peaks in the
chromatogram were not identified. However, as the TPCs
content measured by the Folin-Ciocalteu method was much
higher than the sum of individual phenolic concentration,
which identified and quantified by HPLC, it can be concluded
that some of them contributed significantly to the TPCs
content in the extract. The results for TPCs content of opti­
mized extract was obtained 205.33 mg GA/g of dried grape
pomace. It was higher than that TPCs content reported by
ref., (Milinčić et al., 2021) for aqueous methanolic extracts of
grape pomace and corresponding skin and seed in a con­
ventional extraction process. It also showed higher amount
 Chemical Engineering Research and Design 183 (2022) 382–397 389

Fig. 4 – Response surface plots for the extraction efficiency showing the interactions between; (A) time and temperature, (B)
solvent-to-feed ratio and temperature, (C) solvent-to-feed ratio and time.

of TPCs compared to ref., (Drevelegka and Goula, 2020) for
extracts obtained by two extraction techniques of ultra­
sound- and microwave-assisted extraction. Moreover, our
results for the content of TPCs were lower as compared to
ref., (Macedo et al., 2021) for extracts of olive pomace samples
obtained by various extraction techniques, and ref., (Spigno
et al., 2007) for aqueous ethanolic extract of grape marc. The
difference between results might be due to several reasons
including the grape species, different operating conditions,
solvent type and effect of various extraction techniques,
which influenced on the quantity and quality of the extracts.
It is noted that the TPCs content of prickly pear peel extract
obtained by water maceration method reported by ref.,
(Gómez-Salazar et al., 2022) was 47.85 mg GA /g of extract,
which was calculated based on the weight of the dried ex­
tract, not dried fruit powder.
3.1.3. Statistical analysis in the bench-scale operation
Table 1 presents the experimental design tests and the cor­
responding responses, yield of PCs (mg GA plus Procyanidins
/g of dried grape pomace), and efficiency of extraction (%) for
the bench-scale operation. The results of the experimental
runs were fitted to quadratic correlations in accordance with
the model obtained using the RSM-BBD technique. Eq. 14 and
15 present the proposed correlations for the efficiency of
extraction and the yield of PCs as the function of the in­
dependent variables. The main statistical characteristics of
the second-order polynomial models are as followed: The p-
value (Prob > F) = 0.0011, 0.0193, F-value = 13.96, 5.27, coeffi­
cient of determination (R2 ) = 0.95, 0.90, Standard deviation
= 0.6, 1.93, Adequate precision = 13.83, 7.9 for the efficiency of
extraction and the yield of PCs, respectively. The p-value
(Prob > F) is known as an index for determining the statistical
significance of models. A low p-value (p < 0.05) and/or high F-
value implies the model terms are significant. Adequate
precision indicates the signal to noise ratio which is a mea­
sure of the range in predicted response relative to its asso­
ciated error. A ratio greater than 4 is desirable (Montgomery,
2017). Moreover, the graph of the actual experimental results
versus the predicted responses values is represented in
Fig. 3A. The graph also confirms that the prediction is rea­
sonably close to the experimental data using the proposed
correlation. Fig. 3B indicates the variance between the pre­
dicted response and the actual data in terms of the normal
390 Chemical Engineering Research and Design 183 (2022) 382–397
Fig. 5 – Response surface plots for the yield of PCs showing the interactions between; (A) time and temperature, (B) solvent-
to-feed ratio and temperature, (C) solvent-to-feed ratio and time.
probability plot of residuals. The normal probability plot in­
dicates that whether the residuals follow a normal distribu­
tion. In this case, the points follow a straight line (Fig. 3B). As
can be seen from Fig. 3B, the points trail a normal distribu­
tion around a straight line. Fig. 3C also displays the residuals
versus fitted response which is a plot of the residuals versus
the ascending predicted response values. It exams the as­
sumption of constant variance. The plot should behave
random scatter i.e., constant range of residuals across the
graph. These results confirm the accuracy and reliability of
the proposed model. The similar results were obtained for
yield of PCs.
Efficiency of extraction (%) =7·52722+0·007438X1-0·637986X2-
0·002578X3+0·008562X1X2-0·000289X1X3-
0·002031X2X3+0·000187X12+0·008264X22+0·001533X32 (14)
Yield of PCs (mg·g−1) =9·98600–0·473225X1
+0·317917X2+0·156396X3+0·013750X1X2-
0·003281X1X3+0·004010X2X3+0·005042X12-0·058417X22-
0·001125X32 (15)
3.1.4. Impact of variables on the yield of PCs and efficiency of
extraction
According to Figs. 4A and B, the factor temperature could
impact significantly and positively on the efficiency of ex­
traction. The trend seen for the efficiency of extraction
showed that maximal efficiency can be achieved by rise in
temperature because high temperatures could increase the
solubility and diffusion of the target compounds as well as
decrease the medium viscosity in the solid-liquid extraction
process (Drevelegka and Goula, 2020). However, higher tem­
peratures than 80 °C were not tested due to the limitation of
working with water solvent and preventing the decomposi­
tion of valuable compounds. The plots show that at the ex­
traction time between 10 and 16 h, the greatest recovery
appears to be obtained due to increasing mass transfer to the
solvent. As can be seen from Fig. 4B and C there are no
 Chemical Engineering Research and Design 183 (2022) 382–397 391

Fig. 6 – The TPCs content of the extracts of different runs determined using Folin–Ciocalteu method. The data were analyzed
using one-way ANOVA. A significant difference was considered at p < 0.01 * ** and P < 0.05 * * compared to different runs.

significant differences in efficiency at high ranges of solvent-
to-feed ratio and low ones, while lower ratios are more eco­
nomical for industrial purposes. Fig. 5 also displays the plots
of the interactions between various independent variables
(i.e., time, solvent-to-feed ratio, and temperature) and yield
of PCs as a response. As can be seen from Fig. 5A and B in­
creasing the temperature from 50 to around 80 °C leads to
obtaining more yield of PCs. From Fig. 5B when the factor
temperature is fixed at any value the yield of PCs slightly
increases as the solvent-to-feed ratio increases, and then
started to partly decrease. Moreover, according to Fig. 5B, for
the greater values of temperatures, the factor solvent-to-feed
ratio plays a more significant role in which raising the sol­
vent-to-feed ratio can cause a lower yield of PCs. Therefore,
working in lower solvent-to-feed ratios would be appropriate
in terms of industrial application. It has been expected that
increasing the time of contact between solvent and plants,
would lead to more yield of PCs. However, both Fig. 5A and C
indicated that at high temperatures and low solvent-to-solid
ratios, the addition of time more than ten hours will not
cause remarkable changes in the yield of PCs (nearly flat
area). Moreover, it is worth noting that comparing HPLC
chromatograms (see Fig. S2 in Supporting information) of
run-3 (80 °C, 10 h, 40 mL. g−1) with run-16 (80 °C, 16 h, 24 mL.
g−1) also showed that by increasing the extraction time over
10 h, marked peak which is related to catechin as one of the
most important PCs that we are looking for has been dis­
appeared. It could be possibly due to the tendency of these
compounds to polymerize or to interact with anthocyanins
(Es-Safi et al., 1999) or epimerization of catechin to epi-ca­
techin under following pathway (Fig. S3 in Supporting
Information) (Lončarić et al., 2018). Therefore, due to our
tendency to shorter extraction duration for production in
industrial scale, 10 h was chosen as the best extraction time
for our purposes.
Also, the total phenols analysis was executed to monitor
the effect of variables. As demonstrated in Fig. 6 boosting
temperature has led to the remarkable increase in the
amount of TPCs in run-1 (80 °C, 4 h, 24 mL. g−1), run-3 (80 °C,
10 h, 40 mL. g−1), and run-12 (80 °C, 10 h, 8 mL. g−1). Despite
high temperature at run-16 (80 °C, 16 h, 24 mL. g−1), low total
phenols amount was attained which might be due to the
addition of extraction time and possibly decomposition of
compounds, as was mentioned before. By considering run-1
it can be concluded that even too low extraction time can be
compensated by the addition of operating temperature.
392 Chemical Engineering Research and Design 183 (2022) 382–397

Fig. 7 – (A) Kinetic curve and fitness plots for (B) Pseudo-first-order kinetic model, (C) Pseudo-second-order kinetic model,
and (D) fraction power model for PC adsorption from GPE.

Therefore, results of total phenol tests confirm that higher experimental and predicted values validate each other,
temperature could be needed for extraction of max­ which approve that the fitted model is reliable.
imum PCs.
3.2. Enrichment of PCs

3.1.5. Validation of the response surface model
The optimum conditions among various-suggested combi­
nations of the variables were achieved as follows:
Temperature = 80 °C, Time = 10 h, and Solvent/feed = 20 mL.
g−1. A case study was performed with the new condition to
certify the accuracy of the fitted correlation. According to the
optimum condition the predicted value of 10.67% and ex­
perimental result of 9.43% for efficiency of extraction, and
the predicted value of 31.94 mg. g−1 and experimental result
of 29.96 mg. g−1 for yield of PCs were attained. Both
3.2.1. Adsorption kinetics of TPC on LXA-10 resin
In order to obtain more detail in the adsorption mechanism,
the adsorption kinetic of TPCs on LXA-10 resin were as­
sessed, and the kinetic curve and the fitted models are de­
picted in Fig. 7(A-D), respectively. As can be observed from
Fig. 7 A the adsorption capacity of TPCs increased rapidly in
the first 15 min, then raised slowly after 40 min, and reached
equilibrium at about 50 min, where the equilibrium adsorp­
tion capacity was 1.42 mg. g−1. Table 2 presents the fitting
equations and parameters of the kinetic models. The

Table 2 – Parameters of the kinetic models for the adsorption of TPCs on LXA-10 resin.
Pseudo-first order model Pseudo-second order model
−1 2
qe (mg. g ) k1 (min−1) R qe (mg. g−1) k2 (g. mg−1.min−1) R2

0.26 0.02 0.58 1.40 0.52 0.99

Fractional power model Intra-particle diffusion model

v (min )−1
K3 (mg. g )
−1
R 2
Ki (mg. g−1. min−0.5) C R2

0.13 0.79 0.91 0.05 0.87 0.63

 Chemical Engineering Research and Design 183 (2022) 382–397 393

Fig. 8 – The equilibrium adsorption isotherms (A); and linear correlations based on the Freundlich (B), (C) Langmuir, and (D)
Temkin isotherm models for TPCs on LXA-10 resin.

The experimental data fitted by the intra-particle diffu­

Table 3 – Parameters of the isotherm model for the
sion model was also evaluated (Fig. S4 in Supporting
adsorption of TPCs on LXA-10 resin.
Information). With increasing adsorption time, the diffusion
Isotherm model Equation Parameters Values
curve becomes multi-linearity, suggesting that the adsorp­
Langmuir y = 63.68x + 0.0427 Kl 0.001 tion process is divided into three stages. In the first stage
R2 0.92 (0–3 min0.5), the initial boundary layer diffusion is plays sig­
RL 0.87 nificant role in rate determination where the phenolic mo­
qm 23.42
lecules diffuse from the GPE to the surface of the resin
Freundlich y = 0.8977x - 3.7624 Kf 0.02
particle which has the maximum mass transfer. The second
R2 0.90
stage (4.5–5.5 min0.5) is the gradual adsorption phase when
1/n 0.90
the internal diffusion had a rate limiting-step. Ultimately, the
Temkin y = 1.0221x - 3.2724 KT 0.04
third stage (9.5–13.5 min0.5) is the final equilibrium stage
R2 0.93
B 1.02 which is explained as the diffusion control period.

3.2.2. Adsorption isotherms of TPCs on LXA-10 resin

correlation coefficient (R2) of the pseudo-second-order model
(0.99) is higher than other models which means this model
better correlates with the adsorption kinetics. Moreover, the
calculated qe of the pseudo-second-order model (=1.39 mg.
g−1) showed good agreement with the experimental result
(=1.40 mg. g−1) which indicates that the adsorption process of
TPCs on LXA-10 resin could be represented through this
model. Fig. 8.
The adsorption characterization to illustrate TPCs adsorption
mechanism on LXA-10 resin was investigated. The isotherm
plots and parameters of various models have been shown in
Fig. 7(A-D) and Table 3. The results disclosed that the ex­
perimental data fitted well to the Temkin model as compared
to the other models. This was ascribed to the high value of
the correlation coefficient (R2 = 0.93) attained for the Temkin
isotherm compared to other models. Furthermore, the ad­
sorption capacities measured through the Temkin model are
394 Chemical Engineering Research and Design 183 (2022) 382–397
Fig. 9 – The breakthrough curve at various times during adsorption of PCs in bench-scale operation.
also in good agreement with the experimental values. The
order of the models followed based on the correlation coef­
ficient (R2) is Temkin > Langmuir > Freundlich. The calcu­
lated value of 1/n in Freundlich isotherm is 0.898, which also
established that adsorption is favorable (Li et al., 2018). The
amount of RL in Langmuir (= 0.873) was between 0 and 1,
which also confirmed the favorable adsorption of TPC on
LXA-10 resin (Ayawei et al., 2017). The value of B > 0 in the
Temkin model (=1.022) indicated that during adsorption, the
heat is released, and the process is exothermic.
3.2.3. Dynamic adsorption/desorption tests on LXA-10 resin
for the enrichment of the GPE
A breakthrough curve study (Fig. 9) was performed to obtain
the parameters which are necessary for scaling up of fixed-
bed adsorption column. In this regard, dynamic adsorption of
PCs from grape pomace was tested in a bench-scale column
filled by LXA-10 resin with a working bed height of 24 cm for
the 170 mL BV of the wet resin. The solution containing the
PCs with C0 = 195.24 mg. L−1 was continuously supplied to the
resin column for a 55 h operation time. According to the ki­
netic data, the flow rate for loading an aqueous solution of
the phenolic extract on the resin was fixed at 4 mL. min−1 to
keep the time of contact in 40 min. It must be noted that to
have the uniform flow distribution 40 mL distilled water was
loaded into the column following the extract loading at the
early stage of operation. The most important parameters
were estimated based on some general concepts and equa­
tions (McCabe et al., 1993) are as follow: The breakpoint (tBP )
time of 23.2 h, the ideal breakthrough curve (tIBC ) indicating
the time for full bed exhaustion at infinite rapid adsorption is
29.1 h, exhaustion point time (tEP ) of 51.2 h, the mass transfer
or active zone representing the length of the unused bed
(HUNB) which is independent of the total length of the column
was estimated as 4.93 cm, and the bed capacity (BC)
representing to the total amount of PCs adsorbed is calcu­
lated as 825.86 mg. It should be noted that the volume of the
GPE treated till tBP , tIBC and tEP were 5.57 L, 7.01 L and 13.2 L,
respectively.
In the desorption process of PCs from LXA-10 resin, at first
the saturated resin was washed with 3 BV of water to elim­
inate possible impurities. Then, 7 BV of aqueous pure me­
thanol at a flow rate of 40 mL. min−1 was utilized to
effectively desorb and separate of phenolics from the ad­
sorbent resin. The purity of phenolics in the obtaining pro­
duct was 99% and the yield of products in the ratio of initial
grape pomace powdered was 1.91%. These results may
helpful in developing large-scale adsorption-desorption sys­
tems for efficient production of the grape phenolic extract.
3.3. Scale-up study
After collecting data in lab-scale the optimized results were
employed in the larger scale pilot plant particularly the
newly designed fixed-bed adsorption systems for the en­
richment of PCs from V. vinifera pomace. Fig. S5 (in
Supporting Information) proposes the whole process asso­
ciated with PCs extraction and enrichment from grape po­
mace. In the first step, the crude feed was fed into the size
reduction unit P-1/GR-101. The grinded solids and water
solvent through the P-3/V101 were sent into solid extraction
unit P-2/SMSX-101. By keeping the factors constant, similar
results (efficiency of extraction= 10.67% and yield of PCs
=15.97 mg. g−1) were achieved in pilot-scale as in bench-scale.
The enriched extract was sent to the filtration unit P-4/PFF-
101 for removing suspended solids. Then the liquid extract
was loaded on a newly designed pilot-scale adsorption
column (three columns P-5/C101, P-6/C102, and P-7/C103) to
separate and purify the target compounds.
Fig. S7 (Supporting Information) presents the real picture
of the multistage continuous flow pilot-scale of adsorption
 Chemical Engineering Research and Design 183 (2022) 382–397
column along with some detailed information, applied for
GPE enrichment. According to the bench-scale tests data and
using some general relation between the laboratory scale and
pilot scale such as tBP , HUNB, empty bed contact time (EBTC)
representing the same residence time (McCabe et al., 1993),
together with incorporating criteria in terms of internal
column diameter to particle diameter ratio (Di /dp >50) and
(H /Di 8–18) to prevent channeling and minimize the side-
wall effect in the column which create the dead zone and
limit the mass transfer, this system has been developed.
Three cylindrical-type columns were constructed by the
glass each with an internal diameter of 15 cm, length of
120 cm, and a working volume of 8 L (8-kilogram resin)
equivalent to 84 cm depth of adsorbent for 500 L per day
operation. The extract was transferred into the first column
from the storage tank through the pump (Shimge model
XPS25–6–180) at a flow rate of 300 mL. min−1. Then, the outlet
of the first column was directed into the second and third
columns via the pipeline and circulation pumps, respec­
tively. Eventually, the resulting was poured into a specified
storage tank for the next operation. The output of the col­
umns was collected as waste in the storage tank P-9/V-103.
After the completion of the adsorption process, the elution
solvent was pumped from P-8/V102 into the columns to
desorb the target components. The enriched liquid has to be
concentrated before sending to the drying unit, which was
done using vacuum evaporator unit P-10/VE-101 (Fig. S6B in
Supporting Information). The solvent was recovered after
cooling in P-11/HX101 unit and sent back to P-8/V102. At the
final stage spray dryer unit, P-12/SDR-101 was utilized to
obtain the product from thick liquor. The results of pilot-
scale operation showed that by using this method, the pri­
mary extract containing 1% PCs was increased to 30% in the
enriched extract, with an efficiency of about 2% as compared
to the initial grape pomace powder. However, comparing
between (Fig. S8A and S8B in Supporting Information) the
concentration of GA has approximately been halved in the
final product, corresponding to their peak area (from 10.06 to
4.96 ppm) (Fig. S8B). This shows the weak ability of LXA-10 in
the adsorption of GA. Since obtaining this compound as one
of the main PCs is very important for us, in the future at the
end of this process we would pass the output of the third
column through another resin that is able to adsorb it.
4. Conclusion
Numerical optimization conducted the optimum extraction
conditions to be temperature 80 °C, extraction time 10 h and
solvent to feed ratio 20 mL. g−1. It was revealed that the re­
covery of PCs was not affected by upgrading a 1000-fold
scale-up from bench to pilot scale in the extraction process.
The adsorption process of the target PCs on the LXA-10 resin
could be well-described with the pseudo-second-order ki­
netic model (R2 =0.99) and Temkin isotherm model (R2 =0.93).
The highest adsorption capacity of 4.86 mg. g−1 was achieved
when variables including the initial concentration of PCs and
feed flow rate were 50 mg. L−1 and 300 mL. min−1, respec­
tively. Ultimately, a purified product containing more than
1570 mg. L−1 PCs was obtained. The current study suggests
that this process can be considered as an efficient, safe, and
practical technique for studying any natural source with
potential benefits for cosmetic, food and pharmaceutical in­
dustries.
395
CRediT authorship contribution statement
Sarvenaz Heravi: Laboratory experiments, Methodology,
Writing – original draft and Resources. Masoud Rahimi:
Conceptualization, Project management, Writing – review &
editing, and Supervision. Mahshad Shahriari: Data curation,
Investigation, Formal analysis, Writing – review & editing.
Samad Nejad Ebrahimi: Conceptualization, Experimental
validation, Formal analysis, Visualization, Writing – review &
editing.
Declaration of Competing Interest
The authors declare that they have no known competing fi­
nancial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Acknowledgment
The authors gratefully acknowledge the support provided by
Shahid Beheshti University Research Council and MPDRI.
Vasha Darou Pars Herbal Pharmaceutical Co. financially
supports this work.
Appendix A. Supporting information
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.cherd.2022.05.011.
References
Pretreatment of Ion Exchange Resin. 〈https://www.seplite.com/
pretreatment-of-ion-exchange-resin.html〉.
Ayawei, N., Ebelegi, A., Wankasi, D., 2017. Review article: mod­
eling and interpretation of adsorption isotherms. J. Chem. 11.
https://doi.org/10.1155/2017/3039817
Bayati, M., Tavakoli, M.M., Ebrahimi, S.N., Aliahmadi, A.,
Rezadoost, H., 2021. Optimization of effective parameters in
cold pasteurization of pomegranate juice by response surface
methodology and evaluation of physicochemical character­
istics. LWT 147, 111679. https://doi.org/10.1016/j.lwt.2021.
111679
Beres, C., Costa, G.N., Cabezudo, I., da Silva-James, N.K., Teles,
A.S., Cruz, A.P., Mellinger-Silva, C., Tonon, R.V., Cabral, L.M.,
Freitas, S.P., 2017. Towards integral utilization of grape po­
mace from winemaking process: a review. Waste Manag. 68,
581–594. https://doi.org/10.1016/j.wasman.2017.07.017
Câmara, J.S., Albuquerque, B.R., Aguiar, J., Corrêa, R.C.,
Gonçalves, J.L., Granato, D., Pereira, J.A., Barros, L., Ferreira,
I.C., 2021. Food bioactive compounds and emerging techni­
ques for their extraction: polyphenols as a case study. Foods
10, 37. https://doi.org/10.3390/foods10010037
Che Zain, M.S., Lee, S.Y., Teo, C.Y., Shaari, K., 2021. Adsorption/
desorption characteristics and simultaneous enrichment of
orientin, isoorientin, vitexin and isovitexin from hydrolyzed
oil palm leaf extract using macroporous resins. Processes 9,
659. https://doi.org/10.3390/pr9040659
Chen, X., Wang, H., Huang, X., Xia, S., Chen, C., Nie, Q., Nie, S.,
2022. Efficient enrichment of total flavonoids from kale
(Brassica oleracea L. var. acephala L.) extracts by NKA-9 resin
and antioxidant activities of flavonoids extract in vitro. Food
Chem. 374, 131508. https://doi.org/10.1016/j.foodchem.2021.
131508
Drevelegka, I., Goula, A.M., 2020. Recovery of grape pomace
phenolic compounds through optimized extraction and ad­
sorption processes. Chem. Eng. Process. 149, 107845. https://
doi.org/10.1016/j.cep.2020.107845
396 Chemical Engineering Research and Design 183 (2022) 382–397
Drosou, C., Kyriakopoulou, K., Bimpilas, A., Tsimogiannis, D.,
Krokida, M., 2015. A comparative study on different extraction
techniques to recover red grape pomace polyphenols from
vinification byproducts. Ind. Crops Prod. 75, 141–149. https://
doi.org/10.1016/j.indcrop.2015.05.063
El‐Missiry, M.A., Fekri, A., Kesar, L.A., Othman, A.I., 2021.
Polyphenols are potential nutritional adjuvants for targeting
COVID‐19. Phytother. Res. 35, 2879–2889. https://doi.org/10.
1002/ptr.6992
Es-Safi, N.-E., Fulcrand, H., Cheynier, V., Moutounet, M., 1999.
Studies on the acetaldehyde-induced condensation of
(−)-epicatechin and malvidin 3-O-glucoside in a model solu­
tion system. J. Agric. Food Chem. 47, 2096–2102. https://doi.
org/10.1021/jf9806309
Food and Agriculture Orgaization of the United Nations, 2019.
Table And Dried Grapes, 2019, July 12. 〈http://www.fao.org/
faostat/en/#data/QC〉.
Garrido, T., Gizdavic-Nikolaidis, M., Leceta, I., Urdanpilleta, M.,
Guerrero, P., de la Caba, K., Kilmartin, P.A., 2019. Optimizing
the extraction process of natural antioxidants from char­
donnay grape marc using microwave-assisted extraction.
Waste Manag. 88, 110–117. https://doi.org/10.1016/j.wasman.
2019.03.031
Ghafoor, K., Choi, Y.H., Jeon, J.Y., Jo, I.H., 2009. Optimization of
ultrasound-assisted extraction of phenolic compounds, anti­
oxidants, and anthocyanins from grape (Vitis vinifera) seeds.
J. Agric. Food Chem. 57, 4988–4994. https://doi.org/10.1021/
jf9001439
Gómez-Salazar, J.A., Patlán-González, J., Sosa-Morales, M.E.,
Segovia-Hernandez, J.G., Sánchez-Ramírez, E., Ramírez-
Márquez, C., 2022. Multi-objective optimization of sustainable
red prickly pear (Opuntia streptacantha) peel drying and bio­
compounds extraction using a hybrid stochastic algorithm.
Food Bioprod. Process. 132, 155–166. https://doi.org/10.1016/j.
fbp.2022.01.003
Gupta, M., Dey, S., Marbaniang, D., Pal, P., Ray, S., Mazumder, B.,
2020. Grape seed extract: having a potential health benefits. J.
Food Sci. Technol. 57, 1205–1215. https://doi.org/10.1007/
s13197-019-04113-w
Hamid, H., Thakur, A., Thakur, N., 2021. Role of functional food
components in COVID-19 pandemic: a review. Ann.
Phytomed. Int. J. 10 (1), 240–250. https://doi.org/10.21276/ap.
covid19.2021.10.1.22
Hassani, A., Vafaei, F., Karaca, S., Khataee, A., 2014. Adsorption of
a cationic dye from aqueous solution using Turkish lignite:
kinetic, isotherm, thermodynamic studies and neural network
modeling. J. Ind. Eng. Chem. 20, 2615–2624. https://doi.org/10.
1016/j.jiec.2013.10.049
He, Z., Xia, W., 2008. Preparative separation and purification of
phenolic compounds from Canarium album L. by macro­
porous resins. J. Sci. Food Agric. 88, 493–498. https://doi.org/10.
1002/jsfa.3112
Jiménez-Moreno, N., Volpe, F., Moler, J.A., Esparza, I., Ancín-
Azpilicueta, C., 2019. Impact of extraction conditions on the
phenolic composition and antioxidant capacity of grape stem
extracts. Antioxidants 8, 597. https://doi.org/10.3390/
antiox8120597
Kammerer, D., Kljusuric, J.G., Carle, R., Schieber, A., 2005.
Recovery of anthocyanins from grape pomace extracts (Vitis
vinifera L. cv. Cabernet Mitos) using a polymeric adsorber
resin. Eur. Food Res. Technol. 220, 431–437. https://doi.org/10.
1007/s00217-004-1078-z
Kammerer, D.R., Carle, R., Stanley, R.A., Saleh, Z.S., 2010. Pilot-
scale resin adsorption as a means to recover and fractionate
apple polyphenols. J. Agric. Food Chem. 58, 6787–6796. https://
doi.org/10.1021/jf1000869
Karvela, E., Makris, D.P., Kalogeropoulos, N., Karathanos, V.T.,
Kefalas, P., 2009. Factorial design optimisation of grape (Vitis
vinifera) seed polyphenol extraction. Eur. Food Res. Technol.
229, 731–742. https://doi.org/10.1007/s00217-009-1105-1
Khodaei, B., Rahimi, M., Sobati, M.A., Shahhosseini, S., Jalali, M.R.,
2018. Effect of operating pressure on the performance of ul­
trasound-assisted oxidative desulfurization (UAOD) using a
horn type sonicator: experimental investigation and CFD si­
mulation. Chem. Eng. Process. 132, 75–88. https://doi.org/10.
1016/j.cep.2018.08.006
Li, H., Hou, G., Li, Y., Zhao, F., Cong, W., Wang, C., 2018.
Preparative separation of phloridzin from apple leaves using
macroporous resins followed by preparative high‐­
performance liquid chromatography. J. Sep. Sci. 41, 3918–3924.
https://doi.org/10.1002/jssc.201800634
Liu, X., Xiao, G., Chen, W., Xu, Y., Wu, J., 2004. Quantification and
purification of mulberry anthocyanins with macroporous re­
sins. J. Biomed. Biotechnol. 2004, 326. https://doi.org/10.1155/
S1110724304403052
Lončarić, A., Pablo Lamas, J., Guerra, E., Kopjar, M., Lores, M., 2018.
Thermal stability of catechin and epicatechin upon dis­
accharides addition. Int. J. Food Sci. Technol. 53, 1195–1202.
https://doi.org/10.1111/ijfs.13696
Lv, L., Tang, J., Ho, C.T., 2008. Selection and optimisation of
macroporous resin for separation of stilbene glycoside from
Polygonum multiflorum Thunb. J. Chem. Technol. Biotechnol.
83, 1422–1427. https://doi.org/10.1002/jctb.1964
Macedo, G.A., Santana, Á.L., Crawford, L.M., Wang, S.C., Dias, F.F.,
de Moura Bell, J.M., 2021. Integrated microwave-and enzyme-
assisted extraction of phenolic compounds from olive po­
mace. LWT 138, 110621. https://doi.org/10.1016/j.lwt.2020.
110621
Massart, D.L., Vandeginste, B.G., Buydens, L., De Jong, S., Lewi, P.
J., Smeyers-Verbeke, J., 1998. Handbook of chemometrics and
qualimetrics: Part A.
McCabe, W.L., Smith, J.C., Harriott, P., 1993. Unit Operations of
Chemical Engineering. McGraw-hill, New York.
Milinčić, D.D., Stanisavljević, N.S., Kostić, A.Ž., Bajić, S.S., Kojić,
M.O., Gašić, U.M., Barać, M.B., Stanojević, S.P., Tešić, Ž.L., Pešić,
M.B., 2021. Phenolic compounds and biopotential of grape
pomace extracts from Prokupac red grape variety. LWT 138,
110739. https://doi.org/10.1016/j.lwt.2020.110739
Ministry of Jahad in Agriculture, 2017. in statistics of horticultural
products, 2017 〈http://www.agriis.ir/doc/46762/〉.
Montgomery, D.C., 2017. Design and Analysis of Experiments.
John wiley & sons.
Muhlack, R.A., Potumarthi, R., Jeffery, D.W., 2018. Sustainable
wineries through waste valorisation: a review of grape marc
utilisation for value-added products. Waste Manag. 72,
99–118. https://doi.org/10.1016/j.wasman.2017.11.011
Nielsen, S.S., 2010. Determination of moisture content. In:
Nielsen, S.S. (Ed.), Food Analysis Laboratory Manual. Food
Science Texts Series. Springer, Boston, MA. https://doi.org/10.
1007/978-1-4419-1463-7_3
Rahimi, M., Shahhosseini, S., Movahedirad, S., 2017. Continuous-
flow ultrasound assisted oxidative desulfurization (UAOD)
process: an efficient diesel treatment by injection of the
aqueous phase. Ultrason. Sonochem. 39, 611–622. https://doi.
org/10.1016/j.ultsonch.2017.05.033
Seeram, N., Lee, R., Hardy, M., Heber, D., 2005. Rapid large scale
purification of ellagitannins from pomegranate husk, a by-
product of the commercial juice industry. Sep. Purif. Technol.
41, 49–55. https://doi.org/10.1016/j.seppur.2004.04.003
Spigno, G., Tramelli, L., De Faveri, D.M., 2007. Effects of extraction
time, temperature and solvent on concentration and anti­
oxidant activity of grape marc phenolics. J. Food Eng. 81,
200–208. https://doi.org/10.1016/j.jfoodeng.2006.10.021
Teixeira, A., Baenas, N., Dominguez-Perles, R., Barros, A., Rosa, E.,
Moreno, D.A., Garcia-Viguera, C., 2014. Natural bioactive
compounds from winery by-products as health promoters: a
review. Int. J. Mol. Sci. 15, 15638–15678. https://doi.org/10.3390/
ijms150915638
Trikas, E.D., Papi, R.M., Kyriakidis, D.A., Zachariadis, G.A., 2017.
Evaluation of ion exchange and sorbing materials for their
adsorption/desorption performane towards anthocyanins,
total phenolics, and sugars from a grape pomace extract.
Separations 4, 9. https://doi.org/10.3390/separations4010009
Wang, X., Su, J., Chu, X., Zhang, X., Kan, Q., Liu, R., Fu, X., 2021.
Adsorption and desorption characteristics of total flavonoids
from acanthopanax senticosus on macroporous adsorption
 Chemical Engineering Research and Design 183 (2022) 382–397 397

resins. Molecules 26, 4162. https://doi.org/10.3390/
molecules26144162
Xiong, Q., Zhang, Q., Zhang, D., Shi, Y., Jiang, C., Shi, X., 2014.
Preliminary separation and purification of resveratrol from
extract of peanut (Arachis hypogaea) sprouts by macroporous
adsorption resins. Food Chem. 145, 1–7. https://doi.org/10.
1016/j.foodchem.2013.07.140
Zagklis, D.P., Paraskeva, C.A., 2015. Purification of grape marc
phenolic compounds through solvent extraction, membrane
filtration and resin adsorption/desorption. Sep. Purif. Technol.
156, 328–335. https://doi.org/10.1016/j.seppur.2015.10.019
Zhang, J., Lee, T.G., 2021. Optimization of phenolics and flavo­
noids extraction from the fruit of Empetrum nigrum var. ja­
ponicum from Jeju Island in South Korea. J. Ind. Eng. Chem. 98,
350–357. https://doi.org/10.1016/j.jiec.2021.03.031