Sustainable Chemistry and Pharmacy 25 (2022) 100592

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Sustainable Chemistry and Pharmacy

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

Recovery of phenolic compounds from spent coffee grounds

through optimized extraction processes
Nikoletta Solomakou , Anastasia Loukri , Panagiota Tsafrakidou , Alexandra-
Maria Michaelidou , Ioannis Mourtzinos , Athanasia M. Goula *
Department of Food Science and Technology, School of Agriculture, Forestry and Natural Environment, Aristotle University, 541 24, Thessaloniki,
Greece

A R T I C L E I N F O A B S T R A C T

Keywords: The aim of the present study was to compare novel methods and technologies of phenolics
Cyclodextrin extraction from spent coffee grounds, as “green” alternative techniques of the conventional
Conventional extraction ethanol extraction. Three extraction techniques, ultrasound- and microwave-assisted extraction,
Microwaves along with the use of β-cyclodextrin as a solvent have been studied and optimized as the eco-
Phenolics friendly solutions for the efficient extraction of phenolic compounds from Spent Coffee
Spent coffee grounds
Grounds (SCG). The investigated factors were temperature (20–60 ◦ C), solvent concentration
Ultrasounds
(0–100% v/v water ethanol, EtOH), amplitude (20–60%), and liquid/solid ratio (5–60 mL/g) for
ultrasound-assisted extraction (UAE). In the case of microwave extraction (MAE), the effects of
solvent concentration (0–100% v/v), liquid/solid ratio (5–60 mL/g), and power (100–600 Watt)
were studied. Ethanol (0–100% v/v) and β-cyclodextrin (β-CD, 1–18.5 mg/mL) were also
compared as solvents, under the same range of liquid/solid ratio (5–60 mL/g) and temperatures
(20–60 ◦ C). In addition, the effect of the drying method (oven drying and freeze-drying), as well
as a defatting pretreatment of SCG, were studied under the optimum conditions of each extraction
method. The optimum extraction yield (31.79 ± 0.25 mg GAE/g SCG) was achieved using MAE
with a liquid/solid ratio of 60 mL/g, a power level 600 W, and a solvent concentration of 68% v/v
EtOH. While the maximum yield (34.43 mg GAE/g SCG) was also obtained by the same method
from the freeze-dried sample.

Nomenclature

Symbol Description Unit

A Amplitude Level of Ultrasounds %
Cβ-CD β-Cyclodextrin Concentration mg/mL
CCD Central Composite Designs n. a
CD Cyclodextrin n. a
EtOH Aqueous Ethanol %v/v
FTIR Fourier-transform infrared spectroscopy n. a
GAE Gallic Acid Equivalent mg

* Corresponding author.
E-mail address: athgou@agro.auth.gr (A.M. Goula).

https://doi.org/10.1016/j.scp.2021.100592
Received 26 October 2021; Received in revised form 8 December 2021; Accepted 28 December 2021
Available online 7 January 2022
2352-5541/© 2021 Elsevier B.V. All rights reserved.
N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

L/S Liquid to Solid ratio mL/g

MAE Microwave-Assisted Extraction n. a
P Microwave Power W
SCG Spent Coffee Grounds n. a
T Temperature ◦ C
UAE Ultrasound-Assisted Extraction n. a
Y Extraction Yield mg GAE/g dry SCG
β-CD β-Cyclodextrin mg
n a: not applicable

1. Introduction
According to the International Coffee Organization (ICO, 2021), the worldwide total consumption of coffee reached 9.98 × 106 kg
in 2020, corresponding to a compounded annual growth rate of 1.0% since 2017/2018. The ever-increasing consumption of coffee
could be attributed to its unique flavor and aroma as well as its linkage with various cultural and heritage customs in many countries.
Furthermore, this tendency may also be ascribed to its enhanced antioxidant compounds content and the stimulant effect on the central
nervous system (Kourmentza et al., 2018; Mostafa et al., 2021).
As life cycle analysis “from farm to cup” reveals, increased coffee consumption results in accordingly high amounts of wastes
(husks, spent coffee grounds, defective coffee beans, etc.) that undoubtedly lead to environmental pollution (Karmee 2018). It is worth
mentioning that from 1 kg of soluble coffee preparation, 2 kg of wet Spent Coffee Grounds (SCG) are obtained (Rajesh Banu et al.,
2020).
The European Union promotes “waste hierarchy” and principles of sustainable waste management through certain legislations and
directives (Directive, 2008/98/EC, 2008; Directive, 1999/31/EC, 1999). The preferable waste management methods in descending
order of priority are: (a) waste prevention, (b) re-use, (c) recycling, (d) recovery, and (f) disposal. This hierarchy aims mainly to the
reduction of CO2 emission. More specifically, the European Union, as well as other regulatory institutions globally, have underlined the
significance of biomass as a renewable source and various strategic plans such as the “Biomass Action Plan” and the “Multi-Year Plan”
have been developed. SCG falls in the description of biomass, as it is a lignocellulosic material originating from human activities (Tursi
2019). In this context, many researchers have recently focused on the valorization of SCG for the production of added-value com­
pounds, including fertilizers and chemicals (Karmee 2018; Rajesh Banu et al., 2020). SCG as a matrix is an important source of phenolic
compounds, e.g. chlorogenic acids, but also non-phenolic acids, such as caffeine and trigonelline (Abrahão et al., 2019). Phenolics,
although toxic for microorganisms, are considered valuable compounds, since they present various physiological activities, such as
antioxidant, antimicrobial, anti-mutagenic, anti-inflammatory, and anti-allergenic, and are currently used in the fields of biology,
medicine, food technology, and so on (Mussatto et al., 2011 a; Kovalcik et al., 2018). The extraction of these ingredients from SCG
could be accomplished by various methods that exhibit different efficiency levels. In this direction, diverse maximum recovery rates
have been obtained by the utilization of conventional solid-liquid methods using organic solvents (Mussatto et al., 2011 b) up to the
application of novel water-based autohydrolysis (Ballesteros et al., 2017). The drawbacks of the latter method are related to high
energy input and consequently high cost. Nevertheless, issues related to safety aspects (flammability, toxicity), and more importantly
to environmental burdens, are of concern in the case of conventional methods using organic solvents (Ruesgas-Ramón et al., 2017).
To tackle these challenges, green chemistry proposes the replacement of conventional solvents with eco-friendly, non-toxic, and
low-cost natural solvents like water solutions of cyclodextrins (CDs). CDs are cyclic oligosaccharides composed of α (1 → 4)-linked D-
glucopyranose subunits and characterized by a hydrophilic surface and a hydrophobic cavity. Their unique structure favorites the
creation of complexes with phenolics through non-covalent bonds. Kalantari et al. (2021) have suggested a novel highly efficient
technique capable to extract bioactive compounds with enhanced stability, using water solutions of CDs. Several studies examined the
formation of complexes between cyclodextrins and bitter compounds of coffee, such as chlorogenic acid and caffeine (Górnas et al.,
2009; Aree,2019). However, to our best knowledge, CDs have not been employed to extract phenolics from SCG.
Irrespective of the solvent type, new technologies, such as microwave-assisted extraction (MAE), ultrasound-assisted extraction
(UAE), accelerated solvent extraction, and supercritical fluid extraction have been recently reported as alternative approaches for the
recovery of phenolic compounds from various waste streams (Al-Dhabi et al., 2017). The effects of ultrasound are mainly associated
with the cavitation phenomenon that includes the collapse of bubbles formed in the liquid medium resulting in fast adiabatic
compression of gases and vapors inside the bubbles that helps solvent penetration and increases the transport between solid and liquid
phases. The technology of UAE has shown high extraction efficiency and low energy and solvent consumption and thereby its usage as
an alternative method has been on the rise. As far as MAE is concerned, microwaves can penetrate the medium and produce heat within
the cell to enable cell rupture, thus improving the dissolution of target compounds in the solvent. MAE is one of the most employed
alternative extraction methods, due to its low extraction duration and solvent consumption (Pettinato et al., 2019). As far as the re­
covery of SCG phenols is concerned, only a few studies have been carried out based on ultrasound- and microwave-assisted extraction
(Pavlović et al., 2013; Ranic et al., 2014; Al-Dhabi et al., 2017; Budaraju et al., 2017; Severini et al., 2017; Caballero-Galván et al.,
2018; Arauzo et al., 2020; Okur et al., 2021). However, the variety of process dimensions that present themselves being combined with
conventional process variables (temperature, time, solid/liquid ratio, etc.), should be further investigated to optimize the whole
process for future industrial implementation.

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The objective of this study was to investigate the effect of the solvent system and ultrasound and microwave technologies on the
extraction yield of phenolic compounds from SCG. The ultrasound- and microwave-assisted extractions, along with the extraction with
a system of a water solution of β-cyclodextrin (β-CD), were compared with the conventional extraction with ethanol. The parameters
affecting the efficiency of phenolic compounds recovery for each method were optimized. Finally, the effect of SCG drying method
(freeze-drying, hot air drying) and defatting on total phenolics extraction yield was studied under the optimum conditions of the novel
methods (MAE, UAE, CD).

2. Materials and methods

2.1. Raw material and chemicals
Samples of SCG, Coffea arabica species, were collected from a local coffee shop in Thessaloniki (Greece). The samples were mixed to
obtain a homogenous and representative raw material. SCG was dried at 45 ◦ C for 24 h to reach a moisture content of about 3% w/w, to
avoid microbial spoilage, and kept at room temperature in sealed glass containers until further use. To study the effect of the drying
method and defatting process, samples of SCG were freeze-dried (CoolSafe, Labogene, Denmark) and defatted as described in 2.2.
Folin–Ciocalteu phenol reagent and Na2CO3 (99.8%) were obtained from Chem-LAB (Zedelgem, Belgium). β-CD was purchased
from Gangwal Chemicals Private Limited (Mombai, India), BIOSYNTH Carbosynth. Gallic acid (99.8%) was provided by Alfa Aesar
(Karlsruhe, Germany). All the organic solvents used for extraction studies were of analytical grade and purchased from Sigma-Aldrich,
Chemie GmbH (Taufkirchen, Germany).

2.2. Physicochemical characterization

The moisture and ash content of the dried SCG sample were estimated gravimetrically (APHA/AWWA/WEF, 2012). Crude fat/oil
content of dried SCG (~5 g) was determined with a Soxhlet extractor using diethyl ether for 6 h at 70 ◦ C. The defatted solid residue
(defatted SCG) was stored for further use. The concentration of nitrogen compounds was determined by Kjehdal method and the
overall protein content was calculated using the conversion factor of 6.25. SCG’s total sugar concentration was determined based on
the NREL standard procedure (Sluiter et al., 2008) and was estimated as glucose equivalent (DuBois et al., 1956).
The Fourier transform infrared spectra (FTIR spectra) were obtained at room temperature in the spectral range of 4000–400 cm− 1
with a 4.0 cm− 1 resolution and 32 scans per sample on 6700 IR (Jasco, Essex, UK) spectrometer. The Spectral Manager software (Jasco,
Essex, UK) was used to operate the FTIR spectrometer and collect all the data. The particle size distribution of the dried SCG was
determined by a sieve shaker using a set of American Society for Testing and Materials (ASTM) standard sieves (DIN 10–45) (Retax,
Labor Siebmaschine, Type LS10, Nr 4082, Germany).
All experiments/measurements were carried out in triplicates and the data are presented as mean values ± standard deviation (SD).

2.3. Experimental designs and extraction methods

Central composite designs (CCD) were applied to determine the effects and the optimum levels of the examined parameters οn the
recovery of phenolic compounds from SCG. The levels of the tested independent variables of each extraction method are given in
Table 1.

2.3.1. Conventional solvent extraction

Conventional solvent extraction was applied. Specifically, a sample of SCG was mixed with 50 mL of solvent (EtOH) to produce
different solvent to SCG ratios under stirring conditions using a thermostatic magnetic stirrer. During the extraction process, two T-
type thermocouples were immersed into the extraction solution. The extraction temperature (T, oC), the liquid/solid ratio (L/S, mL/g),

Table 1
Experimental values and coded levels of the independent variables used for the central composite designs of each extraction method.

Extraction method Independent variable (Symbol) Unit Levels

Conventional ¡1.682 ¡1 0 1 1.682

o
Temperature (T) C 20 28 40 52 60
Liquid/solid ratio (L/S) mL/g 5 16 32,5 49 60
Solvent concentration (EtOH) % v/v ethanol 0 20 50 80 100
Ultrasound-assisted ¡2 ¡1 0 1 2
o
Temperature (T) C 20 30 40 50 60
Solvent concentration (EtOH) % v/v ethanol 0 25 50 75 100
Liquid/solid ratio (L/S) mL/g 5 19 32,5 47 60
Amplitude level (A) % 20 30 40 50 60
Microwave-assisted ¡1.682 ¡1 0 1 1.682
Power (P) W 100 201 350 499 600
Liquid/solid ratio (L/S) mL/g 5 16 32,5 49 60
Solvent concentration (EtOH) % v/v ethanol 0 20 50 80 100
β-cyclodextrin-assisted ¡1.682 ¡1 0 1 1.682
Solvent concentration (Cβ-CD) mg/mL 1 4.55 9.75 15 18.5
Liquid/solid ratio (L/S) mL/g 5 16 33 49 60
o
Temperature (T) C 20 28 40 52 60

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and the solvent concentration (EtOH, % v/v) varied between 20 and 60 ◦ C, 5 and 60 mL/g, and 0 and 100% v/v EtOH, respectively.

2.3.2. Extraction with β-cyclodextrin water solutions

The appropriate quantity of dried SCG was mixed with different concentrations of β-CD (Cβ-CD, 5–18.5 mg/mL), at various liquid/
solid ratios (L/S, 5–60 mL/g), and different temperatures (T, 20–60 ◦ C). SCG was subjected to extraction under stirring at 600 rpm for
1 h in a water bath.

2.3.3. Ultrasound-assisted extraction

As far as ultrasound-assisted extraction technique is concerned, it was performed with a 130 W, 20 kHz VCX-130 sonicator (Sonics
and Materials, Danbury, USA) equipped with a Ti–Al–V sonoprobe (13 mm). A sample of SCG was mixed with 330 mL solvent to
produce different liquid/solid ratios. The extraction temperature was kept constant by holding the sample container in a water bath
and periodically adding ice in the bath. No additional agitation was applied. All extracts were collected at 20 min, as a further increase
of extraction time did not improve extraction, according to preliminary experiments. The studied variables were extraction temper­
ature (T, 20–60 ◦ C), liquid/solid ratio (L/S, 5–60 mL/g), amplitude level (A, 20–60%), and solvent concentration (S, 0–100% water
ethanol).

2.3.4. Microwave-assisted extraction

Microwave-assisted extraction was carried out with a Multiwave microwave system (B30MC030A, AntonPaar, Graz, Austria) with
a rotor for 6 sample vessels, type H (operating pressure 75 bar). A sample of powdered SCG was mixed with 20 mL solvent to produce
different solvent/solid ratios. The extracts were collected at 5 min. Microwave power (P, 100–600 W), liquid/solid ratio (L/S, 5–60
mL/g), and solvent concentration (S, 0–100% water ethanol) were the studied variables.

2.4. Total phenolic content determination

Total phenols were determined using the spectrophotometric Folin-Ciocalteau method. The method was modified each time ac­
cording to the specific characteristics of each extraction procedure and extract. More specifically, for the extraction methods using
ethanol (conventional, ultrasound-assisted, microwave-assisted), the total phenolic content was measured according to the method
described by Kaderides et al. (2019). Briefly, 0.2 mL of extract was added to a 25 mL flask and additional distilled water was added to
make a final volume of 10 mL. Folin-Ciocalteu phenol reagent (0.5 mL) was added to the mixture and shaken vigorously. After about 5
min, 5 mL of 5% Na2CO3 solution was added with mixing. The solution was immediately diluted to 25 mL, mixed carefully, and then
allowed to stand for 90 min. For the β-cyclodextrin-assisted extraction, the procedure was modified as follows. In a 5 mL Eppendorf
tube, 2.37 mL of distilled water, 0.03 mL of sample appropriately diluted, and 0.150 mL of the reagent were added and mixed.
Consequently, 0.450 mL Na2CO3 (20%) was added and the mixture was vortexed. The samples were allowed to stand in the dark, at
room temperature for 120 min. The absorbance in all cases was measured at 750 nm. The total phenolic content was expressed as gallic
acid equivalents (GAE) mg/mL. Extraction yield, (Y) (mg GAE/g of dry SCG), was defined as the ratio of the total weight of gallic acid
equivalents extracted to the dry sample weight.

2.5. Statistical analysis

The effects of the process variables on extraction yield were analyzed using the software MINITAB. An analysis of variance was used
to identify the significant effects and interactions between factors. A p-value less than 0.05 was statistically significant.

3. Results and discussion

3.1. Physicochemical characterization
Table 2 presents the main physicochemical characteristics of SCG used in the present study. According to the literature, the
composition of SCG presents a wide variability due to the different characteristics of the coffee species, cultivating conditions, roasting,
and brewing processes (Hejna 2021). SCG is considered a lignocellulosic material with high hemicelluloses concentration (Ballesteros
et al., 2014). For the purposes of this study, the determination of the structural carbohydrates was not deemed necessary and thus, only
the total carbohydrates’ content was quantified, which was found 24.09 g/100 g. This result falls in the range of the published data
regarding carbohydrates content (cellulose plus hemicellulose content), which vary from 18 (Passadis et al., 2020) to more than 50%
w/w (Wang et al., 2016). Furthermore, SCG contains a notable amount of proteins and lipids (10–20% w/w) (Kourmentza et al., 2018).

Table 2
Physicochemical characteristics of SCG used in this study. Data are mean values (n = 3, ±SD).

Parameter Mean value (% w/w) (SD)

Moisture a 62.08 (0.33)

Total carbohydrates b 24.09 (1.51)
Total Kjeldahl nitrogen 1.94 (0.21)
Protein 12.13 (1.31)
Fat 13.74 (0.12)
Ash 1.40 (0.18)
a
In wet basis for the raw material.
b
In glucose equivalents.

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The determined values of these components were 12.13 and 13.74% w/w, respectively. It must be noted that the polarity of the oil
extraction solvent plays a crucial role in the derived oil content and consequently, the published data present differences (Passadis
et al., 2020).
The obtained FTIR spectrum for the SCG sample is shown in Fig. 1a, where the characteristic bands of the functional groups can be
identified. More specifically, the fingerprint region (1800- 500 cm-1) includes the bands of interest that are attributed to lignin,
chlorogenic acids, and caffeine, as well as hemicelluloses (Tsafrakidou et al., 2018). According to Ballesteros et al. (2014), bands
between 1,135 and 952 cm− 1 are characteristic for glycosidic bonds, due to the stretching vibration of C–O in C–O–H bonds and thus,
are linked with the presence of galactomannans. Regarding the sharp peaks at 2,922.59 and 2,853.17 cm-1, they have been related to
caffeine and lipids (Li et al., 2014), whereas bands in the range of 1,543 and 1,455 cm-1, are attributed to aromatic rings found in lignin
molecules. Likewise, bands near 1,742 cm− 1 are common in lignocellulosic material and may be associated with the existence of acetyl
and/or uronic acid groups of hemicelluloses or the ester linkages of ferulic and p-coumaric acids of lignin (Timung et al., 2015;
Tsafrakidou et al., 2018). It must be noted that the assignment of each band demands a rigorous approach and is beyond the scope of
the present work. However, the FTIR spectrum is used for qualitative and characterization purposes as previously reported (Silva et al.,
2011).
Fig. 1b presents the particle size distribution of the used SCG. These results indicate that more than 50% of the sample had an
average particle diameter of 240 μm, without any prior treatment for particle size reduction. In general, particle size is an important
parameter during extraction and smaller particle size shortened the extraction time to achieve the highest yield due to the fact that
smaller size means a shorter mass transfer distance and a larger surface area (Goula 2013).

Fig. 1. (a) FT-IR spectra and (b) particle size distribution of SCG used.

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3.2. Effect of different parameters on extraction yield

3.2.1. Conventional extraction with ethanol
Various extraction techniques including conventional maceration using ethanol and β-cyclodextrin or novel techniques, such as
UAE and MAE, have been investigated for the recovery of phenolic compounds from SCG. As far as conventional extraction with
ethanol is concerned, extraction yield ranged from 4.89 to 22.01 mg GAE/g dry SCG. These values are lower than those reported in the
literature for organic solvents such as ethanol (28.26 mg GAE/g SCG, ethanol 60%, 50 mL/g, 60 ◦ C, 30 min) (Panusa et al., 2013) or for
autohydrolysis (32.92 mg GAE/g SCG, 20 mL water/g, 120 ◦ C, 20 min) (Conde and Mussatto 2016). According to the literature,
extraction of phenolics from SCG can potentially reach higher efficiencies, for example, Gonçalves et al. (Gonçalves et al. 2019) re­
ported yields up to 49 mg GAE/g dry SCG. These differences in the obtained yield can be associated with the different protocol that was
followed, either during pretreatment before beverage production (e.g., roasting method) or during extraction, in which higher tem­
peratures were used (up to 80 ◦ C), while the procedure also took place under increased pressure (50 bar).
As far as solvent is concerned, this parameter greatly affects solubility and therefore, extraction efficiency. A common practice is to
use solvents with similar polarity to that of the solute, to enhance the extraction process. Most widely used solvents include organic
solvents, such as ethanol and methanol (Mussatto et al., 2011a; Acevedo et al., 2013; Panusa et al., 2013). Ethanol plays a major role in
the rupture of the hydrogen bonds and hydrophobic bonds existing between phenolics–proteins and phenolics–cellulose in the
water-ethanol system. According to Fig. 2, an increase in the percentage of ethanol in the solvent mixture results in an increase in
extraction yield up to a certain value, where a plateau is reached, and beyond this percentage value, no further increase in yield is
observed. Extraction with 100% ethanol resulted in a relatively low yield (9.8 mg GAE/g dry SCG), which is significantly lower than
the maximum reached yield. Water ethanol, that has been employed as a solvent in the present study, has also been used by many
researchers to study the extraction of phenolics from this by-product, suggesting yields ranging from 87.3 to 90.35% (Mussatto et al.,
2011; Seo and Park 2019; Zuorro and Lavecchia 2013). Drevelegka and Goula (2020) concluded that a mixture of ethanol and water is
more efficient in extracting phenolic compounds compared to a mono-component solvent. The researchers attributed this observation
to the fact that the addition of a small amount of water in organic solvents generates a more polar medium, which accelerates the
extraction of polyphenols. In the present work, the more appropriate ethanol concentration was found around 60%. Similarly, the
maximum extraction yields of phenolics from pomegranate peels, blueberry, and sunflower meal were reached using 50–60% water
ethanol (Taha et al., 2011; Kaderides et al., 2019).
Temperature is also a parameter that may significantly affect extraction yield. Increased extraction yields are observed with higher
temperatures (Fig. 2), however, in the present study extraction temperatures did not exceed 60 ◦ C, as extensively high temperatures
provoke the opposite effect attributable to the decomposition of thermolabile compounds. The observed temperature effect is based on
the effect of temperature on the vapor pressure, surface tension, and viscosity of the liquid medium, which facilitates mass transfer
(Ahmad-Qasem et al., 2013). Furthermore, increased temperatures may be linked with increased ease with which solvent diffuses into
cells and an enhancement of desorption and solubility (Esclapez et al., 2011).
The L/S ratio also plays an important role. Specifically, a higher L/S ratio is associated with a higher extraction yield. A higher L/S
ratio leads to a larger concentration gradient for the duration of the diffusion from solid into the solution and in intense swelling of the
material, thus increasing the contact area between the solvent and the material (Kaderides et al., 2019). This trend was also reported by
many authors (Zhang et al., 2008; Taha et al., 2011; Goula et al. 2016, 2017). Nonetheless, as it can be observed in Fig. 2, an increase
beyond a certain point does not positively affect extraction efficiency, whereas another disadvantage of high L/S ratios can be
translated to an excessive amount of solvent, which is time and energy consuming for its concentration and recovery.

Fig. 2. Effect of solvent concentration (EtOH, % v/v), temperature (T, ◦ C), and liquid/solid ratio (L/S, mL/g) on conventional extraction yield (Y, mg GAE/g dry SCG).

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3.2.2. Extraction with β-cyclodextrin water solutions

Regarding the extractions with the use of water solutions of β-CD as solvent, the obtained yields ranged between 5.66 and 12.69 mg
GAE/g dry SCG, which are lower compared to the maximum yield attained with ethanol, as previously described. Nevertheless, similar
results have been reported with the use of water methanol solutions (from 2.9 up to 16.2 mg GAE/g dry SCG), while when water was
the extraction solvent, phenolics from SCG reached considerably lower yields (from 6 up to 7.4 mg GAE/g dry SCG) (Mussatto et al.,
2011b).
The influence of the solvent’s concentration on the recovery of phenolics is depicted in Fig. 3. Apparently, the increase of β-CD’s
concentration up to 10 mg/mL favored the extraction. According to Cai et al. (2018), as the concentration of CDs increases, higher
amounts of phenolics from raw materials interact with them and are efficiently extracted. Hence, the increase of this solvent’s con­
centration induces the creation of complexes between the CD’s hydrophobic cavity and the semi-polar compounds. The positive effect
of β-CD’s concentration increase on phenolic compounds recovery from various waste streams has been previously reported (Parmar
et al., 2015; Rajha et al., 2015; Favre et al., 2018). Aree (2019) has also studied the formation of complexes among the main phenolics
from coffee by-products (chlorogenic and caffeic acid) and the non-polar central cavity of CDs. In the present study, an increase beyond
10 mg/mL did not seem to have a positive effect on the extraction yield. The observation that a further increase of the CDs concen­
tration after a certain value does not enhance the extraction agrees with the results reported by Alibante et al. (2021) who used β-CD as
a solvent for the extraction of red grape pomace antioxidant polyphenols. Similarly, López-Miranda et al. (2016) reported that the
increase of CD concentration from 8 to 13 mM did not have a significant effect on the extraction of phenolics from red grape pomace as

Fig. 3. Effect of solvent concentration (β-CD concentration, mg/mL), temperature (T, ◦ C), and liquid/solid ratio (L/S, mL/g) on β-CD-assisted extraction yield (Y, mg
GAE/g dry SCG).

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well. The continuous increase of CD could contribute to an increase of the solvent viscosity and contribute to the decrease of the
compounds’ solubility (Wang et al., 2019).
As stated before, the L/S ratio is an important parameter as it is strongly related to the obtained extraction yield and the operating
cost of the system. As it can be seen in Fig. 3a and b, the increase of the ratio from 5 to 60 mL/g had a positive effect on the recovery of
the target compounds. A high ratio can contribute to more diluted conditions and facilitate the encapsulation of phenolics from the CD
cavity (Alibante et al., 2021). The positive effect of this factor has been reported by others as well (Wang et al., 2019; Drevelegka and
Goula 2020; Loukri et al., 2020).
The effect of temperature followed the same trend as in the case of ethanol. As shown in Fig. 3, the increase of the temperature in
the range of 20–60 ◦ C enhanced the phenolics yield. More specifically, the rise of temperature over 40 ◦ C seems to favorite the
extraction in relation to the L/S increase. High temperatures enhance mass transfer by improving the penetration of the solvent into the
materials under treatment and the solubility of the extracted compounds. However, over 50 ◦ C, degradation reactions and destabi­
lization of cyclodextrin complexes may be induced (Del Valle 2004; Kaderides et al., 2015; Loukri et al., 2020; Bozinou et al., 2021).
Cui et al. (2017) and Bozinou et al. (2021) reported that in the range between 20 and 70 ◦ C, the maximum recovery of phenolics from
tea leaves and onion solid wastes. respectively, were also obtained around 60 ◦ C.

3.2.3. Ultrasound-assisted extraction

Extraction yield using UAE technique ranged from 2.85 to 18.54 mg GAE/g dry SCG. Al-Dhabi et al. (2017) used ethanol and
operating conditions similar to these of the present study (P = 100–300 W, T = 30–50 ◦ C, L/S = 5–30 mL/g) and achieved recovery
yields up to 33.84 mg GAE/g. Nonetheless, most studies, mainly using methanol as solvent, reported yields similar or even lower than
those reported in this study (Severini et al., 2017; Caballero-Galván et al., 2018; Arauzo et al., 2020; Okur et al., 2021). For example,
Okur et al. (2021), who investigated and compared the effects of different techniques on the extraction of phenolic compounds from
spent coffee grounds, achieved a yield of about 9.5 mg GAE/g using the ultrasounds method. Severini et al. (2017) reported higher
yield values (19.29–24.95 mg GAE/g). However, in that study the researchers used methanol and the treatment time was 60 min.
One of the most important parameters involved in UAE is considered to be the solvent type and more specifically its physico­
chemical characteristics, such as vapor pressure that affects swelling and therefore collapsing of cavitation bubbles (Syahir et al.,
2020). As it can be seen in Fig. 4, a mixture of ethanol and water was found more efficient than compared to mono-component solvent
systems. Extraction yield initially improved up to an ethanol concentration of about 60% and then decreased with a further increase in
ethanol concentration. According to Simić et al. (2016), an increase in ethanol concentration favors damages on the cell membranes of
the matrix, but after a specific value of ethanol concentration and modification of solvent polarity, the impurities extraction is faster,
and the diffusion is more difficult due to protein coagulation. Many studies have also shown that 50–60% ethanol is the best solvent for
the extraction of phenolic compounds using ultrasounds (Taha et al., 2011; Kaderides et al., 2019; Drevelegka and Goula 2020).
Higher L/S ratio led to a larger concentration gradient during the diffusion from solid into the solution and thus, to a higher

Fig. 4. Effect of temperature (T, ◦ C), solvent concentration (EtOH, % v/v), liquid/solid ratio (L/S, mL/g), and amplitude level (A, %) on ultrasound-assisted extraction
yield (Y, mg GAE/g dry SCG).

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concentration of phenolics in the extract (Fig. 4). This effect can be also associated with the fact that a high amount of SCG results in an
increase of viscosity and thus, prevents diffusion of phenolics. The intensity of cavitation falls with a rise in the viscosity of the medium
since the creation of cavitation needs the negative pressure in the rarefaction region of wave function to overcome the natural cohesive
forces (Maran and Priya, 2016). However, a plateau is observed, beyond which saturation of solvent takes place. Interestingly, results
indicate that the highest extraction yield was not observed with the highest L/S values investigated. This observation may be attributed
to the fact that if the solution is very dilute, an enhanced amount of solvent would not result in an adequate increase in the con­
centration gradient and the increase in extraction yield would be inadequate. A similar observation was reported by Kaderides et al.
(2015) and Goula et al. (2016), who mentioned that the optimum extraction yield of phenolic compounds from pomegranate peels and
grape pomace using the ultrasound technique was achieved at solvent/solids ratios of 33 and 18 mL/g, respectively.
Extraction temperature also plays an important role in extraction efficiency, with higher temperatures generally increasing yield,
although being highly dependent on the matrix under extraction. Specifically, this phenomenon can be explained through the increase
of compounds solubility and higher collapsing speeds of bubbles. In addition, according to Esclapez et al. (2011), the increase in yield
may be associated with the improved ease with which solvent diffuses into cells and the improvement of desorption at high tem­
peratures. Many researchers have proposed that the optimum temperatures that should be used in UAE range between 30 and 60 ◦ C,
with temperatures above this range possibly leading to decomposition of the desired bioactive compounds (Yang et al., 2017; Buddin
et al., 2018). Accordingly, a similar temperature range was investigated in the present work and the optimum temperature was about
60 ◦ C. However, many researchers reported an opposite effect at high-temperature levels and attributed this trend to the fact that at
high temperatures, the vapor pressure is higher and more bubbles are created, but they collapse with less intensity (Hromadkova et al.,
1999). In addition, the bubbles may so easily collapse at a higher temperature that reduces the result of the mass transfer improvement
(Zhang et al., 2008). However, this trend was not observed in the present work. This disagreement about the temperature effect in
phenolics extraction may be linked to the fact that the introduction of a given amount of ultrasound energy into the medium could
mask the temperature effect (Ahmad-Qasem et al., 2013).
The extraction yield improved with an increased amplitude level (Fig. 4). This effect may be associated with the enhanced cavi­
tation and mechanical ultrasounds effects that increase the contact surface area between solid and liquid and result in better dispersion
of the solvent into the SCG matrix. According to Okur et al. (2021), at high amplitude levels, a higher number of waves travel through
the liquid media, and a larger number of bubbles are created and collapse more violently causing enhanced cell disruption and release
of intracellular components. However, many researchers concluded that for high amplitude levels, the increase in amplitude causes a
decrease in yield, due to degradation of the plant material and an increase in bubbles number in solvent during cavitation reducing the
efficiency of the ultrasound energy (Zu et al., 2012; Maran and Priya 2016). With that being said, in the present study, higher ultrasonic
power levels were not investigated.

3.2.4. Microwave-assisted extraction

Another green method used for the recovery of phenolic components as an alternative for conventional extraction is MAE, which

Fig. 5. Effect of solvent concentration (EtOH, % v/v), power (P, W), and liquid/solid ratio (L/S, mL/g) on microwave-assisted extraction yield (Y, mg GAE/g dry SCG).

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N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

can promote the use of lower quantities of solvents and increase efficiency. Using this technique, the highest recovery yield (32.2 mg
GAE/g d.b.) among the other examined methods was observed, in the shortest time (5 min). MAE is based on the elevation of tem­
perature of the solute-solvent mixture through microwave radiation from the inner to the outer surface thus, promoting the diffusion of
compounds in the solvent. The main advantage of MAE is its very low required extraction time, in the case of the present study, the
extraction time was 5 min, with higher times not leading to higher extraction yields. In current literature, higher recovery yields have
been reported for MAE of phenolics from SCG, for example, Budaraju et al. (2017) and Pavlović et al. (2013) reported 57.49 and
398.95 mg GAE/g dry SCG respectively, although this difference can be attributed to variations in the production of coffee and
extraction conditions. Ranic et al. (2014), who used conditions similar to these of the present study, achieved yields ranging from
7.694 to 31.216 mg/g dry SCG.
Extraction yield initially increased up to an ethanol concentration of about 50–60% and then started to decrease with an additional
increase in the ethanol concentration (Fig. 5). Generally, the absorption of microwave energy increases with the dielectric constant of
the molecule, leading to power dispersed inside the solvent and solid matrix and then creating more effective molecular movement and
heating (Drevelegka and Goula, 2020). The loss tangent is a dielectric parameter that can be used as an indicator of the yield with
which electromagnetic radiation is transformed to heat and its value is 0.898 and 0.123 (2.45 GHz and 25–30 ◦ C) for ethanol and
water, respectively. Thus, water is a medium microwave absorber, while ethanol can be considered a strong absorber. In addition, an
increase in ethanol concentration in a binary ethanol-water mixture leads to the addition of the polarity molecular to near that in
phenolic compounds. Thus, the enhancement of phenolics solubility with the ethanol concentration may be based on the “polarity
versus polarity” principle. A similar trend was reported by Kaderides et al. (2019), who concluded that the best ethanol concentration
for microwave-assisted extraction of phenolics from pomegranate peels was about 50%, and Taha et al. (2011), who investigated the
effect of ethanol concentration on the extraction yield of phenolics from sunflower meal, reported that 60% ethanol was the most
appropriate.
As the L/S ratio increases from 10.0 to 55 mL/g, the extraction yield is increased. In general, a higher solvent to raw material ratio
leads to a larger concentration gradient and a higher extraction yield. Another possible effect is the excessive swelling of the plant
matrix improving the contact between material and solvent. However, with an additional increase in the L/S ratio, a decrease in yield
was noted. This trend may be associated with the fact that a large solvent volume may decrease the microwave adsorption of material,
as more energy is required to be absorbed by the solvent (Huang et al., 2017). A similar explanation was mentioned by Galan et al.
(2017), Huang et al. (2017), and Alara et al. (2018), who reported that a high L/S ratio may lead to inadequate energy in enabling the
cell wall rupture for efficient leaching out of phenolics.
As far as the microwave power is concerned, the extraction yield increased with increasing the power from 350 to 600 W, whereas
an opposite effect was observed when power increased from 100 to 350 W (Fig. 5). The first effect may be based on the fact that
increasing the power, more energy was transported on the molecules by dipole rotations and ionic conduction leading to rapidly
heating of the system (Gfrerer and Lankmayr 2005). Thus, the solubility and diffusion coefficients increase, the solvent viscosity
decreases, and the cell rupture is enhanced by rapid internal pressure rise inside the cells resulting in the destruction of sample surface
(Maran et al., 2013). This result is in accordance with previously published works (Brahim et al., 2014; Nagahata et al., 2018;
Kaderides et al., 2019). However, at power lower than 350 W, an increase in microwave power led to a decrease of extraction yield.
This trend may be associated with the fact that high irradiation power offers unnecessary energy to the system disturbing molecular

Fig. 6. Extraction yields (Y, mg GAE/g dry SCG) obtained depending on the applied method.

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N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

interactions.

3.3. Optimization of extraction

In overall, the extraction yields obtained depending on the applied method are presented in Fig. 6. The generated by the MINITAB
software desirability profile for optimum extraction yield indicates that the maximum desirability level of 1.0 (on a scale of 0–1) can be
obtained with the conditions presented in Table 3. Under these optimized conditions, the experimental values of extraction yields were
compared (Fig. 7).
As it can be seen, MAE gives an extraction yield (31.79 ± 0.25 mg GAE/g dry SCG) higher than that of UAE (18.52 ± 0.52 mg GAE/g
dry SCG), conventional extraction (22.02 ± 0.98 mg GAE/g dry SCG), and extraction with β-CD (14.82 ± 0.21 mg GAE/g dry SCG).
Extraction yields were statistically similar for UAE, conventional, and β-CD extraction, but lower (p < 0.05) compared to the MAE. The
key mechanism for improved extraction with MAE was the dipole rotation of the polar solvent in the microwave field, which was
highly associated with the solvent dielectric constant and dissipation factor. Similar conclusions were reported by Drevelegka and
Goula (2020), Kaderides et al. (2019), Cheng et al. (2015), and Ince et al. (2014), who studied the extraction of phenolic compounds
and polysaccharides from grape pomace, pomegranate peels, nettle, and the fruit of Schisandra chinensis Baill. Generally, the re­
searchers attributed the higher yields of the microwave method to the following actions/results: 1) heat and mass transfer take place in
the same direction from inside to outside, accelerating the solutes solubilization, 2) microwave irradiation leads to disruptions of
tissues and cell walls and thus, to a larger contact surface area between solvent and solid, 3) microwave irradiation raises temperature
thus decreasing solvent viscosity. In addition, according to Nayak et al. (2015), the enhancement of phenolics extraction by micro­
waves may be associated with a breakdown of bigger phenolic compounds into smaller ones with their intact properties of the initial
molecules.
Surprisingly, UAE was less effective than conventional extraction. A similar trend was also reported by other researchers. For
example, Özcan et al. (2020), who compared the extraction efficiency of UAE, MAE, and classical extraction in obtaining some
bioactive and allergen compounds, concluded that MAE was the most efficient technique followed by the conventional extraction.
Although ultrasounds can break cell walls with their cavitation power, releasing phenolic compounds, the extent of release is
dependent on the intensity and duration of application. In the present study, the UAE variables selected for treatment and extraction
time led to a lower recovery of phenolic compounds.

3.4. Effect of drying method and defatting process

Extraction yields from plant materials are affected by the drying procedure before extraction. Drying results in changes of chemical
compounds and physical characteristics of the material, such as the structure and solubility of solids in the solvent, and consequently
the amount of solids in the extract. For example, Chan et al. (2008) reported that all thermal drying methods lead to a decrease in the
extraction yield of phenolic compounds from leaves and tea of ginger. Rhim et al. (2009), who studied the effect of various drying
techniques on the extraction of antioxidants from herb, jiwhang, concluded that most drying methods had unfavorable effects on
antioxidant activity of the extracts. Mrkic et al. (2006) mentioned that the critical factor is the drying time and the shorter the drying
time the higher the antioxidant activity. A similar trend was also reported by Dewanto et al. (2002) and Katsube et al. (2009) for the
extraction of phenolic compounds from tomatoes and mulberry leaves, respectively. Dadi et al. (2018), who studied the effects of
different drying methods on total phenolic content of Moringa stenopetala leaves, found that the yield of freeze-dried samples was
significantly higher than those of shed and oven dried samples at temperatures of 60 and 70 ◦ C, respectively. This was associated with
oxidation and decomposition of bioactive compounds during drying. Similarly, Orphanides et al. (2013) found that various drying
treatments had a great effect on phenolic content of dried spearmint and sample prepared using freeze drying had the highest content
of phenolic compounds, whereas convection oven drying led to a notable decrease of phenolic content.
Fig. 8 depicts the effect of the drying method at the optimum conditions for each extraction method tested. In the case of the
conventional and the MAE extraction, the drying method seems to have a statistically significant effect on the recovery of phenolic
compounds. In both cases, the extraction from the freeze-dried samples was higher. This could be attributed to the preservation of the
bioactive compounds by freeze-drying, but also to the physical changes that take place in the raw material that enhance the
extractability of compounds from the matrix. The products of freeze-drying are of high quality due to the structural firmness on the
surface where sublimation occurs, eliminating the matrix disintegration and resulting to a porous, intact structure. On the contrary, no
differences have been spotted between the dried samples in the extraction yield when β-CD and UAE were used. The highest phenolic

Table 3
Optimum extraction conditions for each extraction method.

Method Conditions

Conventional Τ (οC) S (% ethanol) L/S (mL/g)

60 66 50

Ultrasound-assisted Τ (οC) S (%aq. EtOH) L/S (mL/g) A (%)

60 50 53 60
Microwave-assisted L/S (mL/g) S (% aq. EtOH) P (W)
60 68 600
β-cyclodextrin-assisted L/S (mL/g) Τ (οC) Cβ-CD (mg/mL)
60 60 10.1

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N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

Fig. 7. Comparison of the optimum yields (Y, mg GAE/g dry SCG) achieved by different methods for extraction of phenolic compounds from SCG.

Fig. 8. Effect of drying method on the extraction yield (Y, mg GAE/g dry SCG). Values are the means of three independent experiments. Means lacking a common
lowercase (a–f) are significantly different (p < 0.05).

compounds yield was obtained when MAE was used for SCG that has been dried with both drying methods. The preservation role of
freeze-drying compared to other treatments has been observed by others as well (Bravo et al., 2013; Jiménez et al., 2021). The lower
content of the phenolics in oven drying could be related to the phenolics oxidation due to their long-time exposure to oxygen and high
temperature (Papoutsis et al., 2017).
In addition to the effect of the drying method, the impact of SCG’s defatting on phenolics extraction was also studied. Defatting was
evaluated for all the extraction methods at their optimum conditions. Fig. 9 presents the comparison of phenolics extraction yield
between defatted and full-fatted SCG for all the extraction methods. The process of fat removal before the extraction of other com­
pounds is common for materials that contain a high oil content. The reduction of fat can prevent the rancidity and creation of oxidation
products. Therefore, bioactive compounds can be retained during storage (Bravo et al., 2013). As shown in Fig. 9, the defatting seemed
to enhance the recovery in all cases, with a statistical significance being prominent in the cases of MAE and conventional extraction. It
should be underlined that phenolic compounds are not extracted by diethyl ether during the defatting process. Vidal et al. (2022)

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N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

Fig. 9. Effect of the defatting process on the extraction yield (Y, mg GAE/g dry SCG). Values are the means of three independent experiments. Means lacking a
common lowercase (a–f) are significantly different (p < 0.05).

reported that during the extraction of green coffee oil, chlorogenic acid was not detected in the fat fraction. The main phenolic
compounds of coffee by-products seem to have low solubility in oil and thus, the removal of the latter facilitates the mixing of the
extraction solvent with the extractant compound (phenolics). However, there are opposite findings when different raw materials have
been used. In wine-making by-products, the defatting pretreatment reduced the recovery of the phenolic compounds (Spigno and De
Faveri 2007). Probably, non-polar phenolics were extracted during Soxhlet. Additionally, it is hypothesized that in the full fatted
samples, lipophilic compounds may interfere with the phenolic determination assays and contribute to an overestimation of the
phenolic content (Buitimea-Cantúa et al., 2013).

4. Conclusions and future perspectives

Increased concern over the safety of synthetic antioxidants has led to an increased interest in consideration of effective and
economical natural antioxidants. Spent coffee ground could be a good source of phenolic compounds that can be separated through
different extraction processes. In the frame of “green chemistry” principles, different extraction methods of phenolic compounds from
SCG were compared with the conventional extraction using ethanol as solvent.
The optimum extraction yield (31.79 ± 0.25 mg GAE/g SCG) was achieved using microwave-assisted extraction with a liquid/solid
ratio of 60 mL/g, a power level 600 W, and a solvent concentration of 68% v/v water ethanol. Among the investigated methods, the
lower yields were obtained with β-cyclodextrin, while the ultrasound-assisted extraction followed with no statistically significant
differences observed compared to the results from the conventional extraction. The effect of freeze-drying and defatting was statis­
tically significant in the conventional and the microwave-assisted extraction, while in the other cases no difference was observed.
The proposed optimized method meets the terms of green process definition, since decreases process time, permits use of alter­
native solvents and renewable natural products, and guarantee a safe and high quality extract/product. However, there is a major
limitation in this study that could be addressed in future research. Emerging methods need to be evaluated using advanced sustain­
ability assessment tools to reveal their potential environmental consequences (Aghbashlo et al., 2021). In general, decision support
tools considering environmental aspects, valorization efficiency, potential incomes of different valorization methods, market models,
consumer behavior, and regional and international legislations are recommended to have the best choice among different methods
(Khoshnevisan et al., 2020). Thus, the next step of this work is the use of sustainability measurement techniques, such as life cycle
assessment (LCA), thermodynamic-based measures (energy, emergy, exergy), and techno-economic analysis, to determine the entire
environmental cradle to grave consequences of the proposed process by measuring energy and materials consumed and wastes and
emissions discharged to the environment (Rosen, 2018).

Funding
This research has been co-financed by the European Regional Development Fund of the European Union and Greek national funds

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N. Solomakou et al. Sustainable Chemistry and Pharmacy 25 (2022) 100592

through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNO­
VATE (project code:T2EDK-02242)».

Ethics approval
Not applicable.

Consent to participate
Not applicable.

Consent to publish
Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

CRediT authorship contribution statement

Nikoletta Solomakou: Methodology, Validation, Writing – original draft. Anastasia Loukri: Methodology, Validation, Writing –
original draft. Panagiota Tsafrakidou: Methodology, Validation, Data curation, Formal analysis, Writing – original draft. Alexandra-
Maria Michaelidou: Funding acquisition, Resources, Writing – review & editing. Ioannis Mourtzinos: Methodology, Resources,
Writing – review & editing. Athanasia M. Goula: Conceptualization, Project administration, Resources, Methodology, Data curation,
Formal analysis, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to
influence the work reported in this paper.

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