Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx

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Journal of Applied Research on Medicinal and Aromatic

Plants
journal homepage: www.elsevier.com/locate/jarmap

Techno-economic evaluation and mathematical modeling of supercritical

CO2 extraction from Eugenia uniflora L. leaves
Nicholas I. Canabarroa,*, Priscilla C. Veggib, Renata Vardanegac, Marcio A. Mazuttid,
Maria do Carmo Ferreiraa
a
Drying Center for Pastes, Suspensions, and Seeds, Chemical Engineering Department, Federal University of São Carlos, P.O. Box 676, 13565-905, São Carlos, Brazil
b
Departamento de Engenharia Química, Universidade Federal de São Paulo, Brazil
c
LASEFI, Department of Food Engineering, School of Food Engineering, University of Campinas, Monteiro Lobato 80, 13083-862, Campinas, Brazil
d
Department of Chemical Engineering, Federal University of Santa Maria, Av. Roraima No. 1000, Santa Maria, 97105-900, Brazil

A R T I C LE I N FO A B S T R A C T

Keywords: Extracts from Eugenia uniflora L. (pitanga) leaves grown in the Brazilian tropical savanna were obtained by
Eugenia uniflora L. supercritical CO2. The influence of temperature (40, 60 and 80 °C) and pressure (15, 20 and 25 MPa) on the
Bioactive compounds extraction yield, overall extraction curves, kinetic parameters, chemical profiles, antioxidant activity, and total
Supercritical carbon dioxide phenol content were evaluated. Amongst the conditions investigated, the highest global extraction yield (7.9 wt
Sovová model
%) was found at 80 °C and 25 MPa, whereas the highest antioxidant activity (52.9 ± 0.9 %) and total phenol
Economic evaluation
content (63.6 ± 4 mg GAE/g of leaves) were obtained at 40 °C and 25 MPa. Selina-1,3,7(11)-trien-8-one, oleic
acid, phytol, and γ-sitosterol were the main compounds found in pitanga leaves extracts. The overall extraction
curves showed that in most conditions, 67–92% of the extracted mass was recovered before the end of the
constant rate extraction period. To estimate the cost of manufacturing (COM) of pitanga leaves extracts, the
extraction process was simulated using the SuperPro Designer 8.5®. For extraction at 40 °C/25 MPa, the COM
was US$ 654.90/kg, while for extraction at 80 °C/25 MPa, the COM was US$ 475.35/kg, both results for scale
production of 100 L.

1. Introduction
The most conventional separation methods utilized to obtain
bioactive compounds from herbs or other plants make use of organic
solvents (Reverchon, 1997). However, the economic and environmental
costs of such techniques have increased fastly (Casas et al., 2009; Hegel
et al., 2011). Besides the costs, conventional separation methods result
in losses of bioactive compounds due to the purification step, which
reduces the efficiency of the extraction process (Pereira and Meireles,
2010). The presence of terpenoids and phytosterols in the vegetal ma-
terial like the leaves makes the extracts attractive for many applications
(food ingredients, cosmetics, flavors, fragrances, and phytopharma-
ceuticals) (Melo et al., 2014). The supercritical carbon dioxide extrac-
tion (SFE-CO2) appears as an alternative extraction process to get
bioactive compounds from plants. Among numerous advantages, the
SFE-CO2 is non-toxic, non-flammable, inexpensive, odorless, readily
available and has low critical conditions (7.38 MPa, 31.1 °C) (Zhao and
Zhang, 2014).
Supercritical carbon dioxide extracts with bioactive compounds
have been obtained from several vegetal sources (Confortin et al., 2019,
2017a, b; Kueh et al., 2018; Lima et al., 2019). Amongst the many
known plant extracts, Eugenia uniflora leaves extracts are attractive for
their anti-inflammatory activity (Schapoval et al., 1994), hypotensive
effects (Consolini and Sarubbio, 2002), antimicrobial activity (Holetz
et al., 2002) and antifungal activity (Souza et al., 2003). Eugenia uni-
flora (Pitanga tree), belongs to the Myrtaceae family and is found pre-
ferentially in the South and Southeast Brazilian regions. The fruit itself
has great nutritional value due to the considerable concentrations of
vitamins and carotenoids and has also gained popularity due to its
exotic flavors. As already demonstrated (Oliveira et al., 2006; Santos
et al., 2015), the fruit and seeds’ extracts are rich in monoterpenes and
sesquiterpenes with great anti-oxidant activities. Similar antioxidant
compounds with diverse pharmacological effects have been identified
in the leaf’s extracts (Confortin et al., 2017b).
Some studies evaluated SFE-CO2 processes of pitanga leaves com-
bined with different solvents (ethanol and water) and have adopted a
two or three sequential steps methodology, aiming to maximize the
extraction yields. The addition of cosolvents such as ethanol or water

⁎
Corresponding author.
E-mail address: slongo@unicamp.br (N.I. Canabarro).

https://doi.org/10.1016/j.jarmap.2020.100261
Received 20 February 2020; Received in revised form 18 June 2020; Accepted 19 June 2020
2214-7861/ © 2020 Elsevier GmbH. All rights reserved.

Please cite this article as: Nicholas I. Canabarro, et al., Journal of Applied Research on Medicinal and Aromatic Plants,
https://doi.org/10.1016/j.jarmap.2020.100261
N.I. Canabarro, et al. Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx

Nomenclature ṁF Solvent mass flow rate (g.min−1)

YS Solubility of extract in the solvent (g extract.g solvent−1)
SFE Supercritical Fluid Extraction (-) mS Mass of raw material on an extract-free basis (g)
OEC Overall Extraction Curve (-) xk Yield of solute inside the unbroken cells (g extract.g raw
CCD Central Composite Desing (-) material−1)
CER Constant Extraction Rate (-) R Easily accessible extract fraction (1-Xk/X0) (-)
FER Falling Extraction Rate (-) kfa Mass transfer coefficient for the fluid phase (min−1)
tCER End of CER period (min) ksa Mass transfer coefficient for the solid phase (min−1)
tFER End of FER period (min) mext(t) Extract mass as a function of extraction time (g)
S/F Solvent-feed mass ratio (g solvent.g raw material−1) m calc
ext Mass of pitanga leaves extract calculated by the model (g)
ρB Density of the bed (g.cm−3) m exp
ext Experimental value of pitanga leaves mass (g)
ρS Density of pitanga leaves (g.cm−3) COM Cost of manufacturing
ρf Density of the fluid (g.cm−3) DMC Direct manufacturing costs
Ε Porosity of the bed (-) FMC Fixed manufacturing costs
X0 Global yield of extract (g extract.g raw material−1) GE General expenses
m0 Initial mass of pitanga leaves (g) NPV Net present value
m sox Total extract mass obtained by Soxhlet method (g) ROI Return of investment

into the SFE-CO2 process modifies the solvent characteristics, im-
proving the CO2 affinity to polar compounds (Garmus et al., 2014;
Martinez-Correa et al., 2011). Nonetheless, it implies the use of a
greater solvent amount in the process and the increase of the extraction
costs when compared with the one-step SFE-CO2 process. As far as the
costs are concerned, it should be observed that factors such as tem-
perature and pressure might influence the extraction behavior in the
SFE-CO2 process. The overall extraction curve (OEC) is a useful tool to
evaluate the cost of manufacture and the influential parameters in SFE-
CO2 processes, as the extraction kinetics and global yields depend sig-
nificantly on the solvent interaction with the solid matrix (Meireles,
2007). The analysis of kinetic curves through mathematical models
such as spline and Sovová models (Meireles, 2007; Sovova, 1994) may
be useful for the engineering design of SFE processes.
After performing the optimization of extraction conditions to get the
intended product, the SFE-CO2 process should be optimized in terms of
extraction costs. It has a relationship with the processing time that re-
sults in high efficiency and low manufacturing cost of extract
(Albuquerque and Meireles, 2012). The economic viability of SFE-CO2
from pitanga leaf extracts is not readily available in the literature yet,
and this kind of analysis is of utmost importance when aiming the ap-
plication of supercritical technology at the industrial level (Aguiar
et al., 2018; Del Valle et al., 2003). Therefore, the SFE-CO2 of pitanga
leaves extracts can be evaluated according to the cost manufacturing
(COM) and annual operating costs for different scale-up process by si-
mulation using a commercial software such as Aspen® (Aspentech) or
Super Pro® (Intelligen Inc., Scotch Plains, NJ, USA) (Pereira et al., 2015;
Zabot et al., 2015).
The purposes of this study are (i) to evaluate SFE-CO2 extraction
kinetics of extracts from Eugenia uniflora leaves under different pres-
sures (15, 20 and 25 MPa) and temperatures (40, 60, and 80 °C) and to
appraise the influence of extraction parameters (pressure and tem-
perature) on the global extraction yields, recovery, and extracts com-
position; (ii) to fit the OECs to Sovová’s model; (iii) to evaluate the
economic viability of SFE-CO2 to obtain pitanga leaves extracts under
the conditions considered.
2. Materials and methods
2.1. Raw material
exposition of the leaves to the hot air flow are expected to reduce the
losses of bioactive compounds (Goula et al., 2016). Leaves were dried at
60 °C under air velocity of 1.0 m/s with residence time of 60 min, the
study of drying effects on preservation of pitanga leaves supercritical
extracts were previously published by our research group. After, the
leaves were triturated in a knife mill (A-10, Tekmar, Germany) and
their particle size distribution was obtained from a sieve analysis. The
measured mean particle diameter was dp = 204 μm. Leaf powders were
protected from light in tightly sealed vials and stored at -4 °C until
reuse. The leaves powder density, moisture content and bulk density of
static bed were equal to 1.51 ± 0.05 g/cm3, 1.25 ± 0.3 g water/g dry
solid and 0.39 ± 0.01 g/cm3, respectively. The methodology employed
to measure these parameters can be found elsewhere (Canabarro et al.,
2019b). The bed porosity was estimated by Eq. (1) and was equal to
0.74 ± 0.4.
ρB
ε=1−
ρS (1)
2.2. Soxhlet extraction
Soxhlet extraction (n-hexane) was done as already described else-
where (Canabarro et al., 2019b) and the value was used as a standard to
compare the global extraction yields achieved using the SFE-CO2 and to
estimate the extract recovery. The extraction assay was carried out with
100 mL of n-hexane and about 300 min.
2.3. SFE-CO2 procedure
The assays were performed in an extraction unit which is described
in detail elsewhere (Canabarro et al., 2019). Briefly, the extraction unit
consists of a solvent reservoir, two thermostatic baths, a syringe pump
(ISCO 500D), a 100 cm3 jacketed extraction vessel, an absolute pressure
transducer with accuracy of 0.12 bar (Smar, LD301) equipped with a
portable programmer (Smar, HT 201), a collector vessel with a glass
tube, and a cold trap. In each assay, 10 g of ground leaves were sub-
mitted to different extraction conditions (Pressure: 15 MPa, 20 MPa,
25 MPa and Temperature: 40 °C, 60 °C, 80 °C) that were performed at a
solvent flow rate of 4 mL/min for 150 min. The extraction yield and
recovery were obtained as follow:

Eugenia uniflora leaves were randomly selected and collected be- m e (g)
Yield (%) = × 100
tween April and June 2018, from adult plants located in the Federal m 0 (g) (2)
University of São Carlos (São Carlos, Brazil). The leaves were collected
always in the morning (8:30 to 10:00 a.m.) and then dehydrated in a m e (g)
Recovery (%) = × 100
pilot-scale conveyor belt dryer. Short residence time and limited m sox (g) (3)

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N.I. Canabarro, et al. Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx

where the total extract mass (0.1152 g extract/ g leaves) in Eq. (3) was Table 2
obtained from the Soxhlet extraction. Curves of extraction yield as a Experimental data adopted for simulating the SFE−CO2 of pi-
function of time and solvent-feed ratio (S/F, g solvent/g leaves) were tanga leaves.
obtained. Parameter Value

Temperature (°C) 40
2.4. Extracts characterization
Pressure (bar) 250
S/F 25
The extracts characterization was performed about their chemical Extraction time (min) 60
profile, antioxidant activity (AA), and total phenol content (TPC). The Static period (min) 30
methodologies used to characterize the extracts have already been used Porosity 0.74
Extraction yield (%) 4.7
by our research group in other works and can be found in detail else- TPC content (mg GAE/g extract) 63.6
where. (Canabarro et al., 2019b). Antioxidant activity (%) 52.9

2.5. Supercritical extraction modeling

The overall extraction curves were fitted to Sovová’s model
(Table 1), and more details of the model are described elsewhere
(Sovova, 1994). To determine the Sovová’s model parameters (kfa, ksa,
and r) the non-linear regression analysis was performed by minimizing
the objective function (F), given by:
N
calc exp 2
F= ∑ (mext , i − mext , i )
i=1
2.6. Statistical analysis
A 2² experimental design (Central composite design - CCD) with a
triplicate in the central point was performed to investigate the im-
portance of pressure and temperature on the SFE-CO2. The analysis of
variance (ANOVA) was applied to the experimental data at a sig-
nificance level of 5% using software Statistica 7.0 (Statsoft Inc., USA).
2.7. Economic evaluation
To perform the economic evaluation of the production of pitanga
leaves extracts obtained by SFE-CO2 the cost tools of SuperPro Designer
8.5® software (Intellingen Inc., Scotch Plains, USA) were used. For the
process simulation, it was assumed that the performance obtained at
the laboratory scale was also obtained at the industrial scale (Veggi
et al., 2014) by maintaining the same operation conditions (S/F ratio,
pressure, temperature, time, density and porosity). Table 2 shows the
experimental data input to estimate the SFE-CO2 indices.
The cost of manufacturing (COM) is influenced by a series of costs,
which can be related in the following equation:
COM=DMC+FMC+GE
where COM is the cost of manufacturing; DMC is the direct manu-
facturing costs that is composed by operating expenses dependent on
the production rate including raw materials, supplies, utilities, opera-
tors and other operating costs; FMC is the cost not dependent on the
production rate including depreciation of equipment, taxes and in-
surance. Finally, GE is the general expenses that represents the over-
heads costs to run the business such as sale expenses, management,
finance costs and research and development.
Table 2 presents the data used as input for the model. Pitanga leaves
cost includes pre-processing costs, such as the acquisition, transport the
preparation. The costs related to the utilities include electricity that is
consumed in extraction and the energy wasted by the heat exchangers
(4) and distiller. The cost of CO2 assumed the fluid consumption and the
losses, which were estimated by the amount of CO2 emission during
depressurization of the extractor and by the CO2 that remains in the
extract after the separation step (Carvalho et al., 2015). The cost of
waste treatment in SFE-CO2 is disregarded since the solid residue pro-
duced in the extraction process is free of solvent and can be reused to
produce other products (Vardanega et al., 2015) or in further applica-
tions, such as biomass conversion to produce energy (Prado et al.,
2014) or as a nutritional source for agricultural purposes (Odlare et al.,
2011).
SFE-CO2 was designed to run for 7920 h per year, corresponding to
330 days per year with uninterrupted day shifts of 24 h. The project
lifetime considered was 15 years, with annual depreciation rate of 10 %
and the equipment maintenance rate of 6% (Peters and Timmerhaus,
2003). According to Vardanega et al. (2017a) and Zabot et al. (2015),
when processing raw materials that are not considered commodities
and are cultivated in small amounts for obtaining bioactive compounds,
it is proposed to use extractors with capacity between 10 and 100 L. The
number of employees necessary to operate a production plant might
vary with the plant size. Literature recommend about 1–3 operators for
the extractor capacity from 5 L to 500 L (Veggi et al., 2014) (Table 3).
The selling prices of pitanga leaves extracts were set based on the
products available in the market. It was evaluated the selling price ef-
fect on the process profitability ranging costs from US$ 500.00/kg to US
(5)
$ 4000.00/kg. These values were used to determine the return on in-
vestment (ROI), the profit margin and the net present value (NPV)
(Vardanega et al., 2017).

Table 1
Equations of Sovová's model.

First stage: t≤ t CER : m ext(t) = ṁF ∙YS∙ (1 − exp(−Z)) (5)

(6)
Second stage: t CER < t ≤ tFER : m ext(t) = ṁF ∙YS∙ ⎧t−t CER ∙exp
⎨
⎩
( ) ∙ln ⎛⎝ ∙ ⎛⎝exp (
Z∙YS
W∙X 0
1
1 −r
W∙m˙F
ms
∙ (t CER−t) )−r⎞⎠ ⎞⎠−Z⎫⎬⎭
(7)
∙ln ⎡1 + ⎛exp ( ) − 1⎞⎠ ∙exp ( ) ∙ (t
YS W∙X 0 W∙m˙F
Third stage: t>tFER : m ext(t) = ms ∙ ⎧X 0 − CER−t) ∙r
⎤⎫
⎨
⎩
W ⎢
⎣ ⎝ YS ms ⎥⎬
⎦ ⎭
kfa ∙ ms ∙ ρF (8)
Z=
mF ∙ ρS˙ ∙ (1−ε)

W
k ∙m
= sa ˙ S (9)
mF ∙ (1 − ε )
xk (10)
r=1−
X0
m0 (11)
Xo =
F

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Table 3 Table 5
Economic input data considered for the economic evaluation. Estimated effects of the process conditions on the extraction yield.
Industrial Unit Price Effect Standard tcal p-value −95 % +95 %
error Cnf. Limt Cnf limt
a
2×5L US$ 95000.00
2 × 50 Lb US$ 530000.00 Mean/Intercept 6.00 0.30 19.86 0.0 5.04 6.96
2 × 100 Lc US$ 856000.00 Temperature (L) −0.33 0.80 −0.41 0.70 −2.87 2.21
Pressure (L) 1.92 0.80 2.41 0.09 −0.61 4.47
Raw materials Temperature x 3.90 0.80 4.88 0.01 1.36 6.45
Pressure
d L: linear effect.
Pitanga leafs US$ 7.90/kg
CO2e US$ 3.00/kg

Utilities
increase of solid volatility exceeded the decrease in the solvent density,
Watere US$ 4.00/t thus enhancing the solubility and leading to higher global extraction
Steame US$ 12.00/t yields. In the SFE-CO2 of fatty acids from frozen-dried cells of Mor-
Steam (High P)f US$ 20.00/t tierella isabellina a similar behavior was found (Sallet et al., 2017). The
Chilled watere US$ 1.00/t
authors also obtained a higher extraction yield at 25 MPa and 80 °C.
Cooling watere US$ 1.00/t
CaCl2f US$ 0.23/t Similar to the present study, other authors found a strong depen-
Electricityb US$ 0.17/kWh dence of the extraction yield, AA and TPC on the pressure and tem-
Operational labor (wage)b US$ 11.20/h perature (Abaide et al., 2017; Dos Santos et al., 2016; Sallet et al., 2017;
a
Carvalho et al., 2015. Soares et al., 2016a,2016b). As shown in Table 4, the TPC in the pitanga
b
Aguiar et al., 2018. leaves extracts ranged from 23.7 ± 5 mg GAE/g to 63.6 ± 4 mg GAE/
c
Cavalcanti et al., 2016. g and AA ranged from 25 ± 1 % to 52.9 ± 0.9 %. At a constant
d
Space green, 2019. temperature, the TPC and AA increased as the pressure rose and, at
e
Zabot et al., 2018. constant pressure, they decreased with an increase in the temperature.
f
SuperPro Designer 8.5® database. The highest TPC and AA were achieved under 40 °C and 25 MPa
(63.6 ± 4 mg GAE/g and 52.9 ± 0.9 %, respectively) and the lower
3. Results and discussion values were observed at 80 °C and 15 MPa (23.7 ± 5 mg GAE/g and
25 ± 1 %, respectively). The remarkable drop in the TPC and AA ob-
3.1. Extraction yields served from the first to the second condition is attributed to the de-
crease in the solvent density, which is significantly reduced as the
Table 4 presents the values of the global extraction yield, total ex- temperature rises (see Table 4). This result corroborates that combining
tract recovery, AA and TPC values obtained under different pressures high pressure and low temperature in SCE favors the increase of TPC
and temperatures. The results show that both pressure and temperature and AA content (Dos Santos et al., 2016; Pilavtepe and Yesil-Celiktas,
influence the global extraction yield and the extraction recovery 2013). It is well known that the chemical composition of extracts may
(Table 4). The highest yield and recovery (7.9 wt% and 72.1 %, re- vary widely depending on the plant chemotype, geographic origin,
spectively) were found at 80 °C and 25 MPa and were about 3 times post-processing and extraction techniques or conditions (Peixoto et al.,
higher than the lowest ones (2.5 wt% and 21.5 %), observed at 80 °C 2010). The chemical profiles of extracts will be discussed in the next
and 15 MPa. The increase in the pressure is positive to the extraction section.
yield, a result which agrees with the result obtained elsewhere (Peixoto
et al., 2010). However, at 40 °C, the result was reversed and the yield at
15 MPa was approximately 1.4 times higher than the value found at 3.2. Extracts characterization
25 MPa. In the near-critical region, the solubility is enhanced as the
pressure increases (at a constant temperature) due to a sharp decrease Table 6 shows the chemical compounds of pitanga leaves extracts
in the fluid phase solute fugacity coefficient (Pereda et al., 2007). Two analyzed by GC–MS. The most relevant constituents found in the pi-
competitive effects could describe the influence of temperature on the tanga leaves extracts are the alpha-tocopherol, palmitic acid, phytol, γ-
solid solubility: the increase of solid volatility and the decrease of sol- sitosterol, and friedelin.
vent density with temperature rise. In the present study, the effects of Generally, the tocopherols are phenolic compounds with strong
temperature and pressure on the global extraction yields were analyzed antioxidant activity and many studies involving the SFE-CO2 of this
through the CCD. The results are presented in Table 5 and show that in compound are reported in the literature (Imsanguan et al., 2008;
the conditions evaluated, neither the pressure nor the temperature Kraujalis and Venskutonis, 2013; Sovová et al., 2010; Vági et al., 2007).
alone significantly affected the extraction yield at a 95 % confidence In particular, α-tocopherol can lower the risk of cancer formation and
level. However, the interaction between pressure and temperature was prevent Alzheimer’s disease (Xu et al., 2001). The amount of α-toco-
significant and affected the extraction yield positively at this confidence pherol in the extracts ranged from 6.6 %–14.3%. The highest content
level (p-value = 0.016). It is possible that at 80 °C and 25 MPa, the was obtained under 40 °C/25 MPa and the lowest at 80 °C and the same
pressure. Phytol is a diterpene constituent of chlorophyll and appears in

Table 4
Global extraction yields, recovery, antioxidant activity (AA) and total phenolic contents (TPC) in the extracts from pitanga leaves obtained from SFE-CO2.
Temperature/Pressure (°C/bar) CO2 densitya (kg/m3) Yield (wt%) Recovery (%) AA (%) TPC (mg GAE/g)

40/150 792.33 6.7 44.4 35 ± 2 44.4 ± 6

40/250 892.86 4.7 41.1 52.9 ± 0.9 63.6 ± 4
80/150 432.19 2.8 21.5 25 ± 1 23.7 ± 5
80/250 691.82 7.9 72.1 49 ± 1 37.8 ± 5
60/200 732.43 6.3 ± 0.1 47.0 ± 0.5 47.0 ± 0.6 43.9 ± 17

a
Obtained from National Institute of Standards and Technology (NIST).

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N.I. Canabarro, et al. Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx

Table 6 until 175 min. In this period, the change in the accumulated mass and
Concentrations of main compounds identified in the pitanga leaf extracts ob- global extraction yield, although noticeable, is practically negligible.
tained from SFE-CO2. The maximum extraction yield at this condition was reduced to 4.7 %
Compound KI Composition (Area, %) and S/F = 60 g CO2/g leaves.
The results in Section 3.1 have shown that a combination of a high
Assay/Extraction conditions temperature and a high pressure (80 °C and 25 MPa) is adequate to
produce extracts with higher global extraction yield and recovery. Be-
1 40 °C 2 40 °C 3 80 °C 4 80 °C 5 60 °C
15 MPa 25 MPa 15 MPa 25 MPa 20 MPa sides, at 80 °C and 25 MPa the highest extraction rate in the CER period
was obtained. According to the literature, increasing the extraction
Selina-1,3,7(11)- 1850 21.99 19.38 21.22 26.43 21.28 rates in the CER period helps reduce the extraction costs, as in this
trien-8-one
period the solutes are easily solubilized in the solvent (Pereira and
Phytol 2065 19.52 16.66 18.50 22.36 18.13
Oleic Acid 2090 16.66 23.05 19.2 26.40 19.63 Meireles, 2010). Otherwise, if the interest is to obtain extracts with high
Phytol Acetate 2211 3.11 3.04 3.8 4.71 4.08 AA or TPC, the best operating condition was 40 °C and 25 MPa. The
Vitamin E 3036 3.81 4.03 3.46 4.27 3.69 values of AA and TPC in Table 4 are those obtained after 175 min of
γ-sitosterol 3408 14.24 13.34 13.06 6.66 14.18 extraction; however, it is clear from Fig. 1, that the contribution of the
n-Hexatriacontane 3600 7.87 9.0 7.96 2.39 7.16
diffusive period to the process (from approximately 50 up to 175 min)
Vitamine C 3654 2.78 2.34 1.85 0.55 1.81
Friedelin 3840 3.34 2.98 2.47 0.60 2.36 was quite negligible. In this case, the extraction could be stopped after
60 min with no significant losses in the AA and TPC content, which
would reduce S/F to approximately 25 g CO2/g leaves, a slightly lower
various plants’ essential oils. Owing to its remarkable aroma, it is an value than that found at 80 °C and 25 MPa. This is an acceptable value,
ingredient widely used in cosmetics, shampoos, soap, detergents and as the target in industrial processes is to operate with solvent-feed ratios
household cleaners (Islam et al., 2015; Mcginty et al., 2010). The under 30 g CO2/g leaves (Martínez and Vance, 2007). For these reasons,
concentrations found in the pitanga leaves extracts ranged from 16.66 the experimental data for extraction conditions at 40 °C/25 MPa and
to 22.36 %, the highest content was observed at 80 °C and 25 MPa. γ- 80 °C/25 MPa was fitted to Sovová’s model (See Fig. 2). The extraction
sitosterol is a compound considered for developing into a potential performed at 80 °C and 25 MPa shows good agreements between the
antidiabetic drug (Balamurugan et al., 2012). Its isomer, β-sitosterol, simulated and experimental. At 40 °C and 25 MPa, the extraction rate
has been identified in compounds such as Eichhornia crassipes biomass was slightly overestimated by the model in both the CER and FER
(Martins et al., 2016), grape seed oil and sunflower oil (Shunyan Mo periods. Table 7 shows Sovová’s model fitted kinetic parameters. The
et al., 2013). Friedelin is a triterpene, which has already been isolated mass transfer coefficients, kfa, and ksa, were obtained from Eqns. (5), (6)
from leaves of Ageratum coyzoides and Aucuba japonica (Antonisamy and (7). The values of kfa were 369.1 × 10−3 min−1 and
et al., 2011). It has anti-inflammatory, analgesic, and antipyretic 346.3 × 10−3 min−1 for 40 °C/25 MPa and 80 °C/25 MPa, respectively.
properties(Sunil et al., 2013). In this study, the friedelin concentrations The ksa values were 47.8 × 10−3 and 38.7 × 10−3 min−1 for the con-
ranged from 0.60 (80 °C and 25 MPa) to 3.34 % (40 °C and 15 MPa). ditions at 40 °C/25 MPa and 80 °C/25 MPa, respectively, and as can be
To the best of the authors’ knowledge, the presence of compounds seen, the ksa values were one order of magnitude lower than kfa. Since
such as palmitic acid, stigmasterol, α-tocopherol, phytol, and friedelin the particles are small and because cells can be disrupted by mechanical
in supercritical extracts of pitanga leaves has not been reported in milling, the resistance to mass transfer in the solid phase was expected
previous studies (Garmus et al., 2014; Martinez-Correa et al., 2011). to be lower than the resistance to mass transfer in the fluid phase. In
The differences in the extract’s compositions discussed earlier might Sovová’s model, the parameter r is the fraction of broken cells, which is
explain the significant differences in the TPC and AA content among the affected by pretreatments such as drying, milling, and sieving (Casas
different studies. et al., 2005; Santos et al., 2014). The values in the present study were
0.43 (at 40 °C and 25 MPa) and 0.66 (80 °C and 25 MPa) and at constant
3.3. Extraction kinetic curves fitting pressure, they rose with the increase in the extraction temperature. This
wide variation range is worth noting considering that the substrates
Fig. 1 shows the overall extraction curves (OECs) of pitanga leaves used in the different extractions were exposed to identical pretreatment
extracts obtained under different extraction conditions and expressed in
terms of cumulative extract mass as a function of time and the S/F. The
curves also show the extraction yield, defined by Eq. (2). As discussed
earlier in Section 2.6, a typical OEC curve exhibits the CER and FER
periods, followed by the final diffusion-controlled period.
As can be seen in Fig. 1, the maximum yield found at 80 °C and
25 MPa is about 25 % higher than that obtained at 40 °C and 15 MPa,
which was the second-best condition. The extraction rate was much
faster in the first condition. For instance, at 80 °C and 25 MPa, the ex-
traction yield obtained after 45 min (approximately 7.0 %) is compar-
able to the value obtained after 180 min at 40 °C and 15 MPa. For the
most conditions, the CER and FER periods were the predominant per-
iods, and this is possibly explained because using a finely milled powder
in the solid matrix helps the extraction in the first and second stages.
Under 40 °C and 15 MPa, the FER period is extended in comparison to
the other conditions. After 175 min, it can be inferred that the solid
matrix is not completely exhausted yet, as a small increase in the ac-
cumulated mass is observed in the short diffusive-controlled period.
The final extraction yield after 175 min of extraction is approximately
0.6 g extract/g leaves and the S/F is equal to 68 g CO2/g leaves. At 40 °C
and 25 MPa, the FER period is much shorter in comparison to 15 MPa,
and a diffusion-controlled period is observed from approximately 50 Fig. 1. Kinetic curves of supercritical CO2 extraction of pitanga leaves.

5
N.I. Canabarro, et al. Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx

Fig. 3. Extraction and cost of manufacturing (COM) of pitanga leaves extract

obtained by supercritical CO2 extraction at 40 °C and 25 MPa as a function of
processing time.

Fig. 4. Costs of manufacturing (COM) and productivity of the pitanga leaves

extract obtained by supercritical CO2 extraction at 40 °C and 25 MPa for dif-
ferent production scales.
Fig. 2. Experimental data and Sovová’s model fitted curves: (a) 40 °C and
25 MPa; (b) 80 °C and 25 MPa. Table 8
Project indices of SFE-CO2 of pitanga leaves (2 × 100 L scale).
Table 7 Selling price (US Gross margin ROI (%) Payback time NPV
SFE-CO2 extraction of pitanga leaf extracts: fitted parameters in Sovová’s $/kg) (%) (years)
model.
Extraction condition: 40 °C/25 MPa
Condition 40 °C/25 MPa 80 °C/25 MPa 500.00 −29.12 −21.38 N/A −14,061,000
1000.00 35.44 51.17 1.95 15,159,000
tCER (min) 15.1 29.8 2000.00 67.72 172.68 0.58 64,269,000
tFER (min) 41.0 60.9 3000.00 78.48 294.20 0.34 113,194,000
kfa*103 (min−1) 369.1 346.3 4000.00 83.86 415.71 0.24 162,120,000
ksa*103 (min−1) 47.5 38.7 Extraction condition: 80 °C/25 MPa
r (−) 0.43 0.66 500.00 5.97 11.37 8.80 −920,000
YS*103 (g extract/g CO2) 20.3 20.7 1000.00 52.99 57.80 1.73 16,881,000
xK*103 (g extract/g leaves) 27.6 39.1 2000.00 76.49 150.66 0.66 52,249,000
S/FCER (g CO2/g rawmaterial) 7.9 10.5 3000.00 84.33 243.53 0.41 87,528.000
R² (-) 0.96 0.99 4000.00 88.25 336.39 0.30 122,808,000

operations. The solute vapor pressure increases as the temperature
extraction rises and might contribute to increasing the fraction of
ruptured cells.
The values of kfa found in this study are slightly higher than those
found for the extraction of fatty acids from black poplar seeds by SFE-
CO2 at 40 °C/25 MPa (73.2 × 10−3 min−1) and 80 °C/25 MPa
(208.1 × 10−3 min-1) (Soares et al., 2016a). For the ksa values, we
found values in the same order of magnitude of those reported by our
group in supercritical CO2 extraction of bioactive compounds from
olive leaves at 80 °C/25 MPa (Canabarro et al., 2019). The high values
of these parameters suggest that the resistances associated with the
mass transport in the fluid and solid phases are small. The ratio ksa/kfa
can be considered a measure of the contribution of diffusional me-
chanisms to the extraction process. This ratio varied from approxi-
mately 1.5 (for extractions at 60 °C and 20 MPa and 80 °C and 15 MPa)
up to 21 (at 80 °C and 25 MPa), corroborating the significant influence
of the extraction conditions on the mechanisms of solutes transport.

6
N.I. Canabarro, et al.
3.4. Economic evaluation
To evaluate the effect of the extraction time on the COM for pro-
duction of supercritical extracts from pitanga leaves, the process was
simulated at a 5-L scale using the experimental data obtained for the
OEC performed at 40 °C and 25 MPa, the condition that produced the
extracts with the highest AA and TPC (Fig. 3). At the beginning of the
process, the COM decreases to a certain time and, thereafter, it in-
creases continuously. The lower COM is observed close to the end of the
CER period (30 min), corroborating the typical behavior observed for
SFE-CO2 of bioactive compounds (Carvalho et al., 2015; Osorio-Tobón
et al., 2016). Supposedly, the higher is the extraction rate, the shorter is
the time required to reach the minimum COM (Carvalho et al., 2015).
In this case, the lowest COM was US$ 817.50/kg of extract, which was
observed after 20 min of extraction (S/F = 7.9) with an extraction yield
of 3.31 %, representing approximately 70 % of the total extractable
compounds obtained at this process condition.
To compare the effect of the production scale on the COM of SFE-
CO2 of pitanga leaves, an extraction time of 60 min was considered,
because most of the extractable compounds were recovered at this time.
The COM was estimated for units containing 2 × 5, 50, and 100 L ex-
tractors, ranging from US$ 1153.30/kg extract to US$ 654.90/kg ex-
tract (Fig. 4). As expected, the COM decreases by increasing the pro-
duction scale, as reported in the extraction of cupuaçu butter
(Cavalcanti et al., 2016) and extraction of genipin from genipap fruit
(Náthia-Neves et al., 2019).
The 10-fold increase from 5 to 50 L reduced the COM by 38 % while
the increase from 50 L to 100 L reduced the COM by 9%. Although
productivity increases proportionally with scale production, the COM
does not decrease at the same proportion. This behavior is attributed
mainly to the high contribution of the raw materials acquisition cost to
the COM, especially for 50 and 100 L scales, where this cost represents
73 and 80 % of the COM, respectively. For the 5 L scale, the labor and
facility costs correspond to the highest fraction of COM (54 %) and are
gradually reduced by increasing the scale production, as reported by
Rodrigues et al. (2019) for the artemisinin extraction by SFE-CO2. This
observed tendency for the labor cost is because the industrial SFE-CO2
units are generally automated and do not require a large number of
operators (Rodrigues et al., 2019; Viganó et al., 2017), while the impact
of facility cost is mainly mitigated by the productivity increase.
Establishing a commercialization price for the vegetable extracts
obtained by SFE-CO2 is always a challenge due to the characteristics of
these products. However, a sensitivity study can be performed using
different selling prices to verify how the process profitability is affected
by the price (Aguiar et al., 2018; Rodrigues et al., 2019). The project
indices of the SFE-CO2 were calculated at a scale of 100 L and are
presented in Table 8 for selling prices ranging from US$ 500.00/kg to
US$ 4000.00/kg. The gross margin measures the percentage of annual
revenues that is gross profit. The return on investment (ROI) measures
the amount of return of an investment relative to the cost of the in-
vestment. An ROI from 10 to 15 % is adopted as the minimum to accept
or discard a project. The payback time is the time required to recover the
cost of investment and, obviously, the shorter the payback time is, the
more attractive is the project. The net present value (NPV) represents the
total value of future net cash flowing during the lifetime of the project,
i.e. the surplus for the investor to regain the initial investment.
As shown in Table 8, all project indices were negative for the SFE-
CO2 of pitanga leaves at 40 °C and 25 MPa considering a selling price of
US$ 500.00/kg because the COM (US$ 654.90/kg) exceeded the as-
sumed selling price for the extract. As the COM is a ratio between the
annual operating cost and the annual production, i.e. the extract pro-
ductivity, it is drastically affected by the extraction yield of the process
(Vardanega et al., 2017b). Although the extraction at 40 °C and 25 MPa
produced the extract with the highest AA and TPC, the extraction yield
at this condition was only 4.7 %, which possibly explains this negative
result. To verify the impact of the extraction yield on the viability
7
Journal of Applied Research on Medicinal and Aromatic Plants xxx (xxxx) xxxx
indices of the SFE-CO2 of pitanga leaves, a simulation of extraction
under the condition that yields to the highest extraction yield (7.9 %, at
80 °C and 25 MPa) (Table 8), was performed. It can be seen that at this
condition, the COM (US$ 475.35/kg) is lower than the selling price of
US$ 500.00/kg, consequently, the project indices have a positive per-
formance (except the NPV) confirming the importance of the extraction
efficiency for the viability of the process.
By increasing the extracts’ selling price to values higher than US$
1000.00/kg, the project presents good profitability for both extraction
conditions, suggesting that a minimum profitable value around US$
1000/kg of extract would make SFE-CO2 process economically com-
petitive with the current technologies used to obtain pitanga leaves
extracts. Nonetheless, to obtain more accurate results, further studies
should be conducted considering the characteristics of the raw material,
product demand, target market, specific product quality requirements,
packaging and distribution costs, taxes, among others (Aguiar et al.,
2018).
4. Conclusions
This study presents data on SFE-CO2 of pitanga leaves obtained
under different temperatures (40, 60, and 80 °C) and pressures (150,
200 and 25 MPa). The OECs showed that in most conditions, 67–92 %
of the extracted mass was recovered before the end of the constant rate
extraction period. The combination of high pressure and temperature
(80 °C and 25 MPa) led to the highest global extraction yield (7.9 wt %)
among the tested conditions. At 40 °C and 25 MPa the extraction yield
was lower (4.7 wt%), but the highest values of AA and TPC were found.
The results indicate that in both conditions the extractions could be
performed at a S/F lower than 30 g CO2/g leaves. Sovová’s model was
effective in describing the OECs. The parameters in this model corro-
borate the predominance of convective mass transfer mechanisms in all
the extractions, but particularly at 80 °C and 25 MPa, where higher
values of kfa, and r were obtained. The kinetic behavior of extraction
curves was significantly affected by the extraction conditions and
proper choice of pressure and temperature contribute to producing
extracts with high extraction yields and high antioxidant activity. The
economic evaluation demonstrated that the cost of manufacturing
(COM) of supercritical extracts of pitanga leaves can be dramatically
reduced by increasing the production scale and a minimum selling price
around US$ 1000.00/kg is suggested to make the process economically
viable.
Declaration of Competing Interest
The authors confirm that there is no conflict of interest with regard
to this paper.
Acknowledgments
The authors would like to thank the National Council for
Technological and Scientific Development (CNPq) for the financial
support and the Coordination for the Improvement of Higher Education
Personnel (CAPES).
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