Powder Technology 440 (2024) 119782

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Powder Technology
journal homepage: www.journals.elsevier.com/powder-technology

Porous pectin particle formation utilizing spray drying with a

three-fluid nozzle
Tue Tri Nguyen a, Tomoyuki Hirano a, Ridha Nurul Chamida a, Eka Lutfi Septiani a,
Nhan Trung Nguyen b, c, d, Takashi Ogi a, *
a
Chemical Engineering Program, Department of Advanced Science and Engineering, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1
Kagamiyama, Higashihiroshima, Hiroshima 739-8527, Japan
b
Faculty of Chemistry, University of Science, Ho Chi Minh City 70000, Viet Nam
c
Vietnam National University, Ho Chi Minh City 70000, Viet Nam
d
Research Lab for Drug Discovery and Development, University of Science, Ho Chi Minh City 70000, Viet Nam

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Created novel three-fluid nozzle spray

drying technique for porous pectin
particles.
• Overcame the challenges posed by high-
viscosity solutions of pectin and CaCO3.
• Achieved production rates up to 30
times higher than two-fluid nozzle spray
drying.
• Improved CaCO3 nanoparticle distribu­
tion, enhancing overall porosity.

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

Keywords: The development of advanced porous particles with a high surface area and interconnected porosity is pivotal in
Nanosctructured particle material science for various applications. Pectin, a biocompatible and biodegradable polysaccharide, has shown
Porous particle promise for the synthesis of porous particles, especially in the biomedical and food industries. The high viscosity
Pectin
of pectin and CaCO3 nanoparticle (NP) solutions has been a significant challenge for producing these particles.
Spray drying
Three-fluid nozzle
This study introduces a novel spray drying technique with a three-fluid nozzle, designed to handle high-viscosity
Powder process solutions and to increase production rates by 30-fold over the conventional two-fluid nozzle. Using the proposed
technique, notable improvements are achieved in particle surface areas and pore volumes by controlling the
distribution of CaCO3 NPs within the pectin particles, especially at a CaCO3 NPs to pectin ratio of 15. This
resulted in porous pectin particles with sizes of 3.4 to 6.2 μm, surface areas of up to 261 m2/g, and enhanced

Abbreviations: PBS, Phosphate-buffered saline; PFIB, Plasma focused ion beam; SEM, Scanning electron microscope; TOCN, TEMPO-oxidized cellulose nanofiber.
* Corresponding author.
E-mail address: ogit@hiroshima-u.ac.jp (T. Ogi).

https://doi.org/10.1016/j.powtec.2024.119782
Received 5 March 2024; Received in revised form 16 April 2024; Accepted 16 April 2024
Available online 18 April 2024
0032-5910/© 2024 Elsevier B.V. All rights reserved.
T.T. Nguyen et al.
lysozyme adsorption capacities are obtained by varying types of precursor solutions. Thus, this approach facil­
itates the synthesis of multifunctional composites and porous particles.
1. Introduction
Porous particles are at the forefront of advanced material science,
garnering widespread interest for their diverse applications in fields
such as medical therapeutics [1–3] and environmental engineering
[4,5]. These particles are distinguished by their unique structure, which
features a high surface area and interconnected pores, making them
highly functional for various applications [6–9]. Synthesizing these
particles with precise control over their porosity, size, and functionality
is a sophisticated endeavor that drives extensive research and innova­
tion in this domain.
In this landscape, pectin, a natural polysaccharide found in plant cell
walls, has emerged as a promising material for the synthesis of porous
particles due to its biocompatibility and biodegradability, making it
particularly suitable for use in the biomedical and food industries
[10,11]. Our group has previously succeeded in preparing porous pectin
particles with a macroporous structure through template-assisted spray
drying using CaCO3 nanoparticles (NPs) as the template [12–14]. This
one-step aerosol method is rapid, continuous, reproducible, and suitable
for laboratory and industrial settings [15–19], showing significant
promise for large-scale material development. However, producing
porous pectin particles is challenging, particularly due to the high vis­
cosity of precursor solutions containing concentrated pectin and CaCO3
NPs owing to the egg-box model formation [20,21], which hampers the
production rate of former particle fabrication techniques.
To overcome these viscosity-related challenges, an innovative
approach is required. The use of a three-fluid nozzle (3FN) in the
advanced spray drying technology offers a viable solution. The 3FN
Fig. 1. Illustration of the different precursor solutions for the tunable composite pectin-CaCO3 NPs with two-fluid nozzle (2FN) and three-fluid nozzle (3FN).
2
Powder Technology 440 (2024) 119782
features a unique three-layered concentric structure with seperate inner
and outer liquid passages and an outermost gas passage [22–24]. This
intricate design allows for the independent spraying of two different
solvents, ensuring that incompatible materials or active ingredients with
distinct solvent requirements can be encapsulated without encountering
compatibility issues. The inner and outer liquid passages are individu­
ally connected to the center and peripheral nozzles, allowing precise
control over the atomization process [25–27]. This 3FN system enhances
control over the spray drying process, which is crucial when handling
high-viscosity solutions such as pectin. For instance, Pabari et al. pro­
duced multifunctional layered microparticles using a 3FN spray drying
process [28], and Liu et al. utilized the 3FN for effective drug encap­
sulation [22]. They demonstrated that this system could finely adjust air
flow and solvent properties, resulting in particles with uniform size
distribution, controllable pores, and optimal porosity, suitable for tar­
geted drug delivery applications.
Our research builds upon this foundation and employs the template-
assisted spray drying with a 3FN for the synthesis of porous pectin
particles. We focus on overcoming the viscosity challenges associated
with precursor solutions containing pectin and CaCO3 NPs to enhance
the production rate of porous particles compared with the two-fluid
nozzle (2FN) system. Additionally, we explore the formation of porous
pectin particles using various types of precursor solutions with the 3FN
(Fig. 1), and investigate the correlation between the properties of
different types of porous pectin particles and their lysozyme adsorption
capacity. Furthermore, this study aims to contribute to the burgeoning
field of porous particle synthesis, and explore the potential of pectin in
various industrial applications, from pharmaceuticals to food
T.T. Nguyen et al.
technology, by leveraging its inherent benefits and addressing its pro­
cessing complexities.
2. Experimental section
2.1. Materials
total mass of spray − dried powder collected
Spray drying yield (wt/wt%) =
total mass of pectin and CaCO3 NPs in the feed solution
Pectin was sourced from Herbstreith & Fox GmbH & Co. KG Pek­
tin–Fabriken (Neuenbürg, Germany). CaCO3 NPs, provided by Shiraishi
Calcium (Osaka, Japan), were a 30.0 wt% suspension in water with an
average diameter of 80 nm, as determined from scanning electron mi­
croscope (SEM) images of over 300 particles (Fig. S1). Citric acid and
phosphate-buffered saline (PBS) with a pH 7.2 were obtained from
FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Lysozyme,
used as the model protein, was procured from MP Biomedicals (Osaka,
Japan). All chemicals and solvents were used as received, without
further purification.
2.2. Preparation of porous pectin particles
2.2.1. Spray drying process with 2FN
The spray drying process was conducted following previously re­
ported methods [12,13]. Initially, a precursor solution containing raw
pectin and CaCO3 NPs, serving as the template, was prepared in
deionized (DI) water as the dispersion medium. Table S1 lists the
various concentrations of pectin and pectin:CaCO3 NP mass ratios tested
in this study. To disperse the components uniformly, an ultrasonic de­
vice (T 10 basic ULTRA-TURRAX S004) was used to homogenize the
aqueous precursor at a rotation speed of 30,000 rpm for 10 min. Spray
drying was performed using a BÜCHI B-290 mini spray-dryer equipped
with an external 2FN, which had a liquid orifice diameter of 0.7 mm and
a gas orifice diameter of 1.5 mm. The feed rate for the precursor solu­
tions was set at 3.8 mL/min, with an inlet air temperature of 150 ◦ C. The
spray gas flow rate and aspiration rate were adjusted to 10.0 and 583.3
L/min, respectively.
2.2.2. Spray drying process with 3FN
Initially, DI water was utilized as the dispersion medium to prepare
the precursor solution containing raw pectin. This solution was stirred
with a magnetic stirrer for 15 min to ensure thorough dispersion of
pectin in DI water. Subsequently, CaCO3 NPs were incorporated into the
pectin solutions to form the final precursor solution. The aqueous pre­
cursor was then homogenized using an ultrasonic device (T 10 basic
ULTRA-TURRAX S004) for 10 min at a rotation speed of 30,000 rpm to
ensure uniform dispersion of the components. Table S2 details the
components of the inner and outer solutions for spray drying with the
3FN. The B-290 mini spray-dryer, equipped with a 3FN, featured a gas
orifice diameter of 2.8 mm, and liquid orifice diameters of 0.7 mm and
2.0 mm for the inner and outer solutions, respectively. The outer and
inner solutions were concurrently fed into the 3FN as the outer and inner
fluids, respectively. The feed rates for the outer solution were set at 3.8,
9.6, or 15.4 mL/min, while the inner solution was maintained at 3.8 mL/
min. The inlet air temperature was kept constant at 150 ◦ C. The spray
gas flow rate and aspiration rate were adjusted to 12.0 and 583.3 L/min,
respectively.
The yield from spray drying is expressed as a weight/weight per­
centage (wt/wt %), calculated by dividing the total mass of the spray-
dried powder collected by the total mass of pectin and CaCO3 NPs
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Powder Technology 440 (2024) 119782
introduced into the feed solution, as shown in Eq. (1). The production
rate, expressed in grams per minute (g/min), is determined by dividing
the total mass of the spray-dried powder by the duration of the spray
drying process, as shown in Eq. (2).
(1)
total mass of spray − dried powder collected
Production rate (g/min) =
time of spray drying process
(2)
2.2.3. CaCO3 NPs removal process
The dried composite pectin–CaCO3 NP composites were then
immersed in an acidic solution and subsequently washed with ethanol to
create porous structures. The composites were placed in a 10.0 wt%
citric acid aqueous solution and stirred for 15 min to dissolve the CaCO3
NP template. Subsequently, suspensions of composites in citric acid
solution were centrifuged at 8000 rpm for 5 min and the settled particles
were washed twice with ethanol. After washing, the particles were dried
in an oven at 80 ◦ C for 1 h to yield the porous pectin particles.
2.3. Characterizations
The morphology of the prepared pectin porous particles was exam­
ined using field emission scanning electron microscopy (FE-SEM) with
an S-5200 instrument (Hitachi High-Tech. Corp., Tokyo, Japan). Sam­
ples for the observation were prepared by dispersing particles in ethanol,
followed by depositing them dropwise them onto an aluminum plate.
The samples were then dried at 60 ◦ C to evaporate the ethanol. Subse­
quently, they were coated with a thin platinum layer to enhance con­
ductivity. The cross-sectional SEM images were obtained using an Xe+
plasma focused ion beam (PFIB) system by employing a FEI Helios PFIB
Dual Beam FIB-SEM facility. The specific surface areas of the samples
were estimated from their nitrogen adsorption–desorption isotherms
obtained at 77 K using a Belsorp Max instrument (BEL Japan, Osaka,
Japan). Prior to these measurements, samples were preheated at 110 ◦ C
for 2 h. Their specific surface areas were calculated using the Bru­
nauer–Emmett–Teller (BET) method, while pore volume and pore size
distribution were determined using the Barrett–Joyner–Halenda (BJH)
and Horvath–Kawazoe (HK) methods. The zeta potential of the porous
pectin particles was measured using a Zetasizer Nano ZSP (Malvern
Instruments Inc., UK). For this, samples were diluted to a concentration
of 1 mg/mL in DI water and ultrasonicated for 30 min to ensure uniform
dispersion before measurements. Zeta potential measurements were
conducted at 25 ◦ C in a disposable U-shaped capillary cell DTS 1071
(Malvern Instruments Inc., UK). Rheological analyses of solutions con­
taining pectin or pectin mixed with CaCO3 NPs were meticulously
conducted using a concentric cylinder Brookfield rheometer (DV-III+)
(Brookfield Engineering Laboratories, MA, USA), facilitated by a small
sample adapter and two distinct spindles SC4–18 (17.48 mm of diameter
and 31.72 mm length), and SC4–34 (9.39 mm of diameter and 24.23 mm
length) for varied shear rate assessments. A Brookfield TC-501 ther­
mostatic bath meticulously maintained the sample temperature at 23 ◦ C.
Prior to each experimental run, the filled sample cup (10.0 mL) and
spindle underwent a temperature equilibration. The experimental pro­
tocol spanned 25 min, covering a comprehensive shear rate spectrum
tailored to each spindle from 0.056 to 70.0 s− 1 for spindle SC4–34, and
T.T. Nguyen et al. Powder Technology 440 (2024) 119782

Fig. 2. Graphs illustrating the correlation between pectin concentration, CaCO3 NP to pectin mass ratio, and (a) yield, and (b) production rate. Conditions suitable
for 2FN and 3FN use are indicated in blue and red, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the web
version of this article.)

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T.T. Nguyen et al. Powder Technology 440 (2024) 119782

from 0.264 to 330.0 s− 1 for spindle SC4–18, providing a thorough
investigation into the rheological behavior of the solutions.
2.4. Evaluation of the equilibrium liquid adsorption performance of
lysozyme
To assess the adsorption capacity of the prepared porous pectin
particles, lysozyme, with an isoelectric point (pI) of 10.5 and dimensions
of 4.5 nm × 3.0 nm × 3.0 nm, was employed as the model molecule. An
aqueous lysozyme solution with a concentration of 0.4 mg/mL and a pH
of 7 was prepared using phosphate buffer. For static adsorption tests,
10.0 mg of porous pectin particles was immersed in 50.0 mL of the
lysozyme solution and stirred at 25 ◦ C for 2 h. Periodically, a 5.0 mL
sample was taken, centrifuged at 15,000 rpm for 10 min, and the su­
pernatant's lysozyme concentration in the supernatant was measured. A
calibration curve was established for lysozyme in the range from 6.3 ×
10− 3 to 1.5 mg/mL (correlation factor R2 = 0.9999). Changes in the
absorbance of the supernatant were monitored at 281 nm using an
ultraviolet–visible (UV–vis) spectrophotometer (UV-2450, Shimadzu,
Kyoto, Japan) in the wavelength range of 250 to 350 nm at 25 ◦ C. The
adsorption capacity, Qt (mg protein/g adsorbent), at time t, was calcu­
lated using the Eq. (3):
(C0 − Ct )
Qt = V (3)
m
where C0 (mg/mL) is the initial protein concentration, Ct (mg/mL) is the
protein concentration at time t, which was calculated from the calibra­
tion curve, m (g) is the adsorbent weight, and V (mL) is the protein so­
lution volume. All tests were triplicated.
concentrations ranging from 2 to 20 wt%, as depicted in Fig. S3a. At a
20 wt% concentration, numerous clumps were observed, indicating that
pectin could not be fully dispersed. At 10 wt%, the solution exhibited
very high viscosity, making it nearly impossible to flow. At 9 wt%, it was
challenging to completely dissolve and disperse the pectin, with some
powder remaining undissolved. In concentrations ranging from 2 to 8 wt
%, pectin dissolved and dispersed in water with ease. Due to the varying
viscosities of pectin solutions at different concentrations (Fig. S3b, c),
experiments were conducted with pectin concentrations from 2 to 8 wt
%. The pectin:CaCO3 NP mass ratio was increased to 1:15 to explore the
particle formation capabilities. The results concerning yield and pro­
duction rate obtained in these cases are presented in Fig. 2. Typically,
lab-scale spray drying yields are low due to wall deposition and low
cyclone separation efficiency [29–31]. At a pectin:CaCO3 NP ratio of
1:15, increasing the pectin concentration from 2 to 5 wt% did not
significantly affect the product yield, which ranged between 22 and
29%. However, the production rate increased from 0.71 to 1.66 g/min
with increasing pectin concentration. At an 8 wt% pectin concentration,
the high CaCO3 NPs content combined with a rapid delivery rate (15
mL/min) led to nozzle clogging, abruptly ending the experiment and
resulting in low yield and production rate. To evaluate the feasibility of
spray drying at higher pectin concentrations (5 and 8 wt%), the pectin:
CaCO3 NP ratio was reduced to 1:1. The yields at pectin concentrations
of 5 and 8 wt% were 33% and 26%, respectively. The efficiency of the
3FN spray drying process for producing pectin-CaCO3 NPs was found to
be comparable with that of the 2FN at a 2 wt% pectin concentration.
Therefore, using 3FN for spray drying pectin and CaCO3 NPs can
enhance the production rate of composites by up to 30-fold.

3. Results and discussion

3.1. Increasing the production rate of spray drying by using 3FN

We prepared pectin-CaCO3 NPs with varying pectin concentrations

and CaCO3 NP to pectin mass ratios. The yield and production rates
obtained from these experiments are summarized in Fig. 2. In the case of
2FN, we achieved a yield exceeding 40% across all CaCO3 NP to pectin
mass ratios, which varied from 1 to 12, at a 1 wt% pectin concentration.
The relatively highest production rate recorded was 0.19 g/min. To
further improve the production rate, we investigated the effect of
increasing pectin concentration. At a 2 wt% pectin concentration, the
spray drying was feasible up to a maximum pectin to CaCO3 NP mass
ratio of 1:3. Beyond this ratio, the viscosity of the precursor solution
increased considerably due to egg-box interactions between pectin and
CaCO3 NPs [20,21], as shown in Fig. S2, volume of making spray drying
experiments unfeasible. This high viscosity issue was also observed at a
pectin concentration of 3 wt%, where experiments could not be con­
ducted even at lower pectin to CaCO3 NP mass ratios of 1:1, 1:2, or 1:3,
highlighting the limitations of using 2FN for producing pectin-CaCO3
NPs.
To overcome these challenges and enhance the production rate of
spray drying, we proposed the use of a 3FN instead of 2FN. The
advantage of 3FN lies in its ability to manage high-viscosity precursor
solutions effectively. In the 3FN setup, the inner solution contained only
pectin, while the outer solution contained only CaCO3 NPs. This sepa­
ration resulted in lower viscosity for each solution compared to a mixed
solution of pectin and CaCO3 NPs, thereby facilitating the spray drying
Fig. 3. Yield and production rate comparison of pectin-CaCO3 NP samples
process. The unique structure of the 3FN, with separate inner and outer
synthesized using the 3FN spray drying method. The precursor solution con­
liquid passages and an outermost gas passage, enabled the independent
tained 2 wt% pectin. Three experiments were conducted with 3FN: (i) the outer
spraying of pectin and CaCO3 NP solutions. The CaCO3 NP solution, solution with only CaCO3 NPs and the inner solution with only pectin, denoted
sprayed from the outer peripheral nozzle, could mix with the pectin as P2-Ca3; (ii) both solutions containing 2 wt% pectin mixed with CaCO3 NPs,
solution sprayed from the inner center nozzle during the atomization denoted as P2Ca3-P2Ca3; and (iii) the outer solution with only CaCO3 NPs and
process, effectively reducing the overall viscosity challenges. the inner solution with 2 wt% pectin mixed with CaCO3 NPs, denoted as
In addition, we prepared pectin solutions in DI water with P2Ca3-Ca12.

5
T.T. Nguyen et al.
3.2. Effect of different precursor types on the porous pectin formation with
3FN
The adoption of the 3FN system significantly enhances the produc­
tion rate of spray-dried pectin particles, particularly at higher concen­
trations. This study further explored the influence of various precursor
types on porous pectin particle formation. Three distinct experiments
utilizing 3FN were conducted: (i) the inner solution containing 2 wt%
pectin and the outer solution comprising only CaCO3 nanoparticles
(NPs) with a CaCO3 NP to pectin mass ratio of 3, referred to as P2-Ca3;
(ii) inner and outer solutions containing 2 wt% pectin mixed with CaCO3
NPs, resulting in a total pectin concentration of 2 wt% and a CaCO3 NP
to pectin mass ratio of 3, referred to as P2Ca3-P2Ca3; and (iii) the outer
solution containing only CaCO3 NPs and the inner solution comprising 2
wt% pectin mixed with CaCO3 NPs, leading to a total CaCO3 NP to pectin
mass ratio of 15, referred to as P2Ca3-Ca12. The yield and production
rates obtained for these experiments are depicted in Fig. 3. The incor­
poration of additional components into the outer solutions of 3FN sys­
tem, as demonstrated in the P2Ca3-P2Ca3 and P2Ca3-Ca12 samples, led
to production rates of 0.37 and 0.79 g/min, respectively, corroborating
the observations presented in Fig. 2. However, it was noted that the yield
obtained from 2FN experiments was higher than that obtained from 3FN
experiments, possibly due to the different nozzle geometries. The 2FN
featured solution and air orifice sizes of 0.7 mm and 1.5 mm, respec­
tively, whereas the 3FN had solution orifice sizes of 0.7 mm and 2.0 mm
for the inner and outer solutions, respectively, and an air orifice size of
2.8 mm. This resulted in the 3FN producing larger particles than the
Fig. 4. Morphology comparison of pectin-CaCO3 NP samples synthesized using the 3FN spray drying method: (a) P2-Ca3, (b) P2Ca3-P2Ca3, and (c) P2Ca3-Ca12.
SEM images are shown at low magnification (×5000, above) and high magnification (×35,000, below). Non-porous particles are indicated by arrows.
6
Powder Technology 440 (2024) 119782
2FN, potentially causing the product to settle within the spray drying
chamber [28]. The particle size distribution of P2-Ca3, P2Ca3-P2Ca3,
and P2Ca3-Ca12, illustrated in Fig. S4, supported this hypothesis. The
average size of P2-Ca3 particles was 3.4 μm, while the sizes for P2Ca3-
P2Ca3 and P2Ca3-Ca12 increased to 5.1 μm and 6.2 μm, respectively,
due to the richer composition of the precursor solution. These sizes are
larger than those of particles synthesized using the 2FN method (2.5
μm), which were reported in previous studies [12,13]. The settling of
larger particles during the spray drying resulted in less product being
transported by the air aspiration to the cyclone separator and collection
vessel, leading to reduced yields.
Fig. 4 offers an in-depth view of the morphology of porous particles
synthesized from various precursor solutions after the removal of CaCO3
NPs. Fig. 4a depicts particles synthesized with pectin in the inner solu­
tion and CaCO3 NPs in the outer solution, denoted as P2-Ca3. These
particles exhibited porous structures across their surfaces, although non-
porous particles were also observed. When CaCO3 NP concentrations
were varied (mass ratios of 1:1 or 1:15), the morphology of the pectin-
CaCO3 NPs remained similar to that with a mass ratio of 1:3 (Fig. S5).
This suggests that while some particles had an even distribution of
CaCO3 NPs, others had an uneven distribution, with CaCO3 NPs pri­
marily located on their surfaces. Additionally, we conducted an exper­
iment using CaCO3 NPs as the inner solution and pectin as the outer
solution. In this experiment, the concentration of pectin was 2 wt% and
the ratio of pectin to CaCO3 NPs was 1:3. The sample used in this
experiment is denoted as Ca3-P2. The yield, production rate, and par­
ticle morphology obtained for this experiment are shown in Fig. S6. The
T.T. Nguyen et al. Powder Technology 440 (2024) 119782

yield and production rate of the spray drying process were 75.0% and
0.23 g/mL, respectively, which are similar to those obtained for the P2-
Ca3 sample (pectin is the outer solution and CaCO3 NPs is the inner
solution). Regarding the morphology, SEM images of pectin-CaCO3 NPs
particles (before removing CaCO3 NPs) revealed an uneven distribution
of CaCO3 NPs across the particles. Consequently, the porous Ca3-P2
particles exhibited a porous structure with the uneven pore distribu­
tion, alongside the presence of non-porous particles. This phenomeno­
logical observation aligns with the findings obtained for the P2-Ca3
sample. These results underscore the premise that alternating the spatial
arrangement of the pectin and CaCO3 NPs, i.e. changing from an outer to
inner solutions or vice versa, does not facilitate a homogeneous distri­
bution of CaCO3 NPs in pectin-CaCO3 NPs composites.
To address this limitation, a strategic approach involving pre-mixing
pectin with CaCO3 NPs in both the inner and outer solutions was pro­
posed, as seen in particles labeled as P2Ca3-P2Ca3 (Fig. 4b). This
approach achieved a more uniform distribution of CaCO3 NPs on the
pectin particle surfaces, leading to considerably higher porosity of the
resulting pectin particle structures than that of the P2-Ca3 sample.
Additionally, the study examined the effects of pre-mixing pectin and
CaCO3 NPs only in the inner solution (P2Ca3-Ca12, Fig. 4c), with a
pectin to CaCO3 NP mass ratio of 1:15, differing from the previous 1:3
ratio. Despite the higher CaCO3 content in the P2Ca3-Ca12 sample, the
porous structure of pectin remained relatively unchanged, indicating
that the specific arrangement of the formulation's internal and external
components critically influences porosity.

Fig. 5. Cross-sectional SEM images of porous pectin particles synthesized using a 3FN spray drying method for samples (a) P2-Ca3, (b) P2Ca3-P2Ca3, and (c) P2Ca3-
Ca12. The images were captured at magnifications of ×10,000 and ×50,000, revealing the internal porous structure. Notably, the cross-sectional surfaces exhibit
vertical lines due to the polysaccharide nature of the particles when sectioned with an ion beam. The non-porous regions are indicated by arrows. Additionally, the
figure includes (d) nitrogen adsorption–desorption isotherms, (e) specific surface area measurements, and (f) distributions of micropores, mesopores (2–50 nm), and
macropores (>50 nm) for the respective pectin particles.

7
T.T. Nguyen et al. Powder Technology 440 (2024) 119782

Section 3.3 will delve into the potential scenarios that may occur
during the spray drying process of pectin-CaCO3 NPs, highlighting the
complex interactions between pectin and CaCO3 NPs that lead to the
formation of diverse composite particle structures. These insights not
only enhance our understanding of the fundamental mechanisms behind
the formation of pectin-CaCO3 NP composites but also provide a foun­
dation for further optimizing their production process. This compre­
hensive analysis is essential for grasping the intricate material
interactions that occur during the synthesis of composite particles,
which is pivotal for advancements in various fields that rely on such
sophisticated materials.
The internal structural characteristics of the porous pectin particles
P2-Ca3, P2Ca3-P2Ca3, and P2Ca3-Ca12 were meticulously examined
(Fig. 5). Upon spray drying pectin solution (without CaCO3 NPs) with
concentration of 1 wt%, the morphology of the resulting pectin particles
was dense without any porous structure, as reported in previous studies
[12,13] and illustrated in Fig. S7. In this experiment, cross-sectional
SEM images of porous pectin particles P2-Ca3, P2Ca3-P2Ca3, and
P2Ca3-Ca12 revealed that the particles harbored numerous densely
interconnected pore networks, highlighting the efficacy of the chemical
etching process in template removal and pore formation. Additionally,
these findings underscore the capability of the 3FN to distribute CaCO3
NPs not only on the surface but also within the droplets. However, a non-
porous region was observed in the P2-Ca3 sample (Fig. 5a), correlating
with the analysis results presented in Fig. 4. For the P2Ca3-P2Ca3
(Fig. 5b) and P2Ca3-Ca12 (Fig. 5c) samples, there was an enhance­
ment in the number of pores compared to the P2-Ca3 sample, suggesting
Fig. 6. Lysozyme adsorption capacity of porous P2-Ca3, P2Ca3-P2Ca3, and
that pre-mixing pectin with CaCO3 NPs before introduction to the 3FN
P2Ca3-Ca12 particles, showcasing the adsorption capacity as a function of time
leads to a more even distribution of CaCO3 NPs within the pectin par­ under specific conditions: an initial lysozyme concentration of 0.4 mg/mL, an
ticles. High-magnification images of all porous pectin particles showed adsorbent dosage of 0.2 mg/mL, a pH of 7, and an equilibrium time of 120 min.
that the pore shapes and sizes matched those of the CaCO3 NPs used as The error bars represent the standard deviation of mean values from triplicate
templates, with an average pore diameter of approximately 80 nm, experiments, underscoring the reproducibility of the adsorption performance.
mirroring the size of the CaCO3 NPs. Additionally, larger pores were
observed due to the interlacing of CaCO3 NPs within the pectin particles, pore network within the porous pectin particles.
forming an interconnected porous structure, which is beneficial for The porous structure of pectin particles facilitates the adsorption of
adsorption as it facilitates free molecule movement between channels proteins, with lysozyme serving as the model protein, through its voids,
[32,33]. This in turn enhances mass transfer and processing efficiency, windows, mesopores (2–50 nm), and macropores (>50 nm). Herein,
which is advantageous for adsorbent applications. lysozyme was used as the model protein. Lysozyme adsorption is pri­
The specific surface area of P2-Ca3, P2Ca3-P2Ca3, and P2Ca3-Ca12 marily driven by electrostatic interactions between the carboxyl
was evaluated using nitrogen adsorption–desorption techniques (as (− COOH) groups of pectin and the positively charged lysozyme at pH 7.
shown in Fig. 5d and e), with their pore size distribution by volume The surface charge measuremments of porous pectin particles P2-Ca3,
depicted in Fig. 5f, and pore volume detailed in Table S3. The nitrogen P2Ca3-P2Ca3, and P2Ca3-Ca12 at pH 7 revealed nearly identical
adsorption–desorption isotherms for all porous particle samples negative values, ranging from − 35 to − 38 mV (Fig. S8), indicating a
exhibited a combination of type II and IV curves, indicative of meso­ conducive environment for electrostatic interactions. Consequently, the
porous and macroporous structures in accordance with IUPAC classifi­ substantial adsorption of lysozyme by the porous pectin particles can be
cations [34]. Furthermore, the hysteresis loops observed in all porous attributed to the combined effects of electrostatic and π–π interactions,
pectin samples were of the H2 type, implying the existence of particles along with the contribution of the porous structure in facilitating protein
characterized by narrow necks and wider bodies. As illustrated in diffusion to the binding sites. From Fig. 6, it is observed that after 2 h of
Fig. 5e, the specific surface areas of the P2-Ca3, P2Ca3-P2Ca3, and reaching equilibrium, P2Ca3-Ca12 exhibited the highest adsorption
P2Ca3-Ca12 porous particles showed a progressive increase from 131.2 performance, with an adsorption capacity of 1786 mg/g. Following this,
m2/g to 183.9 m2/g, and ultimately to 261.1 m2/g. This increase is P2Ca3-P2Ca3 demonstrated superior lysozyme adsorption capacities of
associated with an increase in the total pore volume, attributed to the 1467 mg/g compared to P2-Ca3, which had an adsorption capacity of
augmented formation of pores as the mass ratio of CaCO3 NPs to pectin 838 mg/g. This enhanced adsorption efficiency can be attributed to the
escalates, as presented in Table S3. The surface area obtained in this macroporous structure coupled with a high surface area, which not only
study was higher than the value reported for non-porous particles in augments protein adsorption but also expedites the diffusion process.
previous researchers [12,13], which was only 1.5 m2/g. For all samples The pectin particles, with their extensive surface areas and inter­
of porous pectin particles, a wide pore-size distribution was evident connected pore networks, offer a high proportion of accessible active
within the meso− /macropore range, accompanied by a consistent pore binding sites within the macropores, thereby facilitating efficient pro­
volume distribution. This pattern implies the formation of highly tein adsorption.
interconnected pore networks featuring open pores predominantly
within the 40–120 nm range, as presented in Fig. 5f. The pore sizes
mostly equal to the size of CaCO3 NPs particles were used as templates. 3.3. Particle formation mechanisms
This result indicates that the size of the CaCO3 NPs particles affects the
size of the pores formed. These findings underscore the efficacy of the We delve into the nuanced dynamics of the interaction between
3FN approach in not only enhancing the production rate but also in pectin and CaCO3 NPs during the spray drying with a 3FN, providing
maintaining the integrity of the porous structure and the interconnected crucial insights for the precise engineering of composite particles. In the

8
T.T. Nguyen et al.
Fig. 7. Schematic illustration of the assembly of pectin and CaCO3 NPs during spray drying using 3FN with different types of precursor solutions.
case of the P2-Ca3 sample, the introduction of pectin and CaCO3 NPs are
introduced into the spray drying process via 3FN results in an uneven
distribution of CaCO3 NPs within the formed pectin-CaCO3 NP com­
posite particles. The distribution of CaCO3 NPs in composite particles is
illustrated in Fig. 7. Here, a low concentration of CaCO3 NPs in the
droplet leads to CaCO3 NPs being partially located on the surface and
inside the composite particles. Over time, before the droplet was
completely dries, the droplet surface undergoes isotropic shrinkage
[35–37]. During this process, the CaCO3 NPs migrate into the droplet
along with the contraction of the gas–liquid interface, facilitated by
diffusion-controlled surface rearrangement. The CaCO3 NPs move to the
surface and form a flexible shell, while pectin migrates to the droplet's
9
Powder Technology 440 (2024) 119782
interior beneath the shell. This phenomenon is attributed to the differing
diffusion coefficients of nanoparticles of various sizes and the thermo­
phoretic effect during spray drying [38], resulting in an uneven
dispersion of CaCO3 NPs throughout the entire composite structure.
Additionally, the uneven distribution of CaCO3 NPs can be attributed
to several parameters in the spray drying process and the physical-
chemical properties of the precursor solutions. Firstly, the relative
rates of solvent evaporation and solute diffusion play a crucial role. The
Peclet number (Pe), defined as the ratio of the rate of evaporation to the
rate of diffusion [39–42], serves as a fundamental descriptor in this
context. The equation for the Peclet number is given by Eq. (4):
T.T. Nguyen et al.
Pe =
κ
(4)
8D
where κ is the evaporation rate, and D is the diffusion coefficient of the
solute within the droplet. As generally indicated by the Peclet number
analysis, when evaporation is considerably higher than diffusion, it can
lead to a concentration gradient within the droplet. This gradient favors
the migration of CaCO3 NPs toward the droplet surface; however, in this
case, the viscosity of the precursor solution could influence the mobility
of the NPs within the droplet. This study further elucidates the critical
role of solution viscosity in modulating these processes. A higher vis­
cosity facilitates reduced convective flow toward the droplet surface,
reducing the constant rate drying phase. This condition enhances the
local liquid saturation near the droplet center. Furthermore, higher
viscosity can impede the diffusion of CaCO3 NPs, further exacerbating
the uneven distribution [39,43]. The resultant effect of this phenomena
on the precipitation profile within the droplet is instrumental in
dictating the distribution of CaCO3 NPs within the formed pectin par­
ticles, as well as the overall drying time.
For the P2Ca3-P2Ca3 sample, a homogeneous structural integration
is consistently observed, arising from the complete agglomeration of
pectin and CaCO3 NPs within both the inner and outer phases of the
dispersion prior to spray drying. This leads to a uniform distribution of
these constituents within the pre-existing agglomerates. During the
spray drying process, the composition of these agglomerates remains
unaltered, however, they are transformed into composite particle en­
tities. Owing to the elevated concentrations of both pectin and CaCO3
NPs relative to the P2-Ca3 samples, culminated in the formation of
comparatively larger composite particles. In the case of the P2Ca3-Ca12
sample, the similar phenomenon similar to that of the P2Ca3-P2Ca3
sample occurs. In this case, both pectin and CaCO3 NPs were agglom­
erated together in the inner solution. When CaCO3 NPs were added to an
outer solution, the content of CaCO3 NPs within the droplet increased,
resulting in an enlarged particle size, and a greater porosity. In these
cases, evaporation and diffusion occur in a manner that is not distin­
guishable from the previous case of P2-Ca3; however, the pre-mixing of
pectin and CaCO3 NPs plays a remarkable role in controlling uniformity
of CaCO3 NPs.
These insights are invaluable for researchers aiming to engineer
composite particles with precise control over their composition and
morphology. Thus, our work lay a foundation for the development of
tailored materials across various scientific and industrial applications.
The findings presented in Fig. 7 provide a roadmap for for controlling
formulations, and future research in the realm of composite particle
synthesis.
4. Conclusions
This study introduced a 3FN spray drying process to effectively
prepare porous pectin-CaCO3 NP composites, addressing the challenge
due to the high viscosity of precursor solutions containing pectin and
CaCO3 NPs, which has been a barrier to industrial scaling. The ability to
spray dry pectin at high concentrations using 3FN significantly
enhanced the production rate of the spray drying process by up to 30
times compared to the conventional 2FN method. Furthermore, this
study examined the impact of various precursor solution types on par­
ticle formation. It was found that the non-uniform distribution of CaCO3
NPs within droplets, a challenge arising due to the separate introduction
of pectin and CaCO3 NPs using 3FN, could be mitigated by pre-mixing
pectin with CaCO3 NPs in both the inner and outer solutions. Further­
more, when the CaCO3 NP to pectin ratio reached 15, the porosity of the
particle structure increased substantially compared with that observed
in previous studies. The results demonstrated that particle size could be
adjusted from 3.4 to 6.2 μm, and the specific surface area could be
increased from 131.2 to 261.1 m2/g, depending on the precursor solu­
tion used. Additionally, the lysozyme adsorption capacity was enhanced
10
Powder Technology 440 (2024) 119782
in correlation with the specific surface area, ranging from 838 to 1786
mg lysozyme/g of porous pectin particles. Thus, this approach offers
new perspectives for the preparation of a wide array of multifunctional
composites from otherwise incompatible components, paving the way
for innovative applications in various fields.
CRediT authorship contribution statement
Tue Tri Nguyen: Writing – original draft, Visualization, Validation,
Investigation, Data curation. Tomoyuki Hirano: Writing – review &
editing. Ridha Nurul Chamida: Writing – review & editing. Eka Lutfi
Septiani: Writing – review & editing. Nhan Trung Nguyen: Writing –
review & editing. Takashi Ogi: Supervision, Methodology,
Conceptualization.
Declaration of competing interest
The authors declare no known competing financial interests or per­
sonal relationships that can influence the work reported in this paper.
Data availability
The authors do not have permission to share data.
Acknowledgments
This work was supported by JSPS KAKENHI Grant Number
JP23H01745 (T.O.), JP22K20482 and JP23K13590 (T.H.). This work is
partly supported by the International Network on Polyoxometalate
Science at Hiroshima University, the JSPS Core-to-Core Program, the
Information Center of Particle Technology, Japan, and the Hosokawa
Powder Technology Foundation. This work was supported by JST, the
establishment of university fellowships toward the Creation of Science
Technology Innovation, Grant Number JPMJFS2129 (T.T.N). The au­
thors thank the Natural Science Center for Basic Research and Devel­
opment (N-BARD) for supporting the SEM image measurements. They
also thank Enago English proofreading service (https://www.enago.jp/)
for checking a draft of this manuscript.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.powtec.2024.119782.
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