chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694

Contents lists available at ScienceDirect

Chemical Engineering Research and Design

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

A comparative study of spray-dried medicinal

plant aqueous extracts. Drying performance and
product quality

Loreana Gallo a,b , María Verónica Ramírez-Rigo a,b , Juliana Piña b ,

Verónica Bucalá b,∗
a Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, San Juan 670,
8000 Bahía Blanca, Argentina
b Department of Chemical Engineering—PLAPIQUI—Universidad Nacional del Sur—CONICET,

Camino La Carrindanga Km. 7, 8000 Bahía Blanca, Argentina

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

Article history: In the manufacture of herbal medicinal tablets, dried plant extracts are employed as the
Received 24 June 2015 therapeutic ingredient. These powders, usually obtained by spray drying, are typically hygro-
Received in revised form 10 scopic and possess poor flow and compactability for the manufacture of tablets by direct
September 2015 compression (DC). Besides, spray-drying operating conditions and liquid feed composition
Accepted 7 October 2015 are reported to be dependent on the herbal medicine. Consequently, the production of dried
Available online 23 October 2015 extracts implies long new product development times. Therefore, the goal of this paper was
to: (a) provide recommendations as initial production point of herbal powders suitable for
Keywords: DC by spray drying and (b) study the powder properties to identify those that are affected
Spray drying by the extract nature. Particularly, a unique set of operating conditions was found to be
Herbal medicinal extracts appropriate to produce powders of seven different medicinal plant extracts. In fact, all the
Tablets spray-dried products showed adequate flowability, stability and compactability.
Direct compression Powders properties, as particle size and morphology, moisture content, hygroscopicity,
flowability and compact hardness were not a function of the type of herb. Conversely, the
process yield and glass transition temperature, particle and bulk densities, powder compo-
sition, compact porosity, wetting and disintegration times were found to be dependent on
the chemical nature of the herbs.
© 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

1. Introduction last years some developed countries (e.g., Canada, France,

According to the World Health Organization, herbal medicine
includes “herbal medicines composed of herbs, herbal mate-
rials, herbal preparations, and finished herbal products, that
contain as active ingredients parts of plants, or other plant
materials, or combinations thereof” (Robinson and Zhang,
2011). Currently, the 80% of the world population that lives in
developing countries depends essentially on medicinal herbs
for the first line of primary health care. In addition, in the
Australia, United Stated and Belgium) increased the use of
herbal medicinal products, as dietary supplements or as alter-
native/complementary medicines (Shyu, 2012). As reported by
the Secretariat of the Convention on Biological Diversity, the
herbal products worldwide market was about US $83 billion
in 2008, with a steady growth rate ranging between 3% and
12% per year (Zhang et al., 2012), and is estimated to reach
US $107 billion by the year 2017 (Global Industry Analysts, Inc,
2013). Among other reasons, this situation could be ascribed

∗
Corresponding author. Tel.: +54 291 486 1700x209; fax: +54 291 486 1600.
E-mail address: vbucala@plapiqui.edu.ar (V. Bucalá).
http://dx.doi.org/10.1016/j.cherd.2015.10.009
0263-8762/© 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
682 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
to increasing consumer awareness concerning general health,
the people’s assumption that herbal medicines are free from
side effects and the high cost of synthetic drugs (Pandey et al.,
2011).
Nowadays, herbal products are marketed in the form of liq-
uid preparations (i.e., teas, tinctures) and powders (i.e., dried
and comminuted herbs or dried and liquid plant extracts).
Dried extracts are available as capsules and tablets (Banker
and Rhodes, 2002). Tablets are the most common oral solid
pharmaceutical dosage forms (Nguyen et al., 2013). These
drug delivery vehicles offer advantages for both patients
(ease consumption and handling) and manufacturers (vari-
ety of manufacturing methods and low-cost production). In
addition, tablets contain accurate dosage and good stability
compared to oral liquid forms (Gad, 2008).
Direct compression (DC) is the most efficient process for
tablets manufacturing. This method involves the mixing of
drug and excipients in a blender and the direct compres-
sion of the powder in a tablet press. Direct compression is
a relatively simple process that requires fewer unit opera-
tions, shorter processing time and lower energy consumption
than wet or dry granulation processes (Dokala and Pallavi,
2013). Nevertheless, the production of tablets by means of
DC normally needs a careful selection of the materials to
achieve a free-flowing and compactable powder blend. Flowa-
bility is essential for adequate filling of the dies in the tablet
machine and, thus, for producing tablets of uniform weight.
Powder compactability is another critical property for success-
ful tabletting (Swarbrick and Boylan, 2007).
In the manufacture of herbal medicinal tablets, dried plant
extracts are typically employed as the therapeutic active
ingredient (Soares et al., 2005a). In general, these materi-
als are highly sensitive to atmospheric moisture. The high
hygroscopicity of dried medicinal plant extracts affects the
particle–particle interactions and contributes to their poor
flow and compactability properties (Souza et al., 2007; Tong
et al., 2008). In addition, phytomedicine tablets commonly
contain a high dose of dried plant extract. Therefore, the
amount of excipients that can be incorporated in order to
obtain reasonable size tablets is usually insufficient to improve
the flow and compactability properties of dried plant extracts
(Souza et al., 2001). Consequently, the development of new
processes/formulations for the production of dried medicinal
plant extracts with appropriate characteristics for DC is one of
the important challenges facing the phytomedicine industry.
Several drying techniques can be utilized for the dehydra-
tion of herbal medicinal extracts, such as freeze-, spouted-bed
and spray drying (Cortés-Rojas and Oliveira, 2012). In particu-
lar, spray drying is the preferred method due to its capacity to
convert a liquid (i.e., aqueous or organic solution, emulsion,
dispersion or suspension) into a powder with accurate spec-
ifications (moisture content, size, morphology, bulk density
and physicochemical stability) in a continuous and relatively
economic operation (León-Martínez et al., 2010; Oliveira and
Petrovick, 2010). The physicochemical properties of the spray-
dried powders as well as the process yield depend on the
operating conditions (i.e., inlet air temperature, atomization,
liquid and drying air flowrates) and the liquid feed compo-
sition (e.g., total solids content, ratio of drying adjuvant to
the solid residue (SR) of the fluid plant extract, solvent type)
(Mujumdar, 2006). The adequate selection of these parameters
implies trial-and-error assays and/or factorial design (Couto
et al., 2012; Krishnaiah et al., 2012; Şahin-Nadeem et al., 2013),
being this a high time-consuming step.
Several investigations reported the influence of the spray-
drying operating variables on the physical properties of dried
herbal medicinal extracts (i.e., moisture content, hygroscop-
icity, flowability and compactability) and the process yield.
Vasconcelos et al. (2005) found that an inlet air tempera-
ture of about 140 ◦ C and the highest adjuvant concentration
used (SiO2 :SR, 0.43:1), allowed producing a dried extract of
Schinus terebinthifolius with the lowest moisture content and
hygroscopicity and the highest process yield (about 80%). The
flowability of these dried medicinal extracts is not given. Souza
and Oliveira (2006) reported that a fixed concentration of dry-
ing adjuvant (SiO2 :SR, 0.8:1), an inlet temperature of 150 ◦ C (the
highest temperature tested) and a drying air flowrate of about
0.023 kg/s led to a Bauhinia forficate dried extract with the low-
est moisture content but poor flowability and low process yield
(around 49%). In this case, the product hygroscopicity is not
informed. Souza et al. (2008) studied the production of a spray-
dried extract of Rosmarinus officinalis Linné. For all the tested
operating conditions and a fixed proportion of drying adju-
vant (SiO2 :Maltodextrine DE 14:SR, 1:0.5:1) they found poor
powder flow properties. In addition, the highest tested tem-
perature (80 ◦ C) produced the highest loss of the extract active
compounds. The powders moisture content and hygroscopic-
ity are not reported. Gallo et al. (2011) studied the spray drying
of Rhamnus purshiana (Cascara sagrada bark) extract in order
to obtained powders with good rheological properties for DC.
Through a fractional factorial statistical design, the authors
found the optimal operating conditions and liquid feed com-
position (SiO2 :SR, 1:1) to produce a dried plant extract with
adequate flowability, compactability, high yield, low moisture
content and hygroscopicity.
Spray-drying operating conditions and liquid feed compo-
sition are reported to be dependent on the herbal medicine.
In consequence, the production of medicinal dried extracts
implies long new product development times, being one of
the main challenges facing the phytomedicine industry. For
this reason, the goal of this paper was to: (a) provide recom-
mendations for the production of herbal medicinal powders
suitable for DC by spray drying of aqueous extracts (i.e., a
unique set of operating variables and a single formulation
of the liquid feed suitable to produce powders from different
herbal aqueous extracts was proposed as initial production
point) and (b) study the key powder properties to identify those
that are affected by the extract nature. To this end, seven
aqueous plant extracts (used for the treatment of different
pathologies) were selected and spray dried according to the
recommendations given by Gallo et al. (2011) for the R. pur-
shiana powder production. Complementarily, the spray-dried
products were thoroughly characterized (i.e., particle size,
density and morphology, flowability, moisture content, hygro-
scopicity, glass transition temperature, powder composition).
Also the powders’ compact properties (hardness, porosity,
wetting and disintegration times) were analyzed. For those
properties that were different between medicinal plants, rela-
tionships to the relevant herbal chemical constituents were
explored.
2. Materials and methods
2.1. Materials
The selected medicinal herbs were: R. purshiana D.C., Peu-
mus boldus Mol., Centella asiatica (L.) Urb., Valeriana officinalis
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694 683

Table 1 – Selected medicinal herbs, parts containing the therapeutic components (according to WHO, 2002; Real
Farmacopea Española (RFE), 2005; United States Pharmacopeia and National Formulary (USP 30-NF 25), 2007 and Alonso,
2007).
Medicinal herb Medicinal uses Parts used Major chemical constituents Sugars Phenolic
acids

R. purshiana Laxative for Dried bark Hydroxyanthracene glycosides (6–9%), Glucose No

short-term within this group about 70–90% are
treatment of C-10 glycosides and the remaining
occasional 10–30% is constituted by aloins A and
constipation B, and chrysaloins A and B
P. boldus Cholagogue, liver Dried leaves Alkaloids (boldine 0.06% (major), 3–5% in the dried No
stimulant isoboldine, isocorydine, leaves, composition
isocorydine-N-oxide, norisocorydine, not detailed
laurotetanin, among others);
flavonoids and volatile oils
C. asiatica Venotonic Dried aerial parts Triterpenes asiatic acid and Rhamnose, No
Anti-cellulite madecassic acid, and their derived arabinose, glucose,
triterpene ester glycosides, fructose, sucrose,
asiaticoside and adecassoside raffinose,
oligosaccharide
centellosa
V. officinalis Mild sedative and Rhizomes, roots Volatile oils (0.2–2.8%: bornyl acetate Glucose, sucrose Yes
sleep-promoting and stolons and bornyl isovalerate, valerenic acid,
agent acetoxyvalerenic acid, valerenal,
among others); non-glycosidic bicyclic
iridoid monoterpene epoxy-esters
(0.05–0.67%)
H. virginiana Venotonic for the Dried leaves Hydrolysable and condensed tannins No Yes
treatment varicose (up to 10%), the latter predominant.
veins Leaves tannins are a mixture of free
gallic acid (10%), hydrolysable
hamamelitannin (1.5%) and
condensed proanthocyanidins (88.5%)
H. perforatum Treatment of mild Dried aerial parts Naphthodianthrones (0.05–0.30%: No Yes
and moderate hypericin, pseudo-hypericin,
depressive episodes hyperforin, adhyperforin); flavonoids
(2–4%: hyperoside, quercitrin,
isoquercitrin, rutin); and 7–15%
catechin tannins
C. scolymus Adjunct treatment Dried leaves Phenolic acids (up to 6%: chlorogenic No Yes
of mild to moderate acid, caffeic acid, cynarin, among
hypercholestero- others); sesquiterpene lactones (up to
laemia 5%: cynaropicrin, grosheimina);
Antioxidant flavonoids (0.35–0.75%: scolymoside,
cynaroside, among others)

L., Hypericum perforatum L., Hamamelis virginiana L. and Cynara
scolymus L. The herbs and their quality control certifi-
cates were provided by Droguería Argentina (Buenos Aires,
Argentina). The physical appearance of the used parts was in
agreement with the description of various pharmacopoeias
and literature (WHO, 2002; Real Farmacopea Española (RFE),
2005; Alonso, 2007; United States Pharmacopeia and National
Formulary (USP 30-NF 25), 2007). For the studied herbs,
Table 1 presents the pharmacological action, the plant
parts that contain therapeutic chemical components and
a brief list of them. In order to identify common or dif-
ferent chemical structures between the studied medicinal
herbs, the reported non-therapeutic components were also
explored. According to this study, the plants could be grouped
into herbs with/without sugars and phenolic acids (see
Table 1).
Colloidal silicon dioxide (SiO2 , Aerosil 200® , Evonik Degussa
Argentina S.A, Buenos Aires, Argentina) was selected as the
drying adjuvant (Gallo et al., 2011) and used as received from
the supplier. Distilled water was employed for the preparation
of fluid plant medicinal extracts and aqueous dispersions to
be spray dried.
2.2. Fluid plant medicinal extracts (FPMEs)
preparation
For all the tested herbs, Table 2 gives details about the
employed extraction methods, as well as the final volume of
FPME (either diluted, concentrated or as obtained).
The FPME of R. purshiana was prepared by mixing the bark
with the boiling water. This mixture was macerated for 3 h
and then transferred to a percolator. Extra boiling water, used
as menstruum, was continuously poured into the percolator
until 5000 ml of the fluid extract were collected (United States
Pharmacopeia and National Formulary (USP 30-NF 25), 2007).
H. virginiana fluid extract was obtained by decoction of dried
leaves in boiling water for 160 min, according to European
Medicines Agency Evaluation of Medicines for Human Use
(EMA) (2009). The FPME was separated from the leaves by fil-
tration through a cellulose based filter paper (Whatman No. 1,
GE Healthcare Bio-Sciences Corp., Piscataway, United States).
The FPMEs of P. boldus, C. asiatica, V. officinalis, H. perfora-
tum and C. scolymus were prepared as an infusion according
to Alonso (2007). The herbal material was poured into a
given volume of boiling water, and then allowed to stand
684 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694

Table 2 – Details of the extraction methods and FPMEs properties.

Medicinal herb Extraction Mass herb (g) Initial volume Final volume Initial solid Final solid Final
method of water (ml) of FPME (ml) residue residue viscosity of
(g/100 ml) (g/100 ml) FPMEs (cSt)

R. purshiana Maceration 900 4000 5000 3.8 ± 0.12 0.7 ± 0.10 1.479 ± 0.009
percolation
H. virginiana Decoction 40 1000 850 0.8 ± 0.12 0.8 ± 0.12 1.494 ± 0.009
P. boldus Infusion 20 1000 950 0.6 ± 0.10 0.6 ± 0.10 1.444 ± 0.009
C. asiatica Infusion 2.4 1000 920 0.3 ± 0.10 0.6 ± 0.10 1.444 ± 0.009
V. officinalis Infusion 12 1000 900 0.2 ± 0.10 0.6 ± 0.10 1.474 ± 0.009
H. perforatum Infusion 16 1000 890 0.3 ± 0.06 0.6 ± 0.12 1.464 ± 0.009
C. scolymus Infusion 40 1000 820 0.7 ± 0.02 0.7 ± 0.02 1.484 ± 0.015

for approximately 40 min. The obtained FPMEs were filtered
through filter paper (Whatman No. 1, GE Healthcare Bio-
Sciences Corp., Piscataway, United States).
The solid residue (SR) content of the FPMEs was deter-
mined by evaporation of the solvent under reduced pressure,
followed by drying in an oven at 80 ◦ C to constant weight. Mea-
surements were taken in triplicate. As it is shown in Table 2,
different initial SR values were obtained. For comparative pur-
poses, some FPMEs were diluted (R. purshiana) or concentrated
(C. asiatica, V. officinalis and H. perforatum) in order to obtain
final SR values within a narrow range (0.6–0.8 g/100 ml) (see
Table 2). The viscosity of the final FPMEs was measured in
triplicate, using a capillary Cannon-Fenske Routine-type vis-
cometer (Tube size 100, IVA Cannon Instrument Company,
State College, United States) immersed in a constant temper-
ature bath at 25 ◦ C. The viscosity values are given in Table 2.
2.3. Spray drying and dispersions preparation
The selected operating conditions and feed formulation cor-
responded to the ones reported by Gallo et al. (2011) as the
optimal ones to produce a dried extract of R. purshiana with
good flow properties and adequate stability attributes. There-
fore, the components used to prepare the dispersions to be
spray dried were the FPMEs and the drying adjuvant (SiO2 ) in
a 1:1 ratio. This carrier demonstrated to be an effective excipi-
ent to produce powders with good flow and stability properties
from fluid plant extracts, and to reduce the adhesion of the
products on the spray-dryer chamber walls (Albertini et al.,
2004; Oliveira and Petrovick, 2010; Gallo et al., 2011, 2013).
The aqueous dispersions were mixed for 30 min before
atomization and during the spray-drying process by means
of a magnetic stirrer bar rotating at 1000 rpm to keep them
homogenized. The liquid feeds were spray dried in a Mini
Spray-Dryer Büchi B-290 (Büchi, Flawil, Switzerland). A two-
fluid nozzle with a cap-orifice diameter of 0.5 mm was used.
According to Gallo et al. (2011) the operating conditions
were: drying air inlet temperature: 130 ◦ C, atomization air vol-
umetric flowrate: 400 l/h, feed volumetric flowrate: 3 ml/min,
drying air volumetric flowrate: 35–38 m3 /h. The air outlet tem-
perature was measured for the spray drying of each plant
extract.
For every plant extract four spray-drying batches were car-
ried out.
2.5. Angle of repose (˛)
The angle of repose was determined by pouring around 7 g of
spray-dried powder through a funnel located at a fixed height
above a graph paper (20 × 20 cm) placed on a flat horizontal
surface and measuring the height (h) and radius (r) of the con-
ical pile formed. A height of 5 cm between the funnel bottom
and the graph paper was selected to minimize the impact of
falling powder on the tip of the cone. The inverse tangent of
the h/r ratio is the angle of repose (Rattes and Oliveira, 2007).
2.6. Bulk (Db ) and tap (Dt ) densities
In order to determine the spray-dried extracts density, the
powder was gently poured into a 10 ml graduate cylinder. Bulk
density (Db ) was calculated as the ratio between the weight
of the sample contained in the cylinder and the volume occu-
pied. Tap density (Dt ) was estimated by tapping the cylinder
until no measurable change in volume was noticed. Powder
compressibility was evaluated using the Carr’s compressibil-
ity index (CI) shown in Eq. (1) (Schüssele and Bauer-Brandl,
2003)
(Dt − Db )
CI = × 100 (1)
Dt
2.7. Loss on drying (LOD)
The loss on drying was determined by a moisture analyzer
with halogen heating (model MB45, Ohaus, Pine Brook, United
States). The analysis was performed immediately after the
spray-drying step. About 500 mg of powder were heated at
70 ◦ C (to prevent thermal degradation of the active com-
pounds) until the weight change was less than 1 mg in 90 s.
2.8. Hygroscopicity (HYG)
Hygroscopicity was determined by adapting the method
proposed by Tonon et al. (2008). Spray-dried samples (approx-
imately 0.2 g) were stored in containers at 25 ◦ C and 75.3%
RH (given by a saturated aqueous solution of NaCl). After 7
days, the samples were reweighted. The hygroscopicity was
expressed as grams of adsorbed moisture per 100 g of dry
solids.

2.9. Thermal analysis. Glass transition temperature

2.4. Process yield (PY) (Tg ) determination

The process yield was calculated as the ratio of the weight of The glass transition temperature (Tg ) of the powders was
powder collected after every spray-drying experiment to the measured by differential scanning calorimetry (Pyris 1, Perkin
initial amount of solids contained in the liquid feed dispersion. Elmer, Massachusetts, United States). Selected samples of
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
10 mg were placed in aluminum pans and scanned from 30
to 150 ◦ C at a heating rate of 10 ◦ C/min. The purpose of this
first thermal scan was to remove the residual moisture that
could affect the determination of Tg . Then, the samples were
cooled from 150 to 30 ◦ C at a cooling rate of 10 ◦ C/min, and re-
heated from 30 to 150 ◦ C at the same rate. Tg was calculated
from the thermograms as the temperature at which one-half
of the change in heat capacity, Cp, occurred (i.e., by the half
Cp method) (Shrestha et al., 2007).
2.10. Evaluation of the content of solid residue (SR) in
the spray-dried medicinal plant extracts
In order to determine if the SR:SiO2 ratio (1:1) selected for
the formulation of the liquid feed dispersion was altered by
the spray-drying process (i.e., if a selective deposition of the
components on the spray-dryer walls took place), the SR con-
tent in the spray-dried extracts was also evaluated. To this
end and for each medicinal herb, a sample of 0.2 g of the
spray-dried extract powder was placed in a 25 ml volumetric
flask and diluted to volume with distilled water. This volume
was centrifuged (Hettich centrifuge Universal 16A, Tuttlin-
gen, Germany) three times at 2000 rpm for 20 min (Dixit and
Nagarsenker, 2008; Choudhari et al., 2014). After centrifuga-
tion and precipitation of the SiO2 , 10 ml of the supernatant
(containing the fluid plant extract) were transferred to a pre-
weighted beaker. The fluid extract was dried in an oven to
constant weight at 80 ◦ C. The amount of SR in the 10 ml vol-
ume was estimated by weight difference and then referred to
the initial volume (25 ml). The experiment was performed in
duplicate.
2.11. Particle morphology and size distribution
The obtained powders were dried under air flow on a porthole.
Afterwards, the samples were metalized with gold in a PELCO
91000 sputter coater (TellPella, Canada). Particle size distribu-
tion was measured using a laser light diffraction instrument
under the dry powder method (LA 950 V2, Horiba, Kyoto,
Japan). Average particle size was expressed as volume mean
diameter D [4,3], and the distribution width was characterized
in terms of span. The span index was calculated as follows:
(D90 − D10 )
span = (2)
D50
where D90 , D50 and D10 are the diameters for which 90%, 50%
and 10% of the population is below each value, respectively.
The closer the span value is to 1, the narrower the particle
size distribution (Sarrate et al., 2015).
2.12. Skeletal density
The skeletal density of the spray-dried products was deter-
mined by nitrogen adsorption (NOVA 1200e, Quantachrome
Instruments, Florida, United States). For each medicinal herb,
a sample of 600 mg was placed in a precalibrated cell and its
volume was determined by nitrogen intrusion. Skeletal den-
sity is the mass of the solid divided by the volume of the solid
excluding open pores and including closed hollows. For very
porous particles and well-connected pores the skeletal density
can be assumed to be close to the solid density, while for non-
porous particles the skeletal density represents the particle
one.
685
2.13. X-ray diffraction (XRD)
XRD patterns of the spray-dried products were recorded using
a Rigaku Geigerflek (DMAX 3 C, Tokyo, Japan). X-ray diffraction
system and the software JADE 7 were used to identify crys-
talline materials. The anode X-ray tube was operated at 35 kV
and 15 mA. Measurements were taken from 2◦ to 60◦ on the 2
scale at a step size of 4◦ /min.
2.14. Compact production
The final formulation of tablets, containing plant extract
powders as active ingredient, requires the use of additional
excipients (i.e., fillers, disintegrants and lubricants) that have
to be properly selected (Ansel et al., 2009; Soares et al., 2005b).
However, in this work, a pre-formulation study was firstly car-
ried out to test the ability of the spray-dried extract powders
to form compacts without the addition of other excipients. In
this sense, the spray-dried powders were directly compressed
in a hydraulic press with manometer (Delfabro, Córdoba,
Argentina) at 4.9 kN for 5 s. Flat punches (10 mm of diameter)
were used. For each plant extract, 30 compacts were produced
(18 for the disintegration studies, 2 for wetting time deter-
mination and 6 for hardness measurement). The hardness of
each compact was determined using a hardness tester (Scout,
Ciudad Autónoma de Buenos Aires, Argentina). For compara-
tive purposes, the weight of the compact was established in
150 mg.
2.15. Compacts’ properties
2.15.1. Compacts’ porosity
The compact porosity (εc ) was calculated as follows (Mesnier
et al., 2013):
 
a
εc = 1− (3)
p
where a is the compact apparent density and p the particle
density. a was established from the following equation:
 m 
t
a = 4 (4)
HD2
where mt denotes the compact mass, H represents the com-
pact height and D its diameter.
2.15.2. Wetting time (WT)
A Whatman No. 1 filter paper disk (GE Healthcare Bio-Sciences
Corp., Piscataway, United States) folded once diametrically
was placed in a Petri dish of 8.5 cm in diameter. A small vol-
ume (8 ml) of distillated water was added to the filter. Then,
the compact was carefully placed on the wetted tissue paper
at t = 0 (initial time) and the time for complete wetting of the
compact was recorded (Pabari and Ramtoola, 2012).
2.15.3. Disintegration time (DT)
The compact disintegration time was determined in a disinte-
gration apparatus (Scout, Ciudad Autónoma de Buenos Aires,
Argentina) according to the United States Pharmacopeia and
National Formulary (USP 30-NF 25) (2007) specifications. For
each formulation, 6 randomly selected compacts were tested.
One compact was placed in each of the six tubes of the disinte-
gration apparatus’ basket, which has a stainless-steel screen
686 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
(10 mesh) at the bottom. To operate the apparatus, the bas-
ket was immersed in 800 ml of distilled water (immersion
fluid) maintained at 37 ± 0.5 ◦ C. The basket moves vertically
up and down. The disintegration time was defined by the time
for which no residue of the total tested number of compacts
remained on the basket screen (United States Pharmacopeia
and National Formulary (USP 30-NF 25), 2007). The experiment
was performed in triplicate.
2.16. Statistical analysis
The significant differences between the process yield, pow-
ders’ and compacts’ properties were determined by means of
one-way ANOVA, followed by the Least Significant Difference
(LSD) multiple comparison method. Statistical significance
was established through the p-value; values lower that 0.05
indicate that the factor impacts significantly with at least 95%
confidence.
3. Results and discussion
The selected operating conditions and feed formulation, that
corresponded to the optimal ones reported by Gallo et al. (2011)
for R. purshiana dried powders, were found to be appropriate
to process seven medicinal herbal extracts of very different
chemical nature. Based on many measured properties, the
discussion of the results is grouped into three categories: the
powder, process-related, and compact properties.
3.1. Powder properties
3.1.1. Particle size and morphology
As reported for other spray-dried products, the powders
showed unimodal and log-normal particle size distributions
(Fig. 1) (Gallo et al., 2013; Pang et al., 2014). The non-normality
of data was proved by testing the cumulative normalized dis-
tributions in the normal probability plot (Rhodes, 2008). The
mean volume particle diameter was between 7.79 ± 1.48 and
9.81 ± 1.60 ␮m (Table 3). The values of D10 , D50 and D90 were
employed to calculate the span of the spray-dried extracts’
particle size distributions (Table 3). For all the seven extract
powders, the span values were close to 1, indicating that nar-
row particle size distributions were obtained (Sarrate et al.,
2015). Since the FPME’s viscosity and the total solids content
within the liquid feed were similar for all the extracts (Table 2),
and the FPMEs were processed at identical operating condi-
tions, it can be concluded that the type of medicinal herb did
not strongly affect the particle size.
For all the plant extracts, the particles were quite spher-
ical and showed rough surface (Fig. 2). The rough surface
was reported as characteristic of particles containing SiO2
(Chauhan et al., 2005; Tewa-Tagne et al., 2006) and could be
attributed to the migration of small SiO2 particles (7–16 nm)
suspended in the liquid feed to the surface of the droplets
during the spray-drying process (Rowe et al., 2009; Nandiyanto
and Okuyama, 2011). As it was discussed for the particle size,
the type of herbal extract did not affect the particle morphol-
ogy.
3.1.2. Powders’ loss on drying, hygroscopicity and Tg
The mean moisture contents of the powders were in the range
2.00 ± 0.17 to 2.69 ± 0.03% (Table 4). These values are relatively
low for spray-dried plant extracts; in fact, the maximum mois-
ture contents recommended for this type of products is around
4% (Souza and Oliveira, 2006). In addition, the obtained spray-
dried extracts showed moderately hygroscopicity, between
9.11 ± 0.03 and 11.09 ± 0.08 g per 100 g of dry solids (Table 4),
values that are well below other higroscopicities reported
for herbal medicinal powders (Vasconcelos et al., 2005). The
selected SR:SiO2 proportion (1:1) allowed the carrier to hold
substantial quantities of liquid extract within the interstitial
volume of its agglomerates (Gonnissen et al., 2008; Evonik
Technical Information TI 1367, 2012a). This distinctive prop-
erty of the SiO2 may be responsible of the low and similar
higroscopicities found for the powders obtained by processing
seven different aqueous extracts.
The stability of the spray-dried extracts was also charac-
terized by measuring the glass transition temperature (Tg ).
Structural alterations occur in amorphous powders when
stored at temperatures above the Tg (i.e., the temperature at
which these materials undergo transformation from a glassy
to a rubber-like state). Hence, powders with low moisture
content and Tg above the storage temperature can be con-
sidered stable. Table 4 shows Tg and Cp values for all the
obtained spray-dried extracts. The glass transition tempera-
ture was always well above room temperature. Even though
all the powders showed adequate physical stability, the dif-
ferent Tg values indicate that the plant chemical composition
strongly impacts on the thermal behavior of the powders.
3.1.3. Powders flow properties
Good flow properties are a prerequisite for the successful
manufacture of tablets by DC. Proper flowability of pow-
ders is essential for the transport through the hopper to the
filling station of the tablet machine at an appropriate rate
and without segregation (Gad, 2008). The angle of repose
is a common method to characterize the powder flow with
small amounts of material. According to the United States
Pharmacopeia and National Formulary (USP 30-NF 25) (2007),
repose angles between 25 and 30◦ represent an excellent pow-
der flow, between 31 and 35◦ the flow can be considered good,
and within the 36–40◦ range the flow is fair. For values higher
than 41◦ , the material has poor flow properties. The obtained
spray-dried extracts showed repose angles values between
20 ± 2 and 31 ± 3◦ , being the differences significant (p < 0.05)
(Table 4). The results suggest that all the co-processed pow-
ders presented very good flow. Other common indicator of
powder flowability is the Carr’s compressibility index (Eq. (1)).
Carr’s compressibility indexes of 10% indicate an excellent
flow, between 11 and 15% denote good flowability, between 16
and 20% reveal fair flow, between 21 and 25% indicate accept-
able flow, and between 26 and 31% are an indication of poor
flow (United States Pharmacopeia and National Formulary
(USP 30-NF 25), 2007). Table 4 shows the bulk and tap densi-
ties measured values and the resulting Carr’s compressibility
indexes (p < 0.05). The CI values of the spray-dried medici-
nal extracts were in the range 17.42 ± 0.87 to 25.60 ± 0.69%,
indicating acceptable flowability (Table 4). The relative good
agreement found between the angle of repose and CI values
reveal that all the spray-dried powders had adequate flow
properties (Gallo et al., 2011, 2013). Despite the diverse chem-
ical composition of the extracts, by using the suggested set
of operating conditions and the same liquid feed formulation
(SR:SiO2 , 1:1), the spray-dried powders showed good rheolog-
ical properties for DC.
The two main factors that generally affect powders flowa-
bility are the particle shape and size. The more spherical
the particles, the better the flow. Coarse spherical particles
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694 687

Table 3 – Particle sizes and span index of the powders obtained by spray drying.
Powder D [4,3] (␮m)a D10 (␮m)a D50 (␮m)a D90 (␮m)a Span

R. purshiana 9.56 ± 1.54 5.52 ± 0.02 9.59 ± 0.04 16.30 ± 0.03 1.12
H. virginiana 8.14 ± 1.48 4.89 ± 0.03 8.22 ± 0.03 13.26 ± 0.01 1.02
P. boldus 7.90 ± 1.48 4.78 ± 0.02 7.94 ± 0.02 12.86 ± 0.02 1.02
C. asiatica 9.81 ± 1.60 5.38 ± 0.01 9.88 ± 0.04 17.54 ± 0.04 1.23
V. officinalis 8.30 ± 1.49 4.96 ± 0.01 8.37 ± 0.02 13.68 ± 0.02 1.04
H. perforatum 8.67 ± 1.47 5.25 ± 0.01 8.77 ± 0.01 14.15 ± 0.02 1.01
C. scolymus 7.79 ± 1.48 4.60 ± 0.01 7.55 ± 0.01 12.48 ± 0.01 1.05

a
The values represent the mean of three determinations ± standard deviation.

(>50 ␮m) with smooth surface often flow better than rough
non-spherical particles. For small particles (<50 ␮m) this state-
ment is not necessarily true, as the interparticle adhesive
forces become relevant. A pronounced roughness can hin-
der the ability of particles to approach each other as smooth
particles can. Therefore, rough particles may exhibit a more
favorable flowability (Schulze, 2008). As it can be seen in Fig. 2,
the spray-drying process usually produces spherical parti-
cles since this is the most stable droplet shape (Nandiyanto
and Okuyama, 2011). Although the spray-dried particles were
small (<50 ␮m), adequate flow properties could be attributed
to their rough surface. Regardless of the different chemical
composition of the medicinal extracts, the SiO2 seemed to be
located on the spray-dried particle surface, diminishing the
cohesion among particles and promoting good flow charac-
teristics.
3.1.4. Skeletal density
As shown in Fig. 2, the SEM micrographs of the spray-
dried extracts suggest that the particles do not present pores

Fig. 1 – Particle size distributions. (a) R. purshiana, (b) H. virginiana, (c) P. boldus, (d) C. asiatica, (e) V. officinalis, (f) H. perforatum
and (g) C. scolymus.
688 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694

Fig. 1 – (Continued).

on the external surface. Consequently, the skeletal density
(Table 4) can be assumed to be representative of the parti-
cle density. According to this, the particle density ranged from
1.497 ± 0.026 to 1.980 ± 0.003 g/ml (Table 5), being common val-
ues for pharmaceuticals powders (Hancock et al., 2003). The
different chemical nature of the tested extract affected the
density of the particles; in fact, the differences were significant
(p < 0.05).
3.1.5. Powders bulk and tap densities and final SR:SiO2
ratio
Although all the obtained spray-dried extracts showed good
flow properties, the powders bulk and tap densities were sig-
nificant different (p < 0.05). In particular, the P. boldus and C.
asiatica powders exhibited the lower values. Powder bulk den-
sity depends primarily on particle size and shape, and the
tendency of particles to adhere to each other (Qiu et al., 2009).

Table 4 – Loss on drying, hygroscopicity, Tg and flow properties of the powders obtained by spray drying.
Powder LOD (%)a HYG (g/100 g)b Tg (◦ C) Cp (J/g ◦ C) ˛ (◦ )c Db (g/ml)d Dt (g/ml)d CI (%)d

R. purshiana 2.53 ± 0.02 9.11 ± 0.03 113.82 0.105 28 ± 1 0.202 ± 0.004 0.267 ± 0.013 24.25 ± 3.30
H. virginiana 2.66 ± 0.05 10.22 ± 0.01 110.57 0.180 28 ± 1 0.216 ± 0.017 0.288 ± 0.027 24.79 ± 2.24
P. boldus 2.69 ± 0.03 10.48 ± 0.05 67.64 0.178 31 ± 3 0.122 ± 0.003 0.164 ± 0.003 25.60 ± 0.69
C. asiatica 2.17 ± 0.09 10.18 ± 0.01 80.53 0.174 30 ± 2 0.127 ± 0.003 0.170 ± 0.007 25.33 ± 2.14
V. officinalis 2.10 ± 0.03 11.09 ± 0.08 78.40 0.303 21 ± 1 0.218 ± 0.011 0.264 ± 0.016 17.42 ± 0.87
H. perforatum 2.00 ± 0.17 9.85 ± 0.11 89.06 0.300 20 ± 2 0.239 ± 0.013 0.295 ± 0.020 19.09 ± 1.05
C. scolymus 2.30 ± 0.04 10.28 ± 0.02 93.86 0.110 30 ± 1 0.209 ± 0.016 0.271 ± 0.014 22.75 ± 4.06

a
The values represent the mean of three determinations ± standard deviation.
b
The values represent the mean of four determinations ± standard deviation.
c
The values represent the mean of twenty determinations ± standard deviation
d
The values represent the mean of sixteen determinations ± standard deviation.
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694 689

In the present study, the particle size and shape were similar
for all the dried extracts; therefore, the differences between
the bulk densities could be related to the particle cohesivity.
The repose angle gives a qualitative assessment of the inter-
nal cohesive and frictional effects under low levels of external
loading; the higher the repose angles the higher cohesivity
(Jain et al., 2012). For this reason, the relationship between the
bulk density and the repose angle was investigated. As gen-
eral trend, it was observed that the bulk density decreased
as the repose angle increased (Table 4). Therefore, it can be
assumed that the dried extracts showing lower bulk densities
(i.e., higher angles of repose) were more cohesive.
As above mentioned, the SR:SiO2 ratio was assessed for
all the spray-dried extracts. The relative composition values
showed in Table 5 indicated that the powders of P. boldus and C.
asiatica had noticeably lower values of SR than those expected
from the liquid feed dispersions formulation (SR:SiO2 ,1:1)
(p < 0.05). The major proportion of SiO2 in the P. boldus and C.
asiatica powders could be responsible of their lower bulk den-
sity and higher cohesivity with respect to the values found for
the other herbal medicinal powders. In fact, this carrier has
a low bulk density, about 0.029–0.042 g/ml (Rowe et al., 2009),
and tendency to cohesion (Evonik Technical Information 1281,
2012b).
3.1.6. Powders X-ray diffraction patterns
The X-ray diffraction technique is usually and satisfactory
employed to evaluate the crystalline or amorphous state of
spray-dried plant extracts and fruit juice powders (Cano-
Chauca et al., 2005; Wang and Zhou, 2012; Fernandes et al.,
2013; Chang et al., 2014). In this work, it has been used to char-
acterize the spray-dried powders obtained from the FPMEs

Fig. 2 – SEM micrographs. (a) R. purshiana 8000 and 1000×, (b) H. virginiana 8000 and 1000×, (c) P. boldus 8000 and 1000×, (d)
C. asiatica 8000 and 1000×, (e) V. officinalis 8000 and 1000×, (f) H. perforatum 8000 and 1000× and (g) C. scolymus 8000 and
1000×.
690 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
Fig. 2 – (Continued).
of R. pushiana, H. virginiana, P. boldus, C. asiatica, V. officinalis,
H. perforatum and C. scolymus and the SiO2 as supplied. The
R. pushiana, H. virginiana, P. boldus, C. asiatica, V. officinalis
and H. perforatum spray-dried powders (including SiO2 as car-
rier) and pure SiO2 exhibited a completely amorphous state,
confirmed by the presence of broad non-defined peaks with
abundant noises (Fig. 3a–g). On the other hand, the C. scoly-
mus powder (with SiO2 as adjuvant) showed an amorphous
halo together with defined peaks associated to crystalline
compounds (Fig. 3h). The amorphous halo is indicated with a
box in Fig. 3h. The crystalline peaks corresponded to KCl and
NaCl (International Centre for diffraction Data (ICDD), 1993).
The presence of these minerals could be related to the high
percentage of potassium and sodium in this medicinal herb
(Mejías, 2008).
3.2. Process yield and powders relative composition
Since the aqueous extracts were obtained by using boiling
water as extraction fluid, as recommended by Alonso (2007),
United States Pharmacopeia and National Formulary (USP 30-
NF 25) (2007) and European Medicines Agency Evaluation of
Medicines for Human Use (EMA) (2009), degradation at tem-
peratures lower than 100 ◦ C is not expected. Even though at
the entrance of the dryer chamber the sprayed liquid formula-
tions were exposed to hot air at 130 ◦ C; the high water content
(98.5%, w/v) of the sprayed droplets minimized thermal degra-
dation. In fact, the water evaporation is a very endothermic
process that leads to a significant cooling of the droplets
(Information Bulletin best@buchi, 2008). From the thermal
point of view, the outlet air temperature becomes the criti-
cal one, because it is the highest temperature at which the
almost dried powder is exposed (Training Papers Spray Drying
BÜCHI Labortechnik AG, 2002). The air outlet temperatures
were between 86 and 87 ◦ C for all the experiments, well below
100 ◦ C; then thermal degradation of the active compounds is
minimized. In fact, Fang and Bhandari (2011) spray dried a
Bayberry juice using an inlet temperature of 150 ◦ C (air out-
let temperature: 80 ◦ C) and observed high recoveries (about
94%) of the antioxidant bioactive components (i.e., phenolic
content and total anthocyanin) in the dried powder.
For lab-scale spray dryers, typical process yields are usually
in the 50–70% range (best@buchi, 2010). Table 5 reports the pro-
cess yield for the seven tested herbs, whose differences were
significant (p < 0.05). For the dried extracts of R. pushiana, H. vir-
giniana, V. officinalis, H. perforatum and C. scolymus the process
yield was between 65 and 95% (Table 5), being these values
more than acceptable. The process yield for the dried extracts
of P. boldus and C. asiatica was lower, around 46% (Table 5). For
these two herbal medicinal powders, the SR:SiO2 ratio found
in the dried product indicated that a selective stickiness of the
herbal extract on the dryer walls took place.
Generally, the main reported cause for stickiness on spray-
dryer walls is the low glass transition temperature given by the
presence of low-molecular weight sugars (essentially sucrose,
glucose, and fructose) in herbal liquid extracts (Tong et al.,
2008; Goula and Adamopoulos, 2010). Among the selected
herbs and according to Table 1, P. boldus, C. asiatica and
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
Fig. 3 – Powder X-ray diffraction patterns. (a) R. purshiana, (b) H. virginiana, (c) P. boldus, (d) C. asiatica, (e) V. officinalis, (f) H.
perforatum, (g) SiO2 and (h) C. scolymus.
V. officinalis contain sugars in their chemical composition. In
good agreement, these medicinal plants exhibited the lowest
Tg values. However, only P. boldus and C. asiatica presented rel-
atively low process yields and powder SR:SiO2 ratios. Although
the spray-dried powder of V. officinalis showed a relatively low
Tg value, its process yield was the highest one (about 94%)
and the powder kept the 1:1 SR:SiO2 proportion. Therefore,
not only the presence of sugars in the chemical composition
of the extracts can be related to the process yield. As it can
be seen in Table 1, the reviewed literature does not report the
presence of phenolic acids in the chemical composition of the
three medicinal plants (i.e., P. boldus, C. asiatica and R. pushiana)
that exhibited the lower process yields and SR:SiO2 ratios dif-
ferent from 1:1. Consequently, the existence of phenolic acids
in the tested herbs appears to be involved in avoiding the
extract stickiness. Regarding the presence of phenolic acids
in spray-drying processes, Medina-Torres et al. (2013) dried a
plant extract with and without gallic acid. The results reported
by these authors indicated that the powder containing gallic
acid had a much higher glass transition temperature than the
691
powder without phenolic content, being this variable strongly
related to stickiness. Certainly, further studies about the influ-
ence of these components on the process yield are needed
in order to understand this effect when chemically complex
extracts are processed (Medina-Torres et al., 2013).
3.3. Compacts’ properties
3.3.1. Compacts’ hardness
For the tested compression force and all the extract powders,
the compact hardness was above 4 kgf (Table 5), indicating
that the co-processed materials were suitable for direct com-
pression (Aulton, 2004). In spite of the different chemical
composition, all the powders had good compactability. This
characteristic together with the good dried extracts’ flowabil-
ity are relevant properties for tablets production.
3.3.2. Compacts’ porosity
The particle and compact apparent densities allow calcu-
lating the compact porosity (Eq. (3)). The compact porosity
692 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694

values ranged from 0.30 to 0.57 (p < 0.05), being this prop-
erty a function of the herbal medicinal powder (Table 5).

DT (min)c

27.5 ± 0.6
11.2 ± 1.5
The P. boldus and C. scolymus dried extracts had similar par-

4.6 ± 0.6
5.5 ± 0.6
8.5 ± 0.6
ticle densities (1.958 and 1.980 g/ml, respectively), however

>30
>30
the P. boldus compact porosity was higher than that obtained
for C. scolymus (Table 5). Additionally, the bulk density of
the P. boldus powder was lower than the one found for C.
scolymus (Table 4). For these two herbal medicinal materials,
0.06
0.12
0.03
0.05
0.13
0.08
0.05
WT (min)b

an inverse relationship between bulk density and compact

±
±
±
±
±
±
±
porosity was found. Analyzing another group of spray-dried
120.24
105.39
6.08
2.47
108.21
113.15
50.49
extracts exhibiting similar particle density (R. purshiana, C. asi-
atica and H. virginiana), the inverse relationship between bulk
density and compact porosity was also verified. The trend
found between the compact porosity and the bulk density can-
not be verified for H. perforatum and V. officinalis, since these
0.014
0.003
0.017
0.005
0.069
0.040
0.001
Compact
porositya

materials have both different compact porosity and particle

±
±
±
±
±
±
±

density.
0.45
0.44
0.55
0.57
0.30
0.38
0.46

3.3.3. Wetting time

Wetting is closely related to the inner structure of the com-
apparent density

pacts and the hydrophilicity of their components (Pabari and

Compact

0.933
0.955
0.879
0.750
1.052
1.007
1.062
(g/ml)

Ramtoola, 2012). The wetting time of P. boldus and C. asiat-

ica compacts were considerably lower than those of the other
extracts (p < 0.05) (Table 5). This behavior can be explained
in terms of: (a) the relatively high porosity of these com-
pacts (∼0.56) and (b) the higher proportion of SiO2 , which is
a hydrophilic material, in the P. boldus and C. asiatica pow-
hardness (kgf )c

ders (0.4:1 and 0.5:1 SR:SiO2 , respectively) with respect to other

Compact

1.1
0.4
0.8
0.6
0.9
0.9
0.6

spray-dried extracts.
±
±
±
±
±
±
±
4.6
5.6
4.5
5.3
5.6
5.1
5.6

3.3.4. Disintegration time

Table 5 – Skeletal density, final SR:SiO2 ratio, process yield and compacts properties.

Disintegration of a tablet into primary particles is relevant,

as it determines the effective surface area for dissolution and
1.52
1.35
1.25
1.06
1.51
2.11
1.57

subsequent absorption of the active principles. In this sense,

PY (%)b

pharmacopoeias establish 30 min as the maximum disinte-

±
±
±
±
±
±
±
65.17
77.24
46.54
46.76
94.34
87.96
79.51

gration time for uncoated tablets in a test liquid (e.g., water)

(Ansel et al., 2009). Taking into account that just aqueous
The values represent the mean of three determinations ± standard deviation.

extracts were spray-dried and that the corresponding pow-

The values represent the mean of two determinations ± standard deviation.
The values represent the mean of six determinations ± standard deviation.

ders were mainly amorphous and constituted by fine particles,

high dissolution rates are expected in aqueous medium, being
Final SR:SiO2

the disintegration time the expected rate-limiting step for the

ratiob

0.8:1

0.5:1
0.4:1

extract release.
1:1

1:1
1:1
1:1

According to the results reported in Table 4, the disin-

tegration time of the compacted spray-dried extracts was
significant different (p < 0.05) and satisfactory, except for P.
boldus and C. asiatica. Despite their high porosity, the com-
pacts of these herbs exhibited disintegration times higher
Skeletal density

0.005
0.009
0.055
0.022
0.026
0.049
0.003

than 30 min (Table 5). These two medicinal herbs were also
(g/ml)a

the ones that had the lowest SR:SiO2 ratio (0.4:1 and 0.5:1,
±
±
±
±
±
±
±

respectively), or in other words the highest SiO2 content. This

1.708
1.720
1.958
1.756
1.497
1.629
1.980

drying adjuvant is practically insoluble in water (Rowe et al.,

2009); therefore, this property could explain the very high dis-
integration times found for the compacts of P. boldus and C.
asiatica. A similar behavior, although attenuated, was observed
Spray dried medicinal

for the compacts based on the R. purshiana dried extract (0.8:1

SR:SiO2 ).
Further studies should be done to optimize the tablets
H. perforatum
H. virginiana
R. purshiana

V. officinalis

C. scolymus

properties by means of the addition of other excipients. Par-

C. asiatica
P. boldus
extracts

ticularly, the disintegration time for P. boldus and C. asiatica

could be improved by adding disintegrants into the formula-
tion, common practice in the industry.
a

b
c
 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
4. Conclusions
This work demonstrated that a unique set of spray-drying
operating conditions (drying air inlet temperature: 130 ◦ C,
atomization air volumetric flowrate: 400 l/h, feed volumet-
ric flowrate: 3 ml/min and drying air volumetric flowrate:
35–38 m3 /h, liquid feed formulation: SR:SiO2 , 1:1) was ade-
quate to obtain spray-dried extracts with good flowability,
stability and compactability from different herbal medicine
(P. boldus Mol., C. asiatica (L.) Urb., Valeriana officinalis L., H.
perforatum L., H. virginiana L. and C. scolymus L.). The char-
acterization of the different spray-dried extracts and their
compacts revealed the effect of the herbs’ chemical nature on
the products’ physical behavior. In this sense, it was found
that particle size and morphology, powder loss on drying,
hygroscopicity and flow properties as well as compact hard-
ness were not strongly affected by the chemical composition
of the medicinal herb. On the other hand, the process yield
and some powder and compact properties (i.e., glass transition
temperature, particle and bulk densities, powder composition,
compact porosity, wetting and disintegration times) were dif-
ferent among the tested spray-dried extracts. These properties
were correlated with the different chemical composition of the
studied herbs, by thorough analysis.
In summary, this contribution identifies the powder prop-
erties that significantly change with the chemical nature of
the tested plant extracts and gives a set of operating condi-
tions for the spray-drying step as well as recommendations
for the corresponding liquid feed formulation. Besides, the
powders exhibited adequate properties for direct compression
allowing the production of tablets with high dose, uniform
dosage and weight, which are relevant aspects for a safe
phytotherapy. This information was generated to assist both
phytomedicine researchers and industry in the production of
spray-dried herbal powders from aqueous extracts of medici-
nal herbs, reducing the time and costs of production for new
herbal medicine products.
Acknowledgements
The authors express their gratitude for the financial support
granted by the Consejo Nacional de Investigaciones Científicas
y Técnicas (CONICET), the Universidad Nacional del Sur (UNS)
and the Agencia Nacional de Promoción Científica y Tecnológ-
ica (ANPCyT). The authors thank Lic. F. Cabrera (PLAPIQUI) for
her technical assistance.
References
Albertini, B.CHERD-2042, Passerini, N., González-Rodríguez, M.L.,
Perissutti, B., Rodriguez, L., 2004. Effect of Aerosil® on the
properties of lipid controlled release microparticles. J. Control.
Release 100, 233–246.
Alonso, J., 2007. Tratado de Fitofármacos y Nutracéuticos.
Editorial Corpus, Rosario.
Ansel, H.C., Popovich, N.G., Allen, L.V., 2009. Pharmaceutical
Dosage Forms and Drug Delivery Systems, ninth ed.
Lippincott Williams &Wilkins, Philadelphia, PA.
Aulton, M.E., 2004. Farmacia. La ciencia del diseño de las formas
farmacéuticas, segunda ed. Elsevier, España.
Banker, G.S., Rhodes, C.T., 2002. Modern Pharmaceutics, fourth
ed. Marcel Dekker, New York, NY.
best@buchi, 59 (2010). available at https://partnernet.buchi.com/
uploads/media/59 . Laboratory Scale Spray Drying of
inhalable drugs.pdf (accessed on 2nd October, 2014).
693
Cano-Chauca, M., Stringheta, P.C., Ramos, A.M., Cal-Vidal, J.,
2005. Effect of the carriers on the microstructure of mango
powder obtained by spray drying and its functional
characterization. Innov. Food Sci. Emerg. 6, 420–428.
Chauhan, B., Shimpi, S., Paradkar, A., 2005. Preparation and
evaluation of glibenclamide–polyglycolized glycerides solid
dispersions with silicon dioxide by spray drying technique.
Eur. J. Pharm. Sci. 26, 219–230.
Choudhari, S.B., Nilesh, M., Bhalerao, A.V., 2014. Self
microemulsifying drug delivery system for treatment of
emesis. Asian J. Pharm. Technol. Innov.: AJPTI 02, 01–10.
Cortés-Rojas, D.F., Oliveira, W.P., 2012. Physicochemical properties
of phytopharmaceutical preparations as affected by drying
methods and carriers. Dry. Technol. 30, 921–934.
Couto, R.O., Conceição, E.C., Chaul, L.T., Oliveira, E.M.S., Martins,
F.S., Bara, M.T.F., Rezende, K.R., Alves, S.F., Paula, J.R., 2012.
Spray-dried rosemary extracts: physicochemical and
antioxidant properties. Food Chem. 131, 99–105.
Dixit, R.P., Nagarsenker, M.S., 2008. Self-nanoemulsifying
granules of ezetimibe: design, optimization and evaluation.
Eur. J. Pharm. Sci. 3, 183–192.
Dokala, G.K., Pallavi, C., 2013. Direct compression—an overview.
Int. J. Pharm. Biomed. Res. 4, 155–158.
European Medicines Agency Evaluation of Medicines for Human
Use (EMA), 2009. Assessment Report on Hamamelis virginiana
L. European Medicines Agency Evaluation of Medicines for
Human Use (EMA), London.
Evonik Technical Information TI 1367, 2012a. Converting Liquids
to Dry Flowable Powders and Retaining Flavors on SIPERNAT®
Specialty Silica and AEROSIL® Fumed Silica, Available at
http://www.aerosil.com/lpa-im1-literaturefinder/page/lit/
finder/index?page=3&pattern=rubricId= (accessed on 2nd
December, 2013).
Evonik Technical Information 1281, 2012b. AEROSIL® and
AEROPERL® Colloidal Silicon Dioxide for Pharmaceuticals,
Available at http://www.aerosil.com/lpa-im1-literaturefinder/
page/lit/finder/index?page = 2&pattern = &rubricId= (accessed
on 2nd December, 2013).
Fang, Z., Bhandari, B., 2011. Effect of spray drying and storage on
the stability of bayberry polyphenols. Food Chem. 129,
1139–1147.
Gad, S.C., 2008. Pharmaceutical Manufacturing Handbook:
Production and Processes, ninth ed. John Wiley & Sons, New
Jersey.
Gallo, L., Llabot, J., Allemandi, D., Bucalá, V., Piña, J., 2011.
Influence of spray-drying operating conditions on Rhamnus
purshiana (Cascara sagrada) extract powder physical
properties. Powder Technol. 208, 205–214.
Gallo, L., Piña, J., Bucalá, V., Allemandi, D., Ramírez-Rigo, M.V.,
2013. Development of a modified-release hydrophilic matrix
system of a plant extract based on co-spray-dried powders.
Powder Technol. 241, 252–262.
Global Industry Analysts, Inc, 2013. Herbal Supplements and
Remedies—A Global Strategic Business Report, Available at
http://www.strategyr.com/Herbal Supplements and
Remedies Market Report.asp (accessed on 5th December,
2013).
Gonnissen, Y., Gonçalves, S.I.V., De Geest, B.G., Remon, J.P.,
Vervaet, C., 2008. Process design applied to optimize a directly
compressible powder produced via a continuous
manufacturing process. Eur. J. Pharm. Biopharm. 68, 760–770.
Goula, A.M., Adamopoulos, K.G.A., 2010. New technique for spray
drying orange juice concentrate. Innov. Food Sci. Emerg. 11,
342–351.
Hancock, B.C., Colvin, J.T., Mullarney, M.P., Zinchuk, A.Z., 2003.
The relative densities powders, blends, dry granulations and
immediate-release tablets. Pharm. Technol., 64–80.
Information Bulletin best@buchi, 2008. Scale-up from the Büchi
Mini Spray Dryer B-290 to the Niro MOBILE MINOR , vol. 52.,
pp. 1–8, Available at http://www.buechigmbh.de/uploads/.
media/Best Buchi 52 Scale-up B-
290 Niro MOBILE MINOR 05.pdf (accessed on 30th October,
2012).
694 chemical engineering research and design 1 0 4 ( 2 0 1 5 ) 681–694
International Centre for diffraction Data (ICDD), 1993. Mineral
Powder Diffraction File Databook. ICDD, U.S.A.
Krishnaiah, D., Bono, A., Sarbatly, R., Nithyanandam, R.,
Anisuzzaman, S.M., 2012. Optimisation of spray drying
operating conditions of Morinda citrifolia L. fruit extract using
response surface methodology. J. King Saud Univ.—Eng. Sci.,
http://dx.doi.org/10.1016/j.jksues.2012.10.004.
León-Martínez, F.M., Méndez-Lagunas, L.L., Rodríguez-Ramírez, J.,
2010. Spray drying of nopal mucilage (Opuntia ficus-indica):
effects on powder properties and characterization. Carbohyd.
Polym. 81, 864–870.
Mejías, M., 2008. Todo lo que debería saber sobre las plantas
adelgazantes. Editorial Edaf, Madrid S.L.
Mesnier, X., Althaus, T.O., Forny, L., Niederreiter, G., Palzer, S.,
Hounslow, M.J., Salman, A.D., 2013. A novel method to
quantify tablet disintegration. Powder Technol. 238, 27–34.
Mujumdar, A.S., 2006. Handbook of Industrial Drying, third ed.
CRC Press, Singapore.
Nandiyanto, A.B.D., Okuyama, K., 2011. Progress in developing
spray-drying methods for the production of controlled
morphology particles: from the nanometer to submicrometer
size ranges. Adv. Powder Technol. 22, 1–19.
Nguyen, T.H., Morton, D.A.V., Hapgood, K.P., 2013. Application of
the unified compaction curve to link wet granulation and
tablet compaction behavior. Powder Technol. 240, 103–115.
Oliveira, O.W., Petrovick, P.R., 2010. Secagem por aspersao (spray
drying) de extractos vegetais: bases e aplicaçoes. Rev. Bras.
Farmacogn. 20, 641–650.
Pabari, R.M., Ramtoola, Z., 2012. Effect of a disintegration
mechanism on wetting water absorption, and disintegration
time of Oro dispersible tablets. J. Young Pharm. 4, 157–163.
Pandey, M., Debnath, M., Gupta, S., Chikara, S.K., 2011.
Phytomedicine: an ancient approach turning into future
potential source of therapeutics. J. Pharmacognosy Phytother.
3, 27–37.
Pang, S.F., Yusoff, M.M., Gimbun, J., 2014. Assessment of phenolic
compounds stability and retention during spray drying of
Orthosiphon stamineus extracts. Food Hydrocolloid. 37, 159–165.
Qiu, Y., Chen, Y., Zhang, G.G.Z., Liu, L., Porter, W., 2009.
Developing Solid Oral Dosage Forms: Pharmaceutical Theory
and Practice, first ed. Elsevier Inc., New York, NY.
Rattes, A.L.R., Oliveira, W.P., 2007. Spray drying conditions and
encapsulating composition effects on formation and
properties of sodium diclofenac microparticles. Powder
Technol. 171, 7–14.
Real Farmacopea Española (RFE), 2005. Ministerio de Sanidad y
Consumo, tercera ed. Agencia Española del Medicamento,
Madrid.
Robinson, M.M., Zhang, X., 2011. The world medicine situation
2011 (Traditional medicine: global situation, issues, and
challenges), third ed. World Health Organization, Geneva.
Rowe, R.C., Sheskey, P.J., Quinn, M.E., 2009. Handbook of
Pharmaceutical Excipients, sixth ed. Pharmaceutical Press,
London.
Şahin-Nadeem, H., Dinçer, C., Torun, M., Topuz, A., Özdemir, F.,
2013. Influence of inlet air temperature and carrier material
on the production of instant soluble sage (Salvia fruticosa
Miller) by spray drying. LWT—Food Sci. Technol. 52,
31–38.
Sarrate, R., Ticó, J.R., Miñarro, M., Carrillo, C., Fàbregas, A.,
García-Montoya, E., Pérez-Lozano, P., Suñé-Negre, J.M., 2015.
Modification of the morphology and particle size of
pharmaceutical excipients by spray drying technique. Powder
Technol. 270, 244–255.
Schulze, D., 2008. Powders and Bulk Solids: Behavior,
Characterization, Storage and Flow. Springer-Verlag, Berlin,
Heidelberg.
Schüssele, A., Bauer-Brandl, A., 2003. Note on the measurement
of flowability according to the European Pharmacopoeia. Int. J.
Pharm. 257, 301–304.
Shrestha, A.K., Howes, T., Adhikari, B.P., Bhandari, B., 2007. Water
sorption and glass transition properties of spray dried lactose
hydrolyzed skim milk powder. LWT—Food Sci. Technol. 40,
1593–1600.
Shyu, L.F., 2012. Recent Trends in Medicinal Plants Research, first
ed. Elsevier, London.
Soares, L.A.L., González Ortega, G., Petrovick, P.R., Schmidt, P.C.,
2005a. Dry granulation and compression of spray-dried plant
extracts. AAPS PharmSciTech 6, 359–366.
Soares, L.A.L., Ortega, L.L., Petrovick, P.R., Schmidt, P.C., 2005b.
Optimization of tablets containing a high dose of spray-dried
plant extract: a technical note. AAPS PharmSciTech 6,
E367–E371.
Souza, T.P., Bassani, V.L., González Ortega, G., Dalla Costa, T.C.T.,
Petrovick, P.R., 2001. Influence of adjuvants on the dissolution
profile of tablets containing high doses of spray-dried extract
of Maytenus ilicifolia. Pharmazie 56, 730–733.
Souza, C.R.F., Oliveira, W.P., 2006. Powder properties and system
behavior during spray drying of Bauhinia forficata link extract.
Dry. Technol. 24, 735–749.
Souza, T.P., Martínez-Pacheco, R., Gómez-Amoza, J.L., Petrovick,
P.R., 2007. Eudragit E as excipient for production of granules
and tablets from Phyllanthus niruri L. spray dried extract. AAPS
PharmSciTech 8, E1–E7.
Swarbrick, J., Boylan, J.C., 2007. Encyclopedia of Pharmaceutical
Technology, second ed. Marcel Dekker, New York, NY.
Tewa-Tagne, P., Brian(on, S., Fessi, H., 2006. Spray-dried
microparticles containing polymeric nanocapsules:
formulation aspects, liquid phase interactions and particles
characteristics. Int. J. Pharm. 325, 63–74.
Tong, H.H., Wong, S.Y., Law, M.W., Chu, K.K., Chow, A.H., 2008.
Anti-hygroscopic effect of dextrans in herbal formulations.
Int. J. Pharm. 363, 99–105.
Tonon, R.V., Brabet, C., Hubinger, M.D., 2008. Influence of process
conditions on the physicochemical properties of açai (Euterpe
oleraceae Mart.) powder produced by spray drying. J. Food Eng.
88, 411–418.
Training Papers Spray Drying BÜCHI Labortechnik AG, 2002.
United States Pharmacopeia and National Formulary (USP 30-NF
25), 2007. The United States Pharmacopeial Convention.
United States Pharmacopeia and National Formulary,
Rockville, MD.
Vasconcelos, E.A.F., Medeiros, M.G.F., Raffin, F.N., Moura, T.F.A.L.,
2005. Influência da temperatura de secagem e da
concentração de Aerosil® 200 nas características dos extratos
secos por aspersão da Schinus terebinthifolius Raddi
(Anacardiaceae). Rev. Bras. Farmacogn. 15, 243–249.
Wang, W., Zhou, W., 2012. Characterization of spray-dried soy
sauce powders using maltodextrins as carrier. J. Food Eng. 109,
399–405.
WHO, 2002. Monographs on Selected Medicinal Plants. World
Health Organization, Geneva.
Chang, Y.X., Yang, J.J., Pan, R.L., Chang, Q., Liao, Y.H., 2014.
Anti-hygroscopic effect of leucine on spray-dried herbal
extract powders. Powder Technol. 266, 388–395.
Zhang, J., Wider, B., Shang, H., Li, X., Ernst, E., 2012. Quality of
herbal medicines: challenges and solutions. Complement.
Ther. Med. 20, 100–106.