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Ball Milling Synthesis of Silica Nanoparticle from

Rice Husk Ash for Drug Delivery Application

Article in Combinatorial chemistry & high throughput screening · August 2012

DOI: 10.2174/1386207311316060006 · Source: PubMed

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458 Combinatorial Chemistry & High Throughput Screening, 2013, 16, 458-462

Ball Milling Synthesis of Silica Nanoparticle from Rice Husk Ash for Drug
Delivery Application
Masoud Salavati-Niasari*,1,2, Jaber Javidi1 and Mahnaz Dadkhah1

1
Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167, I.R. Iran
2
Department of Inorganic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, P.O. Box. 87317-51167, I.R.
Iran

Abstract: Silica nanoparticles were synthesized from rice husk ash at room temperature by using high energy planetary
ball mill. The milling time and mill rotational speed were varied in four levels. The morphology of the synthesized
powders was investigated by the FE-SEM and TEM image as well as XRD patterns. The results have revealed that the
nano-sized amorphous silica particles are formed after about 6 h ball milling and they are spherical in shape. The average
particle size of the silica powders is found to be around 70 nm which decreases with increasing ball milling time or mill
rotational speed. The as-synthesized silica nanoparticles were subsequently employed as drug carrier to investigate in
vitro release behavior of Penicillin-G in simulated body fluid. UV-Vis spectroscopy was used to determine the amount of
Penicillin-G released from the carrier. Penicillin-G release profile from silica nanoparticles exhibited a delayed release
effect.
Keywords: Drug release, penicillin-G, planetary ball mill, porous silica nanoparticles, rice husk ash.

1. INTRODUCTION raw material and chitosan as a template to prepare bimodal

Rice husk is one of the main waste products of the rice
milling industry which contains about 20% ash. The annual
global production of rice husk is approximately 100 million
tons [1]. During the burning of rice husk, the residual ash is
called rice husk ash with chemical composition of: 94.95%
SiO2, 0.85% loss on ignition, 0.54% CaO, 0.26% Fe2O3,
0.90% MgO, 0.25% Na2O, 0.39% Al2O3, 0.16% MnO,
0.74% P2O5, 0.02% TiO2 and 0.94% K2O [2]. Due to silica as
its main component, rice husk ash has wide applications as
filler, adsorbent, additive, oil adsorbent, water purifier, and
also a source for synthesis of high performance silicon and
its compounds [3-5]. Silicon which is extracted from rice
husk can be employed as an excellent source in the
preparation of amorphous nanosilica [6]. Amorphous silica
powder is a basic raw material that is widely used in
industries associated with ceramics, rubber, electronics,
catalysis, pharmaceutics, and dental materials [7, 8]. Several
methods have been reported for extraction of pure silica
from rice husk ash including fluidized bed [9],
decomposition in oxidizing atmospheres [10], chemical
treatment using acid and base solutions [11], pressurized hot-
water treatment processes [12], and carbonization and
combustion [13]. Zhang et al. [14] used rice husk as a
precursor to obtain nano-sized silica with a diameter of 30–
200 nm by incinerating the pre-treated sample in stationary
air. Recent studies have shown production of silica
nanoparticles by rice husk biotransformation using Fusarium
oxysporum fungus [15] or through a bio-digestion process
using worms [16]. Witoon et al. [17] used rice husk ash as
*Address correspondence to this author at the Institute of Nano Science and
Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167,
I.R. Iran; Tel: +98 361 591 2383; Fax: +98 361 555 29 30;
E-mail: salavati@kashanu.ac.ir
porous silica. Rice husk ash has good adsorption properties and
has been used as adsorptive for removal of metal ions [18] and
dyes [19]. But the ball milling method is not still used for the
synthesis of silica nanoparticles from rice husk. In comparison
with other methods, this process has many advantages such as
cost effectiveness, high purity of products, low-temperature
reaction, controllability, facility, and reproducibility. Particulate
drug carriers are mainly in the forms of oil-in-water emulsions,
liposomes, microparticles and nanoparticles based on synthetic
polymers or natural macromolecules [20, 22]. For controlled
release of drugs in delivery systems, silica is capable of storing
and gradually releasing of drugs, therapeutically. Furthermore,
silica nanoparticles were used to enhance the biocompatibility
of several drug delivery systems, such as magnetic nanoparticles
[23], biopolymers [24], and micelles [25]. Recently novel silica
carriers have been developed [26, 27]. For instance, Vallet-Regí
et al. have demonstrated the release of ibuprofen, erythromycin
and alendronate from silica [28-30] and moreover, Suzuki et al.
[31] reported a kind of silica–poly(N-isopropylacrylamide)
hybrid gels as drug carrier.
In this paper, a novel pathway for extraction and the
mechanochemical synthesis of porous silica nanoparticles
from rice husk ash at room temperature without applying
additional heat treatment or any chemical reagent and
surfactant is presented. Then, these nanoparticles were
employed as drug carrier to investigate their performance on
the controlled release of Penicillin-G.
2. MATERIALS AND METHODS
2.1. Materials
Rice husk (RH) was collected from a rice mill in Shiraz,
Iran and Penicillin-G was purchased from Jaberebne Hayyan
Pharma. Co., Iran. Other materials used in our experiments

1875-5402/13 $58.00+.00 © 2013 Bentham Science Publishers

Ball Milling Synthesis of Silica Nanoparticle Combinatorial Chemistry & High Throughput Screening, 2013, Vol. 16, No. 6 459

were of analytical grade and were used as received without of the solution was collected from the released media and
further purifications. XRD patterns were recorded by a replaced with fresh SBF. Then the released Penicillin-G was
Rigaku D-max CIII, X-ray diffractometer using Ni filtered analyzed by UV-Vis spectrophotometer.
Cu K radiation. FE-SEM images were obtained on Table 1. Experimental Condition for the Preparation of
HITACHI S-4160. Transmission electron microscopy (TEM) Porous Silica Nanoparticles
images were obtained on a Philips EM208 transmission
electron microscope with an accelerating voltage of 100 Kv.
Fourier transform infrared (FT-IR) spectra were recorded on Sample Rotational Speed (rpm) Milling Time (h)
Shimadzu Varian 4300 spectrophotometer in KBr pellets.
1 100 1
2 100 2
2.2. Preparation of Porous Silica Nanoparticles
3 100 3
The rice husk (RH) was washed with water for several 4 300 1
times to remove dirt and other contaminants and dried at 5 300 2
80oC for 12 h. The cleaned pure RH was then burnt inside a 6 300 3
muffle furnace and heated at 400°C for 1 h and then kept at 7 500 1
700°C for 1 h. At 400°C the organic compounds 8 500 2
decomposed off and at 700°C the large amount of ash with
9 500 3
high silica content was obtained. The obtained white rice
10 600 1
husk ash (RHA) was used for silica extraction and
preparation of silica nanoparticles. 5.0 g of the RHA sample 11 600 2
was added to 250 mL of HNO3 solution (1.0 M) and stirred 12 600 3
for about 10 h at room temperature to remove the metal
oxide (CaO, Fe2O3, MgO, Na2O, Al2O3, MnO, P2O5, TiO2
and K2O) from RHA and extract the silica. The resulting The loading capacity and the encapsulation efficiency of
white powder was filtered and washed three times with the Silica nanoparticles were calculated according to the
ethanol and distilled water. The washed powder was dried at following formula:
80°C for 3 h under vacuum. For preparation of silica Drug loading capacity =
nanoparticles 0.45 g of extracted silica was ball milled in a (Wadministered dose - Wresidual dose in solution) / WSilica nano particl
50 ml agate jar with 10 numbers of 10 mm diameter and 1.49
Encapsulation efficiency =
g weight agate milling balls at 100, 300, 500 and 600 rpm in
(Wadministered dose - Wresidual dose in solution) / Wadministered dose
100%
a high energy planetary ball mill. Different samples were
prepared by varying the milling duration such as 1, 2 and 3 where Wadministered dose is the weight of Penicillin-G for
h. Table 1 shows the experimental conditions in detail and a loading, Wresidual dose in solution is the weight of residual
flow diagram of the above procedure is shown in Fig. (1). Penicillin-G in solution after loading onto silica nanoparticle,
and WSilica nano particles is the weight of silica nanoparticles for
2.3. Examination of the Porous Silica Nanoparticles as a loading.
Carrier of Penicillin-G
3. RESULTS AND DISCUSSION
1.0 g Penicillin-G was dissolved in 10 ml of deionized
water. Then 0.5 g of porous silica nanoparticle was added to The effect of mill rotational speed and milling times on
the Penicillin-G solution and was stirred vigorously for about the morphology and particle size of the products was
10 h. After rinsing with acetone to remove unentrapped investigated. FE-SEM images of the formed nanoparticles
Penicillin-G, the powder with the entrapped drug was dried are shown in Fig. (2). With the increasing of mill rotational
in vacuum condition at 50°C for 3 h. In vitro release of speed (from 300 rpm to 600 rpm) at constant milling time,
Penicillin-G was performed by immersing silica powder in the size of nanoparticles became smaller. Also with the
simulated body fluid (SBF). The SBF was prepared by increasing of milling time (from 1h to 3 h) at constant mill
dissolving reagent grade of NaCl, NaHCO3, KCl, Na2HPO4 rotational speed, the size of nanoparticles decreased. The
2H2O, MgCl26H2O, CaCl22H2O, and Na2SO4 in deionized average particle sizes less than 150 nm were obtained by
water. The solution was buffered to pH 7.4 with Tris buffer milling at 300 rpm and increase of the milling time to 3 h.
and hydrochloric acid. For drug release, 0.1 g the silica However, there was an increase in the average particle sizes
powder with the entrapped drug was immersed into 100 ml by milling in higher speeds which occurred in 500 rpm (Fig.
SBF solution at 37°C. At predetermined time intervals, 5 ml 2e). This illustrates the start point of particle aggregations

1. 400 oc HNO 3
Rice husk Rice husk ash SiO 2 extracted
2. 700 oc

Ball milling

Drug loadding
SiO2 +Drug SiO 2 nano
Fig. (1). A flow diagram of synthesis of silica nanoparticles and drug loadding.
460 Combinatorial Chemistry & High Throughput Screening, 2013, Vol. 16, No. 6 Salavati-Niasari et al.

Fig. (2). FE-SEM images of the formed nanoparticles.

where smaller particles aggregate to form larger particles.
Then with the increasing of mill rotational speed to 600 rpm,
the size of nanoparticles became smaller.
(Fig. 3a) shows the size of silica nanoparticles as a
function of mill rotational speed at various milling times.
Generally, the particle size decreases when the milling speed
and time increases and the curves indicate that further size
reduction of silica nanoparticles can be achieved by
increasing the milling time and speed. Roshaida et al. [32]
reported similar observations. In the current work, sample

Fig. (3). Particle size as a function of Grinding parameters (a), TEM image (b), FT-IR spectra (c) and XRD patterns (d) of sample no. 12.
Ball Milling Synthesis of Silica Nanoparticle
no. 3 was prepared at 600 rpm for 3h and its particle size was
70 nm. The particle size of silica nanoparticles were further
analyzed by using TEM. (Fig. 3b) shows the image of the
formed nanoparticles at the highest rate of milling (sample
no. 12). The size of nanoparticles obtained from the SEM
image (Fig. 2k) are in close agreement with the TEM studies
which shows sizes of 70-75 nm for sample no. 12.
The infrared spectra of silica nanoparticles (sample no.
12) are shown in Fig. (3c). The broad band between 3500
1
and 3750 cm is attributed to silinol OH groups and
adsorbed water. The absorption peaks of the Si–O–Si
asymmetric stretching vibration were observed at 1090 cm1.
1
The peaks between 1200 and 700 cm are attributed to
vibration modes of the silica network.
XRD analysis is the most useful technique for
identification of crystalline structure. In Fig. (3d), the X-ray
diffraction pattern of sample no. 12 is shown. Strong broad
peaks of nanosilica are centered in the range of
2223°
(2), which are in agreement with the strong broad peak of a
characteristic of amorphous SiO2, to some extent [33].
In vitro release of Penicillin-G from the nanoporous
silica carrier was also investigated. The drug loading and
drug release content were measured from UV absorbance
spectra on the basis of Beer–Lambert law: A=
cb; where A
is the absorption intensity, c is the Penicillin-G
concentration, b is the path length of the radiation through
the absorbing medium and
is proportionality constant. By
using UV data, Penicillin-G exhibit absorptions at max = 280
nm and 67% Penicillin-G solution was loaded in nanoporous
silica carrier. The release profiles of Penicillin-G from
nanoporous silica are shown in Fig. (4). The release profile
of Penicillin-G could be divided into three levels. The first
level of release phenomenon was due to a rapid release of
Penicillin-G which reached near 40% within the first 1h. It
was due to the releasing the adsorbed drug on the surface of
silica nanoparticles. The second level shows a slow increase
of Penicillin-G release from 40% to near 80% within 30 h
which might be attributed to the release of the entrapped
Penicillin-G between the particles or in the channels pores of
porous silica nanoparticles. The final stage reached a plateau
where the release of Penicillin-G had an insignificant
increase from 30 to 60 h. This might arise from the release of
Penicillin-G from the inside part of nanoporous silica carrier.
Fig. (4). In vitro release profile of Penicillin-G from porous silica.
Combinatorial Chemistry & High Throughput Screening, 2013, Vol. 16, No. 6 461
4. CONCLUSION
A novel method for the synthesis of porous silica
nanoparticles form rice husk ash by high energy planetary
ball mill was developed and effect of grinding parameters on
size of the formed particle were investigated. The silica
nanoparticle had a uniform spherical structure with a
diameter of 70 – 75 nm. The silica nanoparticle was
employed as drug carrier to investigate the release behavior
of Penicillin-G in SBF. The release profile of Penicillin-G
had three levels, which was attributed as the drug release
from the surface, pore channels and the inside part of the
porous silica carrier, respectively. It can be concluded that
the nanoporous silica carrier delayed the release of
Penicillin-G and can be exploited in controlled release of
drugs.
CONFLICT OF INTEREST
The authors confirm that this article content has no
conflicts of interest.
ACKNOWLEDGEMENTS
Authors are grateful to the council of Iran National
Science Foundation and University of Kashan for supporting
this work by Grant No (159271/30).
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Accepted: August 23, 2012