Applied Clay Science 8081 (2013) 8592

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Applied Clay Science

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

Research paper

Claypolymer nanocomposites as a novel drug carrier: Synthesis,

characterization and controlled release study of
Propranolol Hydrochloride
Seema, Monika Datta
Analytical Research Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India

a r t i c l e

i n f o

Article history:
Received 25 May 2012
Received in revised form 17 May 2013
Accepted 1 June 2013
Available online 10 July 2013
Keywords:
Claypolymer nanocomposites,
Montmorillonite
Controlled drug delivery
Antihypertensive drug

a b s t r a c t
Short half life of Propranolol Hydrochloride (PPN), an antihypertensive drug is a prime requirement to develop a formulation which could extend the release of PPN in the human body and also eliminate daily multiple
dosage of PPN. In this study, a system of PPN loaded MontmorillonitePoly lactic-co-glycolic acid (MtPLGA)
nanocomposites has been developed. PPN incorporated PLGA nanoparticles have been compared with
MtPPNPLGA nanocomposites. Mt was used as sustained release carrier for PPN with addition of biodegradable
polymer PLGA by preparing MtPPNPLGA nanocomposites by double emulsion solvent evaporation method.
The drug encapsulation efciency and drug loading capacity of synthesized products were estimated with
HPLC including suitable analytical techniques to conrm the formation of claypolymer nanocomposites
(CPN). The release prole of encapsulated PPN in CPN shows pH dependent release in simulated gastrointestinal uid for a period of 8 h. This study suggests that the methodologies used are suitable for the synthesis of
Mt based PLGA nanocomposites with high drug encapsulation efciency and controlled drug release characteristics and indicates that the MtPPNPLGA nanocomposites are supposed to be better oral controlled drug
delivery system, for a highly hydrophilic low molecular weight antihypertensive drug PPN to minimize the
drug dosing frequency and hence improving the patient compliance.
2013 Elsevier B.V. All rights reserved.

1. Introduction
Drug delivery systems have been of great interest for the past few
decades to realize the effective and controlled drug delivery and minimize the side effects in the eld of pharmaceutics. Oral controlled
drug delivery system is an essential part of the development of new
medicines. The carriers used for control drug release were mainly biodegradable polymers (Langer et al., 1999) and porous inorganic matrix (Suresh et al., 2010; Aguzzi et al., 2007).
In recent years, drug intercalated smectite, especially Montmorillonite
(Mt) pharmaceutical grade clay mineral has attracted great interest of researchers (Joshi et al., 2009a,b). Mt has large specic surface area, exhibits
good adsorption ability, cation exchange capacity, and drug-carrying capability. Mt is hydrophilic and highly dispersible in water and can accommodate various protonated and hydrophilic organic molecules along the
(001) planes which can be released in controlled manner by replacement
with other kind of cations in the release media (Bergaya et al., 2006; Chen
et al., 2010; Iliescu et al., 2011). Therefore the Mt is suggested to be a good
delivery carrier of the hydrophilic drugs. Mt is a potent detoxier with excellent adsorbent properties due to its high aspect ratio. It can adsorb excess water from feces and thus act as anti-diarrhoeic. Mt can also provide
Corresponding author. Tel.: +91 9811487825; fax: +91 11 27666605.
E-mail address: monikadatta_chem@yahoo.co.in (M. Datta).
0169-1317/$ see front matter 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.clay.2013.06.009

mucoadhesive capability for the nanoparticles to cross the gastrointestinal barrier (Dong and Feng, 2005; Feng et al., 2009). It has also been
used as a controlled release system. Mt has been proved to be nontoxic
by hematological, biochemical and histopathological analyses in rat
models (Lee et al., 2005). Mt is utilized as a sustained release carrier
for various therapeutic molecules, such as 5 Fluorouracil (Lin et al.,
2002), sertraline (Nunes et al., 2007), vitamin B1 (Joshi et al., 2009a,b),
promethazine chloride (Seki and Kadir, 2006) and buspiron hydrochloride (Joshi et al., 2010).
Propranolol Hydrochloride [(2RS)-1-(1-Methylethyl) amino-3(naphthalen-1-yloxy) propan-2-ol monohydrochloride] an antihypertensive drug is a nonselective, beta-adrenergic receptor-blocking agent
(Dollery, 1991). It is a white crystalline solid, highly soluble in water.
The dose of Propranolol Hydrochloride (PPN) ranges from 40 to
80 mg/day. Due to shorter half life (3.9 h) the drug has to be administrated 2 or 3 times daily so as to maintain adequate plasma levels of
the drug (Chaturvedi et al., 2010). Thus, the development of controlled
release dosage forms would clearly be advantageous (Sahoo et al.,
2008). Sanghavi et al. (1998), prepared matrix tablets of PPN using
hydroxypropyl methylcellulose which exhibited rst order release
kinetics. Velasco-De-Paola et al., 1999, described dissolution kinetics of
controlled release tablets containing PPN prepared using eudragit. Some
other researchers have also formulated oral controlled release products of
PPN by various techniques (Gil et al., 2006; Mohammadi-Samani et al.,

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Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

2000; Paker-Leggs and Neau, 2009; Patel et al., 2010; Patra et al., 2007).
However, many researchers in the development of PPN sustained release
dosage forms were met with problems, such as the difculty to control
the release of the drug due to the high aqueous solubility of PPN.
Snchez-Martin et al. (1981) and Rojtanatanya and Pongjanyakul
(2010) have reported the interaction of PPN with Mt and magnesiumaluminium-silicate mineral (MAS, a mixture of Mt and saponite) respectively. PPN can intercalate into the interlayer space of MAS and the
obtained complexes showed control of the release of PPN.
However no report has been available in the literature for the
combination of a biodegradable polymer Poly lactic-co-glycolic acid
(PLGA) and Mt for controlled release of PPN. In this study we have
tried to obtain the synergism of biodegradable and biocompatible polymer which has already been widely explored for controlled drug release
properties, with pharmaceutical grade Mt to produce the oral and controlled drug delivery formulations for PPN. Being a highly hydrophilic
drug molecule, it is very difcult to encapsulate a high amount of PPN
within the hydrophobic polymer matrix. Therefore, in the present
study a modied double emulsion solvent evaporation technique has
been developed to entrap a substantial amount of drug in the synthesized formulations.
PPNPLGA nanoparticles and MtPPNPLGA nanocomposites were
prepared by w/o/w double emulsion/solvent evaporation method by
using biodegradable polymer PLGA and non-ionic Pluronic F68 (a triblock
co-polymer selected as an emulsier and stabilizing agent for the formation of PPNPLGA nanoparticles and MtPPNPLGA nanocomposites).
The synthesized products were characterized for interlayer structural
changes in the solid by XRD, surface morphology and particle size by SEM
and TEM with EDX, physical status of the drug and Mt by thermal studies
and drug loading by HPLC technique. The drug release prole of the synthesized PPNPLGA nanoparticles and MtPPNPLGA nanocomposites
was investigated in simulated gastrointestinal uid. The MtPPNPLGA
nanocomposites obtained were intercalated and partially exfoliated in
nature, spherical in shape with about 50300 nm in size, the favorable
size range for intestinal mucosal membrane uptake. DSC results clearly indicate the degradation of the drug encased within synthesized
PPNPLGA nanoparticles and MtPPNPLGA nanocomposites. The drug
release prole of MtPPNPLGA nanocomposites shows up to 14% of
the drug was released in simulated gastric uid whereas in simulated intestinal uid it shows up to 72% of drug release in a period 8 h. Thus we
can suggest that MtPLGA nanocomposites can be used as a potential
drug carrier for the controlled drug delivery of the low molecular weight
cationic hydrophilic drugs like PPN.

form a w/o/w-emulsion. The middle organic phase separated the internal

water droplets from each other as well as from the external aqueous continuous phase. After solvent evaporation the PPNPLGA nanoparticles
were isolated by centrifugation and washed with double distilled water
before freeze-drying.
2.1.2. Synthesis of PPNPLGAMMT nanocomposites
The synthesis of MtPPNPLGA nanocomposites involved the emulsication of rst w/o emulsion in Pluronic F-68 and Mt aqueous dispersion
(Fig. 1) followed by the same procedure as discussed in Section 2.1.1.
2.2. Characterizations
Powder X-ray diffraction (PXRD) measurements of samples were
performed on a powder X-ray diffractometer (XPERT PRO Pananlytical,
model (PW3040160, Netherland) the measurement conditions were a
Cu K radiation, generated at 40 kV and 30 mA as X-ray source 240
(2) and step angle 0.01/s. The differential scanning calorimetric studies
were conducted on a DSC instrument (DSC Q200 V23.10 Build 79). The
samples were purged with dry nitrogen at a ow rate of 10 ml/min
and the temperature was raised at 10 C/min. The effect of Mt content
on thermal stability of the MtPPNPLGA nanocomposites was assessed
by the thermogravimetric analyzer (TGA 2050 Thermal gravimetric
Analyzer). The surface morphology and particle size of the synthesized
products were examined with the Scanning Electron Microscope (Zeiss
EVO 40) and high resolution transmission electron microscope (TECNAI
G2 T30, U-TWIN) with an accelerating voltage of 300 kV.
2.3. Estimation of drug loading and encapsulation efciency with high
pressure liquid chromatography (HPLC technique)
2.3.1. HPLC apparatus and conditions
The HPLC system consisted of a Shimadzu Model DGU 20 A5 HPLC
pump, a Shimadzu-M20A Diode Array Detector, Shimadzu column oven

2. Materials and methods

2.1. Materials
Mt KSF, PLGA 50:50 (molecular weight 4075,000), Pluronic F-68 and
drug PPN (purity >98%) were ordered from Sigma Aldrich St. Louise
USA. HCl, KCl, NaOH, potassium dihydrogen phosphate of analytical
grade for simulated gastric uid HCl (pH 1.2) and simulated intestinal
uid (PBS, pH 7.4) preparation were ordered from MERCK (Germany).
HPLC grade methanol and water were used for drug estimation by
HPLC technique. All other reagents whether specied or not were of analytical grade. Double distilled water was used throughout the experimental work.
2.1.1. Synthesis of PPNPLGA nanoparticles
In this study, the water/oil/water (w/o/w) double emulsion solvent
evaporation method has been selected to encapsulate highly hydrophilic
drug PPN in the nanoparticles. PPNPLGA nanoparticles were synthesized in two steps. First, PPN was dissolved in water and emulsied in
a solution of methylene chloride containing PLGA under magnetic stirring
followed by sonication. In the second step, the primary w/o emulsion was
emulsied in the external aqueous phase of Pluronic F68 (0.2%, w/v) to

Fig. 1. Schematic representation of claypolymerdrug nanocomposite synthesis.

Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

CTO-10AS governed by a LC Solution software. The detector wavelength

was set at 289 nm. Separation was achieved by low pressure gradient elution by modifying the reported literature (El-Saharty, 2003)
on mobile phase (40:60 ratio v/v) delivered at a ow rate of 1.0 ml/min
at ambient temperature through a C18 analytical column Luna 5
(250 4.6 mm i.d., 5 m particle size).
2.3.2. Stock solutions and standards
Stock solutions of PPN were prepared by dissolving 2.50 mg PPN
in 25 ml HPLC water, resulting in a solutions containing 100 g/ml.
This solution was diluted to give working standard solutions in concentration range of 0.5 to 50 g/ml. Standards were prepared with the following concentrations of 0.5, 1, 2, 4, 6, 8, 10, 15, 20, 25, 30 and 50 g/ml
for PPN.
2.3.3. Preparation of sample solutions
Supernatants recovered after centrifugation of the synthesized
samples were used for the estimation of unloaded drug resulting in
indirect estimation of drug encapsulation efciency. 200 l of supernatant was diluted up to 10 ml in a standard volumetric ask, ltered
by 0.22 m milipore lters. The ltered solutions were injected to
HPLC.
The HPLC studies indicate that the calibration curve for known PPN
solutions was linear in the concentration range of 0.5 to 100.0 g/ml in
water with a correlation coefcient of 0.99.
2.4. In vitro drug release studies
In vitro drug release studies of PPN were conducted in a constant
temperature bath with the dialysis bag technique (Joshi et al., 2009a,b).
Buffer solution of pH 1.2 (simulated gastric uid) was prepared by
mixing 250 ml of 0.2 M HCL and 147 ml of 0.2 M KCL. Phosphate buffer
solution (PBS) of pH 7.4 (simulated intestinal uid) was prepared by
mixing 250 ml of 0.1 M KH2PO4 and 195.5 ml of 0.1 M NaOH. In vitro release studies were carried out in simulated intestinal uid at pH 7.4 and
simulated gastric uid at pH 1.2 using the dialysis bag technique. Dialysis
sacs were overnight equilibrated with the dissolution medium prior to
experiments. Weighed amount of the synthesized products was taken
in 5 ml of buffer solution in the dialysis bag. The dialysis bag was dipped
into the receptor compartment containing 100 ml dissolution medium,
which was stirred at 100 rpm at 37 0.5 C. The receptor compartment
was closed to prevent the evaporation losses from the dissolution medium. The stirring speed was kept at 100 rpm. 5 ml of the sample was
withdrawn at regular time intervals and the same volume was replaced
with a fresh dissolution medium. Samples were analyzed for drug
PPN content by UV spectrophotometer at max = 289 nm.

87

Table 1
Formulations of PPNPLGA nanoparticles and MtPPNPLGA nanocomposites.
S.No.

PPN-01
PPN-02
PPN-03
PPN-04
PPN-05

PPN
(mg)

20
20
20
40
60

Mt
(mg)

20
20
20

P-F68
(mg)

50
50
50
50
50

PLGA
(mg)

50
100
50
50
50

Composite
(mg)

27.16
79.97
30.57
40.00
76.48

A amount of PPN in the

composite
mg

D.L. (%)

E.E. (%)

2.389
2.23
3.540
14.072
46.385

08.6
02.82
11.4
35.17
60.69

11.69
12.16
17.69
35.17
77.30

encapsulated in the MtPPNPLGA nanocomposites increases from 18

to 35% in a linear manner (Table 1) with increase in drug to Mt ratio
from 1:1 to 2:1, however with further increase in drug to Mt ratio up
to 3:1, an increase in encapsulation efciency up to 77.30% was
obtained. This excessive increase of encapsulation may be attributed
to the cationic nature of PPN in the nanocomposites, which could enhance the interaction of PPN with negatively charged Mt and polymer
resulting in high encapsulation efciency. The increase in drug loading
can be attributed to the increase in nal yield obtained which is directly
involved in the calculation of drug loading percentage as per Eq. (1).

Drug loading %
Drug amount within the nanoparticles=Total weight of nanoparticles X 100

Encapsulation efficiency%
Drug amount within the nanoparticles=initial drug amount X 100

3. Results and discussion

In the series of experiment, the concentration of stabilizing agent
Pluronic F-68 was kept constant (0.2% wt/v) as per the reported critical micelle concentration (Schmolka, 1977). In the case of PPNPLGA
nanoparticles PPN-01, the amount of drug encapsulated was found to
be about 12% (Table 1) and with further increase in polymer content
(50 mg) the encapsulation efciency was found to increase by about
0.5%. Therefore, in order to avoid the presence of excess non-emulsied
polymer the amount of PLGA was xed at 50 mg for all formulations. It
has also been observed that in the case of MtPPNPLGA nanocomposites,
the maximum amount of drug (PPN-05) retained was 77%. Variations in
the composition of drug polymerclay nanocomposites were further
studied in detail.
3.1. Effect of PPN content on drug loading and encapsulation efciency
The drug loading and extent of drug encapsulation in MtPPNPLGA
as function of PPN content were studied, The amount of PPN

Fig. 2. XRD patterns of a pristine Mt, b MtPPNPLGA nanocomposites (PPN-03), c

MtPPNPLGA nanocomposites (PPN-04), d MtPPNPLGA nanocomposites (PPN-05),
and e pure PPN.

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Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

Fig. 3. Diagrammatic representation of I intercalated, II partially exfoliated, and III exfoliated Mt layers.

3.2. XRD studies

The physical status of Mt and PPN in the synthesized MtPPNPLGA
nanocomposites was investigated with the help of XRD. The XRD pattern of pristine Mt shows characteristic diffraction peak at 2 value of
6.4 corresponding to 001 plane with d spacing of 13.6 A (Fig. 2a). In
the case of MtPPNPLGA nanocomposites, PPN03 (1:1 drug to clay
ratio) an increase in intensity of the 001 plane along with the shift in
the 2 value, from 6.4 to 4.04, was observed (Fig. 2b), the hump in
the background from 2 values of 12 to 28 is due to the presence of
a polymer within the MtPPNPLGA nanocomposites. According to
Bragg's law, a shift in 2 value from higher diffraction angle to lower diffraction angle is indicative of an increase in d spacing i.e., from 13.6 A
to 21.4 A (Joshi et al., 2009a,b; Liu et al., 2006; Lin et al., 2002) and
an increase of 8 A has been attributed to the intercalation of polymer
drug moiety (Fig. 3, case-I) and is further supported by the HRTEM
image (Fig. 7b) by the presence of expanded and uniformly spaced Mt
layers in the PPN-03 MtPPNPLGA nanocomposites. However, presence
of a minor component of a population cannot be ruled out because of the
broad nature of 001 reection at 2 value of 4.04.
With the increase in drug to Mt ratio from 1:1 to 2:1 in the case of
(PPN04) and 3:1 in the case of (PPN-05), exfoliation of Mt layers

Fig. 4. TGA curves of, a Pure Mt, b PPNPLGA nanoparticles (PPN-01), c MtPPN
PLGA nanocomposites (PPN-03), and d MtPPNPLGA nanocomposites (PPN-05).

(Paul and Robeson, 2008) is being proposed (Fig. 2c & d). This is also supported by the substantial suppression of 001 reection at 2 value of 4.5
and corresponding increase in the intensity of broad hump between 2
values of 1228, which is indicative of the release of polymeric material
from the interlayer gallery (Fig. 3, cases II and III). This fact is further supported by the presence of exfoliated Mt layers in the HRTEM image of
PPN-05 MtPPNPLGA nanocomposites (Fig. 7c).
Excessive amount of polymerdrug moiety within the interlayers
can no longer hold the Mt platelets together. Increase in drug encapsulation efciency from 18% (PPN-03) to 35% (PPN-04) and
77% (PPN-05) can be attributed to the change in the nature of Mt
PPNPLGA nanocomposite from intercalation of the drug polymer moiety (to a small extent) to adsorption of the exfoliated negatively charged
Mt platelets on the drugpolymer moiety. The extent of drug encapsulation seems to be proportional to the extent of exfoliation in the case of
PPN-04 and PPN-05.
Further increase in drug content in the MtPPNPLGA
nanocomposites did not show further enhancement in the encapsulation
efciency indicating complete saturation of negative sites on Mt platelets.
The pure crystalline drug PPN shows intense peaks at 14.56,
17.32, 22.84, 23.47, 31.19, 32.30, 35.05, 36.23 and 37.58 and
the observation is in good agreement with the reported values in the literature (Wang et al., 2002). MtPPNPLGA nanocomposites reveal the

Fig. 5. DSC curves of, a Pure PPN, b PPNPLGA nanoparticles (PPN-01), c MtPPN
PLGA nanocomposites (PPN-03), and d MtPPNPLGA nanocomposites (PPN-05).

Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

89

Fig. 6. SEMEDX images of a PPNPLGA nanoparticles and b MtPPNPLGA nanocomposites.

presence of crystalline PPN in the nanocomposites (Fig. 2), with increase

in drug to Mt ratio, the appearance of characteristic peaks of PPN becomes more evident.

3.3. TGA studies

The Mt shows weight loss of 10% from 30 to 140 C and is attributed
to the loss of adsorbed and interlayer water (Fig. 4a). In the case of
MtPPNPLGA nanocomposites (PPN-03) due to the replacement
of surface and interlayer water by organic moiety no such weight
loss was observed in this region. Hence, the stability was observed
in this region.
In the case of MtPPNPLGA nanocomposites (PPN-05) due to exfoliation of Mt no such weight loss was observed. Hence, the stability
was observed in this region.
In the temperature range of 30 to 425 C PPN-PLGA nanoparticles
(PPN-01), MtPPNPLGA nanocomposites (PPN-03) and (PPN-05) show
100%, 43.2% and 89.6% weight loss respectively (Fig. 4). It could be clearly
understood that weight loss observed in the case of MtPPNPLGA

nanocomposites (PPN-03 and PPN05) is because of the thermal degradation of PPN, PF68 and PLGA contents present in the formulation
(Dong and Feng, 2005). Mt content in the nanocomposites (PPN-03)
and (PPN-05) is about 56.8% and 10.4% respectively.
The MtPPNPLGA nanocomposite (PPN-03) shows less weight loss
as compared to the MtPPNPLGA nanocomposite (PPN-05) because in
the case of the intercalated sample (PPN-03) the polymerdrug moiety
is present within the ordered lattice whereas in the case of PPN-05 the
high weight loss is due to the complete degradation of polymerdrug
moiety which is out of the order lattice due to the exfoliation.

3.4. DSC studies

The appearance of small endothermic peak about 4850 C followed
by a broad endothermic peak in the temperature region of 360 C corresponds to the glass transition temperature (Mukherjee and
Vishwanatha, 2009) and thermal decomposition of the polymer PLGA
in PPNPLGA nanoparticles and MtPPNPLGA nanocomposites indicates no change in the polymer chain structure.

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Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

of PPN encapsulated within the PPNPLGA nanoparticles and MtPPN

PLGA nanoparticles and nanocomposites (Fig. 5).

Table 2
SEMEDX analysis report.
Element

Series

C norm (wt.%)

C Atom (at.%)

C error (%)

48.77
7.29
0.04
43.90
100.0

55.42
7.11
0.02
37.45
100.0

14.7
2.2
0.0
13.2

nanocomposites
K series
47.48
K series
45.31
K series
1.34
K series
1.26
K series
0.42
K series
2.98
100.0

57.09
40.90
0.69
0.67
0.42
0.22
100.0

14.5
13.9
0.1
0.1
0.1
0.1

a, PPNPLGA nanoparticles
Carbon
K series
Nitrogen
K series
Silicon
K series
Oxygen
K series
Total
b, MtPPNPLGA
Carbon
Oxygen
Silicon
Aluminium
Iron
Gold
Total

3.5. Scanning electron microscopic and EDX studies

PPNPLGA nanoparticles (PPN-01) and MtPPNPLGA nanocomposites (PPN-03 to 05) appear to be 100300 nm spherical particles (inset Fig. 6), the former has a smooth surface and the latter has a
rough surface because of the presence of Mt nano platelets on the
surface which has been further conrmed by SEMEDX studies
(Fig. 6a & b, Table 2).
Due to the presence of carbon polymer chain and organic drug
moiety in case of PPN-01, high content of carbon, oxygen and nitrogen
was seen on the surface (Fig. 6, a) whereas, samples containing Mt,
PPN-03 to 05, additional peaks of silicon, aluminium and iron conrms
the presence of Mt nano platelets on the surface of the MtPPNPLGA
nanocomposites (Fig. 6b).
3.6. Transmission electron microscopic and EDX studies

Pure PPN reveals a sharp endothermic peak at 166 C and a broad

endothermic peak at 292 C followed by an exothermic peak at
300 C corresponding to the melting point and the decomposition
of PPN (Rojtanatanya and Pongjanyakul, 2010). The short broad endothermic region in the temperature range of 276 C to 296 C has
been observed in the case of PPNPLGA nanoparticles and Mt
PPNPLGA nanocomposites prepared and is due to the decomposition

PPNPLGA nanoparticles (PPN-01) are spherical particles of

50200 nm in size (inset Fig. 7a). In the TEM micrograph of PPN03
(Fig. 7b) uniformly spaced Mt layers are in support of intercalation
(Table 3). In the TEM micrograph of PPN-05 (Fig. 7c), the presence of
exfoliated Mt layers is distinct. Both micrographs are also supported
by their corresponding XRD data.

Fig. 7. TEM-EDX images of a PPNPLGA nanoparticles (PPN-01), b MtPPNPLGA nanocomposites (PPN-03) and c MtPPNPLGA nanocomposites (PPN-05).

Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

91

As has been observed in the case of SEMEDX studies, the TEMEDX

studies (Fig. 7a b and c; Table 3) also indicate the presence of high content of carbon, oxygen and nitrogen in PPN-01 and additional peaks of
silicon, aluminium and iron in samples PPN-03 and PPN-05 which conrms the presence of Mt in the MtPPNPLGA nanocomposites.
4. Drug release prole
PPN-01 and the samples containing Mt, PPN-03 & 05, have been
selected for the study of drug release kinetics, in simulated intestinal
uid PBS (pH 7.4) (Fig. 8). As per the XRD data, encapsulation of drug
has been found in two kinds of MtPPNPLGA nanocomposites in
which the Mt particles were intercalated (PPN-03) and exfoliated
(PPN-04 to PPN-05). In the latter category PPN-05 has been selected
because of its high yield, loading and encapsulation efciency.
Release of pure drug (PPN) in simulated gastric (HCl, pH 1.2) and
intestinal uid (PBS, pH 7.4) was observed to be 86% (Fig. 9) and 89%
(Fig. 8) over a period of 4 h respectively and in both the cases release
pattern was not in a controlled manner (~36% release per minute). With
PPN-01 only 28% of the encapsulated drug was released over a period of
8 h whereas, the MtPPNPLGA nanocomposites PPN-03 and PPN-05
demonstrated a slow controlled cumulative drug release of 59% and
72% in the PBS (pH 7.4) over a period of 8 h (Fig. 8). The increase in the
amount of drug release with respect to the PPN-01 is related to the presence of Mt platelets in the bulk and on the surface (further conrmed by
SEMEDX and TEMEDX results). The presence of these platelets imparts
porosity to the MtPPNPLGA nanocomposites which results in higher
ease of passage through the MtPPNPLGA nanocomposite because of
which the PPN-05 MtPPNPLGA nanocomposites with higher extent
of exfoliation also shows higher release of PPN in a controlled manner
as represented by Fig. 10.
It is well understood that if a drug delivery system is able to retain
high amount of drug in the stomach uid, it would be able to release

Table 3
TEMEDX analysis report.
Element

Fig. 8. Drug release prole of a pure PPN, b PPNPLGA nanoparticles (PPN-01),

c intercalated MtPPNPLGA nanocomposites (PPN-03) and d exfoliated MtPPN
PLGA nanocomposites, (PPN-05) in simulated intestinal uid (PBS, pH 7.4) at 37 C.

more drug in the intestine (Chaturvedi et al., 2010) which is the desired
site of drug absorption. In this study we found that over a period of 8 h
in simulated gastric uid (HCl, pH 1.2), PPN-01 and Mt containing samples PPN-03 and PPN-05 show 18%, 14% and 28% drug release respectively (Fig. 9). This low release of PPN from PPN-03 is probably related
with the stability of Mt in acidic media which prevents the release of
drug in acidic media (Junping et al., 2006). In the case of the formulation
PPN-05, collapse of Mt layered structure was observed which comes out
to be less effective in the acidic media as compared to the PPN-03.
The controlled behavior of PPN release could also be explained by
the barrier properties or hindrance in the path offered by high amount
of Mt layers to release the drug in both the releasing media (Fig. 10).
5. Conclusion

Weight%

Atomic%

a PPNPLGA nanoparticles (PPN-01)

CK
58.6
NK
2.7
OK
11.3
FK
2.2
Ca K
2.9
Cu K
22.3
Total
100.0

77.3
3.1
11.1
1.8
1.1
5.6
100.0

b MtPPNPLGA nanocomposites (PPN-03)

CK
20.9
NK
6.7
OK
35.7
Mg K
4.1
Al K
4.0
Si K
14.5
KK
0.9
Fe K
3.2
Cu K
9.9
Total
100.0

31.5
8.7
40.4
3.1
2.7
9.4
0.4
1.0
2.8
100.0

c MtPPNPLGA nanocomposites (PPN-05)

CK
27.8
NK
6.9
OK
35.2
Mg K
0.2
Al K
6.2
Si K
12.7
KK
0.5
Fe K
2.1
Co K
0.3
Cu K
11.1
Total
100.0

31.5
8.7
40.4
3.1
2.7
9.4
0.4
1.0
0.1
3.0
100.0

In the present study an oral controlled drug delivery system for

PPN loaded PLGA nanoparticles and MtPPNPLGA nanocomposites
was developed by w/o/w double emulsion solvent evaporation technique. About 77% entrapment efciency and 72% release were achieved
for the highly hydrophilic drug, PPN. Two types of MtPPNPLGA

Fig. 9. Drug release prole of a pure PPN, b PPNPLGA nanoparticles (PPN-01),

c intercalated MtPPNPLGA nanocomposites (PPN-03) and d exfoliated MtPPN
PLGA nanocomposites, (PPN-05) in simulated gastric uid (HCl, pH 1.2) at 37 C.

92

Seema, M. Datta / Applied Clay Science 8081 (2013) 8592

Fig. 10. Diagrammatic representation of drug path within a intercalated and b exfoliated MtPPNPLGA nanocomposites.

nanocomposites (intercalated and exfoliated Mt) were obtained. The

presence of drug within the PPNPLGA nanoparticles and MtPPN
PLGA nanocomposites nanoparticles and nanocomposites was also conrmed by DSC data.
50300 nm spherical PPNPLGA nanoparticles and MtPPNPLGA
nanocomposites was obtained with the Mt platelets on the surface
(conrms by SEMEDX and TEMEDX data). The drug release prole
of PPN was found to be pH dependent, the presence of Mt platelets
within the PPNPLGA formulations results in controlled and higher %
release of drug. Therefore, it can be said that the synthesized formulations have high potential as a controlled drug delivery system for PPN.
Disclosure
The authors report no conicts of interest in this work.
Acknowledgments
We sincerely express our thanks to the director, USIC, University
of Delhi for instrumentation facilities, Director, AIRF, JNU for providing
SEM facilities and UGC/RGNF for providing nancial assistance for this
research work under the project of sch/rgnf/srf/f-10/2007-08. The authors are thankful to Dr. R Nagarajan for his valuable suggestions regarding the interpretation of XRD and TGA data.
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