asian journal of pharmaceutical sciences 10 (2015) 452–458

H O S T E D BY
Available online at www.sciencedirect.com

ScienceDirect

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / a j p s

Short Communication

Montmorillonite/Poly (L-Lactide) microcomposite

spheres as reservoirs of antidepressant drugs
and their controlled release property

Shalini Rajkumar a,*, Bhavesh D. Kevadiya a,b, Hari C. Bajaj b,**

a
Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India
b
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council
of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India

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

Article history: This work evaluates intercalation of Nortriptyline (NT) and Venlafaxine (VFX) in an interlayer
Received 20 April 2015 gallery of Na+-MMT (Montmorillonite), which was further compounded with Poly (L-
Received in revised form 2 June Lactide) (PLLA) to form microcomposite spheres (MPs) for oral controlled drug delivery. The
2015 XRD patterns, thermal and spectroscopic analyses indicated intercalation of drugs into the
Accepted 24 June 2015 MMT interlayer that was stabilized by electrostatic interaction. No significant changes in
Available online 9 July 2015 structural and functional properties of drugs were found in the MMT layers. In vitro drug
release studies showed controlled release pattern.
Keywords: © 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Shenyang Phar-
Nortriptyline maceutical University. This is an open access article under the CC BY-NC-ND license
Venlafaxine (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Poly (L-Lactide)
Montmorillonite
Antidepressant

membrane pump mechanism responsible for uptake of nor-

1. Introduction
Nortriptyline (NT) and Venlafaxine (VFX) are most commonly
prescribed antidepressants that inhibit reuptake of norepi-
nephrine and serotonin almost equally. These drugs inhibit the
epinephrine and serotonin in adrenergic and serotonergic
neurons. Clinical studies have demonstrated that controlled
release drug treatment is clinically more valuable to
commence and preserve the anticholinergic properties com-
pared to instantaneous release or conventional therapy [1–7].

* Corresponding author. Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India. Tel.: +91 2717 241900 to 04, +91 2717
241911 to 15; fax: + 91 2717 241916 17.
E-mail address: shalini.rjk@nirmauni.ac.in (S. Rajkumar).
** Corresponding author. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council
of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India. Tel.: +91 278 2471793; fax: +91 278
2567562.
E-mail address: hcbajaj@csmcri.org (H.C. Bajaj).
Peer review under responsibility of Shenyang Pharmaceutical University.
http://dx.doi.org/10.1016/j.ajps.2015.06.002
1818-0876/© 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Shenyang Pharmaceutical University. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 asian journal of pharmaceutical sciences 10 (2015) 452–458
Therefore, there is a need to prepare formulations for the con-
trolled and safe release of drugs, which may be done by using
clay-based materials.
The design of effective, controlled drug delivery systems to
circumvent the problem of high drug clearance rates is an
ongoing challenge. One strategy is the use of layered silicate
material-based delivery systems, consisting of layered struc-
ture constructed from tetrahedrally coordinated silica atoms
fused into an edge-shared octahedral plane of aluminum-
based nanosheets like assemblies, such as Montmorillonite
(MMT), for intercalation of a wide range of toxic drugs. Montmo-
rillonite (MMT) is one of the most commonly used medical clay
that consists of a lamellar stack of crystalline, 1 nm thick alu-
minosilicate sheets. Naturally occurring cations (i.e., Na+) reside
between the sheets to balance the overall negative surface
charge of the MMT. In water, the lamellar stack swells, pro-
ducing an electrostatically stabilized dispersion of nanoscale
sheets. The ion exchange capacity of MMT enables the re-
placement of Na+ with other organic and inorganic cations to
add functionality, spurring research into the use of MMT. Overall,
the ion exchange nature and biocompatibility of clays make
them versatile carrier for many vital drugs [8–14].
Here we report a method for preparation and characteriza-
tion of NT and VFX loaded layered silicates, Montmorillonite
(MMT) (drug–clay hybrids) and further compounding in PLLA
to form microcomposite spheres (MPs), XRD, TGA, FT-IR and
SEM characterizations and their potential applications in drug
delivery. The in vitro release characteristics and release kinet-
ics models are also presented.
2. Materials and methods
2.1. Materials
For the present study, sodium MMT (Cloisite Na+) was given
by Southern Clay Products Incorporation, USA. Poly (L-Lactide)
(PLLA) with MW of 152,000 (inherent viscosity: 2.0 d/g), cellu-
lose acetate dialysis tube (MW: 07014), nortriptyline
hydrochloride were from Sigma–Aldrich, USA, and Venlafaxine
(VFX) was obtained as a gift sample from Lupin Pharmaceu-
ticals Ltd (India). PVA, Mw. 1, 25,000 were purchased from S.D.
Fine Chemicals Pvt. Ltd. All the other HPLC reagents were used
as received. Millipore water was prepared by a Milli-Q plus
system (Millipore Corporation, USA).
2.2. Drug–clay hybrids preparation
For preparing the drug–clay hybrids, 2 g MMT was vigorously
stirred in 100 ml of Milli-Q water for 1 h. Two grams of NT so-
lution (2 wt. % in Milli-Q water) was added drop wise (2 ml/min)
into the suspension of MMT within 1 h at room temperature
using peristaltic pump (Master flex L/S 7518-00, Cole–Parmer,
USA). The mixed solution was further stirred (800 rpm) for 24 h,
filtered, washed several times with water to remove the non-
intercalated NT, dried at 60 °C, and ground with mortar and
pestle to obtain fine powder. This sample was designated as
NT–MMT hybrid. The same method was followed for VFX–
MMT preparation. The remaining concentrations of drugs in
453
the filtrates were measured by UV absorbance at λmax = 236 nm
for NT and λmax = 224 nm for VFX using UV-visible spectropho-
tometer UV 2550 (Shimadzu, Japan), equipped with a quartz
cell having a path length of 1 cm. All the intercalation studies
were performed in triplicates, and the values were averaged
for data analysis.
2.3. Preparation of micro composite spheres
The micro composite spheres (MPs) were prepared with the
oil in water (o/w) solvent evaporation method. Two grams of
PLLA was dissolved in 100 ml dichloromethane and soni-
cated for 20 min, to which NT–MMT hybrid (PLLA:NT–
MMT = 1:0.5% w/w) was added and further sonicated for 10 min
followed by stirring for 1 h. The organic phase was added drop
wise (0.5 ml/min) into the external aqueous phase contain-
ing 0.5% w/v of polyvinyl alcohol (500 ml) with stirring until
dichloromethane evaporation. The microcomposite particles
were collected using filter paper, washed 5 times with Milli-Q
water and resuspended in 25 ml Milli-Q water, frozen in liquid
nitrogen and lyophilized. The samples were designated as NMPs,
and the same methods of preparation followed for VFX with
samples were designated as VMPs.
2.4. Characterization
X-ray diffraction (XRD) analysis was carried out on Phillips
powder diffractometer X’ Pert MPD using PW3123/00 curved
Ni-filtered Cu-Kα radiation with a scanning of 0.3°/min in 2θ
range of 2–10°. Fourier transform infrared spectra (FT-IR) were
recorded on Perkin-Elmer, GX-FTIR as KBr pellet in 4000–
400 cm−1 range. Thermo gravimetric analysis (TGA) was carried
out within 30–800 °C at the heating rate 10 °C/min under ni-
trogen flow (20 ml/min) using TGA/SDTA 851e (Mettler-
Toledo, Switzerland). The particle size distributions were mea-
sured with the Zeta sizer-Nano-ZS90, Nano Series (Malvern
Instruments Ltd., Malvern, UK). The morphology of pristine
MMT, NT/VFX intercalated MMT and microcomposite par-
ticles (MPs) was observed by scanning electron microscope
(SEM), LEO-1430VP, UK. The UV-visible absorbance of drug so-
lutions was measured using UV-visible spectrophotometer
UV2550 (Shimadzu, Japan), equipped with a quartz cell having
a path length of 1 cm.
2.5. In vitro release behavior of drugs
In vitro release of drug was carried out in Julabo shaking water
bath (SW23) using a buffer solution of pH 7.4 (simulated in-
testinal fluid) as release medium. In brief, precise amounts of
pristine NT/VFX, NT/VFX–MMT hybrid and MPs were im-
mersed in cellulose acetate dialysis tube and set in flasks
containing 150 ml release medium. The temperature was main-
tained at 37 ± 0.5 °C with the shaking frequency at 100 rpm.
One milliliter aliquots were withdrawn at regular time inter-
val, and the same volume was restored with fresh release
medium. Samples were analyzed by HPLC in triplicates, and
the average values were used in data analysis. The release be-
havior of the drug from the NT–MMT and MPs was fitted
in Higuchi, Korsmeyer–Peppas, Elovich equation, parabolic
454 asian journal of pharmaceutical sciences 10 (2015) 452–458

diffusion, Bhaskara equation, and modified-Freundlich kinetic
models [12–14].
2.6. Drugs quantification by HPLC
The quantification of drug from release media was deter-
mined by using a validated HPLC method. Briefly, subsequent
to the preparation of samples, analysis by high-performance
liquid chromatography (HPLC) system consisting of photodi-
ode array detector (Waters Alliance model: 2695 separation
module with Waters 2996 Photo Diode Array Detector, Waters
Corporation, Milford, MA, USA) and a reverse-phase C18 column
(for NT: Waters X’Bridge TM C18 HPLC column with
length = 100 mm, ID = 2.1 mm, particle size = 5.0 µm, Waters Cor-
poration, Milford, MA, USA; and for VFX: Phenomenex® make
Luna C18 (2) HPLC column with length = 25 cm, ID = 4.6 mm,
particle size = 5.0 µm, Phenomenex Inc, Torrance, CA, USA) was
carried out. Drug-containing samples were transferred to auto
sampler vials, capped and placed in cassettes of the HPLC auto
sampler. The mobile phase employed for NT analysis was the
mixture of 0.05 M KH2PO4 buffer (pH 3.0 ± 0.05) and acetoni-
trile (50:50% w/v). The injection volume was 10 µl with flow
0.1 ml/min, and detection wavelength (λmax) was set at 240 nm,
while the mobile phase employed for VFX analysis was the
mixture of 0.025 M potassium dihydrogen phosphate (pH: 3.3,)-
acetonitrile (60:40 v/v). The injection volume was 10 µl with flow
1 ml/min, and detection wavelength (λmax) for VFX was at
225 nm. The drug concentration in samples was determined
using the standard curve obtained for known concentrations
of NT and VFX in release medium processed similarly
(r2 = 0.9996–0.9999).
3. Results and discussion
3.1. The chemistry of NT intercalation in interlayer
gallery of Na+-MMT
The ionic exchange reaction between the amine groups (-NH2)
and sodium ions (≡Si—O−—Na+) in the layered MMT is the main
driving force for the cationic drugs intercalation. The NT and
VFX intercalation course was mainly controlled by cationic ex-
change mechanism due to the Coulombic interaction between
the positive amine groups of both the drugs and the posi-
tively charged sodium ions present in the interlayer gallery of
MMT layers.
3.2. The drugs intercalation in MMT confirmation
3.2.1. X-ray diffraction
The XRD was used for the investigation of structural change
of MMT lattice. Fig. 1[A] shows the XRD patterns of pristine
MMT, NT–MMT and MPs. The XRD of MMT exhibited broad-
ened peak at 2θ = 8.0°. The broadened peak reflected the fine
particle size of MMT. After intercalation of drugs, the peak
shifted from 8.0° to 5.8°–5.9°. The XRD results confirmed suc-
cessful intercalation of drug into the interlayer space of MMT
and increased basal spacing of silicate interlayer. The d-spacing
of basal planes of NT/VFX–MMT with 1.5 to 1.45 nm signifi-
cantly increased from the initial value of 1.1 nm in MMT.
However, the intensity of the XRD characteristic peak in-
creased in drug-loaded MMT, which indicated an impervious
ordering of sheet structure caused by cation exchange and
higher restoration of charge density during drug loading. The
chemical structures of NT and VFX are shown in Fig. 1[B], and
2–80° scanning XRD data are presented in supplementary ma-
terial as Fig. S1.
3.2.2. FT-IR spectroscopy
The FT-IR spectra of the drugs-loaded clay hybrid NT/VFX–
MMT and MPs were compared with that of the pristine MMT
and NT/VFX (Fig. 2). The spectrum of MMT revealed the char-
acteristic absorption bands [12–14]. Pristine NT displayed
characteristic absorption bands of aromatic C=C (1592 cm−1)
and aromatic C—H (2945 cm−1) stretch vibrations; peaks at
3400 cm−1 and 608 cm−1 were indicative of a secondary amine
moiety and the C—N—C scissors vibrations, respectively.
Pristine VFX had absorption band at 3347 cm−1, which corre-
sponded to the stretching vibrations of hydroxyl group and

[A] [B]
125 MMT
NT-MMT
VFX-MMT
100
Intensity (cps)

75

50

25

0
2 4 6 8 10
2θ

Fig. 1 – [A] XRD patterns of pristine MMT and drugs loaded MMT and [B] chemical structures of the drugs.
 asian journal of pharmaceutical sciences 10 (2015) 452–458
VFX
NT
Transmittance (%)
VMPs
NMPs
VFX-MMT
NT-MMT
MMT
4000 3000 2000 1000
Cm-1
Fig. 2 – FT-IR spectra.
bands at 2940 cm−1, 1515–1475 cm−1, and 1250 cm−1 corre-
sponded to the stretching vibrations of aromatic -CH, benzene
ring, and methoxy group present in the VFX framework [15].
Moreover, compared with pristine MMT spectrum and pris-
tine both drugs, the NT–MMT/MPs showed bands at 3415 cm−1,
3630 cm−1 and 3660 cm−1 due to —OH stretching for interlayer
water of MMT [12–14]. The overlaid absorption peak at 1610-
1632 cm−1 was attributed to —OH bending mode of adsorbed
water of MMT and absorption bands of aromatic —C=C stretch-
ing vibrations of NT. The peak at 1036-1080 cm−1 was due to
Si—O stretching (in-plane) vibration of MMT. The peak shifted
from 1592 cm−1 to 1480 cm−1 due to —C=C aromatic stretch-
ing vibrations of NT and shifted 2940 cm−1 to 2965 cm−1 due to
CH, benzene ring aromatic stretching vibrations of VFX, which
confirmed that NT/VFX was intercalated and stipulated in the
MMT/MPs.
3.2.3. Thermal analysis and SEM study
Fig. S2 illustrates the thermal analysis (TGA and DTA pat-
terns) of dried MMT and drug-loaded MMT. The TGA profile of
pristine MMT showed weight loss in three steps at the tem-
peratures around 100 °C, 270 °C and 430 °C. We could trace one
strong and two weak endothermic peaks on the DTA pattern
of pristine MMT in the same temperature range. The first weight
loss and endothermic peak at ~100 °C in MMT corresponded
to the loss of adsorbed water. The weight loss at 430 °C was
due to the dehydroxylation of the MMT. The TGA curve of NT–
MMT hybrid had four steps for weight loss at the temperatures
around 150 °C, 230 °C, 330 °C, and 600 °C. One strong and three
weak endothermic peaks were observed in DTA patterns, while
the VFX–MMT hybrid had three steps for weight loss at the tem-
perature around 240 °C, 350 °C, and 600 °C. The first weight loss
and the weak endothermic peak at the temperature around
150 °C were due to the free water evaporation from NT–MMT.
The second and third weight losses at the temperature around
230–350 °C were due to the elimination of the drugs from drug-
intercalated MMT, corresponding to the complete degradation
455
of drugs from drug–MMT hybrids. The third endothermic peak
was due to weight loss at the temperature around 600 °C, con-
sequent to complete disintegration of MMT from drug–MMT
hybrids.
The SEM images of the pristine MMT, NT/VFX–MMT and MPs
are shown in Fig. 3. It is clearly seen that MMT (Fig. 3A) has
layered structure with platelet morphology consisting of stacked
silicate sheets that are approximately 1 nm thick and 200 nm
long. Fig. 3Bi and Bii shows the surface morphology of NT/
VFX–MMT hybrid and revealed a slight swelling of the layered
matrix structure due to drug intercalation in the interlayer gal-
leries of MMT. The SEM images of the MPs are presented (Fig. 3Ci
and Cii where MPs are seen as solid spheres). This demon-
strated the advantage of using MMT over PLLA matrices, which
are fragile and exhibit uncontrollable solidity. The particle size
of MMT increased after intercalation of AT (Fig. 4). However,
the intensity of the size distribution peak increased in drug-
loaded MMT, which indicated higher restoration of charge
density during drug loading.
3.3. In vitro release study
The drug release patterns of drug from NT/VFX–MMT hybrid
and MPs in buffer solutions with pH = 7.4 were studied at the
physiological temperature (37 ± 0.5 °C) by dialysis bag tech-
nique (Fig. 5). The formulations exhibited controlled release
profiles for over 72 h. The NT released from MPs showed the
controlled release pattern with ~8% of drug released in 10 h
followed by sustained release >72 h (~14%). No initial burst
release was obtained from the MPs as compared to NT–MMT
and pristine NT. The initial release of the drug from NT–MMT
hybrid was somewhat quicker compared to that from MPs,
where ~30% of the intercalated drug was released in 10 h and
~42% the drug was released in 72 h, while the VFX released from
VFX–MMT and MPs showed the controlled release patterns with
~32–37% and ~5–6% of drug released in 10 h, respectively, fol-
lowed by sustained release up to 48 h (~38–42% and ~8–9%)
correspondingly. The prolonged delay from MPs can be ex-
plained on the basis of the differences in the distribution of
NT/VFX–MMT hybrid plates within the PLLA matrix and wrap-
ping of the NT/VFX–MMT hybrid plates by PLLA. This was
probably due to low permeability of the water in the interior
of MPs due to PLLA. The burst effect must not be measured
as negative in all cases. At the later stage, the NT/VFX release
from NT/VFX–MMT hybrid was more controlled and sus-
tained, whose rate was determined by the de-intercalation of
drug from the clay plates.
To understand the release mechanism of drug molecules
from the NT/VFX–MMT and MPs carriers better, the Higuchi,
Korsmeyer–Peppas, Elovich equation, parabolic diffusion,
Bhaskara equation, and modified-Freundlich kinetic models
were used (Figs. S3 and S4 (a–f) and Table 1). The best linear-
ity was obtained in the Korsmeyer–Peppas, Bhaskara equation,
Elovich equation and modified-Freundlich model (r2 = 0.9384–
0.9970). Thus, the kinetics of drug release was governed by
diffusion-controlled exchange and partial diffusion through
swollen matrix of the MMT. The Elovich equation has been used
to explain drug adsorption and desorption in clay and release
from MPs. Therefore, the excellent fit of the experimental data
in the Elovich model and modified-Freundlich suggested that
456 asian journal of pharmaceutical sciences 10 (2015) 452–458

1µm

Bi Bii

1µm 2µm

Ci Cii

2µm 2µm

Fig. 3 – SEM images of [A] pristine MMT, [Bi] NT–MMT hybrid, [Bii] NT–MMT hybrid, [Ci] NMPs and [Cii] VMPs.

40
MMT
NT-MMT
35 VFX-MMT
30
Intensities(%)

25

20

15
10
5

0
0 1000 2000 3000 4000
Size (d. nm) Fig. 5 – In vitro release profiles of drugs in simulated
intestinal fluid (pH 7.4) at 37 ± 0.5 °C; data represent mean
Fig. 4 – Particle size distribution. of n = 3.
 asian journal of pharmaceutical sciences 10 (2015) 452–458 457

Table 1 – Linear correlation coefficient (r2) and rate constant (K) of the diffusion kinetic models applied to drug release
from NT/VFX–MMT and MPs (release data were considered from first 24 h at pH 7.4).
Kinetic models Parameters Formulations
NT–MMT NMPs VFX–MMT VMPs
2
Higuchi-equation r 0.9172 0.9623 0.8388 0.9331
KH 6.3487 1.6492 8.9170 1.7149
Korsmeyer–Peppas r2 0.9475 0.9852 0.8216 0.8926
n 0.36311 0.3634 0.4567 0.5894
KHP 0.3062 0.2357 0.3131 0.1701
Elovich equation r2 0.9973 0.9789 0.9026 0.9561
KE 3.8772 1.0047 5.0962 0.9618
Parabolic diffusion r2 0.9068 0.9798 0.8388 0.9331
Kp 0.1459 0.1231 0.2370 0.2188
Bhaskara equation r2 0.9168 0.9829 0.8474 0.9248
K −0.0208 −0.0050 −0.0303 −0.0045
Modified-Freundlich r2 0.9206 0.9043 0.9688 0.9528
K −0.5628 −0.3211 −1.120 −0.5477

drug release from the drug–MMT was from flat surface with
heterogeneous sites for ion exchange diffusion process [16–21].
4. Conclusion
We have successfully intercalated antidepressant agents (NT
and VFX) into MMT galleries, and incorporation of PLLA with
NT/VFX–MMT hybrids achieved controlled drug release prop-
erty. In vitro studies showed release of NT/VFX from MMT/
MPs by partial diffusion through a swollen matrix/de-
intercalation of layers of carriers to its individual components
or nanostructures of different compositions. This simple en-
trapment technology will be valuable in aiding to overcome
burst release of the NT/VFX, and this clay showed great po-
tential to become a new dosage form of NT/VFX, and the
methodology can also be applied to other drugs.
Acknowledgments
Authors are thankful to Director, CSMCRI, Bhavnagar for pro-
viding necessary infrastructure facilities and the Council of
Scientific and Industrial Research, Government of India, New
Delhi, India (CSIR) for Senior research fellowship awarded to
BDK, and funding under Network Project: NWP 0010. Authors
are also thankful for the help and cooperation rendered by Dr.
Harshad Brahmbhatt (HPLC), Mr. V. Agarwal (FT-IR), Mr. Jayesh
C. Chaudhari (SEM) and Mrs. Sheetal Patel (TGA) of the ana-
lytical section of the CSMCRI.
Appendix: Supplementary material
Supplementary data to this article can be found online at
doi:10.1016/j.ajps.2015.06.002.
REFERENCES
[1] Rao MVB, Reddy BCK, Srinivasarao T, et al. Estimation of
venlafaxine in commercial dosage forms using simple and
convenient spectrophotometric method. Rasayan J Chem
2009;2:276.
[2] Be Que JC, Montigny CD, Blier P, et al. Venlafaxine:
discrepancy between in vivo 5-HT and NE reuptake blockade
and affinity for reuptake sites. Synapse 1999;32:198.
[3] Wei Z, Bing-ren X, Cai-yun W. Liquid chromatography–mass
spectrometry method for the determination of venlafaxine
in human plasma and application to a pharmacokinetic
study. Biomed Chromatogr 2007;21:266.
[4] Yildiz A, Gonul AS, Tamam L. Mechanism of actions of
antidepressants: beyond the receptors. Bull Clin
Psychopharmacol 2002;12:194.
[5] Park ES, Lee DS, Kwon SY, et al. A new formulation of
controlled release amitriptyline pellets and its in vivo/in vitro
assessments. Arch Pharm Res 2003;26:569.
[6] Melero A, Garrigues TM, Almudevera P, et al. Nortriptyline
hydrochloride skin absorption: development of a
transdermal patch. Eur J Pharm Biopharm 2008;69:588.
[7] Manzo RH, Olivera ME, Amidon GL, et al. Biowaiver
monographs for immediate release solid oral dosage forms:
amitriptyline hydrochloride. J Pharm Sci 2006;95:966.
[8] Park JK, Choy YB, Oh JM, et al. Controlled release of
donepezil intercalated in smectite clays. Int J Pharm
2008;359:198.
[9] Sun B, Ranganathan B, Feng SS. Multifunctional poly(D,
L -lactide-co-glycolide)/montmorillonite (PLGA/MMT)
nanoparticles decorated by Trastuzumab for targeted
chemotherapy of breast cancer. Biomaterials 2008;29:475.
[10] Dong Y, Feng SS. Poly(D, L-lactide-co-glycolide)/
montmorillonite nanoparticles for oral delivery of
anticancer drugs. Biomaterials 2005;26:6068.
[11] Feng SS, Mei L. Poly(lactide)–vitamin E derivative/
montmorillonite nanoparticle formulations for the oral
delivery of Docetaxel. Biomaterials 2009;30:3297.
[12] Kevadiya BD, Joshi GV, Bajaj HC. Layered bionanocomposites
as carrier for procainamide. Int J Pharm 2010;388:280.
[13] Joshi GV, Kevadiya BD, Mody HM, et al. Confinement and
controlled release of quinine on chitosan–montmorillonite
bionanocomposites. J Poly Sci Part A: Poly Chem 2012;
50:423.
[14] Joshi GV, Kevadiya BD, Bajaj HC. Design and evaluation of
controlled drug delivery system of buspirone using
inorganic layered clay mineral. Micropor Mesopor Mater
2010;132:526.
[15] Shah S, Pal A, Kaushik VK, et al. Preparation and
characterization of venlafaxine hydrochloride-loaded
chitosan nanoparticles and in vitro release of drug. J Appl
Polym Sci 2009;112:2876.
458 asian journal of pharmaceutical sciences 10 (2015) 452–458
[16] Zhang H, Pan D, Zou K, et al. A novel core-shell structured
magnetic organic-inorganic nanohybrid involving drug-
intercalated layered double hydroxides coated on a
magnesium ferrite core for magnetically controlled drug
release. J Mater Chem 2009;19:3069.
[17] Panda HS, Srivastava R, Bahadur D. In-vitro release kinetics
and stability of anticardiovascular drugs-intercalated
layered double hydroxide nanohybrids. J Phys Chem B
2009;113:15090.
[18] Song SW, Hidajat K, Kawi S. pH-Controllable drug release
using hydrogel encapsulated mesoporous silica. Chem
Commun 2007;42:4396.
[19] Gu Z, Thomas AC, Xu ZP, et al. In vitro sustained release of
LMWH from MgAl-layered double hydroxide nanohybrids.
Chem Mater 2008;20:3715.
[20] Zhang H, Pan D, Duan X. Synthesis, characterization, and
magnetically controlled release behavior of novel core−shell
structural magnetic ibuprofen-intercalated LDH
nanohybrids. J Phys Chem C 2009;113:12140.
[21] Yang JH, Han YS, Park M, et al. New inorganic-based drug
delivery system of indole-3-acetic acid-layered metal
hydroxide nanohybrids with controlled release rate. Chem
Mater 2007;19:2679.