A REVIEW ON PHARMACEUTICAL APPLICATIONS OF …
Transcript of A REVIEW ON PHARMACEUTICAL APPLICATIONS OF …
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A REVIEW ON PHARMACEUTICAL APPLICATIONS OF
NANOCOMPOSITE
*Bhavin D. Pandya, Ashok N. Mahajan, Priyal R. Patel
Department of Pharmaceutics, Babaria Institute of Pharmacy, Varnama,
Vadodara, Gujarat, India.
ABSTRACT
In the large area of nanotechnology, nanocomposites are becoming
a prominent area of current research and development. In this
review, particularly focused on an overview of nanocomposite, its
structure, types, methods of preparation, nanocomposite
formulations, evaluation, in–vivo drug release from nanocomposite
and the applications of nanocomposites particularly in biomedical
and pharmaceutical area are included. Specifically, nanocomposite
formulations are used for enhancement of dissolution and
bioavailability of poorly aqueous soluble drugs from BCS class–II
and IV.
KEYWORDS: Nanotechnology, Nanocomposite, Dissolution, Bioavailability, BCS
class–II.
INTRODUCTION
The 90% of drugs are administered through oral route. The absorption, bioavailability and
pharmacokinetic profile of these drugs are highly dependent upon solubility in aqueous
medium. The Biopharmaceutical Classification System is a predictive tool through which
drugs can be classified according to their aqueous solubility and gastrointestinal
absorption. The drugs comes under the BCS class – II and IV which are having poor
aqueous solubility are difficult to design in formulation according to, physicochemical
and biopharmaceutical properties for oral administration. There are various methods
which have been included to improve the solubility such as, salt formation, co-
crystallization, co-solvency, and hydrotrophy, addition of solubilising agent and
nanotechnology through Chemical modification whereas physical modification includes
*Corresponding Author
Bhavin D. Pandya
Department of
Pharmaceutics, Babaria
Institute of Pharmacy,
Varnama, Vadodara,
Gujarat, India.
Article Received on
15 April 2021,
Revised on 4 May 2021,
Accepted on 24 May 2021,
DOI: 10.20959/wjpps20216-19159
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 10, Issue 6, 1040-1064 Review Article ISSN 2278 – 4357
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the particle size reduction, modification of the crystal habit, complexation, solubilization
by surfactants and drug dispersion into carriers.[1]
The Nanocomposite material is a novel drug delivery system having nano fillers
scattered in the lattice. Nanocomposites refer to composites in which one phase has nano
scale morphology such as nanoparticles, nano tubes or lamellar nanostructure. A
Nanocomposite is a composite material, in which one of the components has at least one
dimension that is around 10-9
m. A Nanocomposite is a multiphase solid material where
one of the phases has one, two or three dimensions of less than 100 nm or structure
having nano-scale repeat distance between the different phases that make up the material.
A Nanocomposite is a mix of at least two distinct materials with various properties of
each and that are intertwined, by a push to mix the best properties of both. A composite
comprises of two materials of shifting natures and mix of those shows improved in their
properties more prominent than that of each component. Nanocomposite implies nano
measured particles inserted in various polymer materials. The most widely recognized
materials utilized as lattice in nanocomposites are polymers (for example PLGA).
Nanocomposites are the particles involved numerous nano scale consideration while
nanobiocomposite is a biocomposite of nanoparticles. Both nanocomposite and
nanobiocomposite can also be utilized for different approaches such as, enhancement of
solubility, dissolution and bioavailability of poorly water soluble drugs.[1,2,3]
1.1 Structure of Nanocomposite[4]
Figure 1: Structure of Nanocomposite.[4]
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Nanocomposite consists of basically following components:
1. Polymer:
2. Nanoparticles
1.2 Structural Pattern of Nanocomposite[2,5]
The particles of uniform structure, for example, mixes made up of commonly dissolvable
segments. Center shell structure comprises of center particles secured by another shell
segment. Finely scattered nanocomposites, where nanoparticles are dispersed in the
network material. The structure of polymer/layered silicates composites has explaining
by utilizing Wide Angle X–Ray Diffraction (WAXRD) examination and Transmission
Electron Microscopy (TEM) perceptions.[2,5]
Figure 2: Classification of various types of aggregates that may be present in
nanocomposite particles based on their redispersion behavior.[6]
1.3 Advantages of Nanocomposite[ 7,8]
Superior to the coarser particles.
Drug focusing on effectiveness.
Reduces the poisonous quality of drug to typical cells.
Increase life expectancy of the drug.
Sustained release can be achieved.
Nanocomposite indicates 2.5 fold higher takes-up than 1 µm and 6 to 12 crease
higher takes up than 10 µm.
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Safe and helpful treatment of harmful and intense drugs.
Chitosan is biodegradable polymer and for the most part utilized in drug
conveyance, yet issue with chitosan is it is water delicate. The chitosan cellulose
Nanocrystals composite showed increment elasticity up to 150% and decline
hydrophilicity contrasted with flawless chitosan.
1.4 Disadvantages of Nanocomposite[7]
When preparing nano composites, the conglomeration of nanoparticles in an
inadequate scattering in the ideal plans.
During Solvent Evaporation Method of Nanocomposite Preparation, variety in size of
circles and shape because of changes in plan of impellers, thickness, and heat is
created.
Nanocomposite hydrogel has an issue of undesired lack of hydration during its
utilization in drug conveyance.
1.5 Applications of Nanocomposite[ 3,4]
The utilizations of Nanocomposite are a rising zone of improvement of novel
Nanocarriers for drug.
The Nanocomposites can be utilized as drug transporters because of their surface
properties and rheological upgrades.
The better treatment of infection can be improved by the utilization of
Nanocomposite.
The poisonous quality issue of harmful and potent drugs can be limited and
demonstrates their sheltered use.
Targeted tranquilize conveyance for malignancy and cerebrum issue can be created
for simple drug organization and improve security of patients.
Polymer nano composites utilized in quality conveyance for motivation behind
anticancer drug conveyance, DNA transfection, RNA and DOX conveyance, CPT
drug and report.
It is utilized as actuators in artificial muscle.
Nano bio composite of PLGA – MMT with paclitaxel drug shows upgraded cell take-
up of paclitaxel in destructive cell and better communication of nano molecule with
gastrointestinal tract (GIT).
The nucleation of calcium phosphates and bone cell signalling utilized acidic
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macromolecules as the nanocomposite matrix. Especially amino acids such as,
aspartic acid and glutamic acid are utilized as the matrix protein. Both of these
amino acids are play a vital role in intercellular communication and osteoblast
differentiation that will increase extracellular mineralization.
1.6 Types of Nanocomposite[2]
The Nanocomposite is grouped into following sorts:
1. Nano layered composites are made out of exchanging layers of Nano scale
measurement.
2. Nano filamentary composites are made out of frameworks with inserted (for the
most part adjusted) Nano scale distance across fibers.
3. Nano particulate composites are made out of frameworks with inserted Nano scale
particles.
4. Lamellar Nanocomposites can be isolated into two particular classes which are
Intercalated and Exfoliated. The right choice of molecule is fundamental to guarantee
viable infiltration of polymer or its forerunner into the interlayer dispersing of the
support and results in the ideal shed or intercalated item.
5. Polymer Nanocomposites: Polymer nanocomposites are two phase materials in
which the polymers are reinforced by nanoscale fillers. The most heavily used filler
material is based on the smectite class of aluminium silicate clays, of which the
most common representative is montmorillonite (MMT). This hybrid composition
will increase the tensile strength, modulus an heat distortion temperature. There are
various kinds of industrially accessible nano- particles that can be fused into the
polymer framework to shape polymer nanocomposites. Polymer nanocomposites
comprise of polymeric materials with support of nano-particles. Polymer could join
either as the polymeric species itself or through the monomer, which is polymerized
in situ to give the comparing polymer-clay nanocomposite.
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Figure 3: Formation of Different types of Nanocomposites.[2]
Most usually utilized nano-particles include:
Montmorillonite organoclays (MMT).
Carbon nano strands.
Polyhedral Oligomericsilsesquioxane (POSS).
Carbon nanotubes.
Nano silica (N-silica).
Nano aluminum dioxide (Al2O2).
Nano titanium dioxide (TiO2).
There are two principle challenges in creating nanocomposite materials after the ideal
polymer has been chosen for the reason. In the first place, the decision of nano- particles
requires an interfacial connection and similarity with the polymer framework. Second,
the handling strategy should address appropriate uniform scattering and conveyance of
nano-particles or nano-molecule totals inside the polymer framework.[2]
6. Clay Based Nanocomposites: They give extra property improvements. Clays are
usually utilized in the pharmaceutical industry as excipients or dynamic substances. The
utilization of clays for changed drug discharge framework. Regular clay minerals are
appropriate to be utilized in altered drug conveyance framework in light of the fact that
because of colloidal molecule size, crystalline structure, high explicit surface territory,
charge, higher cation trade limit and swelling limit. They can be joined into a polymeric
host bearer, so as to control the dissemination pace of a scattered moderate discharge
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material. A nano clay molecule diminishes the porosity of the polymer, or generally
discourages the dispersion of the dynamic material being discharged, along these lines
expanding the length of the way of dissemination. Clays are cheap materials, which can
be altered by particle trade, metal/metal complex impregnation, pillaring and acid
treatment to create impetuses with wanted usefulness. Naturally changed layered-silicates
or nano clay have turned into an appealing class of natural inorganic crossover materials
due to their potential use in wide scope of utilizations, for example, in polymer
nanocomposites, rheological modifier in paints, inks, oils and beautifying agents,
adsorbent for harmful gases, gushing treatment and drug conveyance transporter. Clays
are normally happening minerals with fluctuation in their constitution relying upon their
groups and sources. The clays utilized for the readiness of nano clay. The most regularly
utilized clay in the blend of polymer nano composites is montmorillonite (MMT) which
is the significant constituent of bentonite. Because of remarkable structure of
montmorillonite, the mineral platelet thickness is only one nano meter, in spite of the fact
that its measurements long and width can be estimated in many nano meters; with a
larger part of platelets in 200 to 400 nm go after decontamination.[2]
1.7 Ideal Characteristics of Clay[2]
The Ideal characteristics of the clay are as following:
The clay has high angle proportion (enormous length to measurement proportion) in
the 300:1 to 1500:1 range.
The clay having a platy structure.
The clay having thickness of 1 nm.
Length and width of the decision clays are in the μm.
Surface zone of the shed platelets normally in the scope of 700 m2 /g.
Molecular weight of the clay particles is about 1.3*108 Dalton.
1.8 Montmorillonite (MMT) Clay
Montmorillonite (MMT) Clay having a place from the smectite group made out of silica
tetrahedral sheets layered between alumina octahedral sheets. The defect of the crystal
lattice and the isomorphous substitution initiates a net negative charge that prompts the
adsorption of soluble clay metal particles in the interlayer space. Such blemish is in
charge of the action and trade responses with natural mixes. MMT additionally having
free hydroxyl end bunches on the surfaces. It is utilized for preparation of
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nanocomposites, because of the huge explicit surface area, displays great adsorption
capacity, high cation trade limit, champion adhesiveness and drug conveying ability.
Additionally MMT is a typical fixing in pharmaceutical items, both as excipient and as
active ingredient.[2,9,10]
Figure: 4 Molecular Structure of Sodium Montmorillonite (MMT) Clay.[5]
The charged nature of the clays is that they are commonly and profoundly hydrophilic
species and subsequently, normally inconsistent with a wide scope of non-polar
frameworks. Organophilic clay (nano clay) is gotten by just the particle trade response of
hydrophilic clay with a natural cation, for example, an alkyl ammonium or phosphonium
particle. The inorganic particles are traded generally with sodium with increasingly
voluminous organic onium cations.[2]
The ion-exchange reaction promotes two results:[2]
The hole between the single sheets is broadened, empowering natural cations
chain to move in the middle of them.
The surface properties of each single sheet are changed from being hydrophilic to
hydrophobic.
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Figure 5: Ion Exchange Reaction shows to form Organoclays (Hydrophobic) from
Layered Silicates (Hydrophilic)[2]
Clay minerals are normally happening inorganic cationic exchangers and thusly they
may experience particle trade with essential drugs in arrangement. The real instruments
of drug intercalation into the montmorillonite are[2]
(1) Drug adsorbed onto the free surface of the montmorillonite.
(2) Drug supplanted sodium in the interlayer.
(3) Drug replaces clay – OH groups to shape ionic bonds with Al3+
and Mg2+
in the
montmorillonite.
The initial two components are accepted as the real systems for drugs adsorbed onto the
montmorillonite by a focus slope. At the point when the fixation angle is equivalent
among inside and outside of the montmorillonite, subsequent to drenching for a while the
dispersion would stop. In body fluids, "counter particles" can dislodge the drug from the
substrate and convey into the body, while the exchanger is being eliminated.[2]
1.9 Purification of Montmorillonite (MMT)
The virtue of the clay can influence the final product of nano composite properties;
because of this it is critical to have montmorillonite with least contaminations of
crystalline silica (quartz), nebulous silica, calcite, kaolin and so forth. The system
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fundamentally utilized for cleaning of filtration of clay incorporates hydro cyclone,
centrifugation, sedimentation technique and synthetic treatment. The purged
montmorillonite was gotten by scattering bentonite in 0.1M NaCl arrangement and
mixed for 12 hr. The scattering was responded multiple times with 0.1M NaCl
arrangement. After centrifugation, the sodium-rich bentonite was washed with de-
ionized water until free of chloride particle as tried by AgNO3 arrangement. The MMT
scattering was dried at 90 – 1000C and ground to go through the 200 mesh sieve. The
Cation Exchange Capacity (CEC) of montmorillonite was estimated by the standard
ammonium acetate method.[2,11]
1.10 Evaluation of Montmorillonite (MMT)
The Evaluation of Clays and their altered natural subsidiaries can be done by utilizing
straightforward just as present day portrayal instruments which incorporate assurance of
chemical composition by gravimetric examination, Inductively Coupled Plasma (ICP) or
XRF, Cation Exchange Capacity (CEC) utilizing standard ammonium acetic acid
derivation technique, surface territory estimation, Scanning Electron Microscopy (SEM),
Fourier Transform Infra–Red Spectroscopy (FT-IR), Powdered X-beam Diffraction
(PXRD) and others. For the most part, ionic equation is registered based on its substance
creations, charge thickness and cation trade limit of clays which gives data about the sorts
of layered silicates. Essentially, FT–IR and Powdered X–Ray Diffraction methods are
fundamental instrumental methods utilized for distinguishing proof of clay structure.[2,12]
2. Methods for Preparation of Nanocomposite
Methods which are utilized for the preparation of nanoparticles can be utilized to get
ready nano composite with certain changes which are as following:
1. Emulsion/Solvent Evaporation: It is based on the formation of emulsion and then
evaporation of solvent. Evaporation of solvent and high force stirring results in
precipitate formation in nano form. It is suitable for hydrophobic drugs. Both drug
and polymer are dissolved in common organic solvent to make oil phase. Water
phase is made up with water soluble polymer. Oil phase is then dispersed in
Aqueous phase with composite by this method using dichloromethane (DCM) as
solvent. 5 mg paclitaxel and 110 mg PLGA were dissolved in DCM to prepare clear
solution of oil phase. Aqueous solution is prepared with 2% w/v PVA and various
amounts of MMT (0, 0.046%, and 0.092% w/v). Oil phase is then emulsified in the
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aqueous phase with sonication for 120 s. The formed emulsion was allowed to
evaporate overnight at room temperature to harden the particles.[7]
2. Emulsification Solvent Diffusion: This method depends on emulsification then
dissemination of dissolvable to external stage to frame nano composite molecule
encourage. Dissemination of dissolvable is because of its solvency in external stage.
Dissemination of dissolvable and high power mixing brings about accelerate
development in nano structure. Polymers are broken down in different solvents
dependent on dissolvability and swelling nature of polymers. At that point, inner
natural oil stage is emulsified in external fluid stage with keeps mixing or
homogenization to shape nano composite molecule. The readied PLA/MMT nano
composite emulsion by emulsification dissolvable dissemination strategy. PLA
arrangement and MMT scattering were independently arranged in ethyl acetic acid
derivation dissolvable. The PLA arrangement, clay scattering, and lauryl liquor were
then blended and utilized as an oil stage. The fluid stage is set up with surfactants and
PVA in refined water. Oil stage is scattered in the watery stage with homogenization
and afterward magnetic mixing.[7]
3. Solution Intercalation: This method is generally utilized for layered silicates as
nano filler which are to be intercalated in the polymer network. Guideline includes
dissemination of the polymer chain in the exhibitions between silicate layers. In this
strategy, dissolvable is chosen with the end goal that polymer is solvent in
dissolvable while inorganic nano filler just swells. Polymer is broken down in
dissolvable, and after that, inorganic nano filler is included arrangement with mixing.
More often than not, fillers are permitted to swell before expansion in polymer
framework. This prompts intercalation of polymer into silicate to frame nano
composite.[7]
4. Melt Intercalation: This technique works on a similar principle as that of
arrangement intercalation, yet here, heat is utilized rather than dissolvable for
intercalation of polymers into the silicate. In this strategy, the blend of polymer and
layered silicate are warmed till the conditioning purpose of polymer
accomplished. At that point, it is blended with high shear rate. This prompts
intercalation of network into silicate layered. Instruments, for example, single screw
extruder and twofold screw extruder are utilized for liquefy intercalation. It is useful
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over arrangement intercalation as far as the nonappearance of natural solvents and
simplicity of mechanical procedures. Polymer chain diffuses in the displays between
silicate layers. Contingent upon level of infiltration of polymer chain into the silicate,
nano composite might be of two sorts, i.e., intercalated and peeled. Poly (butylene
adipate-co-terephthalate) – MMT nano composite by soften intercalation technique
utilizing entomb bunch blender, counter turning blender at 160°C for 15 min for 50
rpm then 120°C for 20 min for 100 rpm.[7]
5. Double Emulsion Solvent Evaporation: In this technique, two polymers chose are
disintegrated in oil stage and watery stage contingent upon their dissolvability. At that
point, water in oil emulsion is set up with mixing. The subsequent emulsion is then
added to outside stage which is fluid stage with stabilizer like PVA; at that point,
framework is blended to vanish dissolvable at room temperature. The readied
calcium phosphate (Cap)/poly (hydroxyl butyrate-co- hydroxyl valarate) (PHBV)
nano composite by strong in oil in water (strong in- oil-in-water [s/o/w]) emulsion
utilizing dissolvable dissipation technique. W/O emulsion was made by fluid
arrangement of cow-like serum egg whites (BSA) and natural arrangement of PHBV
in chloroform utilizing homogenizer. The subsequent emulsion was included PVA
watery answer for structure w/o/w emulsion. At that point, blend was magnetically
mixed to vanish dissolvable. PHBV-BSA microspheres were sifted, solidify dried.
Altered s/o/w emulsion dissolvable vanishing technique was utilized to deliver BSA-
stacked Ca-P/PHBV nano composite microspheres. Ca-P nanoparticles were
scattered in the PHBV- chloroform arrangement utilizing ultra-sonication and
homogenization to frame an s/o nano suspension and it is scattered in the internal
water stage (the aqueous BSA solution), trailed by a similar method for PHBV-BSA
microsphere readiness.[7]
6. Electrospinning: This method is utilized to plan nano bio composite fiber. The
mechanical assembly comprise of level tip needle, high voltage power supply,
siphon, and directing gatherer plate. Blend of polymer is set up in natural solvents, for
example, dimethyl formamide (DMF) and chloroform. At that point, it is stacked on
electro spun needle and the high voltage connected to shape composite
fiber. The readied PLA/carbonated calcium-lacking hydroxyapatite (CDHA) bio nano
composites strands by this technique. In short, PLA pellets were broken down in
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chloroform; CDHA hasten was added to PLA answer for structure blend pursued by
DMF option with persistent mixing for 4 h. This blend is then stacked into the electro
spun device and infused through the needle to frame filaments. Strands are then dried
in fume hood.[7]
7. Ultra Sonication: Here, transformation of material into nano size is because of high-
recurrence ultrasound waves. For the most part, in this strategy, two polymers are
included dissolvable (typically ethanol), and the blend is then ultra- sonicated to get
nano bio composite. The staying dissolvable is expelled. The recurrence of
illumination, time for light, and power supply are variable which controls size and
morphology of nano bio composite. The readied poly (ester- imides) (PEA) ZnO
nano bio composite by ultra-sonication strategy. They utilized PEA as a framework
and changed ZnO nanoparticles (adjustment by the silane coupling specialist, i.e., γ-
methacryloxy propyl tri-methoxy silane). PEA scattering is made in ethanol utilizing
ice-water ultrasonic shower. Pursued by expansion of various extent of changed ZnO
nanoparticle in PEA suspension and blend was ultra sonicated for 4 h. At that point,
dissolvable was evacuated, and nano bio composite was dried.[7]
Figure: 6 Schematic illustrations of drug-laden nanocomposites by different
methods.[6]
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Table: 1 Nanocomposite Preparations.[7]
Methods Materials Solvent Equipment Evaluation Application
Emulsion/
solvent
evaporati
on method
PLGA, PVA,
paclitaxel, sodium
montmorilloni te,
coumarin – 6
Distilled water,
dichlorometha ne
Centrifuge
machine,
Sonicator, freeze
dryer
SEM,
AFM, zeta
potential
analysis,
drug
encapsulati
on
efficiency
Anti- cancer
Emulsion
solvent
diffusion
Salmon calcitonin,
coumarin – 6,
PLGA, PVA
403, Chitosan,
insoluble lactose,
PLA, Sodium MMT,
Cloisite 30B , PVA,
SLS,
Lauryl alcohol
Acetone,
methanol, Ethyl
acetate
Agglomast er,
lyophilizer,
mechanical fusion,
Homogeniz er
Zeta
potential,
LDSA, in
vitro
evaluation,
DTA,
TGA, zeta
potential,
particle size,
morpholog y
Anti- cancer
Microwav e
Induced
diffusion
Glipizide drug,
acacia gum, ghatti
gum, cassia gum,
gelatin
Distilled water Microwave oven
Solubility
study,
dissolution
studies,
XRD, DSC,
FTIR, SEM,
TEM, in vivo
evaluation
Anti- diabetic
in Diabetes
Mellitus
(Type – II)
In situ sol
– gel
process
Sodium alginate,
hydroxyapatit e,
Diclofenac sodium
Distilled water,
ammonium
hydroxide, Ca
(NO3)2 4H2O,
(NH4)2HPO4
Stirrer, oven,
hypodermic
syringe
FTIR, XRD,
SEM,
swelling
behaviour,
drug
release
Pain Reliever
in Joint Pain
associate with
Rheumatoi
d arthritis
3. Evaluation of Nanocomposites
A. Morphological Characterization: Following techniques are used for morphological
evaluation:
1. X–Ray Diffraction Method: XRD is utilized to decide shape, crystalline, and
indistinct nature of nano filler, drug, and polymer. It is additionally used to decide
stage detachment of nano filler and polymer. Intercalation of layered silicate with
polymer can be recognized that is shed or intercalated.[7]
2. Fourier Transform Infra–Red (FTIR) Spectroscopy: Each practical group
demonstrates some fixed reverberation recurrence during infrared light which is to
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distinguish the useful group. It is utilized to decide changes in nanocomposite or
nanobiocomposite as far as practical group. Compound changes happened during
composite planning by various polymers and drug can be effectively recognized. It
additionally distinguishes obscure metal in test, quality, and consistency of test and
measure of part in blend. It is utilized to decide synthetic arrangement of halfway and
acquired molecule.[7]
3. Transmission Electron Microscopy (TEM): TEM is utilized to identify quality
about inside structure, different imperfections, and space dispersion of various stages.
It gives information about condition of scattering of nano filler in polymer
framework. Nature of intercalation of layered silicate with polymer can be
distinguished, i.e., peeled or intercalated.[7]
4. Atomic Force Microscopy (AFM): Images are shaped by estimating the physical
cooperation between sharp AFM tips. It gives three dimensional pictures of a
molecule and group of particles. Surface morphologies, for example, surface
harshness, surface powers, and size scope of the nanoparticles are resolved. Data, for
example, mechanical, compound, and sticking properties of surface can be gotten.[7]
5. Scanning Electron Microscopy (SEM): Quickened electrons are permitted to
occurrence on test, three-dimensional pic are shaped by optional electrons and
backscattered electrons. It gives information about morphology of single polymer,
medicate, and nanobiocomposite. It gives information about condition of scattering
of nano filler in polymer framework. Surface crack and collection of particles in
nanobiocomposite can be effectively identified.[7]
B. Thermal Analysis
1. Thermo Gravimetric Analysis (TGA): It is utilized to quantify change in weight of
test as temperature or time changes. Change in weight reduction between single
polymer and composite can be looked at. It proposes physical changes, for example,
softening which do not include weight reduction just as synthetic changes, for
example, heating which includes weight reduction. The heaviness of the example is
plotted against time or temperature which proposes warm changes in the material, for
example, loss of dissolvable, water of hydration in inorganic materials, lastly decay
of the material.[7]
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2. Differential Thermal Analysis (DSC): This method is utilized to identify nature of
crystallization, exothermic, and endothermic response. In endothermic responses,
e.g., strong example melts to a fluid; it requires more warmth streaming to the
example to expand its temperature at a similar rate as the reference since test
assimilates warmth to change over into fluid state, henceforth more warmth is require
to raise temperature of test when contrasted with reference. Switch is the situation
with endothermic response which happens during crystallization. It gives information
about warm steadiness of unadulterated polymer and nanobiocomposite by melting
point.[7]
C. Magnetization: It is uniquely utilized in portrayal of magnetic nanobiocomposite. It
gives data about magnetic intensity of nanobiocomposite, i.e., what are the
progressions happened in magnetic property of material subsequent to making
composite. It tests the reaction of outer magnetic field on nanobiocomposite. It
additionally recommend about impact of temperature on magnetic property. The
systems utilized are vibrating test magnetometer (VSM) and SQUID. VSM works on
Faraday's law of enlistment, i.e., changing magnetic field produce electric flow which
can be estimated. At first, example is put in steady magnetic field to prompted
polarization. Magnetic field is made around test by magnetic dipole minute at that
point test is vibrated. This makes change in magnetic field and thus, changes
electric field. It shows magnetic conduct and magnetic quality of materials.[7]
D. In – vitro Drug Release: In this examination, various sorts of contraption and
technique are utilized relying upon definition. Use Centrifuge mechanical assembly
mixed at 100 rpm speed and 37°C ± 0.5°C temperature in phosphate buffer for the
anticancer drug discharge from paclitaxel-stacked PLGA-MMT nanobiocomposite.[7]
E. Swelling Property: Swelling Property of nanobiocomposite hydrogel is generally
performed utilizing hydrogel disc. Temperature, solvent, and time of study shifts as
per formulation. Solvent utilized are distilled water, hydrochloric acid, sodium
hydroxide, etc.[7]
Swelling ratio can be measured by following formula:
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4. In-vivo Drug Release Mechanism from Nanocomposite
At the point when arranged nano composite is regulated in body; biological counter
particles gets traded with cationic drug particles which are available on the outside of
nano clay. Free drug atoms are accessible for retention and emptied molecules which are
having submicron size passes the intestinal layer and goes in circulatory system. Through
the kidney the emptied particles discharged out.[2]
Figure 7: In - vivo Drug Delivery from Clay Nanocomposite Pharmaceutical
Applications of Nanocomposites.[3]
Applications of Nanocomposites in Pharmaceutical Field
Figure 8: Applications of Nanocomposites in Pharmaceutical Field.[2]
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1. Rheological Modifier: Rheological Modifiers control the stream properties of fluid
frameworks, for example, paints, inks, emulsions or color suspensions by improving
the medium thickness or give thixotropic stream conduct to fluid framework.
Likewise give great shading maintenance and inclusion for nail polishes, lipsticks and
eye shadows. As organo clays are non-aggravation for both skin and eye to eye
connection in this way they are appropriate as rheological modifiers in paints, inks
and oil as well as beauty care products.[2]
2. Particulate Delivery Systems based on Clay Minerals: In this Delivery system,
Clay Minerals will give unconstrained submicron scatterings in watery media,
bringing about minimal effort and biocompatible frameworks with huge surface
territory and high incorporation limit. As the polymer/clay nanocomposites are an
ongoing class of half and half frameworks where inorganic or organo-clay
nanoparticles (frequently montmorillonite) are scattered in a polymer lattice. They
make them intrigue points of interest when contrasted with the unadulterated polymer,
for example, improved mechanical just as rheological properties. Alongside these
advantages the great intercalation limit offered by the clay mineral particles have
been utilized to grow new controlled drug release.[2]
3. Hydration–Activated Extended Release System: Smectites effectively goes about
as crumbled specialists in tablet plans due to their hydrophilic and swelling
properties. Broadened discharge tablets by direct pressure of sodium sulphatiazole
and magnesium aluminum silicate demonstrates dynamic development of a thick gel
layer around the tablets during in vitro dissolution test.[2]
4. Improvement of Dissolution Rate: As the Improvement of dissolution of
inadequately water-solvent drugs stays one of the more significant difficulties before
plan advancement researchers. Among them the surface adsorption of drug is one
intriguing methodology. Particles onto finely partitioned solids enormously upgrade
the surface region accessible to the disintegration medium. Smectites were found to
successfully expand the in vitro dissolution rate of non-ionic just as acid insoluble
drugs. Drug discharge from the clay surface is advanced by the frail holding among
them and because of the hydrophilic properties of the clay correspondingly
tranquilize wettability is improved. In examination with phenytoin sodium cases
phenytoin- montmorillonite adsorbents can improve the bioavailability of the drug in
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people.[2]
5. Nano Clay as Drug Vehicle: Nano Clay is possibly valuable materials in the field of
controlled arrival of remedial operator to patients, where it goes about as a drug
vehicle. MMT could adsorb dietary poisons, bacterial poisons related with
gastrointestinal aggravation, hydrogen particles in acidosis and metabolic poisons, for
example, steroidal metabolites related with pregnancy. Every one of these conditions
bring about a large group of normal indications, including queasiness, retching and
the runs, the greater part of which are common side effects of the symptoms brought
about by anticancer drugs. A little expansion of nano clay can incredibly upgrade the
rheological properties. These properties anticipate shade settling and listing on
vertical surfaces and shine is negligibly influenced because of the low degrees of
expansion. Nano clay gives shading maintenance just as great inclusion in
beautifying agents. Quality treatment is increasing developing consideration for the
treatment of hereditary lacks and perilous infections. For the effective presentation of
outside DNA into cells, a transporter framework is required. As of late, it has been
effectively exhibited that novel layered twofold hydroxide could shape a nano half
and half by intercalating with bimolecular anion, for example, mononucleotides,
DNA which demonstrates that antisense oligonucleotide particles bundled in the
layered twofold hydroxide can enter cells, apparently phagocytosis or endocytosis.
The leukemia cells were utilized to investigate the layered twofold hydroxide's
potential as gene carriers.[2]
Figure 9: Nano Clay Drug Targetting to the Biological Cell Nucleus.[2]
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6. Used in Waste – Water Treatment: Now – a – days the utilization of organo clays
in wastewater treatment has turned out to be regular in industry. Organo clays display
a synergistic impact with numerous normally used water treatment unit procedures
including granular-actuated charcoal, switch assimilation, and air strippers. Granular
enacted carbon is especially compelling at evacuating a huge scope of natural
particles from water, be that as it may, is exceptionally poor for expelling enormous
atoms, for example, humic acid and wastewater containing emulsified oil and oil.
Organo clays have demonstrated to be the innovation of decision for treating oily
waste waters.[2,25]
7. Controlled Release: The nano composite of hydrogel with attractive particles can be
utilized in pulsatile tranquilize conveyance framework. Remote control arrival of drug
is planned by attractive nano composite of N-iso propyl acryl amide (NIPAAm). Iron
oxide is utilized as remote warming gadget, and NIPAAm is a temperature delicate
hydrogel. Exchanging high-recurrence attractive field prompts heat age in nano
composite which powers the swelling change of the hydrogel. It was discovered that
drug discharge diminishes with increment in temperature. Nanobiocomposite of
sodium alginate/hydroxyapatite shows control arrival of Diclofenac tranquilize.
Arranged nano composite globules could be utilized in the generation of oral
pharmaceutical details. Nano composite delayed the arrival of Diclofenac sodium for
8 hr more contrasted and the perfect sodium alginate hydrogel dots. Control arrival of
drug saw in glycolic acid g – Chitosan – gold – nano flower nano composite. The
nano half breed platforms were observed to be steady towards the pH of the medium.
The readied nano mixture frameworks are biocompatible. This nano composite
indicated control drug discharge rate in the phosphate buffer (pH 7.4). In this manner,
gold nano blossoms are the reasonable added substance for the glycolic acid united
chitosan-based framework, for drug conveyance.[7,22]
8. Sustained Release: An arrangement for spinal cord damage arranged effectively as
continued discharge nano bio composite containing hyaluronan and methylcellulose
hydrogel with PLGA nanoparticle, it was observed to be sheltered and biocompatible.
It was shown that this readiness is all around endured in intrathecal space of injured
rats for 28 days and demonstrating no expansion in irritation, scarring, or pit volume
in respect to controls and no impact on locomotor capacities.[ 7 ,22]
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9. Anti–cancer: Nanobiocomposite made with PLGA-MMT with paclitaxel tranquilize
for oral conveyance of anticancer. Paclitaxel is anticancer drug can not be given orally
in light of low assimilation through GIT and first-pass impact. PLGA-MMT nano
composite showed expanded GIT ingestion and increment cell take-up by CaCo-2
and HT-29 cells. The drug discharge study demonstrated an underlying burst pursued
by a moderate, continued discharge, which was not altogether influenced by the MMT
part. The examination demonstrates that nanobiocomposite of hydroxyapatite-
chitosan with celecoxib drug is potent and safe vehicle for colon malignant growth
sedate conveyance. It was discovered that nano composite particles conquer reaction
appeared by free celecoxib and furthermore nano composite indicated more strong
anticancer action than free celecoxib.[7, 23, 24]
5.1 Nanocomposite Preparations for an Effective Dissolution Enhancement
Nanocomposites prepared for Dissolution Enhancement of Poorly aqueous soluble drugs
come under BCS class–II (Low Solubility and High Permeability) are as following:
1. Enhancement of solubility and increase the rate of dissolution of drug Celecoxib that
is poorly water soluble which comes under BCS class–II. Enhancement of solubility
has been achieved by formulating the BCS Class II drugs into Bionanocomposite
(BNC) by utilizing natural carriers and Microwave assisted fusion method, which
shows % drug release was found to be 91.58% and ultimately leads to improve the
bioavailability of the drug.[1]
2. Dissolution enhancement of two wet media milled, poorly water-soluble drugs,
Griseofulvin (GF) and Azodicarbonamide (AZD), incorporated into nanocomposite
microparticles (NCMPs) by Fluidized Bed Drying (FBD) and Spray Drying (SD)
were investigated.[14]
3. Irbesartan is an angiotensin–II receptor antagonist and is a poorly water-soluble drug.
Irbesartan nanocomposite particles were prepared by an anti – solvent precipitation
combined with a spray drying process for enhancement of dissolution.[15]
4. Ternary Cyclodextrin complexation of Telmisartan with concurrent high energy
nanonization allows formation of amorphous nanocomposites which are multiphase
(Cyclodextrin + Telmisartan + Meglumine) solids having nano scale dimensions.[16]
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5. Soluble starch mixed Curcumin nanocomposite prepared which increases water
solubility and stability of Curcumin. The hydrogen bonding is responsible for the
interaction between curcumin and starch. Cur@star will be increased the stability of
curcumin against UV radiation and oxidation. Due to the simple preparation
procedures and low price material utilized in curcumin soluble starch nanocomposite
reported as promising to broaden the applications of curcumin in the food industry as
well as chemotherapy in cancer treatment.[17, 18, 25]
6. Bioavailability of a poorly aqueous soluble drug can be enhanced by producing a
nanosuspension of drug and subsequently, spray drying it into nanocomposite
microparticles (NCMPs).[19]
7. A preparation pH–sensitive Ofloxacin/Montmorillonite/Chitosan nanocomposite
microsphere which improves the burst release effect of the drug by the combination
of two methods: Solution Intercalation method and Emulsification Cross – Linking
method.[12]
8. Core – shell type nanocomposite microparticles were prepared by fluidized bed
coating of media –milled GF nanosuspension onto Pharmatose®. The nanocomposite
particles were scattered in water and aqueous solution of SDS by using various
agitation methods such as stirring and sonication. Presence of SDS was found to be
the full recovery of nanoparticles and their dissolution, whereas HPC shows to have
positive yet convoluted effects on the recovery.[20]
9. The Bionanocomposites (BNCs) of poorly water-soluble drug Nifedipine and natural
carriers such as Moringa oleifera Gum and Aegle marmelos (L.) were utilized and
prepared by Microwave Induced Diffusion (MIND) technique to enhance drug
solubility in aqueous medium and increase its dissolution rate which was based on
their wetting and surface active agent property. BNCs were produced through most
convenient and cheap MIND technique. Solubility enhancement might be because of
formation of drug dispersion at micro and nanoscale level.[21]
CONCLUSION
Nanocomposites have turned into a promising area of formulation and development.
Polymer nanocomposites are separated into two classes, the polymer nanocomposites
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which give improvement in mechanical properties and the clay polymer nanocomposites
which give extra property upgrades. The nanocomposites can be utilized as drug
transporters because of their surface properties and rheological enhancements. The uses
of nanocomposites are a rising zone of advancement of novel nano carriers for drug.
Utilization of polymer clay nano composite in drug conveyance framework is a
developing region in the field of uses of nanotechnology. Other than this, another
significant use of these nanocomposites is in tissue building and in recovery of nerve
development in a biological living system. Polymer clay nanocomposites are a promising
nano carrier accessible for the drug conveyance of drug particles. Polymer clay
nanocomposites might be utilized in oral multi particulate drug delivery gives a moderate
and controlled drug discharge with improved mechanical properties.
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