a review on pharmaceutical applications of …

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Bhavin et al. World Journal of Pharmacy and Pharmaceutical Sciences

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 nanoparticles 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 nanoparticles

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.

REFERENCES

1. Bhatt Mahesh, Patil Ashish, Batra A K, Chimkode R M, Payghan Santosh,

“Celecoxib Bionanocomposite: Investigation of the effect of microwave irradiation

using natural solubilizer.” Asian Journal of Biomedical and Pharmaceutical

Sciences, 2015; 23: 24.

2. Omdip R. Sohani, Atul A. Phatak, Pravin D. Chaudhari, “Use of Nanocomposites in

Drug Delivery Systems.” Pharma Times, 2015; 14: 31 – 34.

3. Sambarkar PP, Patwekar SL, Dudhgaonkar BM, “Polymer Nanocomposites: An

Overview.” International Journal of Pharmacy and Pharmaceutical Sciences, 2012;

60: 62.

4. Pande VV and Sanklecha VM, “Bionanocomposite: A Review.” Austin J Nanomed

Nanotechnol., 2017; 2.

5. D.R. Paul, L.M. Robeson, “Polymer nanotechnology: Nanocomposites.” Polymer.,

2008, 3187, 3189, 3192.

6. Anagha Bhakay, Mahbubur Rahman, Rajesh N. Dave and Ecevit Bilgili,

“Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites:

Formulation–Processing Aspects and Challenges.” Pharmaceutics, 2018; 4: 5.

7. Shailesh L. Patwekar, Prasad Jamkhande, Surendra G. Gattani, Santosh A. Payghan,

“Nanobiocomposite: A New Approach to Drug Delivery System.” Asian Journal of

Pharmaceutics, 2016; 648 – 654.

8. Baumann MD, Kang CE, Tator CH, Shoichet MS, “Intrathecal delivery of a

polymeric nanocomposite hydrogel after spinal cord injury.” Biomaterials, 2010; 31:


1063


7631 – 7639.

9. Khalil H, Mahajan D, Rafailovich M, “Polymer – Montmorillonite Clay

nanocomposite.” Polym. Int., 2005; 54: 423 – 427.

10. Wang X, Dul Y, Luo J, “Biopolymer/Montmorillonite nanocomposite: preparation,

drug – controlled release property and cytotoxicity.” Nanotechnology, 2008; 19:

65 – 70.

11. Joshi GV, Patel HA, Kevadiya BD, Bajaj HC, “Montmorillonite intercalated with

vitamin B1 as drug carrier.” Appl. Clay Sci., 2009; 45: 248 – 253.

12. Shuibo Hua1, Huixia Yang, Aiqin Wang, “A pH-sensitive nanocomposite

microsphere based on chitosan and montmorillonite with in vitro reduction of the

burst release effect.” Drug Dev Ind Pharm, 2010; 1106.

13. R. Suresh, S. N. Borkar, V. A. Sawant, V. S. Sinde, S.K. Dimble, “Nanoclay Drug

Delivery System.” International Journal of Pharmaceutical Sciences and

Nanotechnology, 2010; 901, 902, 904.

14. Anagha Bhakay, Mohammad Azad, Ecevit Bilgili, Rajesh Dave, “Redispersible fast

dissolving nanocomposite microparticles of poorly water- soluble drugs.”

International Journal of Pharmaceutics, 2014; 367.

15. Zhiliang Zhanga, Yuan Lea, Jiexin Wanga, Hong Zhaoa, Jianfeng Chen, “Irbesartan

drug formulated as nanocomposite particles for the enhancement of the dissolution

rate.” Particuology, 2012; 10: 462.

16. Mayur Sangwai, Pradeep Vavia, “Amorphous ternary Cyclodextrin nanocomposites

of Telmisartan for oral drug delivery: Improved solubility and reduced

pharmacokinetic variability.” International Journal of Pharmaceutics, 2013; 431.

17. Jinglei Li, Gye Hwa Shin, Woo Lee, Xiguang Chen, Hyun Jin Park, “Soluble starch

formulated nanocomposite increases water solubility and stability of curcumin.”

Food Hydrocolloids, 2015; 1.

18. Valodkar M, Thakore S, “Organically modified nano sized starch derivatives as

excellent reinforcing agents for bionanocomposites.” Carbohydrate Polymer, 2011;

86: 1244 – 1251.

19. Mohammad Azad, Colby Arteaga, Beshoy Abdelmalek, Rajesh Dave, Ecevit Bilgili,

“Spray drying of drug – swellable dispersant suspensions for preparation of fast –

dissolving, high drug-loaded, surfactant-free nanocomposites.” Drug Dev Ind

Pharm., 2014; 1.

20. Anagha Bhakay, Rajesh Dave, Ecevit Bilgili, “Recovery of BCS Class II drugs


1064


during aqueous redispersion of core–shell type nanocomposite particles produced via

fluidized bed coating.” Powder Technology, 2013; 236: 221.

21. Mahesh R. Bhatt, Shailendra Sharma, G. K. Derkar, R. M. Chimkode, S. A. Payghan,

“Microwave-generated Bionanocomposites for Solubility Enhancement of

Nifedipine.” Asian Journal of Pharmaceutics, 2016; 741.

22. Zhang J, Wang Q, Wang A, “In situ generation of sodium alginate/hydroxyapatite

nanocomposite beads as drug – controlled release matrices.” Acta Biomatter, 2010; 6:

445 – 454.

23. Zhang M, Ishii A, Nishiyama N, Matsumoto S, Ishii T, Yamasaki Y, “PEGylated

calcium phosphate nanocomposites as smart environment sensitive carriers for

siRNA delivery.” Adv Mater. Sci., 2010; 21: 3520 – 3525.

24. Venkatesan P, Puvvada N, Dash R, Kumar BN, Sarkar D, Azab B, “The potential of

celecoxib – loaded hydroxyapatite – chitosan nanocomposite for the treatment of

colon cancer.” Biomaterials, 2011; 32: 3794 – 3806.

25. Patel HA, Somani RS, Bajaj HC, Jasra RV, “Nano clays for polymer

nanocomposites, paints, inks, greases and cosmetics formulations, drug delivery

vehicle and waste water treatment.” Bull. Mater. Sci., 2006; 29: 133 – 145.

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