REVIEW ARTICLE Am. J. PharmTech Res.

2013; 3(4) ISSN: 2249-3387

Journal home page: http://www.ajptr.com/

Mucoadhesive Microspheres for Novel Drug Delivery System: A

Review
Atul Kumar1*, Shubhendra Jha1, Ravindra Rawal1, P.S.Chauhan1, Sheo Datta Maurya1
1.Department of Pharmacy, IEC Group of Institutions, Knowledge Park - I, Greater Noida, U.P.
India

ABSTRACT
There are various approaches for the delivery of therapeutic substance to the target site in a
controlled release fashion. One such approach is using microspheres as carriers for drugs or
active pharmaceutical compound. However, the success of this drug delivery system is limited
due to their short residence time at the site of absorption. Mucoadhesive microspheres can be
tailored to adhere to any mucosal tissue including those found in stomach, thus offering the
possibilities of localized as well as systemic controlled release of drugs. This article presents the
advantages of Mucoadhesive microsphere, mechanism, theories involved in mucoadhesion,
factor that affect the mucoadhesion, polymer in Mucoadhesive drug delivery system,
methodology of preparation of Mucoadhesive microsphere, method of evaluation and their
applications in drug delivery. Mucoadhesive drug delivery systems promises several advantages
that arise from localization at a given target site, prolonged residence time at the site of drug
absorption and an intensified contact with the mucosa increasing the drug concentration gradient.
Keywords: Microsphere, Mucoadhesion, Bioadhesion, Bioavailability.

*Corresponding Author Email: [email protected]

Received 05 July 2013, Accepted 16 July 2013

Please cite this article in press as: Atulkumar et al., Mucoadhesive Microspheres for Novel Drug
Delivery System: A Review. American Journal of PharmTech Research 2013.
Atulkumar et. al., Am. J. PharmTech Res. 2013; 3(4) ISSN: 2249-3387

INTRODUCTION
The most desirable and convenient method of drug administration is the oral route due to the
ease of administration and patient compliance. One limitation for oral delivery is poor
bioavailability and for the drug candidates who show absorption window in the proximal gut and
is the major obstacle to the development of controlled release formulation. A number of
approaches have been developed to increase the residence time of dug formulation. 1
Microsphere carrier systems made from the naturally occurring biodegradable polymers have
attracted considerable attention for several years in sustained drug delivery. Recently, dosage
forms that can precisely control the release rates and target drugs to a specific body site have
made an enormous impact in the formulation and development of novel drug delivery systems.
Microspheres form an important part of such novel drug delivery systems. 2-4
The problem frequently encountered with controlled release dosage forms is the inability to
increase the residence time of the dosage form in the stomach and proximal portion of the small
intestine, due to the rapid gastrointestinal transit phenomenon of the stomach which may
consequently diminish the extent of absorption of many drugs since almost most of the drug
entities are mostly absorbed from the upper part of the intestine, therefore it would be beneficial
to develop a sustained release formulation which remain at the absorption site for an extended
period of time.5
Microspheres constitute an important capacity. Microspheres are the carrier linked drug delivery
system in which particle size is ranges from 1-1000 μm range in diameter having a core of drug
and entirely outer layers of polymer as coating material. However, the success of these
microspheres is limited due to their short residence time at site of absorption. It would, therefore
be advantageous to have means for providing an intimate contact of the drug delivery system
with the absorbing membrane. This can be achieved by coupling bioadhesion characteristics to
microspheres and developing “Mucoadhesive microspheres.6
Drug action can be improved by developing new drug delivery system, such as the
Mucoadhesive microsphere drug delivery system. Mucoadhesive microspheres remain in close
contact with the absorption tissue, the mucous membrane, releasing the drug at site of action
leading to a bioavailability increase and both local and systemic effects. 7
The gastroretentive drug delivery systems can be retained in the stomach for long time and
improve the oral bioavailability of drugs that have an absorption window in a particular region of
the gastrointestinal tract.8

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Mucoadhesive system (Bioadhesion):

Mucoadhesive drug delivery systems are used to enhance drug absorption in a site-specific
manner .9 Mucoadhesion or bioadhesion can be defined as the state in which two materials, at
least one of which is biological in nature, are held together for a prolonged time period by means
of interfacial forces. In biological systems, bioadhesion can be classified into three types.
 Type 1: adhesion between two biological phases, for example, platelet aggregation and
wound healing.
 Type 2: adhesion of a biological phase to an artificial substrate, for example tissue, cell
adhesion to culture dishes and biofilm formation on prosthetic devices and inserts.
 Type 3: adhesion of an artificial substance to a biological substrate, for example,
adhesion of synthetic hydrogels to soft tissues.
For drug delivery purpose, the term “Bioadhesion” implies attachment of a drug carrier system to
a specific biological location. The biological surface can be epithelial tissue or the mucus coat on
the surface of a tissue. If adhesive attachment is to a mucous coat, the phenomenon is referred to
as “Mucoadhesion”. Mucoadhesion is defined as the interaction between a mucin surface and a
synthetic or natural polymer.10
Microspheres, in general, have the potential to be used for targeted and controlled release drug
delivery; but coupling of bioadhesive properties to microspheres has additional advantages e.g.
efficient absorption and bioavailability of the drugs due to high surface to volume ratio, a much
more intimate contact with the mucous layer, specific targeting of drugs to the absorption site.
Bioadhesive microspheres can be tailored to adhere to any mucosal tissue including those found
in eye, nasal cavity.
Theories of mucoadhesion:11,12
The phenomena of Bioadhesion occur by a complex mechanism. Six theories have been
proposed which can improve our understanding for the phenomena of adhesion and can also be
extended to explain the mechanism of Bioadhesion. The theories include:
Electronic theory
Electronic theory is based on the premise that both mucoadhesive and biological materials
possess opposing electrical charges. Thus, when both materials come into contact, they transfer
electrons leading to the building of a double electronic layer at the interface, where the attractive
forces within this electronic double layer determine the mucoadhesive strength.
Adsorption theory
According to the adsorption theory, after an initial contact between two surfaces, the material
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adheres because of surface forces acting between the atoms in the two surfaces.
Two types of chemical bonds resulting from these forces can be distinguished.
1. Primary chemical bonds of covalent nature, which are undesirable in bioadhesion because
their high strength may result in permanent bonds.
2. Secondary chemical bonds having many different forces of attraction, including
electrostatic forces, Vander Waals forces, and hydrogen and hydrophobic bonds.
Wetting theory
The wetting theory applies to liquid systems that present affinity to the surface in order to spread
over it. This affinity can be found by using measuring techniques such as the contact
angle. The general rule states that lower the contact angle greater will be the affinity. The contact
angle should be equal or close to zero to provide adequate Spreadibility .
The Spreadibility coefficient, SAB, can be calculated from the difference between the surface
energies γB and γA and the interfacial energy γAB, as indicated in equation 1.
SAB = γB – γA – γAB (1)
The greater the individual surface energy of mucus and device in relation to the interfacial
energy, the greater the adhesion work, WA, i.e. the greater the energy needed to separate the two
phases.
WA = γB + γA – γAB (2)
Mechanical theory
The mechanical theory assumes that adhesion arises from an interlocking of a liquid adhesive (on
setting) into irregularities on a rough surface. However, rough surfaces also provide an increased
surface area available for interaction along with an enhanced viscoelastic and plastic dissipation
of energy during joint failure, which are thought to be more important in the adhesion process
than a mechanical effect.
Diffusion theory
According to diffusion theory, the polymer chains and the mucus mix to a sufficient depth to
create a semi-permanent adhesive bond. The exact depth to which the polymer chains penetrate
the mucus depends on the diffusion coefficient and the time of contact. This diffusion
coefficient, in turn, depends on the value of molecular weight between crosslinks and decreases
significantly as the cross-linking density increases .
Fracture theory
Fracture theory differs a little from the other five in that it relates the adhesive strength to the
forces required for the detachment of the two involved surfaces after adhesion. This assumes that
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the failure of the adhesive bond occurs at the interface. However, failure normally occurs at the
weakest component, which is typically a cohesive failure within one of the adhering surfaces.
Polymers used in the formulation of Mucoadhesive microspheres: 13
Mucoadhesive polymers are water-soluble and water insoluble polymers, which are swellable
networks, joined by cross-linking agents. These polymers possess optimal polarity to make sure
that they permit sufficient wetting by the mucus and optimal fluidity that permits the mutual
adsorption and interpenetration of polymer and mucus to take place. Mucoadhesive polymers
that adhere to the mucin– epithelial surface can be conveniently divided into three broad classes.
 Polymers that become sticky when placed in water and owe their mucoadhesion to
stickiness.
 Polymers that adhere through nonspecific, noncovalent interactions that is primarily
electrostatic in nature (although hydrogen and hydrophobic bonding may be significant).
 Polymers that bind to specific receptor site.
Table 1.Relative Mucoadhesive performance of some potential mucoadhesive
pharmaceutical polymers:
S.No. Mucoadhesive Properties of polymer Bioadhesion
Polymers property
1. Alginate Sodium Anionic polymer High mucoadhesive properties
Rapid swelling and dissolution
2. Chitosan Cationic polymer, Mucoadhesive properties
High to moderate swelling
3. Sodium carboxymethyl Anionic polymer, High swelling High mucoadhesive
Cellulose (SCMC) properties that does not plateau, properties
4. Carbopol good water sorption property, High mucoadhesive
forms a hydrogel upon hydration properties
5. Hydroxyethyl Non ionic polymer, High Low mucoadhesive properties
Cellulose (HEC) swelling properties and rapid increased by the addition of
erosion, SCMC
6. Hydroxypropyl Non ionic polymer, Increased Moderate
cellulose (HPC) swelling in ethylcellulose/HPC mucoadhesive properties
films
7. Hydroxypropylmethyl Non ionic polymer, Rapid Moderate mucoadhesive
cellulose (HPMC) swelling that plateau properties
8. Polyvinyl alcohol Non ionic polymer, Moderate Mucoadhesive properties
swelling
9. Poly vinyl Pyrrolidone As film forming polymer, High Used as co-adjuvant
swelling properties to increase mucoadhesion
10. Carrageenan Poor and stable swelling Moderate mucoadhesive
properties
11. Guar gum As an additive, conveyed Good mucoadhesive properties
moderate swelling

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12. Poly ethylene oxide Non ionic polymer, High mucoadhesion with high
molecular weight
13. Xantham gum Anionic polymer, High swelling high mucoadhesive properties
properties
Characteristics of an ideal Mucoadhesive polymer:14
 The polymer and its degradation products should be nontoxic and should be
nonabsorbable from the GI tract.
 It should be nonirritant to the mucus membrane.
 It should preferably form a strong noncovalent bond with the mucin–epithelial cell
surfaces.
 It should adhere quickly to most tissue and should possess some site specificity.
 It should allow easy incorporation of the drug and should offer no hindrance to its
release.
 The polymers must not decompose on storage or during the shelf life of the dosage form.
 The cost of the polymer should not be high so that the prepared dosage form remains
competitive.
PREPARATION METHODS OF MUCOADHESIVE MICROSPHERES:
Incorporation of solid, liquid or gases into one or more polymeric coatings can be done by micro
encapsulation technique. The different methods used for various microspheres preparation
depends on particle size, route of administration, duration of drug release and these above
characters related to rpm, method of cross linking, drug of cross linking, evaporation time, co-
precipitation etc. The various methods of preparations are:-
Phase separation Coacervation technique:
This process is based on the principle of decreasing the solubility of the polymer in organic
phase to affect the formation of polymer rich phase called the coacervate. In this method, the
drug particles are dispersed in a solution of the polymer and an incompatible polymer is added to
the system which makes first polymer to phase separate and engulf the drug particles. Addition
of non-solvent results in the solidification of polymer. Polylactic acid (PLA) microspheres have
been prepared by this method by using butadiene as incompatible polymer. The process variables
are very important since the rate of achieving the coacervate determines the distribution of the
polymer film, the particle size and agglomeration of the formed particles. The agglomeration
must be avoided by stirring the suspension using a suitable stirrer since as the process of
microspheres formation begins the formed polymerize globules start to stick and form the
agglomerates. Therefore the process variables are critical as they control the kinetic of the

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formed particles since there is no defined state of equilibrium attainment.15

Emulsion cross linking method:
In this method drug is dissolved in aqueous gelatin solution which is previously heated for 1 hr at
40 0C. The solution is added drop wise to liquid paraffin while stirring the mixture at 1500 rpm
for 10 min at 35 0C, results in w/o emulsion then further stirring is done for 10 min at 15 0C
Thus the produced microspheres are washed respectively three times with acetone and isopropyl
alcohol which then air dried and dispersed in 5mL of aqueous glutaraldehyde saturated toluene
solution at room temperature for 3 hrs for cross linking and then treated with 100mL of 10mm
glyciene solution containing 0.1%w/v of tween 80 at 37 0C for 10 min to block unreacted
glutaraldehyde. An example for this technique is Gelatin microspheres.
Solvent Evaporation:
The processes are carried out in a liquid manufacturing vehicle. The microcapsule coating is
dispersed in a volatile solvent which is immiscible with the liquid manufacturing vehicle phase.
A core material to be microencapsulated is dissolved or dispersed in the coating polymer
solution. With agitation the core material mixture is dispersed in the liquid manufacturing
vehicle phase to obtain the appropriate size microcapsule. The mixture is then heated if
necessary to evaporate the solvent for the polymer of the core material is disperse in the polymer
solution, polymer shrinks around the core. If the core material is dissolved in the coating
polymer solution, matrix – type microcapsules are formed. The core materials may be either
water soluble or water in soluble materials. Solvent evaporation involves the formation of an
emulsion between polymer solution and an immiscible continuous phase whether aqueous (o/w)
or non-aqueous. The comparison of mucoadhesive microspheres of hyaluronic acid, Chitosan
glutamate and a combination of the two prepared by solvent evaporation with microcapsules of
hyaluronic acid and gelatin prepared by complex coacervation were made. 6

Figure 1: Solvent evaporation method for preparation of microspheres.

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Ionic gelation:
Alginate/chitosan particulate system for diclofenac sodium release was prepared using this
technique. In this method drug is added to aqueous solution of sodium alginate. In order to get
the complete solution stirring is continued and after that it is added dropwise to a solution
containing Ca2+ /Al3+. Microspheres which are formed were kept in original solution for 24 hr
for internal gellification followed by filtration for separation. The complete release is obtained at
pH 6.4-7.2 but the drug will not release in acidic pH.16
Spray Drying:
In Spray Drying the polymer is first dissolved in a suitable volatile organic solvent such as
dichloromethane, acetone, etc. The drug in the solid form is then dispersed in the polymer
solution under high-speed homogenization. This dispersion is then atomized in a stream of hot
air. The atomization leads to the formation of the small droplets or the fine mist from which the
solvent evaporate instantaneously leading the formation of the microspheres in a size range 1-
100μm. Micro particles are separated from the hot air by means of the cyclone separator while
the trace of solvent is removed by vacuum drying. One of the major advantages of process is
feasibility of operation under aseptic conditions. This process is rapid and this leads to the
formation of porous micro particles.

Figure 2: Spray drying method for preparation of microspheres.

Multiple emulsion polymerization technique:
Multiple emulsion method involves formation of(o/w) Primary emulsion (non aqueous drug
solution in polymer solution) and then addition of primary emulsion to external oily phase to

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form o/w/o emulsion followed by either addition of cross linking agent (glutaraldehyde) and
evaporation of organic solvent. This method of preparation is ideal for incorporating poorly
aqueous soluble drug, thus enhancing its bioavailability. The microspheres prepared by multiple
emulsion technique make the poorly aqueous soluble drug such as ketorolac tromethamine more
bioavailable.15
FACTORS AFFECTING MUCOADHESION:
Polymers usually diffuse into the mucosal layer and thereafter adhere to the layer by forming
intermolecular entanglements. There are following factors which can affect mucoadhesion:
1. With the increase in the molecular weight (MW) of the polymer chain there is an increase
in the mucoadhesiveness of a polymer.In general, polymers having MW ≥ 100, 000 have
been found to have adequate mucoadhesive property for biomedical applications. A
typical example is polyethylene glycol (PEG). PEG of 20,000 MW shows negligible
mucoadhesive property while PEG of 200,000 MW exhibits improved mucoadhesiveness
and the PEG of 400,000 MW has got excellent mucoadhesiveness. 17 Similarly,
polyoxyethylene of 7,000,000 MW has exhibited excellent mucoadhesive property and
could be tried for the development of buccal delivery systems. 18 Dextrans of 19,500,000
and 200,000 MW, poly(acrylic) acid of ~750,000 MW and polyethylene oxide of
4,000,000 MW also exhibit good bioadhesive property.
2. Polymer chain length plays an important role in bioadhesiveness. With the increase in the
chain length of the polymers there is an increase in the mucoadhesive property of the
polymer. Flexible polymer chains helps in the better penetration and entanglement of the
polymer chains with that of mucosal layer thereby improving the bioadhesive property.
3. The flexibility of the polymer chains is generally affected by the crosslinking reactions
and the hydration of the polymer network. Higher the crosslinking density, lower is the
flexibility of the polymer chains. Keeping this in mind, teethering of long flexible chains
onto the polymer matrices, with high crosslinking density, appears to be an excellent idea
to improve the bioadhesive property. In a recent study, this phenomenon was utilized to
device tethered poly (ethylene glycol)–poly (acrylic acid) hydrogels with improved
mucoadhesive properties.19In addition to the reduced flexibility of the polymer chains,
crosslinking results in the reduced diffusion of water into the crosslinked polymer matrix.
But sufficient hydration of the polymer network is necessary for the complete opening of
the interpolymeric pores within the polymer matrix in addition to the mobilization of the
polymer chains.20 Hence highly crosslinked polymeric matrix limits the interpenetration
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of polymer and mucin chains amongst themselves which in turn results in the decrease in
the mucoadhesive strength.21
4. Apart from the MW and chain length of the polymer chains, spatial arrangement of the
polymer chains may also play an important role. As mentioned above, dextrans of
19,500,000 and 200,000 MW exhibit good Mucoadhesive properties. The efficiency of
both the dextrans and PEG (MW: 200,000) have been found to possess similar
bioadhesive strength. 17, 22
5. Formation of hydrogen-bonds amongst the functional groups of the polymers and
mucosal layer also plays an important role. In general, stronger the hydrogen bonding
stronger is the adhesion. The functional groups responsible for such kind of interaction
include hydroxyl, carboxyl and amino groups. Various polymers which have the ability to
form strong hydrogen bonds include poly (vinyl alcohol), acrylic derivates, celluloses and
starch.22
6. Apart from the hydrogen bond formation, the presence of functional groups within the
polymer structure may render the polymer chains as polyelectrolytes. The presence of
charged functional groups in the polymer chain has a marked effect on the strength of the
bioadhesion and can be demonstrated by cell-culture-fluorescent probe technique.23,24
Anionic polyelectrolytes have been found to form stronger adhesion when compared with
neutral polymers.25
7. In addition to the above facts, the concentration of the polymer also plays a significant
role in the process of mucoadhesion. At lower concentrations of the polymer chains, there
is an inadequate and unstable interaction amongst the polymer and the mucosal layer
resulting in poor Mucoadhesive properties. In general, polymer concentration in the range
of 1-2.5 wt % may exhibit sufficient mucoadhesive property for biomedical applications.
However for certain polymers, like poly (vinyl pyrrolidone) and poly (vinyl alcohol),
solvent diffusion into the polymer network decreases at very high polymer concentration
due to the formation of the highly coiled structure thereby limiting interpenetration of the
polymer and mucin chains with the subsequent reduction in the Mucoadhesive property. 26
8. Apart from the above-mentioned physico-chemical properties of the polymeric network,
various environmental factors also play an important role in mucoadhesion. As
mentioned previously, Mucoadhesive property is dependent on the presence of functional
groups which can ionize so as to give a charge distribution on the polymer chains. The
ionization of the functional group is dependent on the pH of the external medium. Hence
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change in the pH of the external environment may play an important role in tailoring
mucoadhesive property. As for example, chitosan (cationic polyelectrolyte) exhibit
excellent mucoadhesive property in neutral or alkaline medium.27
9. The contact time amongst the polymer matrix and the mucosal layer can also govern the
Mucoadhesive property. With the initial increase in the contact time there is an increase
in the hydration of the polymer matrix and subsequent interpenetration of the polymer
chains. The physiology of the mucosal layer may vary depending on the patho-
physiological nature of the human body.
10. The physiological factors which play an important role in governing the mucoadhesive
property of a polymer matrix include texture and thickness of mucosa. 22
EVALUATION OF MUCOADHESIVE MICROSPHERES:
Particle size analysis:
The Mucoadhesive microspheres were examined by optical microscope. The freshly prepared
suspension of microspheres was examined on an optical microscope and size of the microspheres
was measured by using a pre-calibrated ocular micrometer and stage micrometer.
Drug entrapment efficiency:
The capture efficiency of the microspheres or the percent entrapment can be determined by
allowing washed microspheres to lyse. The lysate is then subjected to the determination of active
constituents as per monograph requirement. The percent encapsulation efficiency is calculated
using following equation:-
% Entrapment = Actual content/Theoretical content x 100

Figure 3- SEM Photograph showing population of Sodium alginate microspheres.

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Surface topography by Scanning Electron:

Microscopy (SEM):SEM of the microspheres shows the surface morphology of the microspheres
like their shape and size. The surface morphology and structure are visualized by scanning
electron microscopy (SEM).The samples is prepared by lightly sprinkling the microspheres
powder on a double side adhesive tape which already shucked to on aluminum stubs. The stubs
is then placed into fine coat ion sputter for gold coating. After gold coating samples are
randomly scanned for particle size and surface morphology.
In vitro Bioadhesivity Studies:
Bioadhesivity testing is done by a novel in situ method. A freshly cut 5-6cm long piece of small
intestine of rat is obtained and cleaned by washing with isotonic saline. The piece is cut open and
the mucosal surface is exposed. Known weights of microspheres are added evenly on the
mucosal surface. The intestinal piece is maintained at 80% (RH) relative humidity for 30mts in a
desiccator. The piece is taken out and phosphate buffer pH 6 is allowed to flow over the
intestinal piece for about 2 mts at a rate of 20ml/min. The perfusate is collected and dried to get
the particles not adhered. The percent of bioadhesion is estimated by the ratio of amount applied
to adhere micro matrices.28
In vitro drug release studies:
In-vitro release studies can be performed according to USP XXII type 2 dissolution apparatus at
suitable pH conditions. The temperature should be maintained at 37±0.5°C and the rotation
speed of 100 rpm. Then 5 ml of sample should be withdrawn at various time intervals and
replenished with an equal volume of fresh dissolution media. The drug content in the sample can
be analyzed spectrophotometrically at specific wavelength (nm). 6
Stability studies:
By placing the microspheres in screw capped glass container and stored them at following
conditions:-
 Ambient humid condition
 Room temperature (27+/-2 0C)
 Oven temperature (40+/-2 0C)
 Refrigerator (5 0C -80C).
It is carried out of a 60 days and the drug content of the microsphere is analyzed. 16
Swelling index:
This technique is used for Characterization of sodium alginate microspheres. Different solution
(100mL) are taken such as (distilled water, buffer solution of pH (1.2, 4.5, 7.4) are taken and
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alginate microspheres (100mg) are placed in a wire basket and kept on the above solution and
swelling is allowed at 37 0C and changes in weight variation between initial weight of
microspheres and weight due to swelling is measured by taking weight periodically and soaking
with filter paper.16
The swelling index of the microsphere is calculated by using the formula:-
Swelling index= (mass of swollen microspheres - mass of dry microspheres/mass of dried
microsphere.
Advantages of Mucoadhesive microspheres drug delivery system: 10
 As a result of adhesion and intimate contact, the formulation stays longer at the delivery
site improving API bioavailability using lower API concentrations for disease treatment.
 The use of specific bioadhesive molecules allows for possible targeting of particular sites
or tissues, for example the gastrointestinal (GI) tract.
 Increased residence time combined with controlled API release may lead to lower
administration frequency.
 Offers an excellent route, for the systemic delivery of drugs with high first-pass
metabolism, there by offering a greater bioavailability. 29
 Additionally significant cost reductions may be achieved and dose-related side effects
may be reduced due to API localization at the disease site. 30
 Better patient compliance and convenience due to less frequent drug administration.
 Uniform and wide distribution of drug throughout the gastrointestinal tract which
improves the drug absorption.
 Prolonged and sustained release of drug.
 Maintenance of therapeutic plasma drug concentration.
 Better process ability (improving solubility, dispersibility, flowability).
 Increased safety margin of high potency drugs due to better control of plasma levels.
 Reduction in fluctuation in steady state levels and therefore better control of disease
condition and reduced intensity of local or systemic side effects. 31
 Drugs which are unstable in the acidic environment are destroyed by enzymatic or
alkaline environment of intestine can be administered by this route e.g. buccal,
sublingual, vagina.32
Applications of microspheres:
Some of the applications of microspheres are described in detail as following: -

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1. Microsphere can be used to prepare enteric-coated dosage forms, so that the medicament
will be selectively absorbed in the intestine rather than the stomach.
2. It has been used to protect drugs from environmental hazards such as humidity, light,
oxygen or heat. Microsphere does not yet provide a perfect barrier for materials, which
degrade in the presence of oxygen, moisture or heat, however a great degree of protection
against these elements can be provided. For example, vitamin A and K have been shown
to be protected from moisture and oxygen through microsphere.
3. The separations of incompatible substances, for example, pharmaceutical eutectics have
been achieved by encapsulation. This is a case where direct contact of materials brings
about liquid formation.
4. The stability enhancement of incompatible aspirin, chlorpheniramine maleate mixture is
accomplished by microencapsulating both of them before mixing.
5. Microsphere can be used to decrease the volatility. An encapsulated volatile substance
can be stored for longer times without substantial evaporation.
6. Microsphere has also been used to decrease potential danger of handling of toxic or
noxious substances. The toxicity occurred due to handling of fumigants, herbicides,
insecticides and pesticides have been advantageously decreased after microencapsulation.
7. The hygroscopic properties of many core materials may be reduced by microsphere.
8. Many drugs have been microencapsulated to reduce gastric irritation. 15
9. Microsphere method has also been proposed to prepare intrauterine contraceptive device.
10. Therapeutic magnetic microspheres are used to deliver chemotherapeutic agent to liver
tumour. Drugs like proteins and peptides can also be targeted through this system.
Mucoadhesive microspheres exhibit a prolonged residence time at the site of application
and causes intimate contact with the absorption site and produces better therapeutic
action.
11. Radioactive microspheres are used for imaging of liver, spleen, bone marrow, lung etc
and even imaging of thrombus in deep vein thrombosis can be done. 16
DRUGS WHICH HAVE BEEN GIVEN AS MICROSPHERES :
Table 2: Drugs which have been given as microspheres:
S.No Drug Polymer Category Ref.
1. Metformin HCl Sodium alginate Antidiabetic 28
2. Amoxicillin Ethyl Cellulose Antibiotic 33
trihydrate
3. Ibuprofen Sodium alginate Analgesic 34

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4. Trimetazidine Hcl Chitosan Antianginal 35

5. Furosemide Sodium alginate,Carbopol Diuretic 36
6. Insulin Sodium alginate,Chitosan Antidiabetic 37
7. Furazolidine Eudragit RS100, Carbopol 974P, Antiulcer 38
HPMC
8. Acyclovir Sodium alginate Antiviral 39
9. Atenolol Polyacrylic acid, Polyvinyl β Blockers 40
Propranolol pyrrolidine
10. Rantidine Hcl Sodium alginate Antacid 41
11. Glipizide Chitosan Oral Hypoglycemic 42
12. Captopril Sodium alginate, HPMC, Chitosan, ACE Inhibitor 43
Carbopol 934P, Cellulose acetate
phthalate
13. Salbutamol sulphate Carbopol, HPMC Bronchodilator 44
14. Torsemide Sodium alginate , HPMC Diuretic 45
15. Ketorolac Eudragit RS100, Eudragit RL100 Anti-inflammatory 46
and Analgesic
16. Acetazolamide Eudragit RS, Eudragit RL Diuretic 47
17. Famotidine SodiumCMC, Sod.alginate Antiulcer 48
CONCLUSION:
To derive maximum therapeutic benefits from certain drug substances, it is desirable to prolong
their residence time. Mucoadhesive microspheres will ensure the maintenance of effective
plasma concentration over prolonged period of time by extending the release of drug release with
enhanced bioavailability over longer periods of time, and for drug targeting to various sites in the
body. Mucoadhesive drug delivery is a promising area for systemic delivery of orally inefficient
drugs as well as an attractive alternative for noninvasive delivery of potent peptide and perhaps
protein drug molecules. Mucoadhesive drug delivery systems are gaining popularity day by day
in the global pharma industry and a burning area of further research and development. Drug
delivery through Mucoadhesive microspheres is a promising area for continued research with the
aim of achieving controlled release with enhanced bioavailability over longer periods of time and
for drug targeting to various sites in the body.
ACKNOWLEDGEMENT:
The authors are thankful to all faculty members of Department of Pharmacy, IEC Group of
Institution Gr. Noida, (U.P) for their guidance.
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