Mucoadhesive Microsphere - Review


The problems of frequent administration and variable low bioavailability (40-60%) after oral administration of conventional dosage forms can be attenuated by designing it in the form of mucoadhesive microspheres which would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance the bioavailability. Mucoadhesive microspheres which are of 1-1000mm in diameter and consisting either entirely of a mucoadhesive polymer or having an outer coating of it and coupling of mucoadhesive properties to microspheres has additional advantages, e.g. efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio, a much more intimate contact with the mucus layer, specific targeting of drug to the absorption site achieved by anchoring plant lectins, bacterial adhesions and antibodies, etc. on the surface of microspheres. Mucoadhesive microspheres can be tailored to adhere to any mucosal tissue including those found in eye, nasal cavity, urinary and gastrointestinal tract, thus offering the possibilities of localized as well as systemic controlled release of drugs .Application of mucoadhesive to the mucosal tissues of of ocular cavity and gastric and colonic epithelium is used for administration of drugs and reduction in frequency of drug administration can highly improve patient compliance.the latter advantage can be obtained for the drugs administered intranasally due to reduction in mucocilliary clearance of drugs adhering to the nasal mucosa.

Keywords: Mucoadhsive microspheres,mucoadhesive polymers,ionic gelation

Oral controlled release systems continue to be the most popular ones among all the drug delivery systems .It offers several advantages over the conventional systems like better plasma level profile, lower dosing and toxicity and many more. The problem frequently encountered with controlled release dosage form is its inability to increase the residence time of the dosage form in the stomach and proximal portion of the small intestine. This may be due to the rapid gastrointestinal transit phenomenon of the stomach , which may consequently diminish the extent of absorption of many drugs since most of drug entities are mostly absorbed from upper part of intestine. Therefore it would be beneficial to develop a sustained release formulation which remain at the absorption site for an extended period of time. several approaches have been immersed to prolong the gastric residence time of the dosage form at the absorption site and one of these is the development of oral controlled release mucoadhesive multipaticulate system.. 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 . They have varied applications and are prepared using assorted polymers . However, the success of these microspheres is limited owing to their short residence time at the site of absorption. It would, therefore, be advantageous to have means for providing an intimate contact of the drug delivery system with the absorbing membranes . This can be achieved by coupling mucoadhesion characteristics to microspheres and developing mucoadhesive microspheres. Mucoadhesive microspheres have advantages such as efficient absorption and enhanced bioavailability of drugs owing to a high surface-to-volume ratio, a much more intimate contact with the mucus layer, and specific targeting of drugs to the absorption site mucoadhesive and biodegradable polymers undergo selective uptake by the M cells of payer patches in gastrointestinal (GI) mucosa and this uptake mechanism has been used for the delivery of high molecular weight drugs (proteins and peptides), antigens Carbopol- 934P (acrylic acid homopolymer) is anionic polymer that has been used in mucoadhesive systems by a several researchers . Carbopol-934P was selected as a polymer in the preparation of mucoadhesive microspheres because of its good mucoadhesive and biodegradable properties and ethyl cellulose as carrier polymer for microspheres,sodium alginate as a matrix material to achieve controlled release drug delivery is due to its hydrogel forming properties.


(1) 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.
(2) The use of specific bioadhesive molecules allows for possible targeting of particular sites or tissues, for example the gastrointestinal (GI)tract.
(3) Increased residence time combined with controlled API release may lead to lower administration frequency.
(4) Offers an excellent route, for the systemic delivery of drugs with high first-pass metabolism, there by offering a greater bioavailability .
(5) Additionally significant cost reductions may be achieved and dose-related side effects may be reduced due to API localization at the disease site .
(6) Better patient compliance and convenience due to less frequent drug administration.
(7) Uniform and wide distribution of drug throughout the gastrointestinal tract which improves the drug absorption.
(8) Prolonged and sustained release of drug.
(9) Maintenance of therapeutic plasma drug concentration.
(10) Better processability (improving solubility, dispersibility, flowability).
(11) Increased safety margin of high potency drugs due to better control of plasma levels.
(12) Reduction in fluctuation in steady state levels and therefore better control of disease condition and reduced intensity of local or systemic side effects .
(13) 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

There are two broad classes of mucoadhesive polymers Hydrophillic polymers and hydrogels .in the large classes of hydrophilic polymers those containing carboxylic moiety exhibit the best mucoadhesive property,poly vinyl pyrrolidone (PVP), Methyl cellulose (MC), Sodium carboxy methyl cellulose(SCMC), Hydroxy propyl cellulose(HPC),Hydroxy propyl methyl cellulose(HPMC).
Hydrogels are the class of of polymeric biomaterial that exhibit the basic characteristics of an hydrogels to swell by absorbing water interacting by means of adhesion with the mucus that covers epithelia i.e.
Anionic group ' Carbopol , Polyacrylates and their cross-linked modifications
Cationic group - Chitosan and its derivatives
Neutral group - Eudragit- NE30D etc..

Characteristics of an Ideal Mucoadhesive Polymer:
1. The polymer and its degradation products should be nontoxic and should be no absorbable from the GI tract.
2. It should be nonirritant to the mucus membrane.
3. It should preferably form a strong no covalent bond with the mucin'epithelial cell surfaces.
4. It should adhere quickly to most tissue and should possess some site specificity.
5. It should allow easy incorporation of the drug and should offer no hindrance to its release.
6. The polymers must not decompose on storage or during the shelf life of the dosage form.
7. The cost of polymer should not be high so that the prepared dosage form remains competitive.
8. It should be inert and compatible with the environment
9. The polymer should be easily available in the market and economical.
10. It should allow easy incorporation of drug in to the formulation.

Robinson and his group using the fluorescence technique concluded that:
1.Cationic and anionic polymers bind more effectively than neutral polymers.
2.polyanions are better than polycations in terms of binding/potential toxicityand further that water insoluble polymer gives greater flexibility in dosage forms design compared with rapidly or slowly dissolving water soluble polymers.
3.Anions polymers with the sulfate groups bind more effectively than those with carboxylic groups. of binding is proportional to the charge density on the polymer.
5.Highly binding polymers include carboxy methyl cellulose ,gelatin,carbapol and polycarbophil.

Molecular characteristics :
Investigations into polymers with various molecular characteristicshave led to number of conclusion regarding the molecular characteristics required for mucoadhesion.the properties exhibited by by a good mucoadhesive may be summarized as a follows
1.Strong hydrogen 'bonding groups[-OH,-COOH]
2.Strong anionic charges
3.Sufficient flexibility to penetrate the mucus network or tissue crevices
4.Surface tension characteristics suitable for wetting mucus /mucosal tissue surface
5.High molecular weight.

SR.NO. POLYMER Relative mucoadhesive force Quality of mucoadhesion
1 CMC 193 Excellent
2 Carbapol 185 Excellent
3 Tragacanth 154 Excellent
4 Sod.alginate 126 Excellent
5 HPMC 125 Excellent
6 Gelatin 116 Fair
7 Pectin 100 Poor
8 Acacia 98 Poor
9 Providone 98 Poor


A. Polymer Related Factors
a. Molecular weight- The interpenetration of polymer molecules into the mucus layer is variable, for low molecular weight polymers penetration is more than high molecular weight polymers because entanglements are favored in high molecular weight polymers.
b. Concentration of active polymer- For solid dosage forms such as tablets, the higher the concentration of polymer, the stronger the bioadhesion force.
c. Spatial Conformation- Bioadhesive force is also dependent on the conformation of polymers, i.e., helical or linear. The helical conformation of polymers may shield many active groups, primarily responsible for adhesion, thus reducing the mucoadhesive strength of the polymer.

d. Degree of Hydration- Another important factor affecting the mucoadhesive strength of polymeric components is the degree of hydration. In this respect many polymers will exhibit adhesive properties under conditions where the amount of water is limited. However in such a situation, adhesion is thought to be a result of a combination of capillary attraction and osmotic forces between the dry polymer and the wet mucosal surface which act to dehydrate and strengthen the mucus layer. Although this kind of 'sticking' has been referred to as mucoadhesion it is important to clearly distinguish such processes from 'wet-on-wet' adhesion in which swollen mucoadhesive polymers attach to mucosal surfaces. Hydration is essential for the relaxation and interpenetration of polymer chains, excess hydration could lead to decreased mucoadhesion and/or retention due to the formation of slippery mucilage. In this situation cross linked polymers that only permit a certain degree of hydration may be advantageous for providing a prolonged mucoadhesive effect .

e. Chain flexibility of polymer- Chain flexibility is important for interpenetration and enlargement. As water-soluble polymers become more and more cross linked, the mobility of the individual polymer chain decreases, also as the cross linking density increases, the effective length of the chain which can penetrate into mucus decrease even further and mucoadhesive strength is reduced.
f. Functional Group Contribution- The attachment and bonding of bioadhesive polymers to biological substrates occurs mainly through interpenetration followed by secondary non-covalent bonding between substrates. Given that secondary bonding mainly arises due to hydrogen bond formation, it is well accepted that mucoadhesive polymers possessing hydrophilic functional such as, carboxyl (COOH), hydroxyl (OH), amide (NH2) and sulphate groups (SO4H) may be more favorable in formulating targeted drug delivery platforms. Typically, physical entanglements and secondary interactions (hydrogen bonds) contribute to the formation of a strengthened network; therefore polymers that exhibit a high density of available hydrogen bonding groups would be able to interact more strongly with mucin glycoprotein.
g. Swelling- The swelling characteristic is related to the polymer itself, and also to its environment. Interpenetration of chains is easier as polymer chains are disentangled and free of interactions. More the swelling of polymeric matrix higher the adhesion time of polymers.

B. Environmental ' Related Factors

a. pH- pH influences the charge on the surface of both mucus and polymers. Mucus will have a different charge density depending on pH, because of difference in dissociation of functional groups on carbohydrate moiety and amino acids of the polypeptide backbone, which may affect adhesion.
b. Applied strength- To place a solid bioadhesive system, it is necessary to apply a defined strength. Whichever the polymer may be the adhesion strength of those polymers increases with the increase in the applied strength.
c. Initial contact time- The initial contact time between mucoadhesive and the mucus layer determines the extent of swelling and the interpenetration of polymer chains. The mucoadhesive strength increases as the initial contact time increases.
d. Selection of the model substrate surface- The handling and treatment of biological substrates during the testing of mucoadhesive is an important factor, since physical and biological changes may occurs in the mucus gels or tissues under the experimental condition


1)Solvent Evaporation :

Fig. Solvent evaporation technique

Solvent evaporation technique involves four major steps, like incorporation of pharmaceuticals, droplet formation, solvent removal, and drying.
Incorporation of pharmaceuticals: The polymer is dissolved in a suitable water immiscible solvent, and the pharmaceutical agent is directly added into the solution of polymeric-matrix materials by dissolution/dispersion in suitable solvents, or emulsification of aqueous solution of the pharmaceutical agents immiscible with the matrix-material solution. For the preparation of solution or dispersion of pharmaceutical agents, impeller or static mixing, high speed-stator mixing or microfluidization techniques are generally used.
a)Droplet formation: This step determines the size of resulting microcapsules. The size of microcapsules affects the drug encapsulation efficiency and the rate of drug release. The following procedures used in droplet formation, namely:
b)Stirring: The external phase is filled into a vessel and agitated by an impeller. The drug/matrix dispersion us then added, drop wise or all at once, under agitation at a speed sufficient to reach the desired droplet size .
c)Static mixing: Static mixer consists of baffles or other flow obstacles installed in a tube. The baffle arrangement repeatedly splits and recombines the stream of fluid passing through the tube.
d)Extrusion: It involves feeding of drug/matrix dispersion through single or multichannel pathways directly into the continuous phase. When drug/ matrix dispersion leaves the pathways, discrete droplets are formed within the slow flowing continuous phase. In extrusion, flow is laminar, the droplets are formed at the site of introduction of drug/matrix dispersion into continuous phase, due to which there is no effect on size of droplets formed thereafter. Where as in static mixing, turbulent flow occur which constantly act on the disperse phase and thus, there is a continuous change in the size of droplets.
e)Dripping: Microcapsules have been prepared by dripping 10 % and 15 % (w/w) solution of poly (ethylene-co-acetate) in dichloromethane, containing dispersed protein particles from a needle into an electric field [23]. The droplet formed was dethatched from the needle by electrostatic forces.
Solvent removal: Solvent removal can be achieved either by evaporation or by extraction. In both processes, the drug/matrix dispersion should be slightly soluble in the continuous phase, so that, partitioning into continuous phase can occur that leads to precipitation of the matrix material. The two ways of solvent removal can be performed, namely:
Solvent evaporation: In this method, the capacity of the continuous phase is insufficient to dissolves the entire volume of disperse phase solvent. Thus, solvent evaporates from the surface of the dispersion to obtain hardened microcapsules.
Solvent extraction: This is a two-step process. Firstly, the drug/matrix dispersion is mixed with a small quantity of continuous phase to yield desired size of droplets. Then secondly, further more continuous phase and/or additional extraction agents are added at an amount sufficient to absorb the entire solvent leaching from droplets of drug/matrix. This results into formation of solid microcapsules.
Drying: Solidified microparticles from the continuous phase are by either filtration or centrifugation. Then the particles are rinsed with suitable liquids to remove adhering substance such as dispersion stabilizers or non-encapsulated drug. Finally, these microparticles are dried at elevated temperature or under reduced pressure to yield free flowing powder.
There are several factors that influence the formation of microsphere when solvent evaporation technique is employed.

1.Type of emulsion used
2.Type and concentration of emulgent used.
3.Solubility of the drug and polymer in dispersed phase and the continuos phase
4.Characteristics of the drug and the polymer and the drug/polymer ratio
5.Stirring rate or agitator characteristics
6.Inner water/oil ratio
7.Other factors.

Selection of phases for the preparation of microspheres
(A)The dispersed phase:
While making the selection ,the factors considered are
-Succesful entrapment of the drug
-Ability to dissolve the polymers and the drug excipients
(B)The continuos phase;
While making the selection ,the factors considered are
-Immiscibility with the dispersed phase solvent
-Inability to dissolve the polymer as well as the drug.
When the drug is hydrophilic the non aqeous medium selected as a continous phase. most commonly liquid paraffin is used as it is inert to the drug as well as the polymers .when the drug is hydrophobic then the aqeous medium is used.

2).Ionic gelation technique:


Sodium alginate and the mucoadhesive polymer are dispersed in purified water (50 ml) to form a homogeneous polymer mixture. Drug is added to the polymer matrix and mixed thoroughly to formsmooth viscous dispersion. Resulting dispersion is then sprayed into calcium chloride (10% w/v) solution by continuous stirring. Produced droplets are retained in the calcium chloride solution for 15 minutes to complete the curing reaction and to produce rigid spherical microspheres. The resulting microspheres are collected by decantation, and the thus separated is washed repeatedly with purified water to remove excess calcium impurity deposited on the surface of microspheres and then dried at 45??C for 12 hrs.

Fig. Ionotropic gelation method


Microspheres prepared by ionotropic gelatin technique mechanism involves electrostatic interaction between amine groups of polymer and negatively charged group of polyanion such as tripolyphosphate.chemical reaction between sodium alginate and calcium chloride to form calcium alginate was utilized for microsphere formation. As calcium ions are being released by ion exchange with sodium ion in the medium,electrostatic repulsion between the carboxylate anions further accelerates the swelling and erosion of alginate gels .on account of short time release in alkaline media ,alginate was not found to be an ideal sustained release wall material for microencapsulation.

Study of effect of various factors :

a)Effect of orifice diameter of needle:

Effect of orifice diameter (needle no 18, 20 and 23) on formation of microspheres is summarized below. Small particle size with rigid nature of microspheres was possible with needle no 20 and 23. However, as viscosity plays important role in passage of solution from needle, a difficulty was observed for needle no 23.Therefore, needle no. 20 was suggested for this process .

b)Effect of dropping height on formation of microspheres:

While doing practically, apart from distance of 15 cm and 6 cm, the observation was also noted for distance more than 15 cm. At this distance, no proper shape of microspheres was observed immediately after formation in beaker and even after drying. Elongated microspheres and sometimes elongation with flat surface of microspheres was observed. Wide particle size distribution was experienced. At distance of 15 cm, shape was slightly spherical but no integrity in surface was observed immediately after formation and subsequent drying. But as the distance was reduced, significant change in shape, size and surface integrity was observed.

c)Stirring speed :

Stirring speed affect on drug entrapment efficiency. It was found that drug entrapment efficiency decreases with increase in stirring speed.

3)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 1-100 ??m. Microparticles are separated from the hot air by means of the cyclone separator while the trace of solvent is removed by vacuum drying.
Process control variables include feed materials properties such as viscosity,uniformity and concentration of core and coating material ,feed rate ,method of atomization and the drying rate and the air stream solvent concentration.

4)Wet inversion technique:

Chitosan solution in acetic acid was dropped in to an aqueous solution of counter ion sodium tripolyposphate through a nozzle. Microspheres formed were allowed to stand for 1 hr and cross linked with 5% ethylene glycol diglysidyl ether. Microspheres were then washed and freeze dried. Changing the pH of the coagulation medium could modify the pore structure of CS microspheres.

5)Hot melt microencapsulation:

The polymer is first melted and then mixed with solid particles of the drug that have been sieved to less than 50 ??m. The mixture is suspended in a non-miscible solvent (like silicone oil), continuously stirred, and heated to 5 ??C above the melting point of the polymer. Once the emulsion is stabilized, it is cooled until the polymer particles solidify. The resulting microspheres are washed by decantation with petroleum ether. The primary objective for developing this method is to develop a microencapsulation process suitable for the water labile polymers, e.g. poly anhydrides. Microspheres with diameter of 1-1000 ??m can be obtained and the size distribution can be easily controlled by altering the stirring rate. The only disadvantage of this method is moderate temperature to which the drug is exposed.

6)Preparation of microspheres by thermal cross-linking:

Citric acid, as a cross-linking agent was added to 30 mL of an aqueous acetic acid solution of chitosan (2.5% w/v) maintaining a constant molar ratio between chitosan and citric acid (6.90 ?? 10'3 mol chitosan : 1 mol citric acid). The chitosan cross-linker solution was cooled to 0 ??C and then added to 25 mL of corn oil previously maintained at 0 ??C, with stirring for 2 minutes. This emulsion was then added to 175 mL of corn oil maintained at 120 ??C, and cross-linking was performed in a glass beaker under vigorous stirring (1000 rpm) for 40 minutes. The microspheres obtained were filtered and then washed with diethyl ether, dried, and sieved.

7)Preparation of microspheres by glutaraldehyde cross linking:

A 2.5% (w/v) chitosan solution in aqueous acetic acid was prepared. This dispersed phase was added to continuous phase (125 mL) consisting of light liquid paraffin and heavy liquid paraffin in the ratio of 1:1 containing 0.5% (w/v) Span 85 to form a water in oil (w / o) emulsion. Stirring was continued at 2000 rpm using a 3- blade propeller stirrer. A drop-by-drop solution of a measured quantity (2.5 mL each) of aqueous glutaraldehyde (25% v/v) was added at 15, 30, 45, and 60 minutes. Stirring was continued for 2.5 hours and separated by filtration under vacuum and washed, first with petroleum ether (60 ??C- 80 ??C) and then with distilled water to remove the adhered liquid paraffin and glutaraldehyde, respectively. The microspheres were then finally dried in vacuum desiccators.


1) Size of microspheres:

Microsphere size was determined by using an optical microscope. The mean microsphere size was calculated by measuring 300 microspheres with the help of a calibrated ocular micrometer.

2) Morphological Study:

Morphological study was carried out by using Scanning electron microscope (SEM). A scanning electron micrograph of drug loaded microspheres was obtained. A small amount of microspheres was spread on glass stub. Afterwords, the stub containing the sample was placed in scanning electron microscope (JEOL JSM-6360A) chamber. The photomicrograph was taken at 5.0 KV.

3) Micromeritics Study:
a) Angle of repose: Angle of repose of each batch was carried out by glass funnel method. Angle of repose was calculated by the formula, ??= tan -1 (h/r).
b) Bulk density: Bulk density of known mass of microspheres in graduated measuring cylinder. The bulk density was calculated by taking ratio of weight of microspheres in gram to bulk volume of microspheres in cm3
c) Tapped density: Tapped density is the volume of powder determined by tapping using measuring cylinder containing pre-weighed amount of sample. Tapped density of microspheres was calculated by the ratio of weight of microspheres in gram to volume of microspheres after tapping in cm3 .

d) Carr's compressibility index

Carr's compressibility index= (Tapped density-Bulk density)/Tapped density x100

4) Percentage yield:

Prepared microspheres of all batches were accurately weighed. Percent yield was calculated by using following formula.
Percentage yield= (Actual weight of product/ Total weight of excipients and drug )x100

5) Drug entrapment efficiency:

Microspheres equivalent to 50 mg of drug were taken for evaluation. Drug entrapment efficiency was estimated by crushing the microspheres and extracting with aliquots of hydrochloric acid buffer of pH 2.2 repeatedly. The extract was diluted to 100 ml in a volumetric flask using hydrochloric acid buffer of pH 2.2. The solution was filtered and amount of metformin hydrochloride was estimated against appropriate blank.

6) In vitro wash off test:

In-vitro bioadhesive properties of microspheres were evaluated by in 'vitro wash off test. A 1cm x 2 cm piece of stomach mucosa of goat was tied on glass slide using thread. A fixed number of microspheres were spread on this mucosa and allowed to wet by mucus for 5 min. This glass slide was hanged in grove of USP disintegration test apparatus containing hydrochloric acid buffer of pH 2.2 and operated for regular up and down movements as shown in figure . After 15 minutes number of microspheres remain adhered on the mucus membrane were counted and further percentage was calculated.

Figure : Bioadhesion testing by in vitro wash off test

8)In Vitro drug release:

In vitro dissolution studies can be studied by using were carried out by using USP paddle type dissolution apparatus Weighed amount of drug loaded microspheres were introduced into 900ml Five ml of aliquots were withdrawn at predetermined time intervals and equal volume of fresh dissolution medium was replaced to maintain sink condition. The samples were analyzed spectroscopically at ??max to determine the concentration of drug present dissolution medium of hydrocholoric acid buffer maintained at 37??c at certain RPM.


Some of the applications of microspheres are described in detail as following: -
1. Controlled and sustained release dosage forms.
2. 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.
3. 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.
4. The separations of incompatible substances, for example, pharmaceutical eutectics have bee achieved by encapsulation. This is a case where direct contact of materials brings about liquid formation.The stability enhancement of incompatible aspirinchlorpheniramine 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 [10].
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 .


Mucoadhesive microspheres drug delivery system have been gaining a lot of interest of various researchers and scholars, because of their advantages of controlled and sustained release action, and versatility as a drug carrier. Mucoadhesive microspheres will ensure the maintenance of effective plasma concentration over prolonged period of time by extending the release of drug. These carrier systems will also increase the residence time of the drug in the gastrointestinal tract. 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.


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3)Poonam patil, Daksha chavanke, Milind wagh, a review on ionotropic gelation method: novel approach for controlled gastroretentive gelispheres, International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491, Vol 4, Suppl 4, 2012
4) Harshad Parmar, Sunil Bakliwal, Nayan Gujarathi, Bhushan Rane, Sunil Pawar,different methods of formulation and evaluation of mucoadhesive microsphere, IJAGPT Volume: I: Issue-3: Nov-Dec -2010 ISSN 0976-4550 .
5)Tahir Ansari , Farheen , M. Saquib Hasnain , M. Niyaz Hoda and Amit Kumar Nayak , Microencapsulation of pharmaceuticals by solvent evaporation technique: Elixir Pharmacy 47 (2012) 8821-8827
6) Madhav S. Mule1,Mr. Kshirsagar R.V. gastroretentive mucoadhesive microsphere: a review , Indo American Journal of Pharmaceutical Research.2011;1(6):483-505, ISSN NO: 2231-6876.
7)N. Venkata Naga Jyothi, P. Muthu Prasanna, Suhas Narayan Sakarkar, K. Surya Prabha, P. Seetha Ramaiah, Microencapsulation techniques, factors encapsulation efficiency influencing Journal of Microencapsulation, 2010; 27(3): 187'197
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