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© 2020 IJRAR March 2020, Volume 7, Issue 1 www.ijrar.org (E-ISSN 2348-1269, P- ISSN 2349-5138)

IJRAR2001532 International Journal of Research and Analytical Reviews (IJRAR) www.ijrar.org 793

A REVIEW ON MUCOADHESIVE DRUG

DELIVERY SYSTEM

Suryawanshi Rhushikesh*, Sudke Suresh

Department of Pharmaceutics, Satara College of Pharmacy, Satara, Maharashtra, 415004, India

ABSTRACT

Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and

mucin molecules and increase the residence time of the dosage form at the site of absorption. Mucosal adhesion is

backed by several theories which include electronic, adsorption, wetting, diffusion, fracture and mechanical. Stages

of mucoadhesion include contact stage and consolidation stage. Mucoadhesion while considering drug delivery is

having several merits, because of the ideal physiochemical characters of the mucosal membrane. Ideally a

mucoadhesive dosage form interacts with the mucosal membrane by ionic bonds, covalent bonds, Van-der-Waal

bonds and hydrogen bonds. Various sites for mucoadhesive drug delivery system are ocular, nasal, buccal cavity;

GIT, vaginal, rectal and several specific dosage forms have been reported. Factors affecting mucoadhesion are

molecular weight, flexibility of polymerchain, pH, presence of carboxylate group and density. Several synthetic and

natural polymers are identified assuitable candidates for mucoadhesive formulation. Ex-vivo/in-vitro studies utilizing

gut sac of rats provides indepth knowledge about the adhesive property of the dosage form as well as polymers.

Keywords: Bioadhesion, Mucoadhesion, Van-der-Waal Force, Consolidation Stage.

INTRODUCTION 1, 2 3

Bioadhesion

Bioadhesion is defined as an ability of a material to adhere to a biological tissue for an extended period of

time. In case of polymer, it attach to the mucin layer of a mucosal tissue, the term mucoadhesion is used. Adhesion

may be defined simply as a process of “fixing” of two surfaces to one another.

Mucus is a viscous and heterogeneous biological product that covers many epithelial surfaces. Cells secreting

mucus are located at various locations in the body like gastrointestinal, ocular, nasal, buccal, reproductive and

respiratory tracts. Its functions as a lubricant to reduce shear stress and acting as barrier against harmful substances.

Goblet cells containing mucus are located in the epithelium. It is located in large granules in the goblet cells. Mucus

granules are located in the apical side of the goblet cell giving a balloon shaped appearance of these cells. It is

released by the process of exocytosis of the whole cell. Secretion of mucus varies with the age, sex, body location and

health condition but the average mucus turnover is nearly 6 hr.

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Fig.1- Structure of Mucus Membrane

SITE FOR MUCOADHESIVE DRUG DELIVERY SYSTEM 4

The common sites of application where mucoadhesive polymers have the ability to deliver pharmacologically active

agents include oral cavity, eye conjunctiva, vagina, nasal cavity and GIT. The buccal cavity has a very limited surface

area of around 50 cm2 but the easy access to the site makes it a preferred location for delivering active agents. The

site provides an opportunity to deliver pharmacologically active agents systemically by avoiding hepatic first-pass

metabolism in addition to the local treatment of the oral lesions. The sublingual mucosa is relatively more permeable

than the buccal mucosa due to the presence of large number of smooth muscle and immobile mucosa. Hence,

formulations for sublingual delivery are designed to release the active agent quickly while mucoadhesive formulation

is of importance for the delivery of active agents to the buccal mucosa, where the active agent has to be released in a

controlled manner. This makes the buccal cavity more suitable for mucoadhesive drug delivery. The various

mucoadhesive polymers used for the development of buccal delivery systems include cyanoacrylates, polyacrylic

acid, sodium carboxymethylcellulose, hyaluronic acid, hydroxypropylcellulose, polycarbophil, chitosan and gellan.

Like buccal cavity, nasal cavity also provides a potential site for the development of formulations where

mucoadhesive polymers can play an important role. The nasal mucosal layer has a surface area of around 150-200

cm2. The residence time of a particulate matter in the nasal mucosa varies between 15 and 30 min, which have been

attributed to the increased activity of the mucociliary layer in the presence of foreign particulate matter. The polymers

used in the development of formulations for the development of nasal delivery system include copolymer of methyl

vinyl ether, hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose, carbopol-934P and Eudragit

RL-100. Due to the continuous formation of tears and blinking of eye lids, there is a rapid removal of the active

medicament from the ocular cavity, which results in the poor bioavailability of the active agents. This can be




minimized by delivering the drugs using ocular insert or patches. The mucoadhesive polymers used for the ocular

delivery include thiolated poly (acrylic acid), poloxamer, celluloseacetophthalate, methyl cellulose, hydroxy ethyl

cellulose, poly (amidoamine) dendrimers, poly(dimethyl siloxane) and poly(vinyl pyrrolidone). The vaginal and the

rectal lumen have also been explored for the delivery of the active agents both systemically and locally. The active

agents meant for the systemic delivery by this route of administration bypass the hepatic first-pass metabolism.

GIT is also a potential site which has been explored for a long time for the development of mucoadhesive

based formulations. The modulation of the transit time of the delivery systems in a particular location of the

gastrointestinal system by using mucoadhesive polymers has generated much interest among researchers around the

world. The various mucoadhesive polymers which have been used for the development of oral delivery systems

include chitosan, poly(acrylic acid), alginate, poly(methacrylic acid) and sodium carboxymethyl cellulose. Each site

of mucoadhesion has its own advantages and disadvantages along with the basic property of prolonged residence of

dosage form at that particular site. In buccal and sublingual sites, there is an advantage of fast onset along with

bypassing the first-pass metabolism, but these sites suffer from inconvenience because of taste and intake of food. In

GIT, there is a chance for improved amount of absorption because of microvilli, but it has a drawback of acid

instability and first-pass effects. Rectal and vaginal sites are the best ones for the local action of the drug but they

suffer from inconvenience of administration. Nasal and ophthalmic routes have another drawback of mucociliary

drainage that would clear the dosage form from the site.

MUCUS COMPOSITION 5,6

The oral mucus is generally secreted by various glands of oral cavity that are sublingual gland, parotid gland, and

other salivary glands. The mucus is a translucent gel secreted by goblet cell or by special exocrine glands with the

mucus cells.

Components Percentage

Water 95%

Glycoprotein's and lipids 0.5-5%

Mineral salts 1%

Free proteins 0.5-1%

Mucus glycoproteins are the high molecular proteins that containattached oligo-polysaccharide units. The mucus

contains following oligosaccharide units.

L-fructose

D-galactose

N-acetyl-D-glucosamine

N-acetyl-D-galactosamine




Sialic acid

Functions of mucus

Cell-cell adhesion

Lubrication

Bioadhesion

Protective

Barrier

NEED OF MUCOADHESIVE DELIVERY 7

Oral administration is the major route for drug delivery. Oral controlled release systems are used for

controlled action of active ingredients to the targeted site. But oral controlled release systems have many problems

such as first pass hepatic metabolism, enzyme degradation, swallowing problem etc. So, as compared to oral

controlled release systems, mucoadhesive delivery system have several advantages like prolongation of residence

time, drug targeting, intimate contact between dosage form and the absorptive mucosa. In addition, mucoadhesive

dosage forms have been used to target local disorders at the mucosal surface to reduce dose and to minimize the side

effects. Mucoadhesive formulations use polymers as the adhesive component. These polymers are water soluble.

When polymers are used in a dry form, they attract water from themucosal surface and leads to a strong interaction,

which increases the retention time over the mucosal surfaces. Prolonged contact time of a drug with a body tissue

using a bioadhesive polymer can significantly improve the performance of many drugs.

MECHANISM OF BIOADHESION 8,9,10

Types of interaction

A) Physical or mechanical bonds: Physical bonds involve the entanglement of mucin glycoprotein with the polymer

chains, and the interpenetration of the mucin chains in the polymer matrix. Factors affecting these are chain flexibility

and diffusion coefficients.

B) Chemical interaction: Chemical interactions include Van der Waals dispersive interactions or Hydrogen Bonds.

Van der waals Forces are further classified into Debye forces due to permanent dipole-induced interactions, Keesom

forces due to permanent dipole-permanent dipole interactions and London forces due to induced dipole-induced

dipole interactions. Hydrogen bond also plays a key role in adhesion. Groups which form hydrogen bonds are

hydroxyl, carboxyl, sulfate, amino groups, and others. Covalent bonds are formed by the chemical reaction of the

polymer and the substrate. This type of bond leads to permanent adhesion. Therefore, only mucus turnover and the

epithelial desquamation would result in the separation and loss of the polymer from the tissue.

Steps in mucoadhesion

a) The contact stage: In this step the intimate contact occurs between the mucoadhesive and mucous membrane.

Initially mucoadhesive and the mucous membrane come together to form an intimate contact. The gastrointestinal

tract is an inaccessible mucosal surface, which means that the adhesive material cannot be placed directly onto the

target mucosal surface, or delivered to the surface by organ design. Generally speaking, adhesion and possible




blockage of the gastrointestinal tract can prove to be detrimental. For larger particles, peristalsis and other

gastrointestinal movement may help to force the dosage form into contact with the mucosa. However, evidence of

successful adhesion of larger dosage forms has yet been less often reported in the literature, other than the potentially

dangerous case of esophageal adhesion. For smaller particles in suspension, adsorption onto the gastrointestinal

mucosa would be an essential prerequisite for the adhesion process.

b) The consolidation stages: In this step, various physicochemical interactions occur to consolidate and strengthen

the adhesive joint, resulting in a prolonged adhesion. It is proposed that in order to achieve strong or prolonged

adhesion, a second ‘consolidation’ stage is required. For achieving strong adhesion, a change in the physical

properties of the mucus layer will be required otherwise it will fail to hold on to the bioadhesive polymer on

application of dislodging stress. There are two theories explaining this process. First theory based on the

intermolecular interaction proposes that the mucoadhesive molecules interpenetrate and bond by secondary

interactions with mucus glycoprotein. The second theory is the dehydration theory, which proposes that when a

material capable of rapid gelation in an aqueous environment is brought into contact with a second gel water

movement occurs between gels until equilibrium is reached.

Fig. 2-Steps in Mucoadhesion

THEORIES OF BIOADHESION 11,12

a) Wettability theory: This theory holds good for liquid or low viscosity mucoadhesive systems. It essentially

measures the “spreadability” of the bioadhesive polymer on the mucus. It proposes that the adhesive component

penetrates the surface irregularities, hardens and anchors itself to the surface. Essential characteristics for the

bioadhesive materials include zero or nearly zero contact angle, relatively low viscosity and an intimate contact that

excludes air entrapment. Therefore, the interfacial energies are responsible for the contact of the two surfaces and for

the adhesive strength. Contact angle can be easily determined experimentally and can be correlated to the Interfacial

tension.




Fig.3- Wettability Theory

b) The electronic theory: Electronic Theory describes adhesion as a phenomenon in which there occurs electron

transfer between the mucus and the mucoadhesive system as a result of the differences in their electronic structures.

This electron transfer leads to a formation of double layer of electric charges at the mucus and the mucoadhesive

interface. The result of this is the formation of attractive forces within this double layer. There is a controversy over

the acceptance of this theory due to the fact that it explains the electrostatic forces, which are much weaker as the

causes of bond adhesion.

c) The fracture theory: This theory states that the adhesive bond between the systems is force required to segregate

both the surfaces from each other. In this case the force of separation of the polymer from the mucus is related to the

strength of the bioadhesive bond. It is found that the work fracture is greater when the polymer network strands are

longer or the case in which the degree of cross-linking within the system is reduced. This theory allows the

determination of fracture strength.

Fig.4- Fracture Theory




d) The adsorption theory: According to this theory, adhesion is an outcome of different surface interactions

(primary and secondary bonding) between the bioadhesive polymer and mucus substrate. Primary bonds, also

stronger, such as ionic, covalent and metallic bonding leads to adhesion and is called chemisorptions. These forces

are somewhat undesirable due to their permanency. Apart from these, there are secondary forces, also weaker, which

constitute the Van der waal forces, hydrophobic interactions and hydrogen bonding. These interactions are weak in

nature requiring less energy to break. But as the mucoadhesion requires being a transient event, it is desirable to have

these forces.

e) The diffusion-interlocking theory: This theory postulates that mucoadhesive polymer chains diffuse into the

glycoprotein chain network of the mucus layer in a time-dependent manner. In the process of interpenetration, the

molecules of the polymer and the glycoprotein network of the mucus come into intimate contact with each other. This

leads to an establishment of a concentration gradient leading to the inter-diffusion of the both polymer inside each

other. The penetration rates of this two-way diffusion process are dependent upon the diffusion coefficient of both the

interacting polymers. Basic properties that affect this process are molecular weight, cross-linking density, chain

mobility/flexibility, and temperature and expansion capability of both networks. Typical values of the polymer

diffusion coefficient through the glycoprotein network of the mucus may be in the range of 10-10 to 10-16 cm2/sec.

Fig.5- Diffusion Theory

ADVANTAGES 13, 14

1) Prolongs the residence time of the dosage form at the site of absorption.

2) To avoid the first pass metabolism.

3) Due to an increased residence time it enhances absorption and hence the therapeutic efficacy of the drug.

4) Excellent accessibility.

5) Rapid absorption because of enormous blood supply and good blood flow rates.

6) Increase in drug bioavailability due to first pass metabolism avoidance.

7) Drug is protected from degradation in the acidic environment in the gastrointestinal tract (GIT).

8) Improved patient compliance & ease of drug administration.




9) Faster onset of action is achieved due to mucosal surface.

DISADVANTAGES

1) Medication administered orally does not enter the blood stream immediately after passage through the buccal

mucosa. Instead they have to be swallowed and then have to pass through a portion of the GIT before being absorbed.

So the action is not very rapid in the GIT as compared when the drug is administered through the buccal route.

2) Certain drugs when ingested undergo drug destruction; there are several drugs which are potentially in this

category. Many drugs affect liver metabolism and also cause destruction via first pass metabolism of other drugs.

3) Oral ingestions results in more exposure of a drug to GI tract.

4) The absorption of mucoadhesive drugs is adversely affected by the presence of food. Tetracyclines, in particular,

complicate the administration of this class of antibiotics via the oral route.

DRUG CANDIDATE SELECTION 15

Drug selection for gastrointestinal mucosal delivery is limited by the physicochemical properties of the drugs

themselves. To be delivered trans-mucosally, drugs must have unique physicochemical properties, i.e. a proper

balance between solubility and lipophilicity. Presently, new classes of drugs are typically not developed specifically

for oral trans-mucosal delivery. It is also important to consider factors influencing drug release from a system. The

release kinetics of a given drug from a system could be governed predominantly by the polymer morphology and

excipients present in the system. Finally, ideal formulation and its degradation products should be non-toxic, non-

irritant and free from leachable impurities. It should not aid in development of secondary infections and prevent the

effects of local drug irritation at the site of application. An ideal gastrointestinal mucosal drug delivery system must

meet several prerequisites to be successful. The first prerequisite for a gastrointestinal mucosal drug delivery system

is that it should rapidly attach to the mucosal surface and maintain a strong interaction to prevent displacement.

Spontaneous adhesion of the system at the target site is critical and can be achieved through mucoadhesive polymers.

Contact time should also be sufficiently long at the target site, normally longer than that needed for complete drug

release. The second prerequisite for a successful and effective gastrointestinal mucosal drug delivery system is that

the bio-adhesion performance should not be impacted by surrounding environmental pH. Other desirable

characteristics of a gastrointestinal mucosal drug delivery system include high drug loading, complete drug release,

and convenient administration. Drug release from a polymeric material takes place either by the diffusion or by

polymer degradation or by their combination. Polymer degradation usually takes place by the enzymes or hydrolysis.

This may happen in the form of bulk erosion or surface erosion. It is also important to consider factors influencing

drug release from a polymer. The release kinetics of a given drug from a polymeric matrix could be governed

predominantly by the polymer morphology and excipients present in the system.

POLYMER USED IN BIOADHESIVE DRUG DELIVERY SYSTEM 16, 17

Mucoadhesive polymers can be water-soluble or -insoluble polymers that are swellable networks, which are

joined by the cross-linking agents. These polymers have optimal polarity for adequate wetting while sufficient

fluidity allowing the mutual adsorption as well as mutual penetration of the polymer and mucus.




Ideal characteristics of bioadhesive polymer

A. Polymer should form a strong non-covalent bond with the mucin-epithelial surfaces.

b. Polymer should quickly adhere to most tissues and should possess some specificity to the desired site.

c. Polymer should allow for the easy incorporation of the drug as well as its release at desired time.

d. Polymer should not be irritating to the mucus membrane.

e. Polymer should not be immunogenic.

f. Polymer and their degradation should not be absorbed from the GIT or if absorbed, should not be toxic to the host.

g. The polymer should possess cohesiveness to provide strength inside the inter layer.

Table. 1 Polymers and their bioadhesive properties

Sr. No. Polymer Bioadhesive property

1. Carboxy methylcellulose (CMC) +++

2. Carbopol 934 +++

3. Polycarbophil +++

4. Tragacanth +++

5. Poly (acrylic acid / divinyl benzene) +++

6. Sodium alginate +++

7. Hydroxy ethylcellulose (HEC) +++

8. Gum karaya ++

9. Gelatin ++

10. Guar gum ++

11. Thermally modified starch +

12. Pectin +

13. Polyvinyl pyrrolidone (PVP) +

14. Acacia +

15. Polyethylene glycol (PEG) +

16. Hydroxy propylcellulose (HPC) +

17. Chitosan +

Where, +++:Excellent, ++ : Fair and + : Poor




Classification of Mucoadhesive Polymers:

Based on source-

1. Synthetic polymer

Cellulose derivatives, Poly(acrylic acid) polymers, Poly

(hydroxyethylmethylacrylate), Poly(ethylene oxide), Poly (vinyl

alcohol), Poly (vinylpyrrolidone), Thiolated polymer

2.Natural polymer Tragacanth, Sodium alginate, Agarose, Guar gum, Xanthan gum,

Karayagum, carrageenan, Chitosan,Soluble starch, Pectin, Gelatin.

Based on solubility-

1.Water soluble polymer

Hydroxy Ethyl Cellulose, Hydroxy Propyl Cellulose,PAA, Sodium

CMC, HPMC, Sodium alginate

2.Water-insoluble polymer Chitosan, Ethyl cellulose, Polycarbofil

Based on charge-

1.Cationic

Chitosan, dimethylamino ethyl-dextran, Amino dextran

2.Anionic Chitosan-EDTA, CMC, CP, pectin, PC, PAA, xanthan gum,sodium

CMC, alginate

3.Non-ionic Hydroxyethylstarch, PVA, PVA, PVP HPC, scleroglucan,

poly(ethylene oxide)

Based on potential

bioadhesiveforces-

1.Covalent

Cyanoacrylate

2.Hydrogen bond CP, PVA, PC, Acrylates

3.Electrostatic bond Chitosan

•Based on Generation-

1.First generation

Chitosan, dimethyl amino ethyl-dextran, Aminodextran Chitosan-

EDTA, CMC, CP, pectin, PC, PAA, sodium, xanthan gum, sodium

CMC alginate , Hydroxy ethyl starch, PVA, PVP HPC,

scleroglucan,poly (ethylene oxide)

2. Second generation Lectins, Thiolated polymers




FACTORS AFFECTING MUCOADHESION 18

1. Polymer related factors:

i) Molecular weight

ii) Concentration of active polymer

iii) Flexibility of polymer chains

iv) Spatial conformation

v) Swelling

2. Environment related factors:

i) pH of polymer - substrate interface

ii) Applied strength

iii) Initial contact time

3. Physiological factors:

i) Mucin turns over

ii)Disease state

Molecular weight

The mucoadhesive strength of a polymer increases with molecular weights above 100,000. Direct correlation between

the mucoadhesive strength of polyoxyethylene polymers and their molecular weights lies in the range 200,000-

7,000,000.

Flexibility

Mucoadhesion starts with the diffusion of the polymer chains in the interfacial region. Therefore, it is important that

the polymer chains contain a substantial degree of flexibility in order to achieve the desired entanglement with the

mucus. The increased chain interpenetration was attributed to the increased structural flexibility of the polymer upon

incorporation of polyethylene glycol. In general, mobility and flexibility of polymers can be related to their

viscosities and diffusion coefficients, as higher flexibility of a polymer causes greater diffusion into the mucus

network.

Cross-linking Density

The average pore size, the number and average molecular weight of the cross-linked polymers, and the density of

cross-linking are three important and inter-related structural parameters of a polymer network. Therefore, it seems

reasonable that with increasing density of cross-linking, diffusion of water into the polymer network occurs at a lower

rate which, in turn, causes an insufficient swelling of the polymer and a decreased rate of interpenetration between

polymer and mucin.




Hydration

Hydration is required for a mucoadhesive polymer to expand and create a proper macromolecular mes of sufficient

size, and to induce mobility in the polymer chains in order to enhance the interpenetration process between polymer

and mucin. Polymer swelling permits a mechanical entanglement by exposing the bioadhesive sites for hydrogen

bonding and/or electrostatic interaction between the polymer and the mucus network. However, a critical degree of

hydration of the mucoadhesive polymer exists where optimum swelling and mucoadhesion occurs.

Concentration

The importance of this factor lies in the development of a strong adhesive bond with the mucus, and can be explained

by the polymer chain length available for penetration into the mucus layer. When the concentration of the polymer is

too low, the number of penetrating polymer chains per unit volume of the mucus is small and the interaction between

polymer and mucus is unstable. In general, the more concentrated polymer would result in a longer penetrating chain

length and better adhesion. However, for each polymer, there is a critical concentration, above which the polymer

produces an "unperturbed" state due to a significantly coiled structure. As a result, the accessibility of the solvent to

the polymer decreases, and chain penetration of the polymer is drastically reduced. Therefore, higher concentrations

of polymers do not necessarily improve and, in some cases, actually diminish mucoadhesive properties. One of the

studies addressing this factor demonstrated that high concentrations of flexible polymeric films based on

polyvinylpyrrolidone or poly(vinyl alcohol) as film-forming polymers did not further enhance the mucoadhesive

properties of the polymer.

Environment-Related Factors

pH of polymer–substrate interface:

pH can influence the formal charge on the surface of the mucus as well as certain ionizable mucoadhesive polymers.

Mucus will have a different charge density depending on pH due to the difference in dissociation of functional groups

on the carbohydrate moiety and the amino acids of the polypeptide backbone. Some studies had shown that the pH of

the medium is important for the degree of hydration of cross-linked polyacrylic acid polymers, showing consistently

increased hydration from pH 4 through pH 7, and then a decrease at alkaline pH levels.

Applied strength:

To place a solid mucoadhesive system, it is necessary to apply a defined strength. Depending on the type of polymer,

poly (acrylic acid/ divinyl benzene) or carbopol, the adhesion strength increases with the applied strength or with the

duration of its application, up to an optimum. The initial pressure applied to the mucoadhesive tissue at the contact

site, can affect the depth of interpenetration. If high pressure is applied for a sufficiently long period of time,

polymers become mucoadhesive even though they do not have attractive interactions with mucin.

Initial contact time:

Initial contact time between the mucoadhesive and mucus layer determines the extent of swelling and interpenetration

of the mucoadhesive polymer chains. More mucoadhesive strength increases as the initial contact time increases.




Physiological Factors

Mucin turnover:

The natural turnover of mucin molecules from the mucus layer is important for at least two reasons. Firstly, the mucin

turnover is expected to limit the residence time of the mucoadhesives on the mucus layer. No matter how high the

mucoadhesive strength, they are detached from the surface due to mucin turnover. The turnover rate may be different

in the presence of mucoadhesives, but no information is available on this aspect. Secondly, mucin turnover results in

substantial amounts of soluble mucin molecules. These molecules interact with mucoadhesives before they have

chance to interact with the mucus layer. Surface fouling is unfavorable for mucoadhesion to the tissue surface. Mucin

turnover may depend on the other factors such as the presence of food. The gastric mucosa accumulates secreted

mucin on the luminal surface of the tissue during the early stages of fasting. The accumulated mucin is subsequently

released by freshly secreted acid or simply by the passage of ingested food; the exact turnover rate of the mucus layer

remains to be determined.

Disease state:

The physiochemical properties of the mucus are known to change during disease conditions such as the common

cold, gastric ulcers, ulcerative colitis, cystic fibrosis, bacterial, and fungal infections of female reproductive tract, and

inflammatory conditions of the eye. The exact structural changes taking place in mucus under these conditions are not

clearly understood. If mucoadhesives are to be used in the disease states, the mucoadhesive property needs to be

evaluated under the same conditions.

EVALUATION OF BIOADHESIVE TABLETS 19, 20

Weight variation

Twenty tablets will be weighed individually and then collectively, average weight of the tablets calculates, then

weight variation calculates.

Hardness

The hardness of the tablets will determine using a Monsanto hardness tester.

Friability test

The tablets will test for friability testing using Roche friabilator. For this test, six tablets weigh and subject to

combine effect of abrasion and shock in the plastic chamber of friabilator revolving at 25 rpm for 4 min and the

tablets then dust and reweigh.

Content uniformity

Ten tablets will be accurately weigh and powder-crush in a glass pestle mortar. An accurately weigh amount

equivalent to 5 mg of pure drug take, and the assay perform UV-Visible spectrophotometrically at 228 nm in

triplicates.




Surface pH

The surface pH of the tablets will determine in order to investigate the possibility of any irritation in the oral cavity.

The tablets will keep in contact with simulated saliva solution for 2 h, and pH note by bringing the electrode in

contact with surface of formulations.

Swelling studies

The tablets (n = 3) will be weigh individually (W1) and placed separately in petri dishes containing 5 ml of isotonic

phosphate buffer (pH 6.5) solution. At regular intervals (0.5, 1, 2, 3, 4, 5, and 6 h), the tablets remove from the petri

dishes, and excess surface water remove carefully using the filter paper. The swell tablet then reweigh (W2), and

swelling index (SI) will calculate using the following formula:

SI = W2 − W1/W1

In-vitro drug release

The in-vitro drug release study will be conduct using Hanson Research-SR8 Plus apparatus (Los Angeles, CA,

USA).Isotonic phosphate buffer (IPB) pH 6.5 (500 ml) use as the release medium. The release media will use to

simulate the physiological in vivo condition of the buccal cavity. The release perform at 37.5 ± 0.5°C, at a rotation

speed of 50 rpm. Samples (5 ml) will withdraw at intervals of 15, 30, 60, 90, 120, 180, 240, 300, 360, 420, and

480 min. The samples filtere using Whatman filter paper, and the drug concentration was measure by UV-Visible

spectrophotometer at 228 nm. The dissolution medium replace with fresh buffer to maintain its constant volume and

sink condition, when the sample withdrawn each time. Teflon block use in order to cover all sides of the tablet except

one, which is used as only the side of drug released to ensure unidirectional release.

Mucoadhesive study

Texture analyzer can be used to determine the bioadhesive strength of the tablets. Bovine buccal mucosa membrane

use as model membrane. It will hydrate with simulated saliva solution and tie to the lower probe of the assembly. The

simulated saliva solution will be prepare by using disodium hydrogen orthophosphate (dihydrate) 38 g, potassium

dihydrogen orthophosphate (anhydrous) 0.18 g, sodium chloride 8.0 g, and demineralized water (for a volume of up

to 1,000 ml). The tablet attach to the upper probe of the assembly using an adhesive. The upper probe allows falling

on the lower probe with a test speed of 0.5 mm/s and a post-test speed of 1 mm/s. The tablet allow to adhere to the

bovine buccal mucosa membrane with applied force 150 g, return distance 10 mm, and contact time 15 s.

Mucoadhesive force then calculate according to the following equation:

Force of adhesion (N) =Bioadhesive strenth (g)

1000 × 9.81




Stability studies

Stability studies will be perform at a temperature of 40°C at 75± 5 % RH, over a period of three months (90 days) on

the promising buccal tablets of formulation. Sufficient number of tablets (15) packs in amber colored screw capped

bottles and keeps in stability chamber maintained at 40±1°C & 75± 5 % RH. Samples will be taken at monthly

intervals for drug content estimation. At the end of three months period, dissolution test and drug content studies will

perform to determine the drug release profiles and drug content.

RECENT ADVANCES IN MUCOADHESIVE DRUG DELIVERY SYSTEM- 21

Mucoadhesive Polymers

Diverse classes of polymers have been investigated for potential use as mucoadhesive. PAA has been

considered as a good mucoadhesive. PAA is copolymerised with polyethylene glycol (PEG) or poly (vinyl

pyrrolidone) (PVP) to improve these properties.

Devices

Several laminated devices have been developed to achieve sustained drug release. It can be classified as-

• Monolithic (or matrix) systems where the drug is dissolved or dispersed in the polymer system.

Diffusion of drug from the drug/polymer matrix controls the overall rate of its release from the device.

• Reservoir (or membrane) systems where diffusional resistance across a polymeric membrane controls the overall

drug release rate.

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Volume 1(3).

3) Miller, N. S.et al (2005). The use of mucoadhesive polymers in buccal drug delivery, Advanced Drug Delivery

Reviews 57, 1666– 1691.

4) Singh, J. et al (2013). A Review Article On Mucoadhesive Buccal Drug Delivery System, Int J Pharm Sci Res Vol.

4(3): 916-927.

5) Phanindra, B. et al., (2013). Recent Advances In Mucoadhesive/Bioadhesive Drug Delivery System: A Review,

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