GASTRORETENTIVE MUCOADHESIVE DRUG DELIVERY SYSTEM

Hatwar et al. World Journal of Pharmaceutical Research

www.wjpr.net Vol 9, Issue 8, 2020.

812

GASTRORETENTIVE MUCOADHESIVE DRUG DELIVERY SYSTEM

Pooja R. Hatwar* and Dr. M. A. Channawar

Department of Pharmaceutics, P. Wadhwani College of Pharmacy, Yavatmal- 445001,

Maharashtra, India.

ABSTRACT

Oral drugs delivery is most preferable route of drug delivery for

administration of therapeutic agents. Gastro retentive drug delivery

system in which dosage forms that can be reserved in stomach and

mucoadhesives enhances the efficiency of drug delivery.

Gastroretentive mucoadhesive drug delivery system have been

developed to expands drug bioavailability by prolonging gastric

retention time, reduce drug waste, and improve the drugs solubility that

are not easily soluble in high pH environment of small intestine by use

of mucoadhesive polymer. For gastro retentive mucosal adhesion drug

delivery system the article exemplify the mechanism by which

mucoadhesion can be adhere to a mucous membrane with respect to

the nature of the adhering surfaces and the forcing to generate intimacy

between them. There are many factors that affect gastric retention and mucous membrane

adhesion.

KEYWORDS: Gastroretentive drug delivery system; mucoadhesive system, Theories,

Factors, Polymers.

INTRODUCTION

Oral route has been the most important route of drug delivery route because of its easiness of

administration, low cost of therapy, patient compliance and flexibility in its formulation. But

drugs that are simply absorbed from gastrointestinal tract (GIT) and have short half-life are

quickly eliminated from the systemic circulation. Frequent dosing of these drugs is required

to achieve suitable therapeutic activity.[1]

To avoid this limitation gastro retentive

mucoadhesive drug delivery system (GRMDDS) has been introduced.[2]

World Journal of Pharmaceutical Research SJIF Impact Factor 8.084

Volume 9, Issue 8, 812-831. Review Article ISSN 2277– 7105

Article Received on

03 June 2020,

Revised on 24 June 2020,

Accepted on 15 July 2020,

DOI: 10.20959/wjpr20208-18175

*Corresponding Author

Pooja R. Hatwar

Department of

Pharmaceutics, P.

Wadhwani College of

Pharmacy, Yavatmal-

445001, Maharashtra, India.



813

GRDDSs are currently used to prolong the residence time of oral administration dosage

forms in the stomach or upper gastrointestinal tract (GIT) with modified release profiles.[3]

Since the introduction of the gastric retention (GR) system about thirty years ago, various

methods have been used to extend the residence time of GR system in the stomach.4 Gastric

retention can achieved by stomach mucosa adhesion system, high density systems, expansion

systems, raft forming systems, low density systems, magnetic systems, super porous

hydrogels, floating system and ion exchange resins.[5]

The basic advantages of gastro retentive drug delivery system are enhanced bioavailability

and when the bioavailability of drug increases then dosages is reduced repetition and

ultimately minimized GI disorder, they have specific site drug delivery for gastrointestinal

diseases.[6]

Formulation of mucoadhesive dosage forms is one of them. In order to overcome

the problems related to gastric emptying time, the key method is that gastric mucosal

adhesion is the phenomenon that the drug tends to combine with gastric mucosa.[7]

Most

mucoadhesive tablets and capsules are retaine in stomach for more than four hours. For

example: Salbutamol, Atenolol.[8]

STOMACH OVERVIEW

Anatomy of Stomach

It represents the main part for gastric retention. Its anatomy and physiology must be

considered during the formulation of GRDDS. The stomach is located directly above the

abdomen just below the diaphragm. The size of the stomach changes according to the

expansion of 1500 ml after a meal; after emptying the food, it becomes folded and the resting

volume of 25-50 ml.[9]

The stomach is storage and mixing organ. Anatomically speaking the

stomach divided into three areas: fundus, body and antrum (pylorus). The proximal stomach,

consisting of the fundus and body area, serves as a reservoir for ingested material, while the

pylorus in the distal area is the major part for mixed movement, acting as drainage pump to

the duodenum to complete gastric emptying, as shown in fig. 1.[10,11]



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Fig. 1: Structure of stomach.[10]

Gastric motility and emptying of food[9,11,12]

Gastric emptying occurs during fasting and eating. The process by which drugs enter the

small intestine from the stomach is called gastric emptying. The gastric emptying process is

characterized by certain period of electro-mechanical activity, called the migration

myoelectric complex (MMC). This is a series of event that occur in the stomach and small

intestine every 1.2– 2 hours and is divided into four stages:

1. Stage I (basic stage)

2. Stage II (pre-explosion stage)

3. Stage III (outbreak stage)

4. Stage IV

Stage I: This is a resting period lasting 30 to 60 minutes, without contractions.

Stage II: It consists of intermittent contractions. As the stage progresses, the intensity

gradually increases and lasts about 20 to 40 minutes. Later in this phase, gastric juice and

very small particles begins to be expelled.

Stage III: This is a short and intense distal and proximal gastric contractions (4–5

contractions /minute), which lasts about 10 to 20 minutes. These contractions, also called

“house-keeper wave”, sweep gastric contents to the small Intestine.

Stage IV: This is a short transition period of approximately 0 to 5 minutes. The contraction

dissipates between the last part of third stage and rest of the first stage.



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After ingesting a mixed meal, the contractions pattern changes from fasting to eating, also

known as digestive motility pattern.

Fig. 2: Stages of Migrating Myoelectric Cycle.[13]

Gastro retentive drug delivery system[14]

Dosage forms that can be kept in stomach are called gastro retentive drug delivery systems

(GRDDS).[14]

Today, Gastro retentive drug delivery system (GRDDS) has become most

preferred drug delivery system because it can increase the bioavailability of the drug by

extending the retention time of stomach,[15]

reduces the waste of drug and increase the

solubility of drugs with lower solubility in a high pH environment.[16]

Drugs with lower

stability in the lower GI tract or drugs acting locally in the stomach may also benefit from the

gastric retentive (GR) system.[4]

Factors affecting drug delivery system[17,18,19]

Many factors affect the retention process of gastric retention, thereby drastically changing the

release of damage and its absorption. It is desirable to improve a drug delivery system whose

extended gastric residence time and a drug release curve are separated from patient related

variables. Factors affecting the gastric emptying and gastric retention of the drugs include the

dosage form density, size, shape, fasting, state, etc.

Density of dosage form: High-density systems require a density close to 2.7g/ml to

achieve good gastric retention.

The size of the dosage form: Due to larger particle size, the dosage form with a diameter

greater than 7.5mm has more gastric retention time. It cannot quickly enter the intestine

through the pyloric sinus.



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Shape of the dosage form: Compared to other shapes, tetrahedral and ring-shaped

devices show better gastric retention.

Eating or not eating state: In the fasting state, the gastrointestinal motility is defined by

the periods of intense motor activity that occur every 1.5-2 hours. Food intake, food

viscosity and volume, caloric value and eating frequency have an intellectual impact on

the gastric retention of the dosage form. The presence of the food in the gastrointestinal

tract affects the gastric retention time of the dosage form. The presence of a food in

gastrointestinal tract can improves the gastroretentive time of the dosage form, therefore,

the drugs absorption of the drug is increased and can stay longer at the absorption site.

Excessively, an increase in acidity and caloric value indicates a decrease in gastric

emptying time (GET), which can enhance the retention of dosage form in stomach.

The nature of meals: Feeding indigestible polymers or fatty acid salts (such as cellulose,

starch) will change the way of stomach motility pattern, delaying MMC and reducing

gastric emptying rate, and lead to longer drug release time.

Caloric content: A diet rich in protein and fat can cause GRT to increase by 4 to 10

hours.

Eating frequency: Due to low frequency of MMC, continuous meals can improve GRT

by 6 to 7 hours compared to continuous meals.

Age: People older than 70 years have a longer GRT.

Gender: The average GRT of men (3.4h) is lower than women of age and race matching

(4.6h).

Posture: For people who are upright, outpatient, and supine, posture has no significant

effect on GRT.

ADVANTAGES & DISADVANTAGES OF GRDDS

Advantages of gastroretentive drug delivery system[20, 21]

Drug delivery with narrow absorption windows in the area of the small intestine.

A longer residence time in the stomach may be beneficial for local effect in the upper part

of the small intestine. E.g. to treat peptic ulcer disease.

Drugs that are easily absorbed after release in the gastrointestinal tract, such as

cyclosporine, captopril, ranitidine, amoxicillin, ciprofloxacin, etc., are expected to

improve their bioavailability.

Compliance is achieved through treatment once a day.



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Reduces the frequency of administration.

Targeted treatment for local disease of the upper digestive tract.

The bioavailability of therapeutic drugs can be significantly improved especially drugs

metabolized in the upper GIT by this gastro retentive drug delivery method compared to

administration of non-gastro retentive drugs.

Gastric retention drug delivery can produce prolonged and sustained release of drugs

from dosage forms for local treatment in the stomach and small intestine. Therefore, they

can be used to treat diseases related to stomach and small intestine.

The drug delivery of gastric retention can minimize the side effect of human body,

thereby improving the efficiency of the drugs.

Extend the retention time of the dosage form at the absorption site.

Excellent accessibility.

Due to first pass metabolism, drug bioavailability increases.

By slowly releasing the drug at a controlled rate, drug minimized mucosal irritation.

Disadvantages of gastro retentive drug delivery system[22]

Need to increase the level of gastric juice.

Not suitable for the following drugs:

o Problems with solubility in gastric juice

o Causing G.I stimulation

o Inefficient in acidic environment

Drugs intended for selective release in the colon.

Due to the constantly updated state of gastric mucus wall lead to unpredictable

compliance.

Hydrogel based swelling system require longer time to swell.

After multiple administrations, the increased size of the drug delivery systems poses a

threat to life due to the potential danger of permanent retention in stomach.

Super porous systems have disadvantages such as problematic storage of easily

hydrolyzed, biodegradable polymers.

Need gastric retention drug delivery system[23]

Drugs absorbed from the proximal end of the gastrointestinal tract (GIT).

For such a drug which degrade or having low solubility in alkaline pH.



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Unpredictable short gastric emptying time.

To extended release of drug in the stomach and proximal small intestine to treat certain

diseases.

It is especially suitable for the treatment of peptic ulcer which cause due to Helicobacter

pylori infection.

Selection criteria for drug candidates for gastric retention drug delivery system[24]

Drugs that work locally in the stomach, such as antacids and misoprostol.

Drugs absorbed mainly in the stomach. Examples include calcium supplements,

cinnarazine and chlordiazepoxide.

Those drug that is poorly soluble at alkaline pH.

Absorption of drug with narrow window. For example, riboflavin and levodopa.

If the drugs disturb normal colonic microorganisms.

Such drug which are unstable in the colon or intestinal environment. For example,

ranitidine and metronidazole.

Drugs with variable bioavailability. E.g. Sotalol hydrochloride.

Approaches for gastro retentive drug delivery system[21,25,26]

Different development approaches have been frequently utilized in pharmaceutical industry

with improved gastric retention capabilities in the GIT.

Fig. 3: Approaches for GRDDS.



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Mucoadhesive drug delivery system

The mucoadhesive system was first introduced by Park and Robinson in 1984.[27]

Mucosal

adhesive enhances the effectiveness of drug delivery through long-term close contact

between the drug delivery device and the absorption site.[28]

Extending the residence time of

stomach by means of the mucoadhesive systems is the latest method developed 35 years

ago.[29]

Mucosal adhesion is a phenomenon that causes natural or synthetic polymers to adhere to

mucosal tissues. In manufacture of mucoadhesive drug delivery systems, the active

pharmaceutical ingredient (API) is mixed with polymers with special surface properties.

Mucoadhesive polymers have a strong attraction for mucosal surfaces and adhere to the

surface of these tissues.[30]

Mucoadhesion may be an approach that can be used in conjunction

with the aforementioned technique in order to achieve not only physical but also chemical

retention of gastric retention.[31]

For drug delivery systems such as tablets, patches,

micro/nanoparticles, Nano suspensions, microemulsions, gels, liposomes, and colloidal

dispersions mucoadhesion is useful strategy.[32]

Mechanism of mucoadhesion[33]

The mucoadhesion can be defined as an interfacial phenomenon, where two materials are

held together by interfacial attraction, one of the materials can be artificial, such as

mucoadhesive polymer, and the other can be the mucin layer of the mucosal tissue.

“Mucoadhesive” is defined as an artificial substance that can be interact with mucus

membrane and remain on mucus membrane or hold them together for longer or longer period

of time. During the bonding process, the following two stages are usually determined. These

mucoadhesion stages are also shown in Figure 1.4.

Contact stage

At this stage, when the mucoadhesive material is in contact with mucosa, tight wetting occurs

between the mucous adhesion and mucosa. This wetting of the mucoadhesives is

accomplished by the mucus present in the mucosa.

Consolidation stage

Through different physical and chemical attractive forces, the mucoadhesive material binds to

the mucous membrane and leads to long-lasting mucous membrane adhesion.



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This is called the merge phase or consolidation stage. After these two stages, the process of

mucous membrane adhesion process is completed.

Fig. 4: Mucoadhesive GRDDS (a) General representation of mucoadhesive systems &

(b) mechanism of mucoadhesive system.[27]

MUCOUS MEMBRANE

Mucous layer composition[34]

The stomach wall is composed of many different tissue layers: the outer mucosa, inner

submucosa, the outer muscles and the serosa. The gastric mucosa or lining consists of

columnar epithelial tissue, the lamina propria (consisting of areola connective tissue) and a

thin layer of smooth muscle. The mucosal cells (goblet cells) emit mucus (translucent and

sticky secretions) which stick to the stomach wall and prevent its destruction from the gastric

juice. In humans, the average thickness of the mucosal layer is about 50 to 450 mm. Mucus is

a complex mixture whose composition depends on the origin and the pathological state of

human beings.

Table 1: Composition of gastric mucus.



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Function of mucous layer[35]

Various functions of mucus layer of different body parts

Protective effects

The protective effect is due in particular to its hydrophobicity and to protect the mucosa from

the diffusion of hydrochloric acid from the cavity to the cavity of epithelial surface.

Barrier Role

The role of mucus layer as barrier for the absorption of molecules, especially drugs. Diffusion

through the mucus layer largely depends on the physicochemical characteristics of the active

constituents, such as hydration radius, molecular charge, ability to form hydrogen bonds, and

molecular weight. There is a dynamic balance between the continuous erosion by proteolysis

and mechanical abrasion and the same continuous new mucus secretion.

Adhesion Role

Mucus has strong cohesion and firmly bonded to the surface of epithelial cell as a continuous

layer of gel and the gel clearly appears as a non-Newtonian fluid. Mucus layer is responsible

for retaining the pharmaceutical formulation while forming an adhesive bond with the

pharmaceutical product based on adhesive material.

Lubrication

The mucus layer keeps the mucous membrane moist. Continuous mucus secretion from the

goblet cells is required to compensate for the elimination of the mucus layer due to digestion,

bacterial degradation and solubilization of mucin molecules. At physiological pH, due to the

presence of sulphate residues and sialic acid, the mucus network may carry a large amount of

negative charge. The high charge density due to negative charge significantly promotes

mucoadhesion.

Advantages of mucoadhesive drug delivery system[36, 37]

Excellent quality being to be entered, rapid onset of action possible.

Extend the residence time of the dosage form at the absorption site, thus increasing the

bioavailability and its therapeutic effect.

Due to better control of plasma levels, the safety of highly effective drug is improved.

Reduced dosing frequency

Maximize the use of drug and reduce the total amount of medication



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Shorter treatment period.

Due to the large blood supply and good perfusion rate

Better patient compliance.

It provides a passive drug absorption system and does not require any activation.

Theory of mucoadhesion[38,39]

Mucoadhesion is a complex process, and many theories have been proposed to explain its

mechanisms. These theories include electronic theory, wetting theory, diffusion theory,

adsorption theory and fracture theory. Based on the study of the properties of several

materials and the adhesion of polymers and polymers, five classic theories are use. These

theories include diffusion interpenetration, mechanical-interlocking, adsorption, electrostatic,

and fracture processes. These various theories should be regarded as complementary

processes including different stages of mucus substrate interaction.

Wetting Theory[27, 36]

The theory is based on the diffusibility mechanism of drug dosage form across the biological

layers. The theory is mainly applicable to liquid or low viscosity mucous membrane adhesion

systems. According to this theory, the active ingredient bioadhesive polymer will penetrate

into irregularities on the surface and form intimate contact with the mucus and make it hard,

eventually leading to mucous membrane adhesion.

Fig. 5: Shows penetration of dosage form into the surface or tissue of the mucosal layer

by wetting or swelling mechanism.[40]

Diffusion theory[38,41]

The diffusion theory indicates that the interpenetration and entanglement of polymer and

mucin chains are the cause of mucous membrane adhesion. The more similar the structure of



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the mucoadhesive and the mucosa, the greater the mucoadhesive force. It is believed 0.2-0.5

µm interpenetration layer are needed to produce effective bonding. This process is driven by

the concentration gradient and is affected by the molecular chain length and its functionality.

This theory describes the physical entanglement and interpenetration of mucous membrane

strands in the porous structure of the polymer matrix. Interpenetration is controlled by

diffusion coefficients and contact time, and the contact time dependent on the molecular

weight and flexibility of the chains. The possible penetration depth (L) can be estimated by

the following formula:

L = (tDb) ½

Where: t = contact time, Db = diffusion coefficient of the bio adhesive materials in mucus.

This is a two-way diffusion process and penetration rate depends on the effective coefficient

of the two interacting polymers. Sufficient polymer chain flexibility, sufficient polymers

surface contact exposure, similar chemical structure and diffusion coefficients of bio adhesive

polymers are all factors that affect the interdiffusion of macromolecule networks.

Fig. 6: Secondary interaction between mucoadhesive device and of mucus.[42]

Fracture theory[42]

This is probably the most commonly used theory in the mechanical measurement of

mucoadhesion. After adhesion is established, analyze the force essential to separate two

surfaces. Since the fracture theory, this force sm, is usually calculated in the maximum tensile

test by the ratio of the maximal detachment force Fm to the total surface area A0, which

involves the adhesion interaction Sm = Fm / A0 Fig.7 only considers the separated parts. The

force required, regardless of the interpenetration or diffusion of polymer chains. Therefore, it

is suitable for calculation of rigid or semi-rigid mucoadhesive materials in which the polymer

chains do not enter into the mucus layer.



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Fig. 7: Fractures occurring for mucoadhesion.[42]

Electronic theory[36,43]

According to the electronic theory, there is difference in the electronic structure of the mucin

surface and bioadhesion system, which results in obtaining an electronic gradient. Due to this

difference in electronic structure, when the mucosal layer and the polymer mucoadhesive

contact with each other, electron are transferred between them. Due to this electron transfer,

electronic double layers formed at the interface of the two surfaces. This interface double

layer exerts an attractive force in the interface of two surfaces, which may produce an

effective mucoadhesion.

Adsorption theory[40]

The definition of adhesion is that the result of interaction between various surfaces (primary

surface and secondary surface) is the chemical bond of the interaction of two types of

adhesives, namely hydrogen bonding and Vander Waals forces polymerization in the

adhesive, there is a deep root between the substance and the mucus matrix. The primary

bonds is generated due chemical absorption and its chemistry ionic bond, covalent bond and

metal bond lead to adhesion, while the secondary bond is mainly due to Vander Waals forces,

hydrophobic interaction and hydrogen bond.

FACTOR AFFECTING MUCOADHESION

Polymer related factor[33,35,44,46]

Molecular weight: The interpenetration of polymer molecules is beneficial for low

molecular weight polymers because higher molecular weights will not wet or diffuse

quickly and may cause entanglements.

Concentration of polymer: A high concentration of mucoadhesive contains a large

number of functional groups to form molecular bonds, so it can improve

mucoadhesiveness. If the concentration of the polymer is too low, the interaction between

polymers is small because the number of polymer chains per unit volume of mucus



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penetrates is small. The mucoadhesive polymer has the best concentration to produce

maximum mucoadhesion. At high concentration above the optimum level, the bond

strength drops significantly.

The flexibility of polymer chains: Considered to be an important parameter of

interpenetration and entanglement. For bio adhesions to be effective the polymer chain

should effectively diffuse into mucus layer. For this, the polymer chain should have

sufficient flexibility. This depends on viscosity and diffusion coefficient. To obtain

greater diffusion into mucus network. The flexibility of polymer should be higher.

Spatial conformation: Mucoadheison also depends on the conformation of polymer, for

example: spiral or linear. Unlike PEG polymer with a linear conformation, the helical

conformation of electrons can shield many active groups mainly responsible for adhesion.

Swelling: The greater swelling of polymeric matrix higher is the adhesion time. It

depends on the polymer concentration, ion strength and the presence of water. This

process involves mechanical entanglement by revealing the bio adhesion sites, thereby

forming hydrogen bonds or electrostatic interaction between polymer and mucus network.

Hydrogen Bonding Capacity: The hydrogen bonding is another important factor in the

adhesion of polymer mucosa. In order for the mucous membrane to adhere, the polymer

must have a functional group capable of forming hydrogen bonds.

Crosslinking Density: When the crosslinking density is larger, then the pore size

becomes smaller, and water diffusions into the polymer network at lower rate, resulting in

insufficient swelling of the polymer which leads to decreased in the permeability of the

polymer to mucin. The degree of crosslinking significantly affects the chain mobility and

solubility resistance.

Charge: The bioadhesive of ionic polymer is always greater than that of nonionic

polymer. The surface of the mucous membrane is negatively charged, so a positively

charged polymer may help the mucosal adhesion. In a neutral or weakly alkaline media,

cationic polymer exhibit higher levels of mucoadhesive properties. Facts have proved that

cationic high molecular weight polymers such as chitosan have good bioadhesive

property.

Factor related to the environment[33,35,44,45,46]

The pH value at the interface of the polymer substrate: The pH value has an important

influence on the surface of mucus and polymer. The increase of middle pH value plays a

prominent role in degree of hydration, because the pH value is very important for the



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degree of hydration of the cross-linked polycyclic acid. From pH 4 to pH 7 the hydration

continues to increase and then decreases as the alkalinity or ionic strength increase.

However, at higher pH values, the chain is fully extended due to the electrostatic

repulsion of the carboxylate anion.

Applied Strength: The solid mucous membrane adhesion system can be achieved by

applying precise strength. Even if there is no attractive property between the polymer and

the mucus, the application of high pressure for a long time causes the polymer and the

mucus to bioadhesively. Therefore, the application of initial pressure will affect the depth

of interpenetration.

Initial contact time: The initial contact time between the mucoadhesive and the mucous

layer determines the degree of swelling and interpenetration of the polymer chain. The

longer the initial contact time, higher the mucoadhesive strength. Initial contact time

directly affects the degree of swelling and diffusion of the polymer chain.

Moistening: Moistening allows the mucoadhesive polymer to spread on the surface and

form a polymer network with the required size to allow the polymer and mucin molecules

to penetrate each other, which will help in increase in the mobility of polymer chain. The

critical level of hydration for mucoadhesive polymers is obtained through optimal

swelling and mucoadhesion.

Swelling: When polymer chains are separated and there is no interaction, Interpenetration

in chains is easier. The higher the swelling, the lower the bio-adhesion. It should not

happen prematurely because it takes some time for bioadhesion. The swelling

characteristics are related to polymer itself and its environment.

Selection of model substrate surface: Since the physical and biological changes of the

mucus gels or tissues may occur under the experimental condition, the treatment and

management of the biological substrates is very critical.

The presence of metal ions: Interaction with charged polymers and mucus groups can

lead to significant reduction in number of interaction sites and the tightness of

mucoadhesive bonds.

Physiological factor[33,35,44,46]

Mucin turnover rate: This is the key parameter. Although the mucoadhesion is very

high, if the mucoadhesive on the mucus layer, this mucin turnover will limit the residence

time. It also results in production of soluble mucin molecules, which interact with the

mucoadhesive agent before interacting with it. This phenomenon plays a role in body’s



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immune system. It removes the pathogen which may be attached to the mucus layer to

prevent damage.

Disease state: The physical and chemical properties of mucus change under disease

conditions, such as stomach ulcers, common cold, fungal and bacterial infections, etc.

Under these disease conditions, mucus undergoes structural changes; this change may

affect bioadhesive properties.

The renewal rate of mucoadhesive cells: For different type of mucosa, it varies gently.

It also limits the stability of the bioadhesive system.

Tissue movement: It occurs during ingestion of fluid and food, (eg, peristalsis of the

gastro intestinal tract) and affects the mucous membrane adhesion system, especially in

the case of gastric retention dosage forms.

Concomitant diseases: Secondary diseases caused by primary diseases, they can change

the physical and chemical properties of mucus or change its viscosity (such as insufficient

and excessive secretion of gastric juice), increased body temperature, tissue fibrosis, ulcer

disease, inflammation, etc.

Mucoadhesive polymer

Types of mucoadhesive polymer[47,48]

Fig. 8: Mucoadhesive polymers.



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