Drugs and systems

MUCOADHESIVE DRUG DELIVERY SYSTEM

INTRODUCTION

 Definition:

“Mucoadhesion is a state in which two components are present, one is biological origin, and second is drug, both are connected simultaneously for long time span of time through interfacial forces. In Mucoadhesion we form bond of drug with a mucosal surface”.

Adhesion:  Ability to stick, adhere or hold.

 Bioadhesion: The addition of synthetic or biological macromolecules to a biological tissue. Mucoadhesion: The attachment of synthetic or biological macromolecules to a mucosa or mucous membrane.

Mucus is a translucent and viscid which forms a thin, relentless gel bedding adherent to the epithelial exterior. Thickness varies from about 50-450um It is secreted by the goblet cells lining the epithelia or by exceptional exocrine glands with mucus units acini. (1,2)

Composition: Water 95% Glycoprotein and lipids 0.5-5% Mineral salts 1% free proteins 0.5-1% Purposes:

1.      Protection

2.      Barrier

3.      Adhesion

4.      Lubrication (1,2)

MECHANISM OF ACTION:

Step1 Contact Stage:

 The first stage is characterized by the contact between the Mucoadhesive and the mucous membrane, with spreading and swelling of the formulation, initiating its deep contact with the mucus layer

Step 2 Consolidation Stage:

 In the consolidation step, the Mucoadhesive materials are activated by the presence of moisture. Moisture plasticizes the system, allowing the Mucoadhesive molecules to break free and to link up by weak Vander Waals and hydrogen bonds.

Consolidation stage has 2 theories

a)Diffusion Theory b) Dehydration Theory

 a)Diffusion Theory: According to diffusion theory, the mucoadhesive molecules and glycoproteins if the mucus mutual interact by means of interpenetration of their chains and build the bond.

b) Dehydration Theory: Accoding to dehydration theory,materials that are able to readily gelify in the aquous environment,when placed incontact with mucus can cause its dehydration,due to difference of osmotic pressure. The difference in concentration gradient draws the water into the formulation until osmotic balance is reached. This process leads to the mixture of formulation and mucus can increase contact time with mucous membrane leads consolidation of the adhesive bond. (3,4)

Theories of mucoadhesion are;

1.      Adsorption theory

2.      Wetting theory

3.       Diffusion theory

4.      Fracture theory

5.       Mechanical theory

6.      Electronic theory.

1. Electronic theory: According to this theory, both mucoadhesive and biological materials possess opposite charges, when both material come incontact to and from electronic double layer that determines the mucoadhesive strength

2. Adsorption theory: This theory states that the bioadhesive bond formed between an adhesive substrate and the tissue is due to the weak Vander Waals forces and hydrogen bond formation.

3. Wetting theory: The wetting theory was developed predominantly in regard to liquid adhesives, uses interfacial tensions to predict spreading and in turn adhesion .The wetting theory present affinity to the surface in order to spread over it. This affinity can be measured by using contact angle, lower the contact angle greater their affinity

4. Diffusion theory: The concept of the interpenetration and entanglement of the bioadhesive polymer chains and mucous polymer chains is supported by the diffusion theory.

5. Fracture theory: This theory explains the forces required to separate the two surfaces after adhesion has taken place. It measures the maximum tensile stress produced during detachment

6. Mechanical theory: The mechanical theory explains the diffusion of the liquid adhesives into the micro-cracks and irregularities present on the substrate surface thereby forming an interlocked structure which gives rise to adhesion.(4)

FACTOR AFFECTING MUCOADHESION

1.      Polymer-Related Factors

2.      Environment Related Factors

3.      Physiological Variables

A)    Polymer founded factors

•        Molecular heaviness of the polymer

•        Engrossment of polymer utilized

•        Flexibility of polymer chains

•        Enlarging component

•        Stereochemistry of polymer

B)    Physical components

•        pH at polymer substrate interface

•        Applied power

•        Communicate time

C)     Physiological factors

•        Mucin revenue rate

•        Diseased state

Polymers used are;

Synthetic polymers:

Ø  Cellulose derivatives polymers:

•         Methylcellulose

•         Hydroxy propyl methylcellulose

•         Sodium carboxy methylcellulose,

Ø  Poly ethylene oxide

Ø  Poly vinyl pyrrolidone

Natural polymers:

•         Tragacanth

•         Sodium alginate

•         Karaya gum

•         Guar gum

•         Xanthan gum,

•         Gelatin

•         Pectin

•         Chitosan

Properties of ideal polymer are;

•         Nontoxic

•         Nonirritant

•         Non absorbable

•         Low cost

•         Adhere quickly

•         Form a strong bond with surface

•         Do not decompose on storage or during the shelf life (5)

TYPES OF MUCOADHESIVE DRUG DELIVERY SYSTEM

1.      Buccal Mucoadhesive drug delivery system

2.      Oral Mucoadhesive drug delivery system

3.      Nasal Mucoadhesive drug delivery system

4.      Ocular Mucoadhesive drug delivery system

5.      Vaginal Mucoadhesive drug delivery system

6.       Rectal Mucoadhesive drug delivery system

BUCCAL MUCOADHESIVE DRUG DELIVERY SYSTEM

INTRODUCTION:

Buccal delivery is that the administration of the drug via buccal mucous membrane (lining of the cheek) to the circulation. Bioadhesion is that the state during which 2 materials, (at least one in all that is biological in nature), square measure control along for a extended amount of your time by surface forces. The term bioadhesion implies attachment of drug-carrier system to specific biological location. This biological surface is epithelium or the mucose coat on the surface of tissue. If adhesive attachment is to mucose coat then development is referred as mucoadhesion. This drug delivery system utilize property of bioadhesion of bound water soluble polymers that become adhesive on association and thus is used for targeting explicit web site. Blood flow in buccal mucous membrane is two.4Ml/min/100 cm2.Mucous membrane of cavum is very tube-shaped structure and provides blood to mouth by carotid artery. Arteria provide blood to Cheek, surface. Arterial blood vessel provides blood to Tongue, gingival, Mouth floor. Arteria maxillaries provide blood to Lips, taste bud. Buccal drug delivery systems are (1) Buccal tablets (Molded tablets, Compressed tablets)(2) Buccal films (3)Buccal patch (4)Buccal gels

ORAL MUCOUS MEMBRANE:

The oral mucous membrane consists of Stratified squamous epithelial tissue, basement membrane, Lamina propria and connective tissue. Epithelial tissue is live a hundred cm2 .it has shield surface layer and deeper tissues. Vital feature of oral mucous membrane is speedy turnover of the cells (3 – eight days). Transport of fabric across the oral mucous membrane by  Transmucosal porosity.It needs Passive mechanism, living thing areas ; protoplasm (permeability barriers),Cell membrane ( liphophillic ).Factors to be thought-about within the transmucosal porosity square measure Liphophilicity of drug secretion , hydrogen ion concentration of spittle, absorption, Binding to oral mucous membrane, Oral epithelial tissue thickness, Molecular size seventy five – a hundred Daltons, mass two hundred – five hundred, Drugs ought to be hydrophilic  / lipotropic in nature, Drug ought to be stable at buccal hydrogen ion concentration.

SALIVA:

About 1.5 Liters of spittle is secreted daily. It achieves secretions by salivary gland, sub jaw, organ glands. Minor secretion glands square measure settled in buccal, palatal regions. The presence of spittle is additional vital for Drug dissolution and Drug permeation (across mucose membrane). Perform of oral mucous membrane square measure give protection, acts as a barrier, and provides adhesion, keep the membrane dampish. Porosity of oral mucous membrane organ is larger in buccal than palatal

There are 2 routes of drug transport in oral cavity;

         Paracellular

         Transcellular

PARACELLULAR ROUTE: is Primary route for hydrophilic medicine as a result of living thing areas is that the most popular route however Disadvantage of this route is restricted expanse

TRANSCELLULAR ROUTE:  is Route for liphophillic compounds and Liphophillic medicine passes through super molecule made plasma membranes of the animal tissue cells.

ADVANTAGES:

1.         Simple administration.

2.         Termination of medical aid is feasible.

3.         Permits localization of drug to the rima for extended amount of your time.

4.         Avoids 1st pass metabolism.

5.         Important reduction in dose is achieved, thereby reducing dose dependent facet effects.

6.         It permits native modification of tissue porosity, inhibition of proteolytic enzyme activity or reduction in immunogenic response, therefore selective use of therapeutic agents like peptides proteins and ionized species is achieved.

7.         Medicine that square measure unstable in acidic setting of abdomen or destroyed by the alkali setting of bowel is given by this route.

8.         Medicine that show poor bioavailability by oral route is administered by this route.

9.         It follows passive diffusion, and doesn't need any activation.

10.       The oral mucous membrane lacks distinguished mucose secreting goblet cells and so there's no downside of diffusion restricted mucose build up.

11.       The presence of spittle ensures great amount of water for dissolution of drug in contrast to just in case of body part and stratum route.

12. Medicine with short life is administered by this methodology. (2-8 hrs) e.g.: Nitrospan (two hrs) & amp; medicament mono nitrate (2-5 hrs)

13.       From the formulation purpose of read a skinny glycoprotein film exist on the surface of rima provides chance to retain delivery system in grips with mucous membrane for prolonged amount of your time with the assistance of mucoadhesive compounds.

14.       The buccal membrane is sufficiently massive to permit delivery system to be placed at completely different sites on constant membrane for various occasions, if the drug or different excipients cause reversible injury or irritate mucous membrane

DISADVANTAGES:

1. Over association might cause formation of slippery surface & structural integrity of the formulation might get discontinuous by the swelling & association of the bioadhesive chemical compound.  

2. Ingestion and drinking might become restricted

3. There’s risk that Patient might swallow the pill

4. The drug contained in enveloped spittle follows the per oral route & blessings of buccal route is lost.

5. Solely drug with tiny dose demand is administered.

6. Drug that irritate mucous membrane or have a bitter or unpleasant style or AN unpleasant odor can't be administered by this route

7. Medicine that square measure unstable at buccal hydrogen ion concentration can't be administered by this route.

8. Those medicine that square measure absorbed by passive diffusion is administered by this route. (7)

ADVANTAGES OF MUCOADHESIVE DRUG DELIVERY SYSTEM:

Ø  Prolongs the residence time of the dosage pattern at the location of absorption.

Ø  Due to an increased house time it enhances absorption and therefore the therapeutic efficacy of the pharmaceutical.

Ø  Fast absorption because of tremendous blood provides and good body-fluid flow rates boost in pharmaceutical bioavailability due to first pass metabolism avoidance.

Ø  Pharmaceutical is defended from degradation in the acidic natural environment in the GIT.

Ø  Improved patient compliance- alleviate of pharmaceutical management.

Ø  Much quicker onset of activity is accomplished due to mucosal exterior.

Ø  Incident of localized ulcerous consequences due to prolonged contact of the pharmaceutical owning.

Ø  Ulcerogenic house.

Ø  One of the foremost limitations in the development of oral mucosal consignment is the lack of a good model for in vitro screening to identify drugs apt for such administration.

Persevering acceptability in periods to taste, irritancy and mouth seem is to be checked.