Formulation and Evaluation of

MUCOADHESIVE DRUG DELIVERY SYSTEMS

Novel drug delivery systems (NDDS) are the system where the man searches

for new methods of entry of drugs in to the body in order to show its activity in the

body .The new drug delivery systems that

have been developed and developing are the mucoadhesive drug delivery systems , drug patches, transdermal patches etc.

Introduction

Definition Adhesion can be defined as the bond produced by contact

between a pressure - sensitive adhesive and a surface. The American Society of testing and materials has defined it as the

state in which two surfaces are held together by interfacial forces, which may consist of valence forces, interlocking

action or both.  Bioadhesion is defined as an ability of a material to adhere to

a biological tissue for an extended period of time In the case of polymer attached to the mucin layer of a

mucosal tissue, the term “mucoadhesion” is used.

Types of Drug delivery systems:Depending upon the route of administration of the mucoadhesive drugs

they are different types .They are

1)Buccal delivery system

2)Sub lingual delivery system

3)Vaginal delivery system

4)Rectal delivery system

5)Nasal delivery system

6)Ocular delivery system

7)Gastro intestinal delivery system

Mechanism of Mucoadhesion Before discussing about the

mechanism of muco-adhesion we must know about the composition of mucous briefly. Mucus is composed mainly of

Water (>95%) Glycoproteins of

exceptionally high molecular weight

Mineral salts -1 % Free proteins – 0.5 to 1%

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Factors affecting Mucoadhesion 1. Polymer related factors

2.Environment related factors

3.Physiological factors

1. Polymer related factorsi) Molecular weight : ii)Concentration of active polymer iii)Flexibility of polymer chains

2.Environment related factors : i)pH of polymer - substrate interface ii) Applied strength iii) Initial contact time iv)Swelling

3. Physiological factors: i)mucin trun over : ii)Disease state

PolymersThe following are the polymers their relative bio adhesive property

Polymer Bioadhesive property Carboxy methyl cellulose +++ Hydroxyl propyl methyl cellulose +++ Carbopol 934 +++ Tragacanth +++ Sodium alginate +++ Polycarbophil +++ Hydroxyl ethyl cellulose +++ Gelatin ++ Guar gum ++ Gum karaya ++ Pectin + Acacia + Polyvinyl pyrrolidone +

NOTE : +++ Excellent ++ Moderate + Poor

Advantages

Mucoadhesive dosage forms have three distinct advantages when compared to conventional dosage forms

• 1)These dosage forms are readily localized in the region applied to improve and enhance the bioavailability of drugs.

• 2)These dosage forms facilitate intimate contact of the formulation with the underlying absorption surface. This allows modification of tissue permeability for absorption of macromolecules ,such as peptides and proteins. Inclusion of penetration enhancers such as Sodium glycocholate, Sodium taurocholate and L-lysophosphotidyl choline 9LPC0 and protease inhibitors in the mucoadhesive dosage forms resulted in better absorption of peptides and proteins.

• 3) Mucoadhesive dosage forms also prolong the residence time of the dosage form at the site of application and absorption to permit once or twice a day dosing.

Disadvantages

• Medications administered orally do 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 buccal route.

• 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.

• Oral ingestions results in more exposure of a drug to the GI tract. One of the side effects of many antibiotics is the destruction of normal GI flora resulting in diarrhea and overgrowth with dangerous organisms such as C. difficile.

• The absorption of mucoadhesive drugs is adversely affected by the presence of food. Tetracyclines, in particular, complicates the administration of this class of antibiotics via the oral route.

• Mucoadhesive drugs cannot bypass liver metabolism. Example, lipids can directly interact with endogenous lipoproteins thus influencing blood lipid levels.

Different mucoadhesive dosage forms • Mucoadhesive Buccal Films:

Mucoadhesive buccal films are most commonly prepared by the solvent casting technique in which various substrates including mercury, Teflon, glass and aluminium are used for film formation. Among these substrates, mercury was found to give best results.

• Mucoadhesive microspheres:

Mucoadhesive microspheres have advantages of efficient absorption and enhanced bioavailability of drugs, a much more intimate contact with the mucus layer, and specific targeting of drugs to the absorption site.

• Mucoadhesive microparticles:

Mucoadhesive microparticles is an improved drug delivery system which are believed to bind to the mucus layer coating the stomach and other regions of the GIT. These mucoadhesive microparticles bind to the mucus layer leading either to slow release into the GIT or direct delivery to the gastrointestinal mucosa.

• Mucoadhesive microcapsules:

Mucoadhesive microcapsules are a type of controlled-release dosage form. They offer numerous benefits including reducing stress resulting from restraint, handling, and dosing and avoiding expensive or difficult drug administration procedures. They can be used for vaginal administration to treat vaginal infections and to increase patient convenience.

• Mucoadhesive tablets:

Mucoadhesive tablets have been developed to increase the retention of drug in GIT and/or to keep a sustained release of drug towards the medium from where it is constantly removed. Thus, treatment of many diseases is done.

• Mucoadhesive patches:

These mucoadhesive formulations offer many advantages in comparison to traditional treatments and can be proposed as a new therapeutic tool against dental and buccal diseases and disturbances.

Evaluation tests of muco-adhesive tablets • 1)Weight variation• 2)Friability• 3)Hardness• 4)Content uniformity• 5) Drug release study of Mucoadhesive tablets• 6) Swelling index • 7)Water sorption studies• 8)Mucoadhesive strength

AIM AND OBJECTIVE• The objective of the

study mainly is to develop, characterize and evaluate mucoadhesive dosage forms employing various mucoadhesive polymers for prolonged absorption.

• The mentioned drugs are most commonly used in the preparation of mucoadhesive drug delivery systems.

• Based on literature survey, the best excipients will be selected and the best method will be followed to obtain the final optimized formulation.

DRUG CATEGORY CLASS HALF-LIFE

Diltiazem Anti-anginal,Anti-arrythmiatic

Calcium channelblocking agent

3-4.5 hours

Atenolol Anti-Hypertensive,Anti-anginal

B-adrenergicblocking agent

6-7 hours

Nifedipine Anti-Hypertensive,Anti-anginal

Calcium channelblocking agent

2-5 hours

Captopril Anti-HypertensiveAnti angial

Acetylcholine inhibitor

2-5 hours

Rationality in the selection of the

experiment• The rationality in carrying out the experiment is well approved

since, it is based on the selection of the optimal dose involved. Mucoadhesive drugs have many properties which make it rationally possible to carry out experiment on its dosage forms. Its various advantages like increasing the residence time of the drug, increasing the bioavailability and contact time of drug are important to be studied and hence build a platform for experimentation.

• Based on literature survey, by taking into account the various physicochemical and pharmacokinetic properties of various drugs, an optimal drug that can be employed in this experiment is selected. Thus, selection of a drug by taking into account mainly the half life value, solubility and availability is carried out. Various procedures for the formulation and evaluation of the selected drug are then carried out resulting in the production, characterization and evaluation of the finalized optimal product.

• Thus, the idea of selecting an optimal mucoadhesive dosage form for experimentation after survey of literature of many drugs is proved to be of great rationality.

Conclusion

The mucoadhesive drug delivery offers several advantages for controlled drug delivery. The mucosa is well supplied with both vascular and lymphatic drainage. The mucous membrane has a large surface area and is well suited for a retentive device and appears to be acceptable to patients. With the proper formulation and dosage form design, the permeability and the local environment of the mucosa can be controlled and manipulated to accommodate drug permeation. 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. However, the need for safe and effective permeation and absorption enhancers is a crucial component for a promising future in the area of mucoadhesive drug delivery. A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug and excipients. Advances in experimental and computational methodologies will be helpful in shortening the processing time from formulation design to clinical use.

Literature survey DRUGS CATEGORY POLYMERS DOSAGE

FORMREFERENCE

Clotrimazole Anti-fungal Carbopol 934 &HPMC

Flims Indian journal of pharmaceutics Vol 60 No. 1, Jan-Feb 1998

Metronidazole Anti infective Ethyl cellulose tablets Journal of pharmaceutical research

Vol 7 No. 3,July 2008