(2015-2016)

Aseminar

on

Mucoadhesive drug delivery system By

Miss. Duduskar Anita Ankush

Under the Guidance ofDr. Pawar P.K.

Head of Department Pharmaceutics Gourishankar Institute of

Pharmaceutical Education & Research Limb, Satara.

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• Introduction• Basics ,concepts & mucosal membrane.• Need of mucoadhesive DDS• Mechanism of mucoadhesion• Theories mucoadhesion• Sites of mucoadhesionSites of mucoadhesion• Penetration enhancerPenetration enhancer• Mucoadhesive polymerMucoadhesive polymer• Factor affecting mucoadhesionFactor affecting mucoadhesion• Advantages & DisadvantagesAdvantages & Disadvantages• Mucoadhesive dosage formMucoadhesive dosage form• Evaluation Evaluation • Case studyCase study• Reference

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• Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.

• Mucoadhesive drug delivery system is a part of controlled delivery system.

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• Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.

• combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.

• MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.

• Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.

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- Inner layers called mucosa - Inner epithelial Cell lining Covered with viscoelastic fluid. -Secreted by Goblet cells -Composed of water and mucin-Other components include proteins,

lipids and mucopolysaccharides ,electrolytes

-Main role is protective and lubricates

-Tendency substance to remain adhered to surface

-If substance adhere to Biological mucosal layers is called as Mucoahesion

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What is mucus ?• Mucoadhesiveinner layers called mucosa inner epithelial cell

lining is covered with viscoelasticfluid• Composed of water and mucin.• Thickness varies from 40 μm to 300 μm• General composition of mucus• Water…………………………………..95%• Glycoproteinsand lipids……………..0.5-5%• Mineral salts……………………………1%• Free proteins…………………………..0.5-1%

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General structure of mucous layer

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Functions of mucus• Protective : Particularly from its hydrophobicity

• Barrier : In tissue absorption of the drugs and

influence the bioavailability.

• Adhesion : Mucus has strong cohesion properties

• Lubrication :keep mucosal membrane moist.

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Avoidance of

First pass Metabolism

Better absorption of peptide by

penetration enhancer

Prolong

residence time

Localization of drug at given site

WHY ?

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Mechanisms of mucoadhesionMechanisms of mucoadhesion

• The mechanism responsible in the formation of mucoadhesive bond

• Step 1 : Wetting and swelling of the polymer(contact stage)

• Step 2 : Interpenetration between the polymer chains and the mucosal membrane

• Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)

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Step-I• Wetting and swelling step occurs when polymer

spreads over the surface of mucosal membrane to develop intimate contact

• Swelling of polymer occur because the components of polymer have an affinity for water

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Step-II• In this step the mucoadhesive polymer chain and the

mucosal polymer chains intermingle and entangles to form adhesive bonds

• Strength of bonds depends upon the degree of penetration of the two polymer groups

Interpenetration of mucoadhesive and mucous polymer chains

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Step-III• This step involves formation of weak chemical bonds

between the entangled polymer chains• Bonds includes primary bonds such as covalent bonds

and secondary interactions such as vanderWaalsand hydrogen bonds

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• Electronic theory• Wetting theory• Adsorption theory• Diffusion theory• Fracture theory

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1) Electronic theory-Attractive electrostatic forces between glycoprotein mucin network & the bioadhesive material.

2) Wetting theory-Ability of bioadhesive polymers to spread & develop intimate contact with the mucous membrane.

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3) Adsorption theory-Surface forces ( covalent bond, ionic bond, hydrogen bond & van der waals forces) resulting in chemical bonding

4) Diffusion theory-Physical entanglement of mucin strands and flexible polymer chains.

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5) Fracture theory-Analyses the maximum tensile stress develop during detachment of the BDDS from mucosal surfaces

Different routes of targeting MDDS

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Penetration enhancer• Substances that facilitate the permeation through mucosa are referred as permeation

enhancers .

• Safe and non toxic, non irritating and non allergenic

• Pharmacologically and chemically inert

• They should have no pharmacological activity within the body

• Eg. Benzalkonium chloride , Dextran sulfate ,Fatty acid , Propyleneglycol,

Men ,Sodium EDTA etc.

•

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Mucoadhesuve polymers• They are water soluble and water insoluble polymers which are

swellable networks joined by cross linking agent• Characteristic of ideal polymer• Degradation products should be non toxic and non absorbable

from GIT• Good spreadibility, wetting, swelling and biodegradable

properties• Optimum molecular weight• Non irritant to mucous membrane• Form a strong non-covalent bond with mucin epithelial cell

surface

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Natural and semisynthetic Synthetic

Agarose Carbopol

Chitosan PVA

Gelatin PVP

Pectin Thiolated polymer

CMC Methacrylic acid

Thiolated CMC Polycarbophil

HPMC

Hydroxypropylcellulose20

Soluble Insoluble

CMC, Sodium CMC, HPMC, MC, PVA, PVP, etc.

Carbopol, Polyacrylicacid,PEG, etc

C) According to charge

Charged Uncharged

Aminodextran, Chitosan, Carbopol, SodiumAlginate, Pectin, SodiumCMC, etc.

Starch, PEG, PVA, PVP, etc.

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Factors affecting mucoadhesionA)Polymer related factors:• Molecular weight• Conc. of polymer

• Flexibility of polymer chains• Presence of functional group• Spatial conformation• Cross linking density

B) Environment related factors:• pH of polymer substrate interface

• Applied strengthC) Physiological factors:• Mucinturn over • Disease state

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-Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.-Targeting & localization of the dosage form at a specific site-Painless administration.-Low enzymatic activity & avoid of first pass metabolism

Advantages

-If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.-Some patient suffers unpleasent feeling.-Unfortunately ,the lack of standardized techniques often leads to unclear results. -costly drug delivery system.

Disadvantages

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Mucoadhesive dosage form

Mucoadhesive

dosage form

LiquidSuspensionsGel forming liquids

SolidTabletsMatrix tabletBioadhesive microparticlesBioadhesive inserts

SemisolidGels & ointmentFilmsPatches

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A) Matrix tablets-(a)Monolithic (b)two layered tabletsIn monolithic mixture of drug + swelling bioadhesive polymer bidirectional release & outer side coated with impermeable hyrophobic substances.

In two layered matrix tablets-Comprises an inner layer based on bioadhesive polymer &an outer non-bioadhesive layer containing the drug for a bi-directional release but only local action .In case of systemic action outer layer is inert & act as a protective layer. B) Patches-Greater patient complaince compared with tablets owing to their physical flexibility that causes only minor discomfort to the patient.

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C) Films-may be preferred over adhesive tablets in terms of flexibility &comfort.An ideal film should be flexible,elastic &soft, without breaking due to stress from mouth movements.

D) Gels & ointments- adv.over other dosage form is that they are easily dispersion throughtout the mucosa.But accuracy of drug dosing may not be as accurate.Certain polymer are used such as NaCMC, xanthan,carbopol,hyaluronic acid .They change from liquid to semisolid.HPMC has been used as an adhesive ointment ingredients.

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METHODS OF EVALUATIONA) In vitro/ Ex vivo methods• Methods determining tensile strength• Methods determining shear stress• Adhesion weight method• Fluorescent probe method• Flow channel method• Mechanical spectroscopic method• Filling liquid film method• Colloidal gold staining method• Viscometer method• Thumb method• Adhesion number• Electrical conductance• Swelling properties• In vitro drug release studies• Muco retentability studies

B) In Vivo methods• Use of radioisotopes• Use of gamma scintigraphy• Use of pharmacoscintigraphy• Use of electron paramagnetic

resonance •(EPR) oximetry

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Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan microspheres for the treatment of ulcerative colitis.

Seema Badhana1, Navneet Garud2, *Akanksha Garud

• Mesalamine (5-ASA) is an anti-inflammatory drug used to treat crohn’s disease and ulcerative colitis.

• Microspheres were prepared by the modified emulsification method using calcium chloride as cross linking agent. The microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach.

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References• Phanindra B, B Krishna (2013) Recent advances in mucoadhesive drug delivery

system: A review. Int. J. Pharm. Med. & Bio. Sc. 1-15.

• Flávia Chiva Carvalho, Marcos Luciano Bruschi (2010) Mucoadhesive drug delivery systems. Brazilian Journal of Pharmaceutical Sciences.1-9.

• Seema Badhana, Navneet Garud, Akanksha Garud (2013) Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan microspheres for the treatment of ulcerative colitis . International Current Pharmaceutical Journal .42-45.

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