mucoadhesive drug delivery system...jayprakash nogaja

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Mucoadhesive Drug Delivery system ,Polymers,factors affecting to mucoadhesion ,Theories of mucoadhesion,mechanisun of adhesion.

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By: utoronto (108 month(s) ago)

Need some mucus thickness distribution on different organ and different location

By: utoronto (108 month(s) ago)

So great. mucosal based delivery system

By: SunnyXav (111 month(s) ago)

sir plz send me this ppt on my id shrutigangwar10@gmail.com

Presentation Transcript

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1 Mucoadesive Drug Delivery System Presented by, Jayprakash S.Nogaja M-Pharmacy Ist (Pharmaceutics) SVERI’s college of Pharmacy, Pandharpur jpnogja@rediffmail.com 9420090124,9766764132 1

CONTENT:

CONTENT Basics ,concepts & mucosal membrane. Theories mucoadhesion Mechanisms of Bioadhesion Drug Absorption Bio( muco )adhesive Polymer Types of Bioadhesive Formulations Targets for Bioadhesive Formulations Oral Bioadhesive Formulations Conclusion Reference 2

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3 Muco + adhesive Inner layers called mucosa Inner epithelial Cell lining Covered with viscoelastic fluid. Secreted by Goblet cells Composed of water and mucin (an anionic polyelectrolyte ) Other components include proteins, lipids and mucopolysaccharides ,electrolytes Thickness varies from ≈40–50 μm to ≈300 μm Tendency substance to remain adhered to surface If substance adhere to Biological membrane is called as Bioadhesion . If substance adhere to Biological mucosal layers is called as Mucoahesion. 3 Main role is protective and lubricates

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4 Mucin Mucin constitute > 95% of water . Gel like consistency due to glycoproteins Chemically oligosacharide chain with terminal Sialic acid ( pka=2.6) Mucins are large molecules with molecular masses ranging from 0.5 to over 20 MDa . Gastric mucin of Mw ≈10 MDa 4

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5 Mucosal membranes These are moist membranes that line passageways and structures in the body that lead to the outside environment such as the mouth, respiratory tract, gastrointestinal tract, nose and vagina

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6 6 Bioadhesion is used to describe the bonding or adhesion between a synthetic or natural polymer and soft tissues biological substrate such as epithelial cells, which allows the polymer to adhere to the biological surface for an extended period of time .

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7 Concept 7 The drug can be incorporated into a cross linked polymer device that would adhere to mucosal membrane in the body .the drug can diffuse from device directly in the tissue. Adhesion ,anchoring of polymer device result in increase residence time , bioavailability & site specificity. Decrease in frequency of administration with low dose , rate of elimination. Can bypass Firstpass metabolisum in route is other than oral

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8 Pharmacological Response Oral Delivery Portal Circulation Pathway to Bypass

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9 9 Theories mucoadhesion The Theories include :- (a) The electronic theory, (b) The wetting theory, (c) The adsorption theory. (d) The diffusion theory, (e) The mechanical theory (f) The cohesive theory. (g) Fracture theory. The phenomena of bioadhesion occurs by a complex mechanism There are seven theories have been proposed till date

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10 10 The electronic theory Proposes transfer of electrons amongst the surfaces due to difference in their electrical structure resulting in the formation of an electrical double layer thereby giving rise to attractive forces. The wetting theory Postulates that if the contact angle of liquids on the substrate surface is lower, then there is a greater affinity for the liquid to the substrate surface. If two such substrate surfaces are brought in contact with each other in the presence of the liquid, the liquid may act as an adhesive amongst the substrate surfaces.

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11 11 The diffusion theory Assumes the diffusion of the polymer chains, present on the substrate surfaces, across the adhesive interface thereby forming a networked , semipermeable structure. The extent depth to which the polymer chain penetrate the mucus depend on diffusion coefficient &time of contact . The adsorption theory After initial contact of the material adhere to surface due to forces acting between the atoms in the two surfaces later result in formation of bonds(primary & secondary )due to the presence of intermolecular forces, viz. hydrogen bonding and Van der Waal’s forces, for the adhesive interaction amongst the substrate surfaces.

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12 Fracture theory :- This theory attempts to relete the difficulty of separation of two surfaces after adhesion . Adhesion Strength = (E ԑ/L ) 1/2 E =Young’s modulus of elasticity ԑ = Fracture energy L = Critical crack length when two surfaces are separated The cohesive theory proposes that the phenomena of bioadhesion are mainly due to the intermolecular interactions amongst like-molecules. 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. Surface roughness =d/h

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13 13 Mechanisms of Bioadhesion The mechanisms responsible in the formation of bioadhesive bonds are not fully known, however most research has described bioadhesive bond formation as a three step process. Step 1 : Wetting and swelling of polymer Step 2 : Interpenetration between the polymer chains and the mucosal membrane Step 3 : Formation of chemical bonds between the entangled chains Process of bioadhesion can be classified, Chemical (electronic and adsorption theories) Physical (wetting, Diffusion and cohesive theory)

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14 14 Step 1 The wetting and swelling step occurs when the polymer spreads over the surface of the biological substrate or mucosal membrane in order to develop an intimate contact with the substrate. Bioadhesives are able to adhere to or bond with biological tissues by the help of the surface tension and forces that exist at the site of adsorption or contact. Swelling of polymers occur because the components within the polymers have an affinity for water. The image below shows swelling of a polymer

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15 Step 2 The surface of mucosal membranes are composed of high molecular weight polymers known as glycoproteins . In step 2 of the bioadhesive bond formation, the bioadhesive polymer chains and the mucosal polymer chains intermingle and entangle to form semi permeable adhesive bonds. The strength of these bonds depends on the degree of penetration between the two polymer groups. In order to form strong adhesive bonds, one polymer group must be soluble in the other and both polymer types must be of similar chemical structure . The interpenetration of polymer chains Bioadhesive polymer chains Mucus polymer chains

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16 16 Step 3 This step involves the formation of weak chemical bonds between the entangled polymer chains. The types of bonding formed between the chains include primary bonds such as covalent bonds and weaker secondary interactions such as van der Waals Interactions and hydrogen bonds. Both primary and secondary bonds are exploited in the manufacture of bioadhesive formulations in which strong adhesions between polymers are formed. Mechanisms of bioadhesion

Types of intecraction Involved:

17 Types of intecraction Involved Physical And Mechanical. Secondary chemical bond. Ionic,primary or covalent chemical bonds

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18 18 Drug Absorption Drug absorption is the process by which a drug leaves its site of administration and enters the general circulation Pinocytosis . Passive diffusion Facilitated passive diffusion Active transport

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19 19 In Bioadhesive Drug Delivery System the drug molecules Is either dispersed in matrix of polymer or matrix type is coated with bio(muco)adhesive polymer. Bio(muco)adhesive Polymer A bioadhesive polymer is a synthetic or natural polymer which binds to biological substrates such as mucosal membranes . Sometimes referred to as biological ‘glues’

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20 2 ) The nonspecific bioadhesive polymers Are the ability to bind with both the cell surfaces and the mucosal layer. e.g.polyacrylic acid, cyanoacrylates Classification of Bio(Muco)adhesive polymers A )Based on Specificity :- The specific bioadhesive polymers Are the ability to adhere to specific chemical structures within the biological molecules e.g. lectins, fimbrin

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21 (I) Synthetic polymers: (a) Cellulose derivatives:-methylcellulose, ethylcellulose, hydroxy-ethylcellulose, Hydroxyl propyl cellulose, hydroxy propyl methylcellulose, sodium carboxy methylcellulose. (b) Poly (acrylic acid) polymers (carbomers, Polycarbophil, poly(methylacrylate). (c) Poly (hydroxyethyl methylacrylate). (d) Poly (ethylene oxide). (e) Poly (vinyl pyrrolidone). (f ) Poly (vinyl alcohol). B ) Based on Origen (II) Natural polymers: Tragacanth ,Sodium alginate, Karaya gum, Guar gum ,Xanthan gum ,Lectin ,Soluble starch, Gelatin, Pectin, Chitosan , Hyaluronic acid .

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22 Relative mucoadhesive performance of some polymers :- Polymer Relative mucoadhesive force Quality of bioadhesion CMC 193 Excellent Carbopol 185 Excellent Tragacanth 154 Excellent Sod. alginate 126 Excellent HPMC 125 Excellent Gelatin 116 fair Pectin 100 Poor Acacia 98 Poor Providone 98 Poor

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23 23 Molecular properties of mucoadhesive : - 1. Strong hydrogen bonding groups (-OH, -COOH). 2. Strong anionic charges.(cellulose derivatives) but some cationic (e.g., Chitosan) 3. Sufficient flexibility to penetrate the mucus network or tissue crevices. 4. Surface tension characteristics suitable for wetting mucus/ mucosal tissue surface. 5. High molecular weight.

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24 24 Characteristics of Bioadhesive polymers 1)Flexibility - important because it controls the extent of the interpenetration between the polymers and mucosal/epithelial surfaces. 2) Hydrophilicity – Polymers that are hydrophilic in nature are able to form strong adhesive bonds with mucosal membranes because the mucus layer contains large amounts of water. 3)Hydrogen bonding – Hydrogen bonding between the entangled polymer chains forms strong adhesive bonds, therefore the presence of hydrogen bond – forming groups such as OH and COOH groups are vital in large quantities. 4)High molecular weight – Polymers with a high molecular weight are desirable because they provide more bonding sites. 5)Surface tensions – Surface tensions are needed to spread the bioadhesive polymer into the mucosal layer epithelial surface.

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25 25 Characteristics of an ideal mucoadhesive polymer 1. The polymer and its degradation products should be nontoxic and should be nonabsorable from the gastrointestinal tract. 2. It should be nonirritant & non abrasive to the mucous membrane. 3. It should preferably form a strong noncovalent bond with the mucin-epithelial cell surfaces. 4. It should adhere quickly to most tissue and should possess some site-specificity.

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26 26 5. It should allow easy incorporation to the drug and offer no hindrance to its release. 6. The polymer must not decompose on storage or during the shelf life of the dosage form. 7. The cost of polymer should not be high so that the prepared dosage form remains competitive. 8.It should get Wash out at desired period. Continued… 9.The mucoadhesive should be with high drug-loading capability.

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27 Factor affecting Mucoadhesion A)Polymer related :- 1)molecular weight –up to 10 00 000 and beyond this there is not much effective . 2)Concentration of active polymer –optimum not too high that significantly drops strength. 3)Flexibility of polymer chain – 4)spatial conformation – B)Environmental related :- 1)PH 2)Applied strength – increase up to optimum level 3)Initial contact time 4)swelling –too greater decrease the adhesion 5)mucus compossion C)Physiological factors :- 1)Mucin turn over 5)Diseased state

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28 28 Delivery Systems 1 ) 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. 2)Reservoir (or membrane) systems :- where diffusion resistance across a polymeric membrane controls the overall drug release rate.

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29 29 Types of Bioadhesive Formulations 1.Solid Bioadhesive Formulations :- Tablets , Inserts , Powders, tapes 2. Semi-solid bioadhesive Formulations:- Gels , Films , solutions, aerosol sprays 3.Liquid Bioadhesive Formulations:- Viscous liquids , Gel-forming liquids

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30 Targets for Bioadhesive Formulations Body site Systems Eye Mucoadhesive eye drops / inserts Nasal cavity Nasal drug delivery systems Oral cavity Dental gels / buccal systems Skin Patches, tapes, dressings Vagina Local vaginal delivery systems Rectum Local/systemic rectal delivery systems

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31 31 Oral Bioadhesive Formulations Oral bioadhesive formulations are topical products designed to deliver drugs to the oral cavity which act by adhering to the oral mucosa and therefore produce localised effects within the mouth The oral cavity Important functions which include chewing, speaking and tasting. Some of these functions are impaired by diseases such as ulcers, microbial infections and inflammation.

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32 In contact with saliva Dosage form become adhesive and render system attached to mucosa Drug solution rapidly absorbed throug the the reticulated vein which is underneath the oral mucosa & transported through facial vein ,internal jugular vein ,Brachiocephalic vein . Rapid absorption –peak 1to 2 min Some of the common conditions - Mouth ulcers , Oral thrush, Gingivitis.

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33 33 The buccal mucosa refers to the inner lining of the lips and cheeks. The epithelium of the buccal mucosa is about 40-50 cells thick and the epithelial cells become flatter as they move from the basal layers to the superficial layers. The buccal mucosa is less preferable compared to other oral drug delivery systems because of vary short transit time. The bioadhesive polymers can retention of a dosage form by spreading it over the absorption site. A ) The Buccal Mucosa

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34 34 B ). The sublingual mucosa The sublingual mucosa surrounds the sublingual gland which is a mucin -producing salivary gland located underneath the tongue. Examples :- Glyceryl Trinitrate (GTN ) (aerosol spray and tablet in prophylactic treatment of angina.) Brand name:- Susadrin , Nitrogard .

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35 3 ) The Gingival Mucosa Hardest muscle of body Can retain dosage form for long duration

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36 36 Conclusion Mucoadhesive dosage forms have a high potential of being useful means of delivering drugs to the body.Current use of mucoadhesive polymers to increase contact time for a wide variety of drugs and routes of administration has shown dramatic improvement in both specific therapies and more general patient compliance. The general properties of these polymers for purpose of sustained release of chemicals are marginal in being able to accommodate a wide range of physicochemical drug properties . Hence mucoadhesive polymers can be used as means of improving drug delivery through different routes like gastrointestinal, nasal, ocular, buccal, vaginal and rectal .

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37 37 Reference 1 ) Donald L. Wise ,Handbook of pharmaceutical Controlled Release Technology ,Marcel Dekker’s Pg .No-168-172255-268. 2) Yie W. Chaine ,NDDS ,Informa Healthcare USA-2009 ,2 nd edition ,pg no- 197-229. 3) S. B. Patil*, R. S. R. Murthy, H. S. Mahajan, R. D. Wagh, S. G. Gattani**,” Mucoadhesive polymers: Means of improving drug delivery” Pharma Times - Vol 38 - No. 4 - April 2006,pg no -25-28. 4) D r s B h a s k a r a J a s t i , X i a o l i n g L i and G a r y C l e a r y,” Recent Advances in Mucoadhesive Drug Delivery Systems” B U S I N E S S B R I E F I N G : P H A R M A T E C H 2 0 0 3,pg no-194-198. 5) S.E. Harding ,” Mucoadhesive interactions” Biochemical Society Transactions (2003) Volume 31, part 5,pg no-1036-1041. 6) S. Roy1, K. Pal, A. Anis, K.Pramanik and B.Prabhakar“ Polymers in Mucoadhesive Drug Delivery System: A Brief Note “esigned Monomers and polymers 12(2009),pg no 483-485. 7)Pharmainfonet.com Prof. G.S. Asane “Mucoahhesive anGI DDS ,Vol 5,issu 06,2007.

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38 Penetration Enhancer :- Reference :- “ Physical and chemical penetration enhancers in trancedermal drug delivery System ” By ;-Vineet Mathur ,Yasmini Satrawala ,et.al Asian Journal of pharmaceutics ,Vol-4,Issue 3 ,Jul-Sep 2010 ,Review Article.Page No ;-173-183

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39 39 Thank You

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