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Ndds 5 MUCOADHESIVE DRUG DELIVERY SYSTEM ppt
This document provides an overview of mucoadhesive drug delivery systems (MDDS). It discusses the basics of MDDS, including how they interact with mucus and increase drug residence time. The key mechanisms of mucoadhesion - wetting, swelling, interpenetration and bond formation - are explained. Various mucoadhesive polymer types and factors affecting mucoadhesion are outlined. Different mucoadhesive dosage forms and evaluation methods are also summarized. As an example, the document briefly describes a study that developed Eudragit S100-coated chitosan microspheres to deliver mesalamine for the treatment of ulcerative colitis in a colon-specific manner.
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Ndds 5 MUCOADHESIVE DRUG DELIVERY SYSTEM ppt
- 1. Prepared By: Prof. SHASHANKCHAURASIYA Bansal College of Pharmacy, Bhopal Mucoadhesive drug delivery system 1
- 2. • • • • • • • • • • 2 Introduction Basics ,concepts &mucosal membrane. Need of mucoadhesive DDS Mechanism of mucoadhesion Theories mucoadhesion Sites of mucoadhesion Penetration enhancer Mucoadhesive polymer Factor affecting mucoadhesion Advantages & Disadvantages Mucoadhesive dosage form Evaluation
- 3. • Mucoadhesive drugdelivery 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. 3
- 4. • Since theearly 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. 4
- 5. - Inner layerscalled 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 5
- 6. What is mucus? 6 • 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% • • • • • • •
- 7. General structure ofmucous layer 7
- 8. Functions of mucus 8 •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.
- 9. Avoidance of First pass Metabo lism Better absorption ofpeptide by penetration enhancer Prolong residence time Localization of drug at given site WHY ? 9
- 10. Mechanisms of mucoadhesion 10 •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) • • •
- 11. Step-I • Wetting andswelling 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 • 11
- 12. Step-II • In thisstep 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 12
- 13. Step-III • This stepinvolves 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 • 13
- 14. • Electronic theory •Wetting theory • Adsorption theory • Diffusion theory • Fracture theory 14
- 15. 1) Electronic theory -Attractiveelectrostatic forcesbetween mucin network & the bioadhesive material. 15 glycoprotein 2) Wetting theory -Ability of bioadhesive polymers to spread & develop intimate contact with the mucous membrane. 3) Adsorption theory -Surface forces ( covalent bond, ionic bond, hydrogen bond & van der waals forces) resulting in chemical bonding
- 16. 4) Diffusion theory -Physicalentanglement of mucinstrands and flexible polymer chains. 5) Fracture theory -Analyses the maximum tensile stress develop during detachment of the BDDS from mucosal surfaces 16
- 17. Different routes oftargeting MDDS 17
- 18. Penetration enhancer • Substancesthat facilitate the permeation through referred as permeation enhancers . mucosa are • 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 , ,Sodium EDTA etc. • Propyleneglycol, Men 18
- 19. Mucoadhesuve polymers 19 • Theyare 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 strongnon-covalent bond with mucin epithelial cell surface • • • • • •
- 20. Natural and semisyntheticSynthetic Agarose Carbopol Chitosan PVA Gelatin PVP Pectin Thiolated polymer CMC Methacrylic acid Thiolated CMC Polycarbophil HPMC Hydroxypropylcellulose
- 21. Soluble Insoluble CMC, SodiumCMC, HPMC, MC, PVA, PVP, etc. Carbopol, Polyacrylicacid,PEG, etc C) According to charge Charged Aminodextran, Chitosan, Carbopol, SodiumAlginate, Pectin, SodiumCMC, etc. Uncharged Starch, PEG, PVA, PVP, etc. 21
- 22. Factors affecting mucoadhesion A)Polymerrelated 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 strength C) Physiological factors: • Mucinturn over Disease state•22
- 23. Advantages -Advantages over othercontrolled oral controlled release systems by 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 virtue of -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 23
- 24. Mucoadhesive dosage form Mucoadhes ive dosage form LiquidSuspensions Gel forming liquids Solid Tablets Matrix tablet Bioadhesive microparticles Bioadhesive inserts Semisolid Gels & ointment Films Patches 24
- 25. A) Matrix tablets-(a)Monolithic (b)twolayered tablets In 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. 25
- 26. C)Films-may be preferredover 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. Certainpolymer are used such as NaCMC, xanthan,carbopol,hyaluronic acid . They change from liquid to semisolid. HPMC has been used as an adhesive ointment ingredients. 26
- 27. METHODS OF EVALUATION A)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 27
- 28. Colon specific drugdelivery of mesalamine using eudragit S100-coated chitosan 28 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.
- 29.