Introduction The Buccal mucosa lines the inner cheek Placed between the upper gingivae and cheek Treat local and systemic conditions An ideal dosage regimen in the drug therapy of any disease. 3
Mucoadhesion can also be explained on the basis of molecular interactions composed of attractive (Vander Waal’s, Hydrogen bonding) and repulsive (Electrostatic, steric)forces. Biological membrane- the membrane of internal tract e.g.-GIT, buccal cavity, eye, nose ,vagina ,rectum are covered with a thick gel like structure know as mucin All polymer bind to mucin 5
6 Impermeable membrane (1) Drug polymer layer (2) Mucoadhesive polymer layer (3) (1) (2) Mucous membrane saliva action Results in swelling (1) (2) (3) Mechanism of Absorption from a MucoadhesiveBuccal Drug Delivery System Drug release Attachment Internal jugular vein Bypasses first pass metabolism Systemic circulation Drug Release
Mechanism of bioadhesion The bioadhesion mainly depends upon nature of bioadhesive polymer . First stage involves an intimate contact between a bioadhesive & a membrane. Second stage involves penetration of the bioadhesive into tissue. Drug released. Bypasses first pass metabolism Enters systemic circulation. 7
Advantages 1.Termination of therapy is possible 2. Permits localization of drug to the oral cavity for extended period of time. 3. Ease of administration 4.Avoids first pass metabolism. 5.Reduction in dose can be achieved 6.Selective use of therapeutic agents like peptides, proteins and ionized species can be achieved. 8
9 7. Drugs which are unstable in acidic environment of stomach or destroyed by the alkaline environment of intestine can be given by this route 8. Administration of drugs with poor bioavailablity 9. It follows passive diffusion. 10. Dissolution of drug is easy unlike in case of rectal and transdermal route.
10 11.Administration of Drugs with short half life. 12. Prolongation of contact time with mucosa. 13.Flexibility in shifting the position of the drug in buccal cavity.
Disadvantages 11 1. Over hydration 2. Eating and drinking may become restricted 3. By mistake tablet can be swallowed 4. Saliva takes some drug into git 5.Only drug with small dose requirement can be administered. 6.Drug which irritate mucosa or have a bitter or unpleasant taste or an obnoxious odour cannot be administered by this route 7. Drugs which are unstable at buccal pH cannot be administered by this route. 8. Only those drugs which are absorbed by passive diffusion can be administered by this route
Anatomy & Physiology of Oral Mucosa The oral cavity is lined by thick dense & multilayered mucous membrane of highly vascularized nature. Drug penetrating into the membrane passes through net of capillaries & arteries and reaches the systemic circulation. There are mainly three functional zones of oral mucosa:- 12
Mucous secreting region
Oral mucosa mucous membranes / mucosae / singular mucosa :- That are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion . They line various body cavities that are exposed to the external environment and internal organs . It is at several places continuous with skin - at the nostrils , the lips , the ears , the genital area , and the anus . The sticky thick fluid secreted by the mucous membranesis termed mucus . 13
Structure of mucous membrane 14 a. Fibrous covering. b. Divided fibers of longitudinal muscular coat c. Transverse muscular fibers d. Submucous or areolar layer. e. Muscularis mucosae f. Mucous membrane, with vessels and part of a lymphoid nodule g. Stratified epithelial lining
The average thickness of various regions of the human oral mucosa Epithelium :-
Basement membrane :- Boundary between basal layer (epithelium) & connective tissue (lamina propria & submucosa)
Submucosa layer :-
Mucus : Secreted by goblet cells / special endocrine glands Connective tissue : Collagen, elastic fibers, cellular components. 15
Secretion of saliva 16 About 1.5 Liters of saliva is secreted daily Chief secretions by : Parotid, sub mandibular, sublingual glands Minor salivary glands are situated in buccal, palatal regions The presence of saliva is more important for:-
Drug permeation (across mucous membrane).
17 Function of oral mucosa Provide protection Acts as a barrier Provides adhesion Keep the mucosal membrane moist Regional Differences In Mucosal Permeability Permeability : Intermediate between epidermis & intestinal mucosa Permeability of oral mucosa : sublingual > buccal > palate Palate(keratinized), sublingual (thinner & immersed in saliva)
Transport of Material Across the Oral Mucosa (Transmucosal Permeability) Drugs may cross a cell membrane by Passive diffusion, Facilitated diffusion, Active transport Pinocytosis Factors To Be Considered In The Transmucosal Permeability Liphophilicity of drug Salivary secretion pH of saliva : Around 6 favour absorption Binding to oral mucosa Oral epithelium thickness 18
Routes of Drug Transport 19 CELL MEMBRANE Two routes of drug transport :- Paracellular Transcellular Paracellular Route :- Primary route for hydrophilic drugs Intercellular spaces is the preferred route Transcellular Route :- Route for lipophillic compounds Lipophillic drugs passes through lipid rich plasma membranes of the epithelial cells. TRANSCELLULAR PARACELLULAR
Ideal Candidates for Buccal Drug Delivery System Molecular size Molecular weight. Drug nature. BuccalpH. Taste Drug should be odourless. Drugs following passive diffusion be used. 10/28/2010 Department Of Pharmaceutics 20
The Fluid Mosaic Model is used to describe the interactions of lipids and proteins in biological membranes. Fluid mosaic model is two dimensional model, which depicts a biological membrane composed of a fluid state lipid bilayer embedded with globular integral proteins. The integral membrane protein may also exist as sub-unit aggregates, which span through entire thickness of the lipid bilayer to form a continuous water-filled channels.
Permeability Enhancers Definition : Substances added to pharmaceutical formulation in order to increase the membrane permeation rate or absorption rate of coadministered drug. E.g. :By using di- and tri-hydroxy bile salts, the permeability of buccal mucosa to fluorescein isothiocynate (FITC) increased by 100-200 fold compared to FITC alone. Applications -Bioavailability of drugs – 5% - 40% Limitations -Potential membrane damage. 10/28/2010 Department Of Pharmaceutics 23
BIOADHESIVE DDSFOR MUCOSAL DRUG DELIVERY
DESIGN OF BUCCAL DOSAGE FORM Matrix type: The Buccal patch designed in a matrix configuration contains drug, adhesive, and additives mixed together Bi-directional patches release drug in both the mucosa and the mouth Drug + Mucoadhesive Matrix …………………………………………………………………. ………………………………………………………………….
Contd… Reserviour type: The buccal patch designed in a reservoir system contains a cavity for the drug and additives separate from the adhesive Impermeable backing is applied to control the direction of drug delivery; to reduce patch deformation and disintegration while in the mouth; and to prevent drug loss Backing Layer MucoadhesiveMatrix+Drug ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
BuccalMucoadhesive Dosage Forms Three types based on their geometry
BUCCAL FORMULATION Buccal patches
laminates consisting of an impermeable backing layer, a drug-containing reservoir layer, a bioadhesive surface for mucosal attachment
similar to those used in transdermal drug delivery
Backing layer control the direction of drug release, prevent drug loss, minimize deformation and disintegration
Semisolid dosage forms, have the advantage of easy dispersion throughout the oral mucosa
may not be as accurate as from tablets, patches, or films
Poor retention of the gels at the site of application has been overcome by using bioadhesive formulations
REFERENCES Y.W. Chein , Novel Drug Delivery Systems, 2 nd edition, revised and expanded , Marcel Dekker , Inc. New York , 1992(pg. no. 195 – 224) N.K. Jain , Controlled and Novel drug delivery , CBS Publishers & Distributors, New Delhi, First edition 1997 (reprint in 2001) S.P. Vyas and R.K.Khar, Controlled Drug Delivery, CBS Publishers & Distributors, New Delhi, First edition 1997.pg no. 259- 260