SEMINAR ON
BUCCAL & SUBLINGUAL DRUG DELIVERY SYSTEM
Prepared by:Motivaras AshishM.Pharm II semRoll No: 05
Guided by:Dr. jaydeep Patel
B.K.MODY GOVT. PHARMACY COLLEGE,RAJKOT.
BSDDS
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CONTENT -
o INTRODUCTION
o WHY BUCCAL/SUBLINGUAL?
o ANATOMY OF BUCCAL MUCOSA
o TRANSPORT ROUTES
o BIOADHESION MECHANISMS
o BASIC COMPONENTS FOR BDDS
o FORMULATIONS
o EVALUATION
o RECENT INNOVATIONS
o REFERENCE
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INTRODUCTIONThe oral mucosa lines includes inner cheek, sublingual, gingival, palatal
Sublingual delivery: floor of the mouth
Buccal delivery: lining of the cheek
Local delivery:cavity, principally ulcers, fungal conditions and periodontal disease.
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Comparison with different part
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Why buccal/sublingual ?
To avoid first-pass metabolism
Protection from pH and digestive enzymes
Improved patient compliance
Rapid onset of action
Ease of drug administration
Rapid and extensive drug absorption
Easy termination of therapy
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ANATOMY OF BUCCAL MUCOSA
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TRANSPORT ROUTES
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BIOADHESION MECHANISMS
Diffusion Theory Entanglements of the polymer
Electronic Theory Attractive forces
Wetting Theory
Fracture Theory the force necessary to seaparate two surfaces
Adsorption Theory Secondary chemical bonds
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BASIC COMPONENTS FOR BDDS
Drug substance
Bioadhesive polymers
Backing membrane
Permeation enhancers
Other excipient
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Drug selection
dose of the drug should be small
half-life between 2-8 hours
exhibit first pass effect or presystemic drug elimination.
absorption should be passive when given orally
Nicotine
Nifedipine
Propranolol
Diclofenac sodium
Cyanocobalamin
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Bioadhesive polymers
must not decompose on storage
inert and compatible with the environment
polymer and its degradation products should be non-toxic absorbable from the mucous layer.
adhere quickly to moist tissue surface
1.Natural polymers
Ex.: Gelatin, sodium alginate.
2. Synthetic and semisynthetic polymers
Ex.: PVA, PEG, HPMC, PVP, Na-CMC etc
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Backing membrane
plays a major role in the attachment of bioadhesive devices to the mucus membrane
inert, and impermeable to the drug and penetration enhancer.
Eg.carbopol, magnesium stearate, HPMC, HPC, CMC, polycarbophil
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Permeation enhancers
Mechanism
Changing mucus rheology
Increasing the fluidity of lipid bilayer membrane
Acting on the components at tight junctions
Increasing the thermodynamic activity of drugs
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Types
1. Bile salts (Sodium glycocholate, sodium taurocholate)
2. Fatty acids(oleic acid, capric acid, lauric acid)
3. Surfactants
4. Chelators(EDTA, citric acid)
5. Others(aprotinin, hyaluronidases,neuraminidase)
6. Thiolated polymers (chitosan-cysteine, polycarbophil-cysteine)
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Factors affecting mucoadhesion
1)Polymer related factors:
Molecular weight: bioadhesive strength of a polymer increases with molecular weights above 100,000
Flexibility: substantial degree of flexibility in order to achieve the desired entanglement with the mucus
Hydrogen bonding capacity
Cross-linking density: increasing density of cross-linking, diffusion of water into the polymer net-work occurs at a lower rate which, causes an insufficient swelling of the polymer and a decreased rate of interpenetration between polymer and mucin
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Charge: Some generalizations about the charge of bioadhesive polymers have been made previously, where nonionic polymers appear to undergo a smaller degree o f adhesion compared to anionic polymers
Concentration
Hydration (swelling): Polymer swelling permits a mechanical entanglement by exposing the bioadhesive sites for hydrogen bonding and/or electrostatic interaction between the polymer and the mucous network
2)Environmental factors
Saliva
pH
Mucin turnover Rate
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BUCCAL & SUBLINGUAL FORMULATIONS
Buccal and Sublingual Tablets
Buccal and Sublingual Patches and Films
Buccal Semisolids (ointments and gels)
Buccal Powders
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Buccal & Sublingual Tablets
Fast-disintegrating sublingual tablets: (Sublingual) there is a need to formulate a dosage form which gives fast relief from angina & headache, while at the same minimising the first pass effect to improve its bioavailability. Fast disintegration sublingual tablet fullfil this criteria.
Bioadhesive Sublingual tablets:a risk that the patient will swallow part of the dose before the active substance has been released
Sublingual vitamin tablet
Lipid matrix sublingual tablet
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S-DBMP-T(slow dissolving buccal mucoadhesive plain tablet)
BCTS(buccal covered tablet system) Dosage forms are soften and lose its shape due to mouth movement, which hindered control of the disintegration of the tablet over long administration periods .
The improved technology involved covering the S-DBMP-T system with a polyethylene film that had a hole in it. We refer to this technology as the buccal covered-tablet system (BCTS ) and have demonstrated that this technology can prolong the duration of absorption of glyceryl trinitrate and isosorbide dinitrate.
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Buccal tablets are small, flat, and oval, with a diameter of approximately 5–8 mm.
Tablets are usually prepared by direct compression, but wet granulation techniques can also be used
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Evaluation of tablet Swelling study
Bioadhesion studies
In vitro residence time
In vitro surface pH studies
In vitro drug release studies
In vitro permeation studies
In vitro mucoadhesion strength
In vivo release studies
Ex vivo mucoadhesion time
Ex vivo mucoadhesion force
Ex vivo transmucosal permeation studies
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Bioadhesion studies
Swelling study
Percentage hydration = [(W2-W1)/ W1] ×100
Residence time (in vitro)
Modified
Disintigration
Apparatus
Glass slab
Buccal tissue
Tablet
Isotonic buffer
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Glass Beaker
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Release rate study(in vitro)
Composition of simulated saliva
KH2PO4 12mM
NaCl 40mM
CaCl2 1.5mM
NaOH To pH 6.2
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Marketed product Baccul Tablet
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Marketed product Sublingual Tablet
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Buccal and Sublingual Patches and Films
Matrix type
Reservoir type
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Design of Patches
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Thin film drug delivery
Thin film drug delivery is a process of delivering drugs to the systemic circulation via a thin film that dissolves when in contact with liquid, often referred to as a dissolving film or strip.
Thin film strips are typically designed for oral administration, with the user placing the strip on or under the tongue. As the strip dissolves, the drug can enter the blood stream enterically, or sublingually.
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Basic component
Drug
Polymers (Mucoadhesive polymers, polymers controlling rate of release and Polymers to prepare backing membrane)
Backing membrane
Plasticizer
Penetration enhancer
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Methods for patch preparation
Solvent casting method
Semisolid casting
Hot melt extrusion
Solid dispersion extrusion
Rolling method
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EVALUATION OF BUCCAL PATCHES
Physical properties
Physical appearance and surface texture of patch
Weight uniformity of patches
Thickness of patches
Folding endurance of patches
Swelling index of patches
Surface pH of patches
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CONT…
Mechanical properties
Bursting strength of patches
In vitro residence time of patches
Drug polymer interaction study of patches
Drug content uniformity of patches
In vitro drug release
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Marketed product of Patches & Films
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BUCCAL SEMISOLID DOSAGE FORMS
Gels are usually clear, transparent, semisolids containing solubilized active substances . e.g.Methylcellulose, carbopols, hydroxyethylcellulose etc
Glibenclamide gel
BUCCAL POWDER DOSAGE FORMS
Buccal bioadhesive powder dosage forms are a mixture of bioadhesive polymers and the drug and are sprayed onto the buccal mucosa. eg hydroxypropylcellulose and beclomethasone- diproprionate
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RECENT INNOVATIONS
BUCCAL WAFERS novel periodontal drug delivery system that is intended for the treatment of microbial infections associated with peridontitis. The delivery system is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers and matrix polymers.
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GEL FORMING LIQUIDS: This type of a formulation is liquid upon instillation and undergoes a phase transition to form a viscoelastic gel in response to stimulus such as temperature, ionic stength or pH. Carbomers become more viscous upon increased pH. Gellan gum and alginate both form gel in response to increased ionic strength (particularly with Ca+2 ions). Poloxamers and smart hydrogel are gel at approximately body temperature.
BIOADHESIVE SPRAY: Buccoadhesive sprays are gaining popularity over other dosage forms because of flexibility, comfort, high surface area availability of drug in solution form. Drugs genrally given by these routes are fentanyl, buprenorphine. Naloxone etc.
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Limitation of Buccal Drug Delivery System
flushing action of saliva
Taste, Irritancy and ‘mouth feel’ is an issue.
Allergic reactions, discoloration of teeth
Antimicrobial agents, affects the natural microbes
Patient cannot eat/drink/speak
Swallowing of saliva lead to the loss of drug
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Questions
Write about buccal & sublingual drug delivery systems. (DEC. 2010)
Explain the structure of buccal mucosa. Give a brief account of mucoadhesive polymers for buccal delivery. (JULY 2010)
Discuss the merits and demerits of mucoadhesive buccal drug delivery. How one can evaluate mucoadhesive buccal formulation? (JULY 2010)
Which are potential sites and dosage forms for bioadhesion? Draw a general schematic diagram for BDDS and classify them.
Write a note on exvivo and invivo methods to study BDDS system. (January 2011)
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Reference
Drug Delivery to the Oral Cavity,Drugs and The Pharmaceutical Sciences, Executive Editor James Swarbrick PharmaceuTech, Inc.Pinehurst, North Carolina
Enhancement in Drug DeliveryEdited by Elka Touitou Brian W. Barry, Page no: 173-215
Encyclopedia of PHARMACEUTICAL TECHNOLOGY, Third Edition, VOLUME 1, Page no:2664-2676
Marcel Dekker, Inc. Modified-Release Drug Delivery Technology, chapter no: 30
Patel V. F., Liu F., et al. (2011). "Advances in oral transmucosal drug delivery." Journal of Controlled Release 153: 106-116.
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Miller N., Chittchang M., et al. (2005). "The use of mucoadhesive polymers in buccal drug delivery." Advanced Drug Delivery Reviews 57: 1666– 1691.
Sudhakar Y., Kuotsu K., et al. (2006). "Buccal bioadhesive drug delivery — A promising option for orally less efficient drugs " Journal of Controlled Release 114: 15-40.
Pankil A. Gandhi,Dr. M.R.Patel, Dr. K.R. Patel, Dr. N. M. Patel , 2011, A REVIEW ARTICLE ON MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM IJPRD, 2011; Vol 3(5): July 2011 (159 - 173)
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http://www.novadel.com/pipeline/index.htm
http://www.medpharm.co.uk
http://www.biodeliverysciences.com/pipeline.php
http://www.generex.com/technology.php
http://www.snoreeze.com/the-snoreeze-range/snoreeze-oral-strips
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