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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