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INTRODUCTION

The Buccal mucosa lines the inner cheek

Placed between the upper gingivae and cheek


Treat local and systemic conditions




Typically large, hydrophilic and unstable proteins, oligonucleotides
and polysaccharides
An ideal dosage regimen in the drug
therapy of any disease is the one, which
immediately attains the desired
therapeutic concentration of drug in
plasma (or at the site of action) and
maintains it constant for the entire
duration of treatment
ADVANTAGES
 Avoids first pass effect
 Abundance of blood vessel
 Less hostile environment than GIT
 Ease of administration and termination
 Fast cellular recovery
 Directly & easily modify microenvironment
 Lower intersubject variability as compared to
 transdermal patches
Contd…
 Permeability enhancers
 Rapid absorption possible & hence relatively
 rapid onset of action
 In comparison to TDDS, mucosal surfaces do
 not have a stratum corneum thus, the major
 barrier layer is absent
DISADVANTAGES
 Relatively small absorptive surface area (0.01 sq
 m vs 100 sq m for GIT)

 Movement affects mucoadhesive systems

 Less permeable than the small intestine

 Salivation and swallowing

 Taste of the drug
BUCCAL MUCOSA: ENVIRONMENT


The cells of the oral epithelia are surrounded by
an intercellular ground substance, mucus

The oral cavity is marked by the presence of
saliva produced by the salivary glands


Mucus which is secreted by the major and minor
salivary glands as part of saliva
Role of Saliva
• Continuous mineralization / demineralization of
  the tooth enamel
• Protective fluid for all tissues of the oral cavity
• To hydrate oral mucosal dosage forms

Role of Mucus
• Bioadhesion of mucoadhesive drug delivery
  systems
• Made up of proteins and carbohydrates
• Cell-cell adhesion
• Lubrication
DRUG DELIVERY PATHWAYS
Two possible routes of drug absorption through
 oral mucosa
BUCCAL DRUG DELIVERY AND
     MUCOADHESIVITY
Mucoadhesion of the device is a key element

The term ‘mucoadhesive’ is commonly used for
 materials that bind to the mucin layer of a
 biological membrane

Achieve systemic delivery of drugs include
 tablets, patches, tapes, films, semisolids and
 powders
BIOADHESIVE DDS
FOR MUCOSAL DRUG DELIVERY
MUCOADHESIVE POLYMERS
  GENERAL PHYSIOCHEMICAL FEATURES


Predominantly anionic hydrophilicity with numerous hydrogen
                      bond-forming groups

 Suitable surface property for wetting mucus/mucosal tissue
                           surfaces and


Sufficient flexibility to penetrate the mucus network or tissue
                               crevices
POLYMER
Carboxymethyl     Carbopol                 Polycarbophil
cellulose
Sodium Alginate   Hydroxyethyl cellulose   Hydroxypropyl
                                           methylcellulose

Chitosan          Gelatin                  Pectin
CONSIDERATION
The drug must resist, or be protected by salivary
 and tissue enzymes

The drug and adhesive materials must not
 damage the teeth, oral cavity

No keratinolysis, discoloration, and irritation
FACTORS AFFECTING DRUG
DELIVERY VIA BUCCAL ROUTE

 Hydrophilic macromolecules such as peptides,
 absorption enhancers have been used
 Smaller molecules greater transport
 No ionized forms have greater transport
 More lipid soluble higher its permeability
 More partition coefficient more permeability
 Lipid-soluble drug stores in Obese individuals
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
    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

                                          Drug + Mucoadhesive Matrix
BUCCAL MUCOADHESIVE DOSAGE FORMS

           Three types based on their geometry

       • single layer device with multidirectional release
Type-l • significant drug loss due to swallowing

        • impermeable backing layer is superimposed
Type-ll • preventing drug loss into the oral cavity

         • unidirectional release device, drug loss is minimal
Type-lll • achieved by coating every face except contact face
BUCCAL FORMULATION


Buccal tablets                          Buccal patches
• Most commonly investigated            • laminates consisting of an
  dosage form for Buccal drug             impermeable backing layer, a
• Tablets are small, flat, and oval,      drug-containing reservoir layer, a
  with a diameter of approximately        bioadhesive surface for mucosal
  5–8 mm                                  attachment
• Tablets can be applied to different   • similar to those used in
  sites in the oral cavity                transdermal drug delivery
• Drawback : lack of physical           • Backing layer control the
  flexibility, poor patient               direction of drug release, prevent
  compliance                              drug loss, minimize deformation
                                          and disintegration
Contd…


 Buccal films                           Buccal gels
 • Most recently developed dosage       • Semisolid dosage forms, have the
   form for Buccal administration         advantage of easy dispersion
 • Preferred over adhesive tablets in     throughout the oral mucosa
   terms of flexibility and comfort     • may not be as accurate as from
 • Flexible, elastic, and soft, yet       tablets, patches, or films
   adequately strong                    • Poor retention of the gels at the
 • Effective in oral disease              site of application has been
                                          overcome by using bioadhesive
                                          formulations
EXPERIMENTAL METHODOLOGY FOR
  BUCCAL PERMEATION STUDIES

             EVALUATION




  In vitro             In vivo
  Methods             Methods
IN VITRO EVALUATION


 Percentage increase in weight
 Swelling properties of films
 Shear stress method
 Folding endurance
 Diffusion study
 Thickness study
IN VIVO EVALUATION




1   2   3   4   5   Intelli Drug Device
ACTIVE INGREDIENTS DELIVERED
     VIA A BUCCAL ROUTE
   Insulin       nicotin      nifedipine       Flurbiprofen


  Acyclovir      pindolol      oxytocin      Diclofenac sodium


  Arecoline      Propolis    Omeprazole         Melatonin


Carbamazepine    Fluride       Danazol         Testosterone


Chlorhexidine   Metoprolol   Chlorhexidine   Morphine sulphate
  diacetate      tartrate      diacetate
RECENT & FUTURE OF BDDS
 Buccal nitroglycerin, can use for acute therapy for an
  anginal attack as well as for chronic prophylaxis

 Novel liquid aerosol formulation of insulin

 Development of suitable delivery devices, permeation
  enhancement, and Buccal delivery of drugs that
  undergo a first-pass effect, such as cardiovascular
  drugs, analgesics, and peptides
 Research yield some successes
 Promote further research; more companies
 Rest depend on delivery technology
CONCLUTION

Buccal drug delivery is a promising area
 for systemic delivery of orally inefficient
 drugs as well as an attractive alternative
 for noninvasive delivery of potent peptide
 and perhaps protein drug molecules
REFERENCES
 Michael J Rathbone, in: Oral Mucosal Drug Delivery
 M.S. Wani*, Dr. S.R. Parakh, Dr. M.H. Dehghan, S.A.
  Polshettiwar, V.V. Chopade, V.V. Pande, in: Current
  Status In Buccal Drug Delivery System: A review
 Amir H Shojaei, Faculty of Pharmacy and
  Pharmaceutical Sciences, University of Alberta,
  Edmonton, Alberta, Canada T6G 2N8, in: Buccal
  Mucosa As A Route For Systemic Drug Delivery: A
  Review
 Yie W. Chien, in: Novel Drug Delivery System
 Hitesh R. Patel*, Dr. M.M. Patel, in: Draw Attention
  Towards Mucoadhesive Buccal Drug Delivery System
 Bio-Images Research Ltd, in: Applications of gamma
  scintigraphy in oral drug delivery
Buccal drug delivery system

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Buccal drug delivery system

  • 1.
  • 2. INTRODUCTION The Buccal mucosa lines the inner cheek Placed between the upper gingivae and cheek Treat local and systemic conditions Typically large, hydrophilic and unstable proteins, oligonucleotides and polysaccharides
  • 3. An ideal dosage regimen in the drug therapy of any disease is the one, which immediately attains the desired therapeutic concentration of drug in plasma (or at the site of action) and maintains it constant for the entire duration of treatment
  • 4. ADVANTAGES  Avoids first pass effect  Abundance of blood vessel  Less hostile environment than GIT  Ease of administration and termination  Fast cellular recovery  Directly & easily modify microenvironment  Lower intersubject variability as compared to transdermal patches
  • 5. Contd…  Permeability enhancers  Rapid absorption possible & hence relatively rapid onset of action  In comparison to TDDS, mucosal surfaces do not have a stratum corneum thus, the major barrier layer is absent
  • 6. DISADVANTAGES  Relatively small absorptive surface area (0.01 sq m vs 100 sq m for GIT)  Movement affects mucoadhesive systems  Less permeable than the small intestine  Salivation and swallowing  Taste of the drug
  • 7. BUCCAL MUCOSA: ENVIRONMENT The cells of the oral epithelia are surrounded by an intercellular ground substance, mucus The oral cavity is marked by the presence of saliva produced by the salivary glands Mucus which is secreted by the major and minor salivary glands as part of saliva
  • 8. Role of Saliva • Continuous mineralization / demineralization of the tooth enamel • Protective fluid for all tissues of the oral cavity • To hydrate oral mucosal dosage forms Role of Mucus • Bioadhesion of mucoadhesive drug delivery systems • Made up of proteins and carbohydrates • Cell-cell adhesion • Lubrication
  • 9. DRUG DELIVERY PATHWAYS Two possible routes of drug absorption through oral mucosa
  • 10. BUCCAL DRUG DELIVERY AND MUCOADHESIVITY Mucoadhesion of the device is a key element The term ‘mucoadhesive’ is commonly used for materials that bind to the mucin layer of a biological membrane Achieve systemic delivery of drugs include tablets, patches, tapes, films, semisolids and powders
  • 11.
  • 13. MUCOADHESIVE POLYMERS GENERAL PHYSIOCHEMICAL FEATURES Predominantly anionic hydrophilicity with numerous hydrogen bond-forming groups Suitable surface property for wetting mucus/mucosal tissue surfaces and Sufficient flexibility to penetrate the mucus network or tissue crevices
  • 14. POLYMER Carboxymethyl Carbopol Polycarbophil cellulose Sodium Alginate Hydroxyethyl cellulose Hydroxypropyl methylcellulose Chitosan Gelatin Pectin
  • 15. CONSIDERATION The drug must resist, or be protected by salivary and tissue enzymes The drug and adhesive materials must not damage the teeth, oral cavity No keratinolysis, discoloration, and irritation
  • 16. FACTORS AFFECTING DRUG DELIVERY VIA BUCCAL ROUTE  Hydrophilic macromolecules such as peptides, absorption enhancers have been used  Smaller molecules greater transport  No ionized forms have greater transport  More lipid soluble higher its permeability  More partition coefficient more permeability  Lipid-soluble drug stores in Obese individuals
  • 17. 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
  • 18. 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 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Drug + Mucoadhesive Matrix
  • 19. BUCCAL MUCOADHESIVE DOSAGE FORMS Three types based on their geometry • single layer device with multidirectional release Type-l • significant drug loss due to swallowing • impermeable backing layer is superimposed Type-ll • preventing drug loss into the oral cavity • unidirectional release device, drug loss is minimal Type-lll • achieved by coating every face except contact face
  • 20.
  • 21. BUCCAL FORMULATION Buccal tablets Buccal patches • Most commonly investigated • laminates consisting of an dosage form for Buccal drug impermeable backing layer, a • Tablets are small, flat, and oval, drug-containing reservoir layer, a with a diameter of approximately bioadhesive surface for mucosal 5–8 mm attachment • Tablets can be applied to different • similar to those used in sites in the oral cavity transdermal drug delivery • Drawback : lack of physical • Backing layer control the flexibility, poor patient direction of drug release, prevent compliance drug loss, minimize deformation and disintegration
  • 22. Contd… Buccal films Buccal gels • Most recently developed dosage • Semisolid dosage forms, have the form for Buccal administration advantage of easy dispersion • Preferred over adhesive tablets in throughout the oral mucosa terms of flexibility and comfort • may not be as accurate as from • Flexible, elastic, and soft, yet tablets, patches, or films adequately strong • Poor retention of the gels at the • Effective in oral disease site of application has been overcome by using bioadhesive formulations
  • 23. EXPERIMENTAL METHODOLOGY FOR BUCCAL PERMEATION STUDIES EVALUATION In vitro In vivo Methods Methods
  • 24. IN VITRO EVALUATION  Percentage increase in weight  Swelling properties of films  Shear stress method  Folding endurance  Diffusion study  Thickness study
  • 25. IN VIVO EVALUATION 1 2 3 4 5 Intelli Drug Device
  • 26. ACTIVE INGREDIENTS DELIVERED VIA A BUCCAL ROUTE Insulin nicotin nifedipine Flurbiprofen Acyclovir pindolol oxytocin Diclofenac sodium Arecoline Propolis Omeprazole Melatonin Carbamazepine Fluride Danazol Testosterone Chlorhexidine Metoprolol Chlorhexidine Morphine sulphate diacetate tartrate diacetate
  • 27. RECENT & FUTURE OF BDDS  Buccal nitroglycerin, can use for acute therapy for an anginal attack as well as for chronic prophylaxis  Novel liquid aerosol formulation of insulin  Development of suitable delivery devices, permeation enhancement, and Buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides  Research yield some successes  Promote further research; more companies  Rest depend on delivery technology
  • 28. CONCLUTION Buccal drug delivery is a promising area for systemic delivery of orally inefficient drugs as well as an attractive alternative for noninvasive delivery of potent peptide and perhaps protein drug molecules
  • 29. REFERENCES  Michael J Rathbone, in: Oral Mucosal Drug Delivery  M.S. Wani*, Dr. S.R. Parakh, Dr. M.H. Dehghan, S.A. Polshettiwar, V.V. Chopade, V.V. Pande, in: Current Status In Buccal Drug Delivery System: A review  Amir H Shojaei, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8, in: Buccal Mucosa As A Route For Systemic Drug Delivery: A Review  Yie W. Chien, in: Novel Drug Delivery System  Hitesh R. Patel*, Dr. M.M. Patel, in: Draw Attention Towards Mucoadhesive Buccal Drug Delivery System  Bio-Images Research Ltd, in: Applications of gamma scintigraphy in oral drug delivery