Novel drug delivery system

1. BUCCAL DRUG DELIVERY
SYSTEM
PRESENTED BY :
Ms PRIYANKA DINKAR TAMBE.
F.Y.M.PHAM. (pharmaceutics) sem-1,2018-19
ROLL NO : PH 113
P.E.S.MODERN COLLEGE OF PHARMACY NIGADI
PUNE -44
GUIDED BY :
Mr U.C. GALGATTE

2. CONTENTS:
 Definition.
 Classification of drug delivery in the oral mucosal cavity.
 Anatomy of buccal cavity.
 Classification of oral mucosa.
 Permeability of drug through buccal mucosa.
 Penetration enhancers and their mechanism of action.
 Examples of Penetration enhancers.
 Barriers of buccal drug delivery system.
 Advantages
 Limitations.
 Selection of drug for buccal delivery

3. BUCCAL DRUG DELIVERY SYSTEM:
 In the oral cavity, buccal region deals with an
acceptable route of administration for local and
systemic drug delivery.
 Buccal cavity mucosa was the most convenient and
also easily approachable site for the purpose of
delivering the therapeutic agents.
 Mucosa has a rich supply so it is highly permeable.

4. CLASSIFICATION OF DRUG DELIVERY IN THE ORAL
MUCOSAL CAVITY
 The oral mucosal cavity , classification of drug delivery is as follows
1. Buccal delivery-
In the buccal drug delivery where administration of
drug is through the buccal mucosa.
2. Sublingual delivery-
In the sublingual drug delivery where administration
of drugs via the sublingual mucosa to the systemic circulation
3. Local delivery-
For the treatment of the conditions of the oral cavity ,
principally ulcers , fungal conditions and the periodontal disease.

5. Anatomy of Buccal Mucosa:-
Structure:-
Cross section area of buccal cavity

6. CLASSIFICATION OF ORAL MUCOSA:
The oral mucosa is divided as:-
1.Epithelium .
2.Basement membrane and connective tissue.
1.Epitheium:-
o The epithelium consists of approximately 40 - 50 layers of
strotified squamous epithelium having thickness of 500-800.
o The epithelium of the oral mucosa serves as a protective
covering for the tissues and a barrier to the entry of foreign
material.
o There are a number of layers that shows a sequence of
differentiation.

7. 2. Basement membrane and connective tissues:-
The basement membrane is a continuous layer of extra cellular
material and forms a boundary between the basal layer of epithelium and
the connective tissues.
This basal complex anchors the epithelium to the connective tissue
and supplements the barrier function of the superficial layer of the
epithelium to prevent some large molecules from passing the oral mucosa
The bulk of connective tissue consist of a collagen fibre network, the
organization of which determines mechanical stability , resistant to
deformation and extendibility of the tissue .
The uppermost layers from a surface that is resistant to physical insult and
penetration to the foreign substances.
o Membrane Coating Granules (MCG) are spherical or oval organelles MCGs
discharge there contents into intracellular space and thus form the permeability
barrier.
o Major MCGs lipid components are cholesterol, glycosphingolipids and
cholesterol esters.

8. PERMEABILITY OF DRUG THROUGH BUCCAL MUCOSA :
ROUTES OF ABSORPTION OF DRUG THORUGH THE ORAL
MUCOSA :
a : Para cellular b :Trans cellular

9. Buccal mucosa is a probable site for controlled delivery of
hydrophillic macromolecular agents such as oligonucleotides,
polysaccharides, peptids.
Drugs having high molecular weight and low permeability
leading to the low bioavailability. To overcome these problems ,
absorption enhancers can be required .
PERMEATION ENHANCERS:-
Agents that facilitate the permeation of drug
through the buccal mucosa are known as permeation enhancers
Selection of enhancers and its efficacy depends
on the physicochemical properties of the drug , nature of the vehicle , site
of administration and other excipients.
Partition coefficient is one of the most critical
factor in drug absorption. Drugs qualifyng different parameters to be
suitably delivered through buccal route except desired partition
coefficient need additionally for better penetration . Therefore penetration
enhancers enhancing drug penetration into buccal mucosa are
coadministred with drug.

10. Penetration enhancers may act in different way as their chemical nature.
At the same time , action of penetration enhancer is specific for different drug.
Penetration enhancer must be safe , non-toxic , therapeutically inert , non
allergenic and compatible with drug and excients.
MECHANISM OF ACTION OF PENETRATION ENHANCERS:-
1.Solubilisation of intercellular lipids and consequently enhancing drug transport
through Para cellular route.
2.Interaction with the lipidsprotein membrane resulting in increased membrane
fluidity and facilitating trans cellular transport.
3. Redution in the viscosity as well as elasticity of mucus layer by change in
mucus rheological properties .
4. Inhibition of the enzyme activity that protect certain drug molecules from
enzymatic degradation .

11. 3. Redution in the viscosity as well as elasticity of mucus layer by change in
mucus rheological properties .
4. Inhibition of the enzyme activity that protect certain drug molecules from
enzymatic degradation .

12. EXAMPLES OF PENETRATION ENHANCERS :-
CATEGORY PENETRATION
ENHANCERS
FATTY ACIDS SODIUM LAURATE,
SODIUM MYRISTATE,
OLEIC ACID .
CYCLO DEXTRINS METHYLATED-
CYCLODEXTRIN,
HYDROXYPROPYL-
CYCLODEXTRIN.
BILE SALTS SODIUM TAUROCHOLATE,
SODIUM DEOXYCHOLATE
CHELATORS EDTA, SALICYLATES,
SODIUM CITRATE
SURFACTANTS SODIUM LAURYL
SULPHATE, SUCROSE
LAURATE

13. BARRIERS OF BUCCAL DRUG DELIVERY SYSTEM:-
The barriers such as saliva mucus, membrane coating granules,
basement membrane , etc retards the rate and extent of drug absorption through
the buccal mucosa. The main penetration barrier exists in the outermost quarter
to one third of epithelium.
1.MEMBRANE COATING GRANULES:-
The permeability barrier property of the oral mucosa is
predominantly due to intercellular materials derived from the so-called membrane
coating granules(MCGS). MCGS are spherical or oval organelles that are 100-
300 nm in diameter and found in both keratinized and non-keratinized epithelium.
2.SALIVA:-
It moistens the mouth initiate digestion and protect teeth from
decay. It also controls bacterial flora of the oral cavity . Because saliva is high in
calcium phosphate ,it plays a role in mineralization of newteeth. It protects the
teeth by forming protective pellicle.
A constant flowing down of saliva within the oral cavity makes
it very difficult for drugs to be retained for sufficient period of time.
Permeability between different regions of oral cavity vary greatly
due to diverse structures and functions.

14. 3.BASEMENT MEMBRANE:-
Although the superficial layers of the oral epithelium represent the
primary barrier to the entry of the substances from the exterior, it represent the
primary barrier to the entry of substances from exterior .it evident that the
basement membrane also plays a role in limiting the passage of materials across
the junction between epithelium and connective tissue.
A similar mechanism appears to operate in the opposite direction.
The charge on the constituents of the basal lamina may limit the rate of
penetration of lipophilic compounds that can traverse the superficial epithelia
barrier relatively easily.
4. MUCUS:-
The epithelial cells of buccal mucosa are surrounded by the
intracellular ground substance called mucus with the thickness varies from 40 -
300 micrometer ,it serves as an a lubricant allowing cells to move relation to one
another and is believed to play a major role to adhesion of bioactive drug delivery
system.
The dense sugar coating of mucins given considerable water holding
capacity and also makes resistant to proteolysis, which may be important in
maintaining mucosal barriers.

15. ADVANTAGES:-
1.The buccal mucosa is a promising delivery route for drugs that need to
avoid the gastrointestinal gastric PH, intestinal enzymes or due to substantial
hepatic first pass effect.
2.The buccal cavity provides a highly vascular mucous membrane site
administration of drugs. And thickness in different areas gives rise to regional
variations in permeability to drugs.
3.Easy access to the membrane site so that the delivery system can be
applied localized and removed easily.
4.Improve the performance of many drugs, as they are having prolonged
contact time with the mucosa.
5.High patient acceptance as compared to the other non-oral routes of
administration of drugs .

16. 6. As a result of adhesion and intimate contact the formulation stays longer at
the delivery site , improving drug bioavailability using lower drug concentration
for disease treatment.
7.Presence of saliva helps in dissolution of drug.
8.It provides an alternative route for administration of several narcotic analgesics
, enzymes, hormones , cardiovascular agents ,steroids , etc .
9.Ability to withstand environmental extremes like change in PH, temperature
,etc.
10.Sustained drug delivery.
11.The potential for delivery of peptide molecules unsuitable for the oral route.

17. LIMITATIONS:
1. In the buccal membrane there is generally low permeability ,
specifically when compared to sublingual membrane.
2. Once placed at the absorption site, the dosage form should not be
disturbed.
3. Eating and drinking are restricted.
4. The secretion of the saliva is continuous, there is ever present
possibility that patient may swallow the formulation. Which may leads to loss of
suspended or dissolved drug
.
5. Drug swallowed with saliva is lost.
6. Drugs which are unstable at buccal PH and which irritate the mucosa or
have a bitter or unpleasant taste or an abnoxious odor can not be administered
by this route
.
7. It has a smaller surface area .Total surface area of membranes of the
oral cavity 170 cm2 denotes non –keratinized tissues ,including the buccal
membrane.

18. SELECTION OF DRUG FOR BUCCAL DELIVERY:
Physiochemical properties of drug :
1.Molecular size :
For hydrophilic substances the rate of absorption is a function of
molecular size .
Small molecules (<75-100Da) appear to cross the mucosa rapidly, but
permeability falls off rapidly as molecular size increases.
2.Lipid solubility:
For any series of un-ionizable compounds , their relative Permeabilities
are function of their oil water partition coefficient ,with the more lipid compounds
having higher permeability.
3.Ionization:
The degree of ionization of permeant is a function of both its Pka and
PH at mucosal surface. For many weak acids and weak bases ,only the
unionized form passes appreciable lipid solubility. The absorption of many
compounds has been shown to be maximal at which they are mostly unionized
tailing off as the degree of ionization increases.

19. TYPES OF BUCCAL DELIVERY FORMULATION:
Buccal delivey formulation
1.Solid buccal adhesive
dosage form
2.Semisolid buccal
dosage form
Liquid buccal
dosage form
They are formulations which
achieve bioadhesion via
dehydration of the local
mucosal surface.
They are prepared by
solvent casting, hot melt
extrusion
They are solution or
suspension of drugs

20. EXAMPLES
1.Solid buccal adhesive
dosage forms
2.Semisolid buccal
dosage forms
3.Liguid buccal
dosage forms
1.Buccal tablets
Example
Buprenorphine- HEMA polymer
tablet
2.Bioadhesive microparticles /
nanoparticles.
Example : Microparticles of
carbopol
3.Bioadhesive wafers
4. Bioadhesive Lozenges
1.Medicated Chewing
Gums.
Example: Caffeine
Chewing Gums
2.Adhesive gels.
Example: Cross linked
polymeric acid –drugs
with narrow therapeutic
window
3.Buccal Patches/ Film
Patches.
1. Buccal
Suspensions.
Example
Antibacterial mouth
washes
2.Buccal Solutions.
Example
Mouth freshener,
Artificial saliva
solution

21. REFERENCES:
 A book of Novel drug delivery system by Dr Dheeraj T. Baviskar & Dr
Dinesh K Jain Page No 5.1-5.3.
 A comprehensive review on buccal drug delivery system by R.
Jagadeshwar Reddy.
 International Journal of Drug Delivery -3 . A Review on Buccal Drug
Delivery Past Present and Future.
International Journal Of Research and development in pharmacy and life
science. Review article on Novel approaches –mucoadhesive buccal drug
delivery system.
The Pharma Innovation . A review article : Recent approaches in buccal
delivery system.