Buccal drug delivery

Makwana Saroj V,
B.k.Mody Government Pharmacy College,
Rajkot.
Buccal drug delivery

Buccal drug delivery:
B.K.Mody Gov. Pharmacy college,Rajkot.
 Introduction
 Structure of oral mucosa
 Route of drug absorption
 Factors Influencing Drug Absorption from the Oral Cavity
 Advantages
 Disadvantages
 List of Drugs Delivered Via Buccal Route
 Approaches Of Buccal Drug Delivery
 Buccal bio adhesive dosage forms
 Basic components of buccal bio adhesive drug delivery system
 Classification of Buccal bio adhesive dosage forms
 Buccoadhesive under clinical trial/approved formulations
2
List of content :

Introduction:
Oral Solid Dosage Foam:
 Most conventional
 Cheaper dosage foam
Hindrance :
 First pass metabolism
 GI toxicity
 Stability problems within the GI environment
 Instability in gastric pH complexation with mucosal membrane
3

Introduction
 Within the oral mucosal cavity, delivery of drugs is classified
into three categories:
1. Sublingual Delivery, which is systemic delivery of drugs
through the mucosal membranes lining the floor of the
mouth,
2. Buccal Delivery, which is drug administration through the
mucosal membranes lining the cheeks (buccal mucosa),
3. Local Delivery, which is drug delivery into the oral cavity.
4

B.K.Mody Gov. Pharmacy college,Rajkot. 5

Buccal drug delivery
 Delivery of drug throw buccal mucosa of oral cavity is known
as Buccal drug delivery.
 Buccal administration involves placement of the drug between
the gums and the cheek.
 Medications available in the form of tablets, films, or sprays.
o Size: 1–3 cm2
o Daily dose: 25 mg or less.
o Maximal duration of buccal delivery :4–6 h.
6

Structure of oral mucosa:
7

Routes of Drug Absorption:

Factors Influencing Drug Absorption from the
Oral Cavity:
9
A
• Biological factors
B
• Physicochemical characteristics of
the drug
C
• Formulation factors

Biological Factors:
10
Permeability Blood flow
(2.4 ml/min/cm)
Thickness
(500-800μm) pH of
environment Saliva flow
rate

Drug Factors:
11
Drug
Solubility
Partition
coefficient
Ionization
Molecular
size

Formulation factors
12
Size and
shape
Properties
of excipient
Retentive
property
Texture
Release
characteris
tics

Advantages of Buccal Drug Delivery:
13
Sustained drug delivery
Excellent accessibility
High bioavailability
Low enzymatic activity
Significant reduction in dose related side effects.

Provides direct entry of drug into systemic circulation.
Offer passive system, which does not require activation.
Rapid cellular recovery following local stress or damage.
Drug degradation in harsh gastrointestinal environment can
be circumvented by administering the drug via buccal route.
14

15
Painless administration
Easy drug withdrawal
Facility to include permeation enhancer/enzyme
inhibitor or pH modifier in the formulation
The potential for delivery of peptide molecules
unsuitable for the oral route.

Eating and drinking are restricted
Barrier properties of the mucosa
Limited absorption area
Disadvantages of Buccal Drug Delivery
System
16
Drug swallowed with saliva is lost

List of Drugs Delivered Via Buccal Route
17
 Metronidazole
 Acyclovir
 Melatonin
 Morphine sulphate
 Carbamazepine
 Nalbuphine
 Cetyl Pyridinium chloride
 Nicotine
 Chlorhexidine diacetate
 Nifedipine
 Chitosan
 Omeprazole
 Chlorpheniramine maleate
 Pindolol
 Diclofenac sodium
 Piroxicam
 Diltiazem Hydrochloride
 Propranolol
 Ergotamine tartrate
 Propolis
 Fluride
 Recombinant human epidermal
growth factor (Rh EFG)
 Flurbiprofen
 Salmon calcitonin
 Glucagon-like peptide (GLP)-1
 Sodium fluoride

Structure and Design of Buccal Dosage Form:
 Matrix type: The buccal patch designed in a matrix
configuration contains drug, adhesive, and additives mixed
together.
 Reserviour type: The buccal patch designed in a reservoir
system contains a cavity for the drug and additives separate
from the adhesive.
 An 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.
18

19
MATRIXSYSTEM
RESERVOIRSYSTEM

Buccal Dosage Forms Design
20
 Type I (Multidirectional): This device has a single layer
with drug release multiple directions.
 Disadvantage: Significant drug loss due to swallowing.
 Type ІІ(Bi-layered): An impermeable backing layer
superimposed on top of the drug loaded bioadhesive layer,
creating a double-layered device and preventing drug loss
from the top surface of the dosage form into the oral cavity.

Buccal Dosage Forms Design
21
 Type ІІІ (Unidirectional):Drug loss is minimal,
• Drug is released only from the side adjacent to the buccal
mucosa.
• Can be achieved by coating every face of the dosage form,
except the one that is in contact with the buccal mucosa.

Cont...
22
 To achieve unidirectional release of drug, water
impermeable materials,
 Ethyl cellulose,
 Hydrogenated castor oil.
• Either by compression or by spray coating to coat every
face of the tablet except the one that is in contact with the
buccal mucosa.

Approaches Of Buccal Drug Delivery
1)Matrix Type.
-Conventional Buccal Tablets.
-Novel Buccal Adhesive Tablets.
2) Reserviour Type.
-Buccal Patches
3) Buccal Films.
4) Buccal Mucoadhesive Hydrogel.
5) Buccal Spray.
6) Fast Dissolving Buccal Tablets.
7) Buccal Wafers.
8) Buccal Microsphere.
23

Matrix Type:
1)CONVENTIONAL BUCCAL TABLETS
2)NOVEL BUCCAL ADHESIVE TABLETS
 Hydrophilic and Hydrophobic matrices have been used.
 For moderately water soluble drugs ,hydrophilic matrices of HPMC
are widely used to control release.
 Carbopol-934 used as a primary polymer (excellent mucoadhesive
property)
 Secondary polymers -HPMC, guar-gum
24

Different Matrix Tablets For Buccal Delivery.
25

Buccal Tablets:
 Methods of preparation:
 Direct compression
 Wet granulation technique
 For delivery of drug via buccal route, the tablets which are inserted into
the buccal pouch may dissolve or erode; therefore, they must be
formulated and compressed with sufficient pressure only to give a hard
tablet.
 Bilayered and multilayered tablets are already formulated using
bioadhesive polymers and excipients.
If necessary, the drug may be formulated in certain physical states, such
as microspheres, prior to direct compression in order to achieve some
desirable properties e.g. enhanced activity and prolonged drug release.B.K.Mody Gov. Pharmacy college,Rajkot.
26

Buccal Tablets:
27

Films:
 Product may look like contact lenses, where one side is
mucoadhesive and the film carries the drug inside.
 Film adheres strongly to the wet mucosal surface.
 Drug released over minutes to hours, for as long the film is
attached to the buccal tissue via Hydrogen bonding.
 Uni-directional drug-delivery into the systemic circulation,
unlike lollipops.
28

Films:
29

Films:
30
 May include:
 Non-eroding systems
 Rapidly Dissolving Film and Solid State Film
 Biodegradable Patches and Multilayer Patches
 Herbal trans mucosal patches

Lollipops:
 Offer multi-directional delivery.
 Used to provide well tolerated dosage forms
 Use:
 Pain relief(Actiq -Fentanyl Citrate)
 Anesthetic
 Smoking cessation aid,
 Nausea relief.
31

Lollipops:

Buccal Sprays:
 Offer a Metered dose that as an alternative to the
use of needles for injections.
33

Buccal Sprays:
34

Buccal Gel
 Hydrophilic matrices that are capable of swelling when
placed in aqueous media.
 Mechanism: Release the drug by swelling allowing drug
transport through the spaces in the polymer network,
 Polyacrylic-based hydrogels
 Commercially available device:
o OTS (oral transmucosal system, TheraTech), -glucagon-like
insulin tropic peptide.
o Chitosan glutamate buccal hydrogel with local anesthetic
activity.
35

Buccal gel
36

Buccal bio adhesive dosage forms
 Bio adhesion :
o Bio adhesion (and mucoadhesion) is the process whereby
synthetic and natural macromolecules adhere to mucosal
surfaces in the body.
o If the materials are then incorporated into pharmaceutical
formulations, drug absorption by mucosal cells may be
enhanced or the drug released at the site for an extended
period of time.
37

Mechanism of bio adhesion
38
1.Wetting and swelling of polymer to permit intimate contact with biological
tissue.
2.Interpenetration of bioadhesive polymer chain and entanglement of
polymer and mucin chains.
3.Formation of weak chemical bonds between entangled chains

Basic components of buccal bio adhesive drug
delivery system:
Drug
substance
Bioadhesive
polymers
Backing
membrane
Penetration
enhancers
Adhesives
39

Drug Substance
 Rapid release/prolonged release and for local/systemic effect.
 Characteristics :
• The conventional single dose of the drug should be small.
• Having biological half-life between 2-8 hours(controlled
drug delivery)
• Tmax of the drug shows wider-fluctuations or higher values
when given orally.
• The drug absorption should be passive when given orally.
40

Bioadhesive Polymers
 Polymers used in matrix devices in which the drug is embedded in
the polymer matrix, which controls the duration of release of drugs.
 Ideal Characteristics :
 Should be inert and compatible with the environment.
 Non-toxic absorbable from the Mucous layer.
 Site Specificity.
 Not decompose on storage.
 Easily available in the market.
 Economical.
41

Classification of bioadhesive polymer:
42
Criteria Categories Examples
Source Seminatural/
natural
Agarose, chitosan,gelatin,Hyalorunic acid,Various
gums(guar, hakea, xanthan, gellan,Carrageenan, pectin
and sodium alginate
Synthetic Cellulose Derivatives
CMC, thiolated CMC, sodium CMC, HEC, HPC, HPMC,
MC, methylhydroxyethylcellulose
Others
polyoxyethylene, PVA, PVP, thiolated polymers
Poly(acrylic acid)-based polymers
polyacrylates, poly(methylvinylether-comethacrylic
acid), poly(2-hydroxyethyl methacrylate),
poly(acrylic acidco- ethylhexylacrylate),
poly(methacrylate),poly(alkylcyanoacrylate),poly(isohex
ylcyanoacrylate)

43
Aqueous
Solubility
Water -soluble HEC, HPC, HPMC (cold
water), sodium
CMC, sodium alginate
Water insoluble Chitosan (soluble in dilute
aqueous acids), EC, PC
Charge Cationic Aminodextran, chitosan,
(DEAE)-dextran, TMC
Anionic Chitosan-EDTA, CMC,
pectin, PAA, sodium
alginate,sodium CMC,
xanthan gum
Non-ionic Hydroxyethyl starch,
HPC, poly(ethylene
oxide), scleroglucan

44Potential
Bioadhesive
forces
Covalent Cyanoacrylate
Hydrogen
bond
Acrylates [hydroxylated
methacrylate,
poly(methacrylic
acid)], CP, PC, PVA
Electrostatic
interaction
Chitosan
biological Biodegradable polymers A) Polyesters: Polylactic
acid, Polyglycolic acid,
Polyhydroxyl
butyrate,
Polycaprolactone, Poly
Doxanones
B) Polyanhydride:
Polyadipic
acid,Polyterphthalicacid,P
olysebacic acid and
Various copolymers

45
C) Polyamides: Poly
iminocarbonates, Poly
amino acids.
D) Phosphorous Based
polymers:
Polyphosphates,
Polyphosphonates,
Polyphosphazenes.
E) Others: Poly
cyanocrylates, Poly
urethanes, Poly ortho
esters,
Polyacetals.
II) Non biodegradable
polymers
A) Cellulose derivatives:
Carboxymethylcellulose,
Ethyl cellulose,
Cellulose acetate HPMC.
B) Silicones:
Polydimethyl siloxanes,
Collodial silica,
C) Others: PVP, EVA,
Poloxamines.

Backing membrane
 Major role in the attachment of bio adhesive devices to the
mucus membrane.
 Characteristics:
 Inert
 Impermeable to the drug
 Commonly used materials:
 Carbopol
 HPMC
 CMC
 Polycarbophil
46

Penetration enhancers
 Improve the release of the drug.
 They aid in the systemic delivery of the drug by allowing the
drug to penetrate more readily into the viable tissues.
 E.g. Lauric acid
 Lauric acid/propylene glycol
 Lysophosphatidylcholine
 Menthol
 Methoxysalicylate
 Methyl oleate
 Oleic acid
47

Bioadhesive
 Bioadhesive are the substances that are capable of interacting with the
biological material and being retained on them or holding them together
for extended period of time.
 It increases duration of contact of the drug with the absorbing membrane.
 Commonly used bio adhesive:
 Sodium alginate
 Carbomer
 HPMC
 Gelatin
48

Bioadhesive
Ideal
characteristics:
Not produce any residue on mucosa
layer.
Inert
Compatible with biological
environment.
Adhere to the mucus membrane
aggressively
Preferably form a strong non-covalent
bond with mucin/ epithelial cell
Surface.
49

Classification of Buccal bio adhesive dosage
forms
Buccal
Bioadhesive
solids
Buccal
Bioadhesive
semisolids
Buccal
Bioadhesive
patch and
films
Buccal
Bioadhesive
Powders
50

Buccal Bioadhesive solid dosage foam:
 Tablets: Buccal bio adhesive tablets are dry dosage forms
that are to be moistened prior to placing in contact with
buccal mucosa.
 Double and multi-layered tablets are already formulated
using bio adhesive polymers and excipients.
 Commercially available buccoadhcsive tablets:
 Buccastem
 Suscard buccaP
51

Muco adhesive Tablets
52

Microparticles:
53
 Bioadhesive microparticles offer the same advantages as
tablets but their physical properties enable them to make
intimate contact with a lager mucosal surface area.
 Can be delivered to less accessible sites including the GI
tract and upper nasal cavity.

Wafers:
 A conceptually novel periodontal drug delivery system.
 Intended for the treatment of microbial infections associated with
periodontitis.
 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.
54

Lozenges:
55
 Used for the delivery of drugs that act topically within the
mouth including :
 Antimicrobials ,
 Corticosteroids ,
 Local anaesthetics,
 Antibiotics ,
 Antifungals .

Buccal bioadhesive semisolid dosage forms:
 Buccal bio adhesive semisolid dosage forms consists of
finally powdered natural or synthetic polymer dispersed in
a polyethylene or in aqueous solution.
 Example: Arabase.
 Gels: Gel forming bioadhesive polymers include
crosslinked polyacrylic acid that has been used to adhere to
mucosal surfaces for extended periods of time and provide
controlled release of drugs.
56

Buccal bio adhesive patches and films:
 Consists of two ply laminates or multi-layered thin film round
or oval as consisting of basically of bio adhesive polymeric
layer and impermeable backing layer to provide unidirectional
flow of drug across buccal mucosa.
 Films are formulated by incorporating the drug in alcohol
solution of bio adhesive polymer.
 Flexible films may be used to deliver drugs directly to a
mucosal membrane.
 Provide a measured dose of drug to the site.
57

Buccal bio adhesive powder dosage forms:
 Buccal bio adhesive powder dosage forms are a mixture of
Bioadhesive polymers and the drug and are sprayed onto
the buccal mucosa the reduction in diastolic B.P after the
administration of buccal tablet and buccal film of
Nifedipine.
58

In Vitro/ Ex vivo methods In vivo method
 Tensile strength
 Shear strength
 Adhesion weight method
 Fluorescent probe
method
 Flow channel method
 Mechanical
spectroscopic method
 Iscometric method
 Electrical conductance
 Radioisotopes
 Gamma scintigraphy
 Pharmaco scintigraphy
 Electron paramagnetic
resonance
 Isolated loop technique
 X-ray
59
Evaluation of Buccoadhesive Dosage Form

Swelling index:
60
 Swelling of tablet excipients particles involves the
absorption of a liquid resulting in an increase in weight
and volume.
 Liquid uptake by the particle may be due to saturation of
capillary spaces within the particles or hydration of
macromolecule..
 The extent of swelling can be measured in terms of %
weight gain by the tablet.
 For each formulation batch one tablet was weighed and
placed in a Petri plate containing 25ml of 1.2 pH buffer
solution.

61
 After each interval the tablet was removed from
beaker, removes excess of buffer by using filter paper
and weighed again up to 12 hours.
 Swelling index was calculated by using the following
formula.
 Swelling index = (w2- w1)/ w1.

Methods determining tensile strength:
62
 Mucoadhesive force was than calculated according to
the following equation:
 Force of adhesion (N) =
[Mucoadhesive strength (g)] ×9.8
1000

Buccoadhesive under clinical trial/approved
formulations:
63

Buccal Delivery System Clinical Trials:
64
 SO-1105
 Generex Oral-Lyn

SO-1105
 On March 12, 2013, Sosei Group Corporation, a Japanese
biopharmaceutical company, announced that it had initiated a
phase III clinical trial for SO-1105.
 SO-1105 is an antifungal agent that is used to treat oropharyngeal
candidiasis.
 Administered as a mucoadhesive buccal tablet that could have the
potential to become the first long-acting (sustained release) tablet
for the treatment of oropharyngeal candidiasis in Japan.
65

66
 It was first developed in France (by Bio-Alliance Pharma)
and has since been authorized and registered in 24
European countries, South Korea, and the US (as
Loramyc/Oravig).
 SO-1105 is a once-daily mucoadhesive tablet and is
expected to improve patient compliance as well as their
overall quality of life.

Generex Oral-Lyn
 Needle less spray -delivers insulin through the buccal.
 Currently in phase III clinical trials within the United States,
but already approved in Ecuador.
 Spray produces a high-velocity fine-particle spray into the
mouth.
 Fine -particles can pass through the thin membrane in the
mouth and rapidly be absorbed into the bloodstream.
 Absorption requires the addition of a mixed micelle which
includes an absorption enhancer that surround insulin in a
capsule allowing it to cross the membrane.
67

68
 Within 10 minutes insulin is already within the peripheral
circulation.
 Delivering insulin as a spray can greatly increase patients'
compliance and allow better control of diabetes.

References :
 An Overview On Buccal Drug Delivery System, by Surender Verma,
Mahima Kaul, Aruna Rawat and Sapna Saini, IJPSR (2011), Vol. 2, Issue
6,page no.:1-19.
 A Review on Buccal Mucoadhesive Drug Delivery Systems, by Santanu
Roychowdhury, Rajesh Gupta, Sourav Saha ,Indo-Global Journal of
Pharmaceutical Sciences, 2011, Vol 1., Issue 3: Page No. 223-233.
 A Review on Buccal Drug Delivery System Nishan N. Bobade , Sandeep C.
Atram, Vikrant P. Wankhade, Dr. S.D. Pande, Dr. K.K. Tapa, International
Journal of Pharmacy and Pharmaceutical Science Research, 2013; 3(1)
page no-35-41,
69

References :
70
 An Overview on: Sublingual Route for Systemic Drug Delivery by,K. Patel
Nibha1 and SS. Panchol, International Journal of Research in
Pharmaceutical and Biomedical Sciences ,Vol. 3 (2) Apr – Jun2012,page
no-913-923
 Formulation And Evaluation Of Bioadhesive Buccal Tablets Of Simvastatin
B. Agaiah Goud, Kumara Swamy. S And Praveen Kumar. V,
JAPS/Vol.1/Issue 1/2011,page no-29-38.
 Buccal Drug Delivery: Past, Present and Future – A Review, by A.
Puratchikody, Prasanth V.V, Sam T. Mathew, Ashok Kumar B,
International Journal of Drug Delivery 3 (2011) page no-171-184.

References :
 A Review on study of Buccal Drug Delivery System,by Rajesh
Mujoriya, Innovative Systems Design and Engineering ,Vol 2, No
3,page no-1-14.
 Sublingual Mucosa As A Route For Systemic Drug Delivery,by
Neha Narang1, Jyoti Sharma, International Journal of Pharmacy
and Pharmaceutical Sciences,Vol 3, Suppl 2, 2011,page no-1-5.
 Buccal Mucosa As A Route For Systemic Drug Delivery: A Review,
by Amir H. Shojaei, J Pharm Pharmaceut Sci
(www.ualberta.ca/~csps) 1 (1):15-30, 1998,page no-15-31.
71

References :
 Recent Advances In Mucoadhesive Buccal Drug Delivery Systems And Its
Marketed Scope And Opportunities ,by K.P.Sampath Kumar
,DebjitBhowmik,AmitsankarDutta ,ShravanPaswan, Issue 1 : 2012,page no:79-
93.
 A review on bioadhesive buccal drug delivery systems: current status of
formulation and evaluation methods by Chinna Reddy P,Chaitanya
K.S.C.,Madhusudan Rao Y, DARU Journal of Pharmaceutical Sciences Vol. 19,
No. 6 2011,page no385-405.
 Sublingual Route For Systemic Drug Delivery Amit Kumar Bind,G. Gnanarajan
and Preeti Kothiyal, Int. J. Drug Res. Tech. 2013, Vol. 3 (2), page no-31-36.
72

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