Mucoadhesive (Buccal) drug delivery system

A seminar on
Mucoadhesive (Buccal) drug delivery system
Presented by :
NIVEDITHA G
1st sem M.Pharm
dept of pharmaceutics
NARGUND COLLEGE OF PHARMACY

Contents:
 Buccal drug delivery systems
 Concepts
 Advantages and disadvantages
 Structure of oral mucosa
 Transmucosal permeability
 Mucosal membrane models
 Permeability enhancers
 In vitro and in vivo methods of buccal absorption.

History of Buccal Delivery
• Discovery - 1879
• US Reg 1982 - Isosorbide dinitrate
- Ergot alkaloids
- Nitroglycerine
- Nicotine
- Testosterone & derivatives
• 1993 - Fentanyl, “Actiq” (Anesta)
• Sept 2006 - Fentanyl, “Fentora” (CIMA)

Concept
► Within the oral mucosal cavity, the buccal
region offers an attractive route of administration for
systemic drug delivery.
► Within the oral mucosal cavity, delivery of drugs is
classified into three categories:
1) sublingual delivery
2) buccal delivery
3) local delivery

Why Oral?
Non - Oral
24% Oral
76%
Top 100 Drugs - U.S. Market Value

Technology and Product Focus
Drug Delivery Systems
Source: IMS America - Drug delivery based products
Oral CR
60%
Implant
10%
Inhalation
27%
Transdermal
8%
All Other
2%

► Adhesion :
the state in which two materials, at least one of which
being biological in nature, are held together for an extended
period of time, by interfacial forces.
► The biological surface can be epithelial tissue or it can be mucus
coat on the surface of tissue.
► If adhesive attachment is to a mucus coat, the phenomenon is
referred as mucoadhesion.
► Bioadhesion :
It is defined as ‘ a substance that is capable of
interacting with biological material & being retained on them or
holding them together for extended period of time’.

► The goal of the development of bioadhesive is to
improve biological adhesives, which are both durable
where required and degradable where necessary and
non toxic at all.
► Mucoadhesive drug delivery system utilize the property
of bioadhesion of certain water soluble polymer which
become adhesive on hydration and & hence can be used
for targeting a drug to a particular region of the body for
extended period of time.

► The mucosal layer lines a number of regions of the
body for attachment of any bioadhesive system
includes mainly,
 Buccal delivery system
 Sublingual delivery system
 Vaginal delivery system
 Rectal delivery system
 Nasal delivery system
 Ocular delivery system
 GIT delivery system

ADVANTAGES OF BDDS
1. BDDS especially for metabolically unstable drugs such as peptides.
2. The mucosa is well supplied with both vascular and lymphatic drainage
which gives :
1. Rapid onset of action
2. High blood levels
3. Excellent accessibility.
3. Because of its natural function, the buccal mucosa is less sensitive to
irritation & damage.
4. Provides an alternative to insufficient oral delivery & inconvenient
parenteral delivery of hydrophilic macromolecular drugs such as
peptides and proteins.
5. A number of small mol. wt.drugs including nitrates, morphine, fentanyl
& buprenorphine have permit through oral mucosa.

6 Ease of administration.
7 Permits localization of the drug for prolonged period of time.
8 Can be administered to unconscious patient.
9 Avoidance of first pass metabolism.
10 Reduction in dose with dose dependent side effect.
11 Selective use of therapeutic agents like peptides, proteins &
ionized species can be achieved.
12 Drugs unstable in GIT.
13 Patient compliance.

Limitations of BDDS
1. The major limitation to buccal delivery is low flux
through the tissue resulting in low bioavailability.
2. Small surface area & low tissue permeability.
3. Drugs which :
1. Irritate the mucosa
2. Have a bitter or unpleasant taste
3. Obnoxious odour.
Cannot be administered by this route.
4. Drugs unstable at buccal pH.

5 Small dose requirement.
6 Only drugs absorbed by passive diffusion can be
administered.
7 Eating & drinking becomes restricted.
8 Patient variability.
9 over hydration of polymer resulting in slippery surface.

Overview of the oral mucosa
► A. Structure :
► The oral mucosa is composed of an;
 outermost layer of stratified squamous epithelium
 Below this lies a basement membrane, a lamina propria.
 Followed by the submucosa as the innermost layer

Epithelium
Lamina Propria
Submucosa

STRUCTURE OF THE ORAL
MUCOSA:-

►Epithelium :
 The oral ep. Which measures about 100cm2 provides
a protective surface layer between the oral
environment and the dipper tissue.
 The thickness of oral ep. Which is partially keratinized
varies considerably between sites.
 Thickness of epithelium in different regions of oral
mucosa
Region Avg. Thickness um
Skin 100-120
Hard palate 250
Attached gingiva 200
Buccal mucosa 500-600
Floor of mouth 100-200

► An imp. feature of oral mucosa is the rapid turnover of
cells (3-8 days)
► It is divided in three functional zones :
1.Mucus secreting regions :- consisting of
soft palate
the floor of mouth
under surface of tongue
labial and
buccal mucosa
having non-keratinized epithelium.
2. Mastcatory mucosa :- consisting of
hard palate
gingiva
having keratinized mucosa

3. Specialized zones :-
borders of lip
dorsal surface of tongue
highly selective keratinization.
BIOCHEMICAL COMPOSITION
The composition of the epithelium also varies
depending on the site in the oral cavity.
► The mucosae of areas subject to mechanical stress (the
gingivae and hard palate) are keratinized similar to the
epidermis.
► The keratinized epithelia contain neutral lipids like
ceramides and acylceramides which have been associated
with the barrier function
► These epithelia are relatively impermeable to water.

► The mucosa of the soft palate, the sublingual, and the
buccal regions however, are not keratinized
► In contrast, non-keratinized epithelia, such as the floor of
the mouth and the buccal epithelia, do not contain
acylceramides and only have small amounts of ceramides
► They also contain small amounts of neutral but polar
lipids, mainly
 cholesterol sulfate and glucosyl ceramides
► These epithelia have been found to be considerably more
permeable to water than keratinized epithelia.

Basement membrane
► A continuous layer of extra cellular material,
forming a boundary between the basal layer of the
epithelium.
► It forms a barrier to the passage of cells across
the mucosa.
lamina propria
► Below the basement membrane lies a lamina
propria.
► A continuous sheet of connective tissue containing
collagen, elastic fibers and cellular components in
a hydrated ground substance.
► It also carries blood capillaries and nerve fibers.

► Basement membrane
The mucosa is the innermost layer of the colon. Major
components of the mucosa include a single layer of
epithelial cells, a layer of connective tissue (the lamina
propria), and a thin muscle layer (the lamina muscularis
mucosae).
The mucosa is lined with goblet cells, which are glands that
secrete mucus to help move material through the colon

Secretion of saliva
► The surface of mucus membrane is constantly washed by a
stream of about 0.5-2 L of saliva daily produced in salivary
glands i.e
► Parotid
► Sub maxillary
► Sublingual
Functions :
for drug dissolving &
for drug permeation.

Vascular system of oral mucosa
► The blood flow in various regions of oral mucosa :
Tissue Blood flow
ml/min/100cm2
Buccal 2.40
Sublingual 3.14
Floor of mouth 0.97
Ventral tongue 1.17
Gingiva 1.47
Palatal 0.89

Permeability of oral mucosae
► It incleudes mainly
► Regional differences in mucosal permeability
► Transport of material across oral mucosae
► Membrane storage during buccal absorption of drug
► Permeability barrier of the oral mucosae

Regional differences in mucosal permeability
► The permeability of the oral mucosae in general is
probably intermediate between that of epidermis
and that of intestinal mucosae.
► The permeability of buccal mucosae to be 4-4000
times greater than that of skin.
► Order of permeability : sublingual > buccal >
palatal.

Transport of material across oral mucosae
► The majority of drugs move across epithelial
membranes, including oral epithelia, by passive
mechanisms i.e. by laws of diffusion.
► In case of simple diffusion two potential routes of
material transport across the epithelium are
- Para cellular and
- transellular pathways.

TRANSMUCOSAL PERMEABILITY:-
Mechanism transmucosal
permeation:-
Majority of drugs move across
the oral epithelium by passive
diffusion.
In case of simple diffusion, two
potential routes of material
transport across the
epithelium are the –
1.Transcellular (lipoidal
pathway)-lipophilic drugs
2.Paracellular (Aqueous
pore pathway)-hydrophilic
drugs

► The Para cellular route involves the passage of molecules
through intercellular space while Tran cellular route involves
transport into and across cells.
► Substances with high lipid solubility traverse the oral mucosae
more easily by moving along or across the lipid rich plasma
membrane of the epithelial cells.
► While water soluble substances and ions probably move
through the intracellular spaces.

Mechanism and kinetics of transmucosal
permeation:-
Based on transmucosal permeation model, the
following equation has been developed to
describe the apparent permeability coefficient
Papp=1/(1/Pa)+[1/(Pp+Pl)]
where,
Pa, Pp, Pl are the permeability coefficient across
the aqueous diffusion layer,aqueous pore
pathway and the lipoidal pathway respectively.

Permeability barrier of the oral mucosa
► For the purpose of drug delivery, it is assumed that non-
keratinized lining mucosa are preferable to the keratinized
regions.
► Keratin layer is an effective barrier to penetration of human
skin by water soluble substances.
► The permeability barrier of oral mucosa is reside within the
superficial layers of the epithelium.

Keratin layer
•Profile of different tissue sites within the oral cavity
exposed to saliva including hard palate, alveolar ridge,
gingiva, and buccal mucosa

► Also some workers suggest that the basement
membrane is the functional permeation barrier of the
oral mucosa or that it represent at least degree of
resistance to permeates.
► The lamina propria is not generally thought to present a
barrier to permeation.
► Another barrier for large water soluble molecules in
both keratinized and non keratinized epithelia is
‘Membrane Coating Granules’(MCG).
► MCG are spherical or oval organelles, having 100-300
nm in diameter and are found in intermediate cell layers
of many stratified epithelia.

► MCG are involved in development of intracellular matrix (itself
or its released contents) which is responsible for permeability of
mucosa particular in Para cellular route.
► Other factors which may affect the permeability of molecule:
 Exogenous substances placed in mouth
► E.g.. Mouthwashes , toothpaste.

MUCOSAL MEMBRANE MODELS:
The fluid mosaic model was proposed by Singer and
Nicolson.
 Fluid mosaic model consists of Amphipathic globular integral
proteins that are embedded in the fluid state of lipid bilayer /
span throughout the entire thickness.
 These proteins have been hypothesized to minimize the free
energy required for the transmembrane permeation by
maximizing both the hydrophilic and lipophilic interactions in
the membrane.
 The ionic and polar portion of the protein molecule are remain
in contact with the aqueous environment on the membrane
surface and its relatively non-polar portion is interact with the
alkyl chain in the lipid bilayer.

Figure:-The fluid mosaic model was proposed by Singer and
Nicolson for the structure of epithelial membrane, which
consists of Amphipathic globular integral proteins:-
Amphipathic
globular integral
protein

Two thermodynamically favored structures
of the globular integral protein molecule:
Fig: Monodisperse structure
in which the hydrophilic
component (H) is
exposed to the aqueous
environment on the
surface of epithelial
membrane and the
lipophilic component (L)
is embedded in the lipid
bilayer.

Fig: Subunit aggregate
structure in which a
subunit aggregate of
two protein molecules
spanning through the
entire thickness of the
lipid bilayer to form an
aqueous solution filled
pore channel.

Strategy to increase penetration
► Success of all Tran mucosal systems depends on the ability
of drug to penetrate mucosa in sufficient quantities to
achieve its desired therapeutic effect.
► Attention is mainly focused on use of penetration enhancer
for enhancing the permeability of the oral mucosa.

PERMEABILITY ENHANCERS:
These are chemicals which disturb the membrane integrity,
affecting increased permeation of drug through buccal mucosa.
Permeability of buccal mucosa can be increased by various
penetration enhancers capable of -
► increasing cell membrane fluidity
► extracting the structural intercellular/intracellular lipids
► altering cellular proteins
► altering mucus structure and rheology
Examples:-
► Bile salts- sod.glycholate, sod.deoxycholate
► Fatty acids-lauric acid ,oleic acid.
► Sodium lauryl sulpfate,cetyl pyridinium
chloride,cyclodextrin,propylene glycol,sulfoxides

► The steady state flux of a lipophilic drug (T) across the transcellular route is given by-
JT = (1-M) DTKP .CD
hp
Where M=area fraction of transcellular route
DT= diffusion coefecient in the lipophilic phase
KP= partition coefficient between lipophilic & aqueous hydrophilic
donor phase
CD= conc. of drug in donor chamber
hp=length of the transcellular route
► The steady state flux of a hydrophilic drug (H) across the paracellular route is given
by-
JH = DPM. CD
hp
Where M=area fraction of transcellular route
Dp= diffusion coefecient in the lipophilic phase
CD= conc. of drug in donor chamber
hp=length of the transcellular route

Sources of Variability
1. Animals
2. Tissue thickness (connective tissue)
3. Excision method/ preparation
4. Storage conditions
5. Experimental temperature
Validate prep/ handling methods

Invitro and invivo methods of buccal absorption:
Invitro methods:

Invivo methods:
Perfusion cell :

► Other in vivo methods include those carried out using
► a small perfusion chamber attached to the upper lip of
anesthetized dogs .
► The perfusion chamber is attached to the tissue by
cyanoacrylate cement.
► The drug solution is circulated through the device for a
predetermined period of time and sample fractions are
then collected from the perfusion chamber (to determine the
amount of drug remaining in the chamber) and blood samples
are drawn after 0 and 30 minutes (to determine amount of drug
absorbed across the mucosa).

Absorption cell
► The simplest absorption cell is a rubber ‘O’ ring with internal
diameter 2.64 mm was fixed to the ventral surface of tongue of
adult male Sprague Dawley rats using a cynanoacrylate
adhesive.
► 10 ml of radiolabelled substance dissolved in a suitable buffer
was placed into the ring and absorption characteristics
determined by blood levels and test solution in ‘O’ ring.

► Buccal Absorption Test:
► Using this method, the kinetics of drug absorption were
measured.
► The methodology involves the :
► swirling of a 25 ml sample of the test solution for up to
15 minutes by human volunteers followed by the
expulsion of the solution.
► The amount of drug remaining in the expelled volume is
then determined in order to assess the amount of drug
absorbed.

►The drawbacks of this method include:
► salivary dilution of the drug,
►accidental swallowing of a portion of the
sample solution,
►and the inability to localize the drug solution
within a specific site (buccal, sublingual, or
gingival) of the oral cavity.

Present Landscape
“At least” 50 US Patents issued*
Generex - Insulin, “Ora-lyn”
- LMW Heparin
- Fentanyl
-Morphine
Novadel - Nitroglycerin
- Sumatriptan
- Zolpidem
- Ondansetron
*Drug Delivery to the Oral Cavity - T.K. Ghosh & W.R.
Pfister (eds.)

REFERENCES:
1. Novel drug delivery systems by Yie.W.Chien. pg:197-228.
2. Controlled and novel drug delivery by N.K.Jain. pg:52-74.
3. Advances in controlled and novel drug delivery by N.K.Jain.
pg:70-82.
4. Indian journal of pharmaceutical sciences.
5. www.google.com.
6. www.elsevier.com

Tablet Fabrication
Core tablet
Drug, Hakea, excipients
Coated tablet
Core tablet compression coated
- except one flat face
H.H. Alur, J.D. Beal, S.I. Pather,
A.K. Mitra and T.P. Johnston.
J. Pharm. Sci. 88 (1999) 1313-
1319.

►Salmon Calcitonin (sCT)
►• Responsible for lowering serum calcium
►• MW = 3432 Da
►• Used to treat Paget’s disease,
►hypercalcemia, and osteoporosis
►• Available as injection and nasal spray

► Cys-Ser-Asn-Leu-Ser-Thr-Cys-
► Val-Leu-Gly-Lys-Leu-Ser-Gln-
► Glu-Leu-His-Lys-Leu-Gln-Thr-
► Tyr-Pro-Arg-Thr-Asn-Thr-Gly-
► Ser-Gly-Thr-Pro-NH2
► 1 7
► STRUCTURE OF CALCITONIN
► (32 amino acid polypeptide with a disulfide bridge
► between cysteine residues 1 and 7).

► Bioadhesive Strength
► Rabbit intestinal mucosa
► Medium: 20 μl of distilled water (pH = 7.0)
► Chatillion LTC universal tension-compression stand
► with DFM-10 digital force gauge
► Force of compression: 5, 10, 15, and 20 N.
► Duration of application: 5, 10, 20, 30, 45, 60 and 90
► min.
► Applied to tablets containing 0, 12 or 32 mg Hakea

►In vitro sCT Release
►• Apparatus: Jacketed glass vessel
►• Medium: Deionized Water, 200 ml
►• pH: 7.0 ± 0.1
►• Temperature: 37° C
►• Analysis: Enzyme Immuno Assay (EIAH)
►after appropriate dilution.

►Animal Model
►New Zealand white Rabbits (2.7 ± 0.4 kg)
►Anesthesia - xylazine (1.9 mg/kg) and
►ketamine (9.3 mg /kg) (I.M.)
►Blood sampling - marginal ear vein

►In vivo sCT Study
►• Dose - 40 μg (200 I.U.)
►• Tablet moistened and compressed onto
►buccal area
►• sCT analysis - Enzyme Immuno Assay
(EIAH)
►• Calcium analysis - o-Cresolpthalein
►complexone method

►Enzyme Activity Studies
►• Mucosal enzymes degrade peptides
►• Rates of enzyme activity with and
►without Hakea studied
►• Evidence that Hakea inhibits enzymes

►Conclusions
►• Hakea is a promising additive
►– sustained-release
►– mucoadhesive properties
►– decreased rate of enzymatic degradation
►• Improved transbuccal delivery system

SEMINAR IN
ADVANCES IN DRUG DELIVERY
SYSTEMS
TOPIC -
MUCOADHESIVE DRUG DELIVERY
SYSTEM

Contents:
 Buccal drug delivery systems
 Concepts
 Advantages and disadvantages
 Structure of oral mucosa
 Transmucosal permeability
 Mucosal membrane models
 Permeability enhancers
 Invitro and invivo methods of buccal absorption

Drug delivery via the membranes of
the oral cavity can be sub
divided as follows:
1. Sublingual delivery.
2. Buccal delivery.
3. Local delivery.
AIMS AND OBJECTIVES:
► Improve patient compliance
► Avoid first pass metabolism
► Reduce side effects which
occur when given by other
routes.
► Reduce pulsed entry and
controls drug appearance in
plasma/systemic circulation.

BUCCAL DRUG DELIVERY SYSTEMS:
Definition:- These may be defined as the drug delivery systems
which when applied on intact mucous membrane of oral cavity,
the passage of drug occurs at a controlled rate into systemic
circulation.
Various buccal mucoadhesive dosage forms are -
► Buccal Tablets
► Buccal Patches
► Buccal Films
► Buccal Gels
► Buccal Ointments

Ideal characteristics of BDDS:
► should be adhesive enough to be retained on the buccal
mucosa for atleast upto 6hours.
► should be non irritant and non allergenic.
► Size of the patch may be 1-5cm2 but should be 1-3cm2 to be
comfortable to the patients .
► should restrict the rate of water ingress.

Components of BDDS:
► Drug
► Polymer
Drug properties:
► Conventional single dose of the drug should be low.
► Should not have bitter taste and obnoxious odour.
► Should be non allergenic and non irritant
► Should have low mol.wt
► Oral bioavailability should be less.
Polymer properties:
► Should have good bioadhesive property.
► Should be non allergenic and non irritant
► Should have high mol.wt.
► Should be compatible with the drug
► Should be stable and economic

Three different categories of polymers:
Bioadhesive polymer-
Egs: carbopol 934,HPMC,CMC,Sodium CMC, PVP,PVA,
chitosan, starch.
Rate controlling polymer-
Egs: ethyl cellulose and Eudragit.
Backing membrane polymer-
Egs: polyglassine and cellulose acetate.

Concept:
For systemic delivery ,the oral route has been the most
preferred route of administration. When administered
by oral route many drugs are subjected to extensive
presystemic elimination by gastrointestinal degradation
or hepatic metabolism.
Delivery of drugs via the absorptive mucosa in various,
easily accessible body cavities like the buccal, ocular,
nasal, rectal and vaginal mucosae has the advantage of
bypassing the hepato-gatrointestinal first pass
elimination.
With the development of mucosal drug delivery system
having controlled drug release characteristics, the
mucosal routes can be exploited for the noninvasive
systemic delivery of organic and peptide based drugs,
with rapid drug absorption and sustained action.

ADVANTAGES:
 Avoids first pass metabolism.
 Drugs degraded in GIT can be given by this route.
Eg: Insulin and other proteins.
 Fast onset of action.
 Permits localization of drug action.
 It is a passive system.
 Can be made unidirectional to ensure only buccal absorption.
 Can be removed in cases of emergency.
 Provides greater permeability.
 Bioavailability is increased and dosing frequency is reduced
 Dose is reduced.
 Reduces the side effects.
 Can be given to nauseating and unconscious patients.

 Oral mucosa is an robust membrane that is less prone
to irreversible damage caused by drugs and additives.
 Both hydrophilic and lipophilic drugs can be given.
Advantages of the oral cavity as a site for systemic drug
delivery are:-
► Sterilization is not required.
► Enzymatic degradation is relatively low.
► Oral cavity contains teeth upon which the DDS can
be physically attached using adhesives.
.

DISADVANTAGES:
 Drugs which undergo metabolism in oral cavity cannot be
given.
 Drugs which are bitter, obnoxious odour and irritant to the oral
mucosa cannot be given.
 Oral mucosa has small surface area for drug absorption
compared to GIT.
 Patient finds difficult to eat, drink or talk.
 Patient can swallow the dosage form accidentally.
 Only drugs with a dose less than 25mg can be given as BDDS.

Factors affecting buccal membrane absorption:
Membrane factors:-
► Degree of keratinisation
► Surface area available for absorption
► Salivary film coat on mucous membrane
► Intercellular lipids of the epithelium
► Basement membrane or lamina propria
► Absorptive membrane thickness
► Blood supply/ cell renewal/ enzyme content
Environmental factors:
► Saliva:-
thickness of salivary film- 0.07 - 0.10mm
► Salivary glands:-
pH= 6.2 - 7.4
► Movement of oral tissues

Mechanism and kinetics of transmucosal
permeation:-
Based on transmucosal permeation model, the following
equation has been developed to describe the apparent
permeability coefficient
Papp=1/(1/Pa)+[1/(Pp+Pl)]
where,
Pa, Pp, Pl are the permeability coefficient across the
aqueous diffusion layer,aqueous pore pathway and the
lipoidal pathway respectively.

MUCOSAL MEMBRANE MODELS:
The fluid mosaic model was proposed by Singer and
Nicolson.
 Fluid mosaic model consists of amphipathic globular
integral proteins that are embedded in the fluid state of
lipid bilayer / span throughout the entire thickness.
 These proteins have been hypothesized to minimize the
free energy required for the transmembrane permeation
by maximizing both the hydrophilic and lipophilic
interactions in the membrane.
 The ionic and polar portion of the protein molecule are
in contact with the aqueous environment on the
membrane surface and the non-polar portion of the
protein is towards the interior which interact with the
alkyl chain in the lipid bilayer.

Figure:-The fluid mosaic model was proposed by Singer and
Nicolson for the structure of epithelial membrane, which
consists of amphipathic globular integral proteins:-

PERMEABILITY ENHANCERS:
These are chemicals which disturb the membrane integrity,
affecting increased permeation of drug through buccal mucosa.
Permeability of buccal mucosa can be increased by various
penetration enhancers capable of -
► increasing cell membrane fluidity
► extracting the structural intercellular/intracellular lipids
► altering cellular proteins
► altering mucus structure and rheology
Examples:-
► Bile salts- sod.glycholate, sod.deoxycholate
► Fatty acids-lauric acid ,oleic acid, eicosapentaenoic acid
► Sodium lauryl sulpfate,cetyl pyridinium
chloride,cyclodextrin,propylene glycol,sulfoxides

THERAPEUTIC APPLICATIONS:-
 Angina – Organic and nitrate compounds
 Acute seizures; asthma & allergy
 Chronic severe pain
 Migraine; hypertension
 Smoking cessation; alcohol abuse
 Hormonal treatments
 Diabetes – Emerging indication for TM delivery
 TM delivery of traditional drugs; proteins, peptides, vaccines

REFERENCES:
1. Novel drug delivery systems by Yie.W.Chien.
pg:197-228
2. Controlled and novel drug delivery by N.K.Jain.
pg:52-74
3. Advances in controlled and novel drug delivery by
N.K.Jain. pg:70-82
4. Indian journal of pharmaceutical sciences
5. Indian drugs
6. www.google.com
7. www.elsevier.com

Mucoadhesive (Buccal) drug delivery system

Mucoadhesive (Buccal) drug delivery system

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