This document provides an overview of buccal mucosa as a route for drug delivery. It discusses how buccal mucosa absorption was first noted in 1847 and was systematically studied in the 1930s-1970s. The buccal mucosa is an attractive delivery site due to its ease of administration and avoidance of first-pass metabolism. Drugs can permeate through either paracellular or transcellular pathways depending on their properties. In vitro and in vivo methods are used to assess buccal drug permeation and absorption. Several drugs have been delivered via buccal formulations including hormones, analgesics, antifungals, and others. Advantages include direct access to systemic circulation and low enzymatic activity

1. BUCCAL MUCOSA AS
ROUTE FOR DRUG
DELIVERY-A REVIEW
INDIAN DENTAL ACADEMY
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2. INTRODUCTION
 Absorption of drug via the mucous membranes
of the oral cavity was noted as early as 1847 by
Sobrero, who discovered Nitroglycerin.
 Systematic studies of oral cavity absorption
were first reported by Walton in 1935 and 1944.
 Reviews of the subject have been provided by
Katz and Barr in 1955,Gibaldi and Kanig in 1965
and Squier and Johnson in 1975.

3.  The oral cavity is an attractive site for drug
delivery due to ease of administration and
avoidance of possible drug degradation in
gastrointestinal tract and first-pass metabolism.
 Routes of Drug delivery via the oral mucous
membrane can be divided as follows:
(1) Sublingual mucosa
(2) Buccal mucosa

4. OVERVIEW OF BUCCAL MUCOSA

5. PERMEABILITY
 Epithelium thickness - 40-50 cell layers thick.
 Turnover time - 5-6 days.
 The permeability - 4-4000 times greater than
that of the skin.
 Main penetration barrier exists in the outermost
1/4th - 1/3rd of the epithelium.
 The permeabilities, thickness and degree of
keratinization of oral mucosae is in order of
sublingual › buccal › palatal.

6.  Permeability barrier in the oral mucosa is a
result of intercellular lipids derived from the so-
called ‘membrane coating granules’ (MCG).
 Loosely packed intercellular lipids and the
presence of large amounts of phospholipids in
non-keratinized, account for the overall higher
permeability.
 Ability of a molecule to permeate through the
mucosa can be related to molecular size, lipid
solubility, and ionization.

7. BUCCAL PERMEATION
PATHWAYS
 Two permeation pathways are depending on the
physicochemical properties of the diffusant.
 Paracellular - hydrophilic drugs
 Transcellular- lipophilic drugs
 The route that provides
The least amount of
hindrance to passage
predominates.

8. THE METHODS USED IN
ASSESSING BUCCAL DRUG
PERMEATION AND ABSORPTION
In Vitro-
 Animals are sacrificed immediately before the
start of an experiment. Buccal mucosa with
underlying connective tissue is surgically
removed from the oral cavity,& are isolated
separately and stored in ice-cold (4°C) buffers
usually Krebs buffer.

9.  Major concern here is about the maintenance of
the viability & integrity of the dissected tissue.
 Best method to assess tissue viability is the
actual permeation experiment itself.
 If the drug permeability does not change during
the time course of the study under the specific
conditions of pH & temperature, then the tissue
is considered viable.

10. In Vivo-
 Buccal absorption test was first originated by
Beckett and Triggs (1967) which measured the
kinetics of drug absorption.
 It 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.
 Amount of drug remaining in the expelled
volume is then determined to assess the
amount of drug absorbed.

11.  Other methods - carried out using a small
perfusion chamber attached to the upper lip of
anesthetized dogs by cyanoacrylate cement.
 Drug solution is circulated through the device for
a period of time and fractions are collected from
the chamber.
 Amount of drug remaining in the chamber is
determined and blood samples are drawn
immediately & then 30 minutes to determine
amount of drug absorbed across the mucosa.

12. ADVANTAGES
 Drugs gain direct access to systemic circulation
avoiding first pass metabolism & acidic digestive
fluids secreted by gastrointestinal tract.
 Buccal mucosa has an expanse of smooth
muscle & relatively immobile mucosa which
makes it a more desirable for retentive system.
 Buccal mucosa has low enzymatic activity &
drug inactivation is not as rapid and extensive.

13.  Application of the dosage form is painless,
precisely located and easily removable without
discomfort.
 Drug toxicity can be promptly terminated by
removal of dosage form.
 This route can be used for unconscious patients
& in patients who have undergone surgery or
have experienced upper GIT disease.

14. LIMITATIONS
 Surface area available for absorption in buccal
mucosa < Gastrointestinal, Nasal, Rectal and
Vaginal mucosae.
 Low flux which results in low drug bioavailability.
 Buccal mucosa is continuously bathed by
saliva- lowers drug concentration at absorbing
membranes.
 Involuntary swallowing of saliva containing
dissolved drug or swallowing the delivery
system itself would lead to a major loss of drug
from the site of absorption.

15.  Talking, eating and drinking affect the retention
of the delivery system.
 Risk of choking by the dislodged drug delivery
device.
 Taste, irritancy & allergies.
 Patient acceptance is may be an obstacle in
many cases, particularly for retentive delivery
systems.
 Difficulties in developing an appropriate dosage
form for buccal delivery.

16. BUCCAL FORMULATIONS
 Many dosage forms have been developed
including toothpastes, mouthwashes, lozenges,
gels, ointments, wafers, micro-particles,
chewing gums, lollipops, films, patches, tablets
and some specialized devices.

17. BUCCAL FORMULATIONS

19. DRUGS DOSAGE FORMS
A. NITRATES-NITROGLYCERINE
ISOSORBIDE DINITRATE
B. STEROIDS-TOPICAL
C. HORMONES- TESTOSTERONE
METHYL
TESTOSTERONE
ESTRADIOL
OXYTOCIN
INSULIN
TSH HORMONE
VASOPRESSIN
D.ANALGESICS-MORPHINE
PIROXICAM
FLURBIPROFEN
E.ANTIFUNGALS-NYSTATIN
AMPHOTERICIN B
CLOTRIMZOLE
F.CHLORHEXIDINE
TRANSMUCOSAL PATCHES.TABLETS
TABLETS
GEL FORM
MUCOADHESIVE PATCHES
TABLET
TABLET
TABLET
SUSPENSION
LOZENGES
MUCOADHESIVE PATCHES
MUCOADHESIVE PATCHES

20. DRUGS DOSAGE FORMS
G. ANXIOLYTIC-LORAZEPAM
H. SEDATIVES- MIDAZOLAM
TRIAZOLAM
ETOMIDATE
I. ERGOTAMINE
J. NICOTINE –SMOKING CESSATION
K. METRONIDAZOLE
L. ANTI-EMETIC-SCOPOLAMINE
PROCHLORPERAZINE
TABLET
TABLET
TABLET
CHEWING GUMS
MOUTH WASHES
TABLET

21. RECENT ADVANCES IN BUCCAL DRUG
DELIVERY
 To allow prolonged localized therapy and
enhanced systemic delivery.
 Buccal penetration enhancers are developed.
 Retentive systems are designed for sustained
delivery for number of hours, improves patient
compliance, favor a more intimate contact of the
drug with the absorption mucosa.
 Bioadhesive polymers used in buccal drug
delivery to retain a formulation.

22.  Newer second-generation bioadhesives have
been developed.
 Micro-encapsulation system is designed.
 Employment of Muco-Adhesive, Enzyme
Inhibitory and Penetration Enhancer
properties.
 The RapidMist drug delivery system places
human recombinant insulin in a liquid
formulation to be delivered to buccal mucosa
with an asthma-like device.

23.  INTELLI-DRUG SYSTEM
 Allows administration of drugs in a precise and
programmable manner without the need for
surgery by delivering directly
to the buccal mucosa.

24.  A new smart oral drug delivery device is the answer to
the problems of people who suffer from drug addiction
or long term diseases. It’s a non invasive drug delivery
tool.
 Device is placed in the mouth in a removable dental
appliance. It looks like a natural tooth and allows the
patient to speak and eat freely.
 Allows medicine to be released in a controlled manner
according to the patient's needs for as long as it is
necessary.

25. CONCLUSION
 Buccal cavity is found to be the most convenient
& easily accessible site for the delivery of
therapeutic agents.
 Local environment of the mucosa can be
controlled and manipulated to optimize the rate
of drug dissolution and permeation.
 Buccal drug delivery is a promising area for
continued research with the aim of systemic
delivery of orally inefficient drugs
 A feasible & attractive alternative for non-
invasive delivery of potent peptide and protein
drug molecules.

26. REFERENCES
 Harris D And Joseph .R . Robin Son; Drug Delivery via the Mucous Membranes of the Oral Cavity;
Journal Of Pharmaceutical Sciences January 1992 Volume 81, Number 1 .
 Smart J R; Expert opinion on drug delivery ;University of Brighton School of Pharmacy and
Biomolecular Sciences; May 2005, Vol. 2, No. 3, Pages 507-517
 Sworbrick J, Boylan J;Encyclopedia of pharmaceutical technology
 Drug Development And Industrial Pharmacy Vol. 29, No. 8, pp. 821–832, 2003
 Hao J and Paul W. S. Heng; Buccal Delivery Systems Department of Pharmacy, National University of
Singapore, Singapore.
 Washington N; Washington C; Clive G.W. Buccal drug delivery ; Physiological Pharmaceutics
 Shojaie A ; Buccal Mucosa As A Route For Systemic Drug Delivery: A Review; Journal of
Pharmaceutical science ; 15-30, 1998.
 Delivery of insulin to the buccal mucosa utilizing the RapidMist system ; Summary expert opinion on
drug delivery ;September 2008, Vol. 5, No. 9, Pages 1047-1055
 LTS - Transdermal Therapeutic Patches, Advanced Oral Wafer Medication and Estradiol Matrix HRT
Patches.
 Paracellular Drug Delivery Through Bakers Yeast Microcapsules; American Association of
Pharmaceutical Scientist.

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