This document provides an overview of mucoadhesive drug delivery systems. It defines mucoadhesion as the interaction between a mucin surface and a synthetic or natural polymer. Some key advantages of mucoadhesive drug delivery systems are that they allow for localized drug delivery, avoidance of first-pass metabolism, and potential dose reduction. The document discusses the anatomy and physiology of the oral mucosa in detail, including its structure, biochemical composition, blood flow, and factors that influence transmucosal permeability. It also provides a brief history of the development of mucoadhesive drug delivery.

1. Mucoadhesive Drug Delivery Systems
Dr. Sunil
Professor, HOD Pharmaceutics.
SVS Group of Institutions, School of
Pharmacy. Warangal. TS
1

2. CONTENTSCONTENTS
• Introduction
• Definition
• Concepts
• Advantages
• Disadvantages
• Structure of oral mucosa
• Trans mucosal permeability
• Mimosa membrane
• Permeablity enhancers
• In-vitro and in-vivo methods for buccal absorption
• Nasal and Pulmonary drug delivery system and its applications
2

3. INTRODUCTIONINTRODUCTION
• Noninvasive systemic administration .Placing a drug or drug
delivery system in a particular region of body for extended
period of time
• Local targeting / systemic drug delivery
• Recent approaches : Bioadhesive polymers
• Mucoadhesive dosage forms : Wet adhesives
• Mucoadhesion is defined as the interaction between a mucin
surface and a synthetic or natural polymer
3

4. BUCCAL CAVITY SITESBUCCAL CAVITY SITES
Sublingual / Buccal siteSublingual / Buccal site
DOSAGE FORMSDOSAGE FORMS TARGET SITESTARGET SITES
Adhesive tablets, gels, patches orAdhesive tablets, gels, patches or
ointments, sprays, lozenges, insert formointments, sprays, lozenges, insert form
Eye, GIT, cervix, vagina, oralEye, GIT, cervix, vagina, oral
cavity, nasal cavitycavity, nasal cavity
YEARYEAR SCIENTISTSCIENTIST STUDYSTUDY
18471847 SobreroSobrero
(Nitroglycerin)(Nitroglycerin)
Absorption of drugs via the mucousAbsorption of drugs via the mucous
membranes of the oral cavitymembranes of the oral cavity
1935/19441935/1944 WaltonWalton Systemic studies of oral cavitySystemic studies of oral cavity
absorptionabsorption
19551955 Kartz & BarrKartz & Barr Reviews of the systemic studies of oralReviews of the systemic studies of oral
cavity absorptioncavity absorption
19651965 GibaldiGibaldi
HISTORY
4

5. Concept of bioadhesion
• Bioadhesion is the state in which two materials, (at
least one of which is biological in nature), are held
together for a extended period of time by interfacial
forces.
• The term bioadhesion implies attachment of drug-
carrier system to specific biological location. This
biological surface can be epithelial tissue or the
mucous coat on the surface of tissue.
• If adhesive attachment is to mucous coat then
phenomenon is referred as mucoadhesion.
5

6. • These drug delivery system utilize property of
bioadhesion of certain water soluble polymers
which become adhesive on hydration and hence
can be used for targeting particular site.
• Definition:- Buccal delivery is the
administration of the drug via buccal mucosa
(lining of the cheek) to the systemic circulation.
6
Concept of bioadhesion

7. Advantages
• Ease of administration.
• Termination of therapy is possible.
• Permits localization of drug to the oral cavity
for extended period of time.
• Avoids first pass metabolism.
• Significant reduction in dose can be achieved,
thereby reducing dose dependent side effects.
7

8. • It allows local modification of tissue permeability,
inhibition of protease activity or reduction in
immunogenic response, thus selective use of
therapeutic agents like peptides proteins and ionized
species can be achieved.
• Drugs which are unstable in acidic environment of
stomach or destroyed by the alkaline environment of
intestine can be given by this route.
• Drugs which show poor bioavailability by oral route
can be administered by this route.
8
Advantages

9. • It follows passive diffusion, and does not require any
activation.
• The oral mucosa lacks prominent mucous secreting goblet
cells and therefore there is no problem of diffusion
limited mucous build up.
• The presence of saliva ensures large amount of water for
dissolution of drug unlike in case of rectal and
transdermal route.
• Drugs with short half life can be administered by this
method. (2-8 hrs)
Eg. Nitroglycerine ( 2 hrs)
Isosorbide mononitrate ( 2-5 hrs)
9
Advantages

10. • From the formulation point of view a thin mucin
film exist on the surface of oral cavity provides
opportunity to retain delivery system in contact
with mucosa for prolonged period of time with
the help of mucoadhesive compounds.
• The buccal membrane is sufficiently large to
allow delivery system to be placed at different
sites on the same membrane for different
occasions, if the drug or other excepients cause
reversible damage or irritate mucosa.
10
Advantages

11. DISADVANTAGESDISADVANTAGES
• Over hydration may lead to formation of slippery
surface & structural integrity of the formulation may
get disrupted by the swelling & hydration of the
bioadhesive polymer.
• Eating and drinking may become restricted
• There is possibility that Patient may swallow the tablet
• The drug contained in swallowed saliva follows the per
oral route & advantages of buccal route is lost.
• Only drug with small dose requirement can be
administered.
11

12. • Drug which irritate mucosa or have a bitter or
unpleasant taste or an obnoxious odour cannot be
administered by this route
• Drugs which are unstable at buccal pH cannot be
administered by this route.
• Only those drugs which are absorbed by passive
diffusion can be administered by this route
12
DISADVANTAGESDISADVANTAGES

13. HUMAN MUCOSAEHUMAN MUCOSAE
Physiological characteristic:-
Human nasal mucosa :- Ciliated
columnar epithelium and squamous
cutaneous epithelium
Human rectal mucosa :- Epithelium,
lamina propria, double layer musclaris
mocasae
 Human vaginal mucosa :- Epithelium,
lamina propria, tunica propria, muscularis
mucosae, outer fibrous layer
13

14. 14

15. ANATOMY & PHYSIOLOGY OF ORAL MUCOSAANATOMY & PHYSIOLOGY OF ORAL MUCOSA
The oral cavity is lined by thick dense & multilayered
mucous membrane of highly vascularized nature. Drug
penetrating into the membrane passes through net of
capillaries & arteries and reaches the systemic
circulation.
There are mainly three functional zones of oral
mucosa:-
Masticatory mucosa :- Covers gingiva/ hard palate
regions, keratinized epithelium
Mucous secreting region :- Consist of soft palate, floor
of mouth underside of tongue, labial & buccal mucosa. this
region shows non-keratinized mucosa.
Specialized mucosa :- consist of lip border & dorsal
surface of tongue with high selective keratinization
15

16. ORAL MUCOSAORAL MUCOSA
The oral mucosa consists of :-
 Stratified squamous epithelium
 Basement membrane
 Lamina propria and submucosa
 Epithelium :-Epithelium :-
• Measure 100 cm2
• Protective surface layer
• Protective to deeper tissues
Important feature of oral mucosa is
rapid turnover of the cells(3 – 8 days)
16

17.  Basement membraneBasement membrane :-:- Boundary between basal layer (epithelium) &
connective tissue (lamina propria & submucosa)
 Submucosa layer :-Submucosa layer :-
• Adhesive interface
• Mucus : Secreted by goblet cells / special endocrine glands
• Connective tissue : Collagen, elastic fibers, cellular components.
RegionRegion Average epithelial thicknessAverage epithelial thickness
Skin (mammary region)Skin (mammary region) 100 - 120100 - 120
Hard palateHard palate 250250
Buccal mucosaBuccal mucosa 500 – 600500 – 600
Floor of mouthFloor of mouth 100 - 200100 - 200
17
The average thickness of various regions of theThe average thickness of various regions of the
human oral mucosa Epitheliumhuman oral mucosa Epithelium

18. BIOCHEMICAL COMPOSITIONBIOCHEMICAL COMPOSITION
Protein :- Tonofilament (Keratinized & non – keratinised
epithelia)
Little known about lipid composition
Keratinized oral epithelium :- Neutral lipids (ceramides)
Non – keratinized epithelium :- Few neutral but polar lipids
(cholesterol sulphate & glucosylceramides)
Oral epithelial cell :- Carbohydrate , protein complexes
Role of matrix :- Cell – cell adhesion, lubricant allowing cells
to move relative to one another
18

19. • About 1.5 Liters of saliva is secreted daily
• Chief secretions by : Parotid, sub maxillary,
sublingual glands
• Minor salivary glands are situated in buccal, palatal
regions
The presence of saliva is more important for:-
Drug dissolution
Drug permeation (across mucous membrane).
19
SECRETION OF SALIVASECRETION OF SALIVA

20. VASCULAR SYSTEM OFVASCULAR SYSTEM OF
THE ORAL MUCOSATHE ORAL MUCOSA
• Vascular system have been
described by Stablein & Meyer
(1984)
• Mucous membrane of buccal
cavity is highly vascular
• Blood supply to mouth : External
carotid artery
TISSUETISSUE BLOODBLOOD
FLOWFLOW
Ml/min/100 cmMl/min/100 cm22
BuccalBuccal 2.402.40
SublingualSublingual 3.143.14
Floor of mouthFloor of mouth 0.970.97
Ventral tongueVentral tongue 1.171.17
FrenulumFrenulum 1.001.00
Gingival(+)Gingival(+) 1.471.47
Palatal (-)Palatal (-) 0.890.89
Table:- Blood flow in the various regions
of the oral mucosa
Maxillary artery
(Cheek, hard palate)
Lingual artery
(Tongue, gingiva,
Mouth floor)
Facial artery
(Lips, soft palate)
20

21. Function of oral mucosa.Function of oral mucosa.
• Provide protection
• Acts as a barrier
• Provides adhesion
• Keep the mucosal membrane moist
REGIONAL DIFFERENCES IN MUCOSALREGIONAL DIFFERENCES IN MUCOSAL
PERMEABILITYPERMEABILITY
 Permeability : Intermediate between epidermis & intestinal
mucosa
 Galey (1976) estimated permeability of oral mucosa :
sublingual > buccal > palatal
 Pimlott & Addy (1985) measured the site dependent absorption
of Isosorbide dinitrate tablets (Buccal, palatal, sublingual)
 Palatal(keratnized), sublingual(thinner & immersed in saliva)
21

22. TRANSPORT OF MATERIALTRANSPORT OF MATERIAL
ACROSS THE ORAL MUCOSAACROSS THE ORAL MUCOSA
(TRASMUCOSAL PERMEABILITY)(TRASMUCOSAL PERMEABILITY)
• Passive mechanism
• Intercellular spaces & cytoplasm (permeability barriers)
• Cell membrane ( liphophillic )
FACTORS TO BE CONSIDERED IN THEFACTORS TO BE CONSIDERED IN THE
TRANSMUCOSAL PERMEABILITYTRANSMUCOSAL PERMEABILITY
 Liphophilicity of drug
 Salivary secretion
 pH of saliva : Around 6 favours absorption
 Binding to oral mucosa
 Oral epithelium thickness
There are two routes of drug transport :-
 Paracellular
 Transcellular
22

23. PARACELLULAR ROUTE :-PARACELLULAR ROUTE :-
 Primary route for hydrophilic drugs
 Intercellular spaces is the preferred route
 Disadvantage : Limited surface area
TRANSCELLULAR ROUTE :-TRANSCELLULAR ROUTE :-
 Route for lipophiollic compounds
 Lipophillic drugs passes through lipid
rich plasma membranes of the
epithelial cells.
MEMBRANE STORAGE DURING BUCCAL ABSORPTIONMEMBRANE STORAGE DURING BUCCAL ABSORPTION
Solid drug powder/
tablet
Dissolved drug
In buccal fluids
Drug removed from oral by
swallowing
Dissolved drug
In buccal membrane
Drug in lymphatic
circulation
Drug in blood
circulation
23

24. The bioadhesion is mainly depends upon nature of
bioadhesive.
First stage involves an intimate contact between a
bioadhesive & a membrane.
second stage involves penetration of the bioadhesive
into tissue.
At physiological pH the mucous network may carry
negative charge because of presence of sialic acid &
sulfate residue & this high charge density due to
negative charge contributes significantly to bioadhesion
24
Mechanism of bioadhesion

25. MECHANISM OF ABSORPTION FROM A MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMMECHANISM OF ABSORPTION FROM A MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM
AttachmentAttachment
Bypasses firstBypasses first
pass metabolismpass metabolism
DRUG RELEASEDRUG RELEASE
Impermeable membrane (1)
Drug polymer layer (2)
Mucoadhesive polymer layer (3)
(1)
(2)
Mucous membrane saliva action
Results in swelling
(1)
(2)
(3)
Internal jugular vein
Systemic circulation
25

26. IDEAL CANDIDATES FORIDEAL CANDIDATES FOR
BUCCAL DRUG DELIVERY SYSTEMSBUCCAL DRUG DELIVERY SYSTEMS
o Molecular size 75 – 100 Daltons
o Molecular weight 200 – 500
o Drugs should be hydrophilic / lipophilic in nature
o Drug should be stable at buccal pH ( 6.4 – 7.2 )
o Drug should be odourless
o Drugs which are absorbed only by passive diffusion should be used
TYPES OF BUCCAL DRUG DELIVERY SYSTEMS
Buccal drug delivery
systems
Buccal tablets
(a) Molded tablets
(b) Compressed tablets
Buccal adhesive tablets
Buccal patch /
Buccal gels
26

27. It has been generally accepted that the biological
membrane can be represented by the Fluid mosaic
model. This model is proposed by Singer &
Nicolson.
Fluid mosaic model is two dimentional model,
which depicts a biological membrane composed of a
fluid state lipid bilayer embeded with globular
integral proteins.
The integral proteins are either embedded in a
portion of lipoidal membrane or spanning
throughout its entire thickness.
27
Mimosa membrane

28. The amphipathic protein molecules have been
hypothesized to minimize the free energy required
to for transmembrane permeation by maximizing
both hydrophilic & lipophilic interaction in the
membrane.
it is visualized that ionic & polar portion
of the protein molecule remain in contact with the
aqueous environment on the membrane surface
relatively nonpolar portions interact with the alkyl
chains in the lipid bilayer
28
Mimosa membrane

29. The integral membrane protein may also exist as
sub-unit aggregates, which span through entire
thickness of the lipid bilayer to form a
continuous water-filled channels.
Thus the mucosa as a biological membrane may
be considered as composed of lipid rich regions
interrupted aqueous channel pores form by
subunit aggregates of membrane proteins.
29
Mimosa membrane

30. Fluid mosaic model
30

31. 31
Fluid mosaic model

32. FUTURE SCOPE
• Management of illness
• Peptide based pharmaceuticals
• Among the non – oral routes available, i.e. the nasal,
intraoral , vaginal & rectal. Major interested route is
nasal mucosa (superior permeability)
• Peptides drugs ( insulin, oxytocin, protirelin, a
vasopressin analog) can effectively permeate the
buccal mucosa
32

33. FUTURE SCOPE
Various strategies are are being employed to achieve
oral absorption of
Peptides:-
 Manipulation of formulation
 Maximizing retention of the delivery system
 Alteration of peptide
 Chemical & metabolic stability
 Maintain balance between lipophilicity & hydrogen
bonding potential
33

34. CONCLUSION
The buccal cavity provides a highly vascular mucous membrane
site for administration of drugs.
The main advantages of the buccal route of administration over
the traditional routes are that drug degradation in the stomach is
avoided, first pass metabolism is avoided & therapeutic drug
levels of drug can be achieved rapidly
34

35. Permeability Enhancers
• These are the Substances added to pharmaceutical
formulation in order to increase the membrane
permeation rate or absorption rate of co-
administered drug.
• Categories of membrane permeation enhancers:-
A. Bile salts and there steroidal detergents-
Sodium glycolate, sodium taurocholate, saponins,
etc.
35

36. B. Surfactants:-
i. Nonionic - Polysorbate 80,sucrose ester, etc.
ii. Cationic - Cetyltrimethyl ammonium
bromide.
iii. Anionic - Sodium laurylsulfate,fatty acids.
C. Other enhancers:-
i. Azone, salisylates, chelating agents,
sulfoxides.
36
Permeability Enhancers

37. Drug Enhancer Result
Insulin Glycocholate Absorption only in
presence of
enhancers
Calcitonin Saponins, Bile
Salts, fatty acids,
SLS
Increase
pharmacological
effect
Propranolol Methanol, lauric
acid
Increases the
permeation
Example of permeability enhancers
37

38. In Vitro Methods For Buccal
Absorption
• Animals are sacrificed immediately before the
start of an experiment.
• Buccal mucosa with underlying connective
tissue is surgically removed from the oral
cavity, the connective tissue is then carefully
removed and the buccal mucosal membrane is
isolated.
38

39. • The membranes are then placed and stored in ice-cold
(4°
c) buffers (usually Krebs buffer) until mounted
between side-by-side diffusion cells for the in vitro
permeation experiments.
• Preservation of dissected tissue is important, which
will directly affect the results and conclusion of the
studies.
39
In Vitro Methods For Buccal
Absorption

40. In Vivo Methods for Buccal
Absorption
• In vivo methods were first originated by Beckett
and Triggs with the so-called buccal absorption
test.
• Using this method, the kinetics of drug
absorption were measured.
40

41. • 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.
41
In Vivo Methods for Buccal
Absorption

42. • It 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.
42
Other in vivo methods

43. • The drug solution is circulated through the device for a
predetermined period of time.
• 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.
43
Other in vivo methods

44. • In-vivo method involve use of animals like
dog, cat, rabbit, hamster to determine the oral
mucosal absorption characteristics of drugs.
44
Other in vivo methods

45. NASAL DRUG DELIVERY
SYSTEM
45

46. INTRODUCTION
Anatomy of nose:-
• The nasal cavity consists of
passage of a depth of
approximately 12-14cm.
• The nasal passage runs
from nasal vestibule to
nasopharynx.
46

47. • The lining is ciliated, highly vascular and rich in mucus
gland.
• Nasal secretions are secreted by goblet cells, nasal
glands and transudate from plasma.
• It contains sodium, potassium, calcium, albumin,
enzymes like leucine,CYP450,Transaminase,etc.
• The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7
in infants.
47
INTRODUCTION

48. Advantages
• Large nasal mucosal surface area for dose absorption
• Rapid drug absorption via highly-vascularized
mucosa
• Rapid onset of action
• Ease of administration, non-invasive
Contd..
48

49. • Avoidance of the gastrointestinal tract and first-pass
metabolism
• Improved bioavailability
• Lower dose/reduced side effects
• Improved convenience and compliance
• Self-administration.
49
Advantages

50. Disadvantages
• Nasal cavity provides smaller absorption surface
when compared to GIT.
• Relatively inconvenient to patients when compared to
oral delivery since there is possibility of nasal
irritation.
• The histological toxicity of absorption enhancers
used in the nasal drug delivery system is not yet
clearly established.
50

51. Factors affecting nasal absorption
1. Molecular weight :-
• The nasal absorption of drugs decreases as the
molecular weight increases.
• Martin reported a sharp decline in drug absorption
having molecular weight greater than 1000 daltons.
51

52. 2. Lipophilicity :-
• Absorption of drug through nasal route is
dependent on the lipophilicity of drugs.
• E.g. Alprenolol and Propranolol which are
lipophilic, has greater absorption than that of
hydrophilic Metoprolol.
52
Factors affecting nasal absorption

53. 3. pH of solution :-
• pH should be optimum for maximum absorption.
• Nonionised lipophilic form crosses the nasal epithelial
barriers via transcellular route and hydrophilic
ionized form passes through the aqueous paracellular
route.
• E.g. Decanoic acid shows maximum absorption at pH
4.5. Beyond this it decreases as solution becomes
more acidic or basic.
53
Factors affecting nasal absorption

54. 4. Drug concentration :-
• The absorption of drug through nasal route is
increased as concentration is increased.
• E.g. 1-tyrosine shows increased absorption at high
concentration in rate.
54
Factors affecting nasal absorption

55. Pathway
• In systemic absorption the drugs generally get
diffused from epithelial cell into systemic
circulation.
• It is reported that nasal cavity have alternative
pathways of drugs absorption through
olfactory epithelium to CNS and peripheral
circulation.
55

56. Enhancement in absorption
• Following approaches used for absorption
enhancement :-
 Use of absorption enhancers
 Increase in residence time.
 Administration of drug in the form of microspheres.
 Use of physiological modifying agents
56

57.  Use of absorption enhancers:-
Absorption enhancers work by increasing the rate at
which the drug pass through the nasal mucosa.
Various enhancers used are surfactants, bile salts,
chelaters, fatty acid salts, phospholipids,
cyclodextrins, glycols etc.
57
Enhancement in absorption

58. Various mechanisms involved in absorption
enhancements are:-
• Increased drug solubility
• Decreased mucosal viscosity
• Decrease enzymatic degradation
• Increased paracellular transport
• Increased transcellular transport
58

59.  Increase in residence time:-
• By increasing the residence time the increase in
the higher local drug concentration in the mucous
lining of the nasal mucosa is obtained.
• Various mucoadhesive polymers like
methylcellulose, carboxymethylcellulose or
polyarcylic acid are used for increasing the residence
time.
59

60.  Administration of drug in the form of
microspheres:-
• Microspheres have good bioadhesive property and they
swell when in contact with mucosa.
• Microspheres provide two advantages-
a. Control the rate of clearance.
b. Protect drug from enzymatic degradation.
The microspheres of various materials showed
increased half-life of clearance. E.g. starch, albumin,
gelatin and dextran.
60

61.  Use of physiological modifying agents:-
• These agents are vasoactive agents and exert their
action by increasing the nasal blood flow.
• The example of such agents are histamine,
leukotrienene D4, prostaglandin E1 and β-
adrenergic agents like isoprenaline and terbutaline.
61

62. Nasal Delivery Systems
• They contain the drug in a liquid or powder
formulation delivered by a pressurized or pump
system.
• Various drug delivery systems are used for nasal drug
delivery.
62

63.  Liquid formulation :-
• These are usually aqueous solutions of the drug. The
simplest way to give a liquid is by nose drops.
• They are simple to develop and manufacture
compared to solid dosage forms but have a lower
microbiological and chemical stability, requiring the
use of various preservatives.
63
Nasal Delivery Systems

64.  Squeezed bottles :-
• These are used for nasal decongestant and work by
spraying a partially atomized jet of liquid into the
nasal cavity.
• They give a better absorption of drug by directing the
formulation into the anterior part of the cavity and
covering a large part of nasal mucosa.
64
Nasal Delivery Systems

65.  Metered-dose pump system :-
• They can deliver solutions, suspensions or emulsions
with a predetermined volume between 25 and 200 μL,
thus offering deposition over a large area.
• Particle size and dose volume are two important
factors for controlling delivery from metered-dose
systems.
65
Nasal Delivery Systems

66. • The optimum particle size for deposition in the nasal
cavity is 10μm.
• The volume of formulation that can be delivered is
limited by the size of the nasal cavity and larger
volumes tend to be cleared faster despite covering a
larger area.
• Better absorption is achieved by administering two
doses, one in each nostril, rather than a single large
dose.
66
Nasal Delivery Systems

67. Applications of Nasal Drug Delivery
A. Nasal delivery of organic based pharmaceuticals :-
• Various organic based pharmaceuticals have been
investigated for nasal delivery which includes drug
with extensive presystemic metabolism.
• E.g. Progesterone, Estradiol, Nitroglycerin,
Propranolol, etc.
67

68. B. Nasal delivery of peptide based drugs :-
• Nasal delivery of peptides and proteins is depend on:
 The structure and size of the molecule.
 Nasal residence time
 Formulation variables (pH, viscosity)
• E.g. Calcitonin, secretin, albumins, insulin, glucagon,
etc.
68
Applications of nasal drug delivery

69. Pulmonary Drug Delivery
System
69

70. • The lung is the organ of external respiration, in which
oxygen and carbon dioxide are exchanged between
blood and inhaled air.
• The structure of the airways prevent the entry of and
promotes the removal of airborne foreign particles
including microorganisms.
Contd..
70
Introduction

71. • The respiratory tract consists of conducting regions
(trachea, bronchi, bronchioles, terminal and
respiratory bronchioles) and respiratory regions
(respiratory bronchioles and alveolar regions).
• The upper respiratory tract comprises the nose, throat,
pharynx and larynx; the lower tract comprises the
trachea, bronchi, bronchioles and the alveolar
regions.
Contd..
71
Introduction

72. Contd..
72
Anatomy of pulmonary system

73. • Trachea branches into two main bronchi- the right
bronchus is wider and leaves the trachea at the
smaller angle than the left.
• The conducting airways are lined with ciliated
epithelial cells.
73
Anatomy of pulmonary system

74. Delivery systems
• Aerosols are used for the delivery of the drug by this
route of administration.
• The aerosols are defined as pressurized dosage from
containing one or more active ingredients which upon
actuation emit a fine dispersion of liquid or solid
materials in gaseous medium.
74

75. • There are three main types of aerosols generating
devices:-
i. Pressurized metered dose inhalers.
ii. Dry powder inhalers.
iii. Nebulizers.
75
Delivery systems

76. i. Pressurized metered dose inhalers:
• In pMDI’s, drug is either
dissolved or suspended in
liquid propellants together with other excipients and
presented in pressurized canister fitted with
metering valve.
• The predetermined dose is released as a spray on
actuation of the metering valve.
76
Delivery systems

77. • Containers:- Aerosol container must withstand
pressure as high as 140-180 psig at 130°F.
• Pharmaceutical aerosols are packaged in tin-plated
steel, plastic coated glass or aluminium containers.
• Aluminium is relatively inert and used uncoated where
there is no chemical instability between containers and
contents.
• Alternatively aluminium containers with an internal
coating of chemically resistant organic material such
as epoxy-resin or polytetrafluorine can be used
77
Delivery systems

78. • Propellants: These are liquified gases like
chlorofluorocarbons and hydrofluoroalkanes.
• These develop proper pressure within the container & it
expels the product when valve is opened.
• At room temperature and pressure, these are gases but
they are readily liquified by decreasing the temperature or
increasing pressure.
• The vapour pressure of the mixture of propellants is given
by Raoult’s law,
Contd… 78
Delivery systems

79. i.e. vapour pressure of the mixed system is equal to
the sum of the mole fraction of each component
multiplied by it’s vapour pressure.
p = pa + pb
where p = total vapour pressure of the system,
pa & pb = partial vapour pressures of the
components a & b.
Contd…
79
Delivery systems

80. • Metering valves:
It permits the reproducible delivery of small volumes of
product.
Depression of the valve stem allows the contents of the
metering chamber to be discharged through the orifice in
the valve stem and made available to the patient.
After actuation the metering chamber refills with liquid
from the bulk and is ready to dispense the next dose.
80
Delivery systems

81. ii. Dry powder inhalers:
In this system drug is inhaled as a cloud of fine
particles.
DPI formulations are propellant free and do not contain
any excipients.
They are breath activated avoiding the problems of
inhalation/actuation coordination encountered with
pMDI’s.
81
Delivery systems

82. iii. Nebulizers:
It delivers relatively large volume of drug solutions
and suspensions.
They are used for drugs that cannot be formulated into
pMDI’s or DPI’s.
There are three categories :-
a. Jet nebulizers
b. Ultrasonic nebulizers
c. Vibrating-mesh nebulizers
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Delivery systems

83. a. Jet nebulizers:-
They are also called as air-jet or air-blast nebulizers
using compressed gas.
The jet of high velocity gas is passed tangentially or
coaxially through a narrow venturi nozzle typically
0.3 to 0.7 mm in diameter.
e.g. Pari LC nebulizer.
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Delivery systems

84. b. Ultrasonic nebulizers:
In this the energy necessary to atomize liquids
come from the piezoelectric crystal vibrating at
high frequency.
c. Vibrating-mesh nebulizers:
In this device aerosols are generated by passing
liquids through a vibrating mesh or plate with
multiple apertures.
84
Delivery systems

85. Applications
• Smaller doses can be administered locally.
• Reduce the potential incidence of adverse systemic
effect.
• It used when a drug is poorly absorbed orally, e.g. Na
cromoglicate.
• It is used when drug is rapidly metabolized orally,
e.g. isoprenaline
85

86. REFERENCES
Y.W. Chein , Novel Drug Delivery Systems, 2 nd
edition, revised and expanded , Marcel Dekker , Inc.
New York , 1992(pg. no. 195 – 224)
N.K. Jain , Controlled and Novel drug delivery , CBS
Publishers & Distributors, New Delhi, First edition
1997(reprint in 2001)
S.P. Vyas and R.K.Khar, Controlled Drug Delivery,
CBS Publishers & Distributors, New Delhi, First
edition 1997.
Indian Journal of Pharmaceutical science, January
1998.
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