Pharmaceutics Lecture On Pulmonary And Nasal

Front 1

Structure of Respiratory tract

Back 1

The lower respiratory tract:
Trachea (generation 0)
Bronchi (generation 1)
Bronchioles
Alveolar ducts
Alveolar sacs (alveoli) (generation 23)

Front 2

Clearance of Inhaled Particles
physiological defense mechanism

Back 2

cough and sneeze

Front 3

Clearance of Inhaled Particles.
conducting airways are lined with ciliated epithelial cells
mucociliary action:

Back 3

particles deposited in the ciliated
conducting airways are trapped by mucus, swept upwards
from lung by beating cilia, and cleared within 24 hours

Front 4

Clearance of Inhaled Particles.
conducting airways are lined with ciliated epithelial cells
alveolar macrophages:

Back 4

can engulf particles, which are then
removed via the lymphatic system, or via the mucociliary
“escalator”

Front 5

Clearance of Inhaled Particles.
Particles deposited in the respiratory regions (peripheral
region, including respiratory bronchioles and alveolar region) are removed:

Back 5

more slowly

Front 6

Mucociliary Clearance Action

Back 6

Mucus is moving towards the mouth

Front 7

Pulmonary Drug Absorption
large surface area

Back 7

70m^2

Front 8

Pulmonary Drug Absorption
Alveoli

Back 8

~ 300,000,000

Front 9

Pulmonary Drug Absorption
abundance of blood vessel capillaries

Back 9

- the lung has the highest capillary
density of all organs

Front 10

Pulmonary Drug Absorption
air-blood barrier

Back 10

(pneumocytes,
basement membrane, endothelial cells
of capillaries) is thin (~800 nm)

Front 11

Pulmonary Drug Absorption
pH partition- drug properties

Back 11

Drug absorption is passive transbilayer
transport with all its attributes

Front 12

Drugs are Delivered as Aerosol
aerosol

Back 12

is a two-phase disperse system of solid or liquid
particles dispersed in gaseous phase.

Front 13

Drugs are Delivered as Aerosol
particle size:

Back 13

critical for the penetration of the conducting
tract and reaching the different respiratory regions. The
particle size range required for pulmonary delivery:
<6 μm for respiratory bronchioles (peripheral)
<2 μm for alveoli

Front 14

Drugs are Delivered as Aerosol
aerodynamic diameter

Back 14

is a better
characteristics of particle deposition.

Front 15

Drugs are Delivered as Aerosol
Hygroscopic influence of environmental
humidity on particle size:

Back 15

water-soluble
particles will absorb the moisture
in respiratory tract (almost 100%)
and increase the size

Front 16

Particle Deposition Mechanisms
aerodynamics

Back 16

Impact

Front 17

Particle Deposition Mechanisms
Patient-dependent factors

Back 17

breathing pattern
other physiology factors

Front 18

Impact

Back 18

Impact affects the import of larger particles (> 5μm)

Front 19

Gravitational Sedimentation

Back 19

Important for particles of 0.5 – 3 μm in small air
ways and alveoli (low velocity)
Stokes’ equation: density and particle size
(see notes for equation)
Residence time needs to be sufficient to allow deposition

Front 20

Brownian Diffusion

Back 20

Important for small particles (< 0.5 μm)

Front 21

Patient-dependent Factors
breathing pattern

Back 21

the larger the inhaled volume, the greater the peripheral
distribution of particles in the lung
the slower the inhalation flow rate, the less the deposition
by impact
breath-holding enhances the deposition by sedimentation and diffusion

Front 22

Patient-dependent Factors
optimal deposition when:

Back 22

slow, deep inhalation to total lung
capacity followed by breath-holding before exhalation

Front 23

Other patient-dependent factors:

Back 23

airways obstruction

Front 24

Advantages of Pulmonary Delivery

Front 25

Challenges of Pulmonary Delivery

Back 25

drug loss by clearance mechanisms

Front 26

Anatomy and Physiology of the Nose

Back 26

Nasal cavity volume: ~ 20 ml

Front 27

Nasal Mucosa and Epithelium

Back 27

Mucosal membrane:
nasal cavity is lined with
mucosa

Front 28

Physiology of Mucosa and Epithelium
nasal mucus membrane

Back 28

contains water, ions,
glycoproteins (viscosity),
enzymes,
immunoglobulins,

Front 29

Physiology of Mucosa and Epithelium
cilia of epithelial cells

Back 29

tiny hair-like projections on the exposed surface of
epithelial cell

Front 30

Physiological Barriers
protection against exogenous chemicals

Back 30

Nasal mucosa possesses mucociliary clearance mechanisms
and enzyme activity

Front 31

Physiological Barriers
mucociliary clearance

Back 31

is a physical barrier for drug absorption

Front 32

Physiological Barriers
nasal metabolism

Back 32

is an enzymatic barrier for drug absorption

Front 33

A physiological barrier is the sneeze reflex

Back 33

true

Front 34

Drug Nasal Absorption

Back 34

Drug molecules need to cross
the mucous layer before being
absorbed through epithelium

Front 35

Factors Affecting Nasal Absorption
change in pH affects drug absorption by:

Back 35

change the drug ionization form

Front 36

Factors Affecting Nasal Absorption
pathological conditions

Back 36

can affect the absorption
and compromise the efficiency (e.g. crusting,
dryness, rhinorrhea, sinusitis, nasal infection)

Front 37

Advantages of nasal drug delivery

Front 38

Challenges of nasal drug delivery

Back 38

possible local tissue irritation

Front 39

Improvement of Nasal Bioavailability
Strategies to improve drug bioavailability in nasal administration:

Back 39

Solubilize the drug

Front 40

Nasal Solutions and Sprays
- nasal solutions and liquid dose forms

Back 40

usually water-based

Front 41

Nasal solutions and sprays

nasal drops

Back 41

simple, cheap and multi dose; but dosing inaccurate

Front 42

Nasal solutions and sprays
nasal spray by squeezed bottle

Back 42

spraying liquid by partially atomized jet

Front 43

Nasal solutions and sprays
nasal spray by metered dose pump

Back 43

delivers solution, suspension, or emulsion in
a predetermined volume between 25 to 200 μl

Front 44

Butorphanol Tartrate

Back 44

Butorphanol tartrate (Stadol MS®)
for migraine and post-operative pain

Front 45

Nasal Cyanocobalamin

Back 45

Vitamin B12 (Cyanocobalamin, Nascobal®by
Schwartz)

Front 46

Salmon Calcitonin

Back 46

Salmon calcitonin (a peptide)

Front 47

Other Systemic Nasal Delivery Systems

Back 47

Narfaralin acetate

Front 48

Inhalants

Back 48

Inhalants are drugs with high vapor pressure that
can be carried by an air current into the nasal
passage

Front 49

Propylhexedrine Inhalant

Back 49

Propylhexedrine
- volatile liquid

Front 50

Amyl Nitrite Inhalant

Back 50

A prescription drug
- a vasodilator to treat
angina pain