3. Background & historical perspective
Physicochemical factors governing
lung deposition
Physiological and anatomical features
governing lung deposition
Mechanism of drug clearance and
pharmacokinetics of disposition
3
4. Inhaled therapies have existed for at
least 5000 year
Modern drug therapy can be traced to
the propellant driven metered dose
inhaler (pMDI) of the 1950
1990 actively alternative methods of
delivering macromolecular drug
Which were difficult to deliver in
therapeutic doses by the oral or parental
route
4
5. The physicochemical properties of the droplet
or particles being delivered the mechanical
aspect of aerosol dispersion
Aerosol are aerodynamic properties
Size of particle
Visual examination
Surface area measurement
Equivalent volume diameter
Shape and density is the important role
5
6. Thermal settling velocity measure this
formula
Pharmaceutical aerosol high level of
rotational symmetry and spherical behavior
Aerosol are hydroscopic nature
Rise to a kinetic reaction change in particle
size so transit though the high humidity
environment of the lungs ( 99.5% RF at 370C )
6
12. The mechanism of drug clearance from the
airway must be considered
Mainly involved mucociliary transport ,
absorption and cell mediated translocation
The nature of the mechanism involved and
the interaction with the aerosol particle
complicate the pharmacokinetic of drug
clearance from the lungs
The site of deposition in the lungs the nasal,
oropharyngeal, tracheobronchial and
pulmonary region
12
14. In this topic discussed about droplet
formation may be characterized in term of
the nature of the propulsive force and liquid
being dispersed
Different type of inhalers
A. Propellant driven metered dose inhalers
B. Dry powder
C. Nebulizers
14
15. Several key components
a) Propellants
b) Drugs
c) Co solvents
d) Surfactants
Propellants are CFCs (chlorofluorocarbons),
hydrofluoroalkanes and alkenes
The vapor pressure and density of
propellants mainly involved in formulation
15
16. The vapor pressure is the force of emission of
the droplet from the metering valve of the
inhaler
A co solvent - ethanol
surfactants are sorbitan , trioleate , oleic acid
16
17. Valve and actuator
Majority of product marketed by plastic
coated glass or aluminum container
The performance should be evaluated in
terms of drug and component physical and
chemical compatibilities
Temperature , humidity and stability of the
product should be considered
17
20. The forces of interaction between particles
present barrier to their flow and dispersion
The major forces of interaction are
1. Vander waals force
2. Electrostatic
3. Capillary force
The dry powder is delivered for local and
systemic effect via to the pulmonary route
The dry powder for inhaler are formulated
loose agglomerates
Size range less than 5μg
20
21. Dry powder inhaler are rapid action
Portable ( essay to handle)
Good bioavailability
21
22. Dry powder inhaler available in
1. tablet
2. Capsule
3. Reservoir system
22
24. Nebulizer formation conforms to sterile
product preparation
Sufficient used antimicrobial agent in the
formulation , notably benzalkonium chloride
The solubility of the drug important the
performance of the solution a selected
nebulizer
Component include an energy source (gas ,
electrical ) a site of energy input to
solution(capillary tubes )
24
25. Mechanism of delivery device is
1. air blast
2. Air jet
3. Ultra sonic system
25
28. Emitted dose
The therapeutic effect of aerosol is
dependent upon their delivery to lungs
Two unit dose
sampler are
popular
These airborne
particulate are
sample at a fixed
flow rate of
60 L/ min
28
29. In vitro characterization
General sizing methods
In vivo characterization
Impaction is the method of choice for
evaluating particle or droplet size delivery
from pharmaceutical aerosol system
Stoke volume determine aerodynamic
diameter of particles being evaluated
In vitro characterization
29
30. Reynold’s number for flow greater than 500
but less than 3000
The linear velocity can be derived from the
ratio of the volumetric flow
Method is used to prepare of mono disperse
aerosols
30
31. It highly accurate sources of monodisperse
particle range from 1-200µm
Produces solid or liquid check the
droplet uniformity by using a
gentle flow of air. Measure size ,
shape , density and surface area
31
32. Measure uniformity
To measure particle size of aerosol
This method are suggested to for preparing
insoluble particle in 2- 10µm
This instrument has proven useful in studies
involving the transport
and deposition of
particle
(Ex) the measure the
particle deposition
In elbow formed in
Aluminium tube
32
33. It is a 8- stage , 8- orifice sampler used in
environment working areas to measure the size
distribution and mass concentration levels of solid
particles and liquid aerosols
33
34. Which can be used for determine the particle
size (aerodynamic size distribution )
34
35. Number of alterative sizing methods are
available
General sizing method
35
36. 36
The Dry Powder Insufflator™ – Model DP-
4M is the world’s only commercially available
device that is pulmonary administration of
dry powders to mice.
It can be used to administer a wide range of
pharmaceutical, biologic, radio-opaque and
toxicological powder formulations – from
nanoparticles to macro porous particles
38. pMDI asthma therapy was introduced a new
product have been developed
The major therapeutic categories are β2
adrenergic agonist , anticholinergics ,
glucocorticosteroids, and anti inflammatory
agents used
Parasympathetic and sympathetic nervous
system induced brochodilatation
38
39. Drug delivery to the respiratory tract has
been characterized by a increase in
knowledge of drug droplet or particle
manufacturing , behavior ,aerosol dispersion ,
lung deposition , clearance
The number of disease for which aerosol
therapy may be applicable has increase
dramatically
39
40. Modern pharmaceutics fourth edition ,
revised and expanded , edited by Gilbert S.
Banker , Christopher T. Rhodes
printed and bound by Replika press pvt. Ltd.
india (pg no) 479-496
40