Nanotechnology for pulmonary & nasal drug delivery

NANOTECHNOLOGY FOR
PULMONARY & NASAL DRUG
DELIVERY
By : M.SOWMYA
M Pharmacy 1st year
Guided by: Prasanna Kumar Desu, M.Pharm(Ph.D.)
Vishnu Institute of Pharmaceutical Education and Research

INTRODUCTION
 The development of nano particle engineering
processes has increased the possibilities of
formulating active pharmaceutical ingredients for
pulmonary and nasal delivery.
 Recently developed techniques, such as cryogenic
and supercritical processes.
 Pulmonary and nasal physiology are correlated to
particle deposition and adsorption.

LUNGS
• The primary function of the lungs resides in its ability
to facilitate gas exchange between the external
environment and the system circulation to maintain a
constant systemic pH.
• The lung can be divided in to two main
compartments:
1. Conducting zone
2. Respiratory zone

COMPARTMENTS
CONDUCTING ZONE
 It includes the trachea
bronching in to intra
pulmonary bronchi further
dividing in to smaller
diameter bronchi and
bronchioles.
 As it name indicates the
conducting zone allows
air circulation in and out
of the lung during the
ventilation process.
RESPIRATORY ZONE
 This zone consists of the
respiratory bronchioles
containing the alveolar
ducts and sac participating
in the gas exchange
function of the lung.
 In this zone, with a mean
alveolar number of
480million,the cross-
sectional area approches
140 to 160 metre square.

Physiology of the nose
• The nasal passage ways function as a means to warm,
humidity, and the filter the inhaled air before it
reaches the lungs the nasal cavity has a large surface
area.
• Substance depositing on the mucus covering the
ciliated epithelium, the mucociliary.
• Clearance will transport the mucus towards the naso
pharynx region where it will either swallowed or
expectorated.
• If the particles are soluble, they may be absorbed
through the mucus and nasal epithelium in to
systemic circulation.

Particles and deposition
• Particle deposition in the nasal cavity highly depends
on the particle size as well as air flow velocity.
• The literature shows evidence of the importance of
the aerodynamic diameter(da) of the particles over
their geometric diameter(dv).
• In fact , even particles exhibiting a large dv have
ability to deposit in the respiratory zone of the lung as
soon as their da is <5 micro meter.
• The (da) accounts for the (dv) of the particles as well
as for their shape and density.

da=dv √ρ/x.ρ˳
Where ρ is the particle density
X is the dynamic shape factor
(x=1 for spherical particles ,but
changes with the geometric of the
Particles)and ρ˳ is the reference
density (usually ρ˳=1)

The mechanisms of deposition can be organized in to five
categories inertial impaction, sedimentation, diffusion
interception, and electrostatic precipitation. Inertial
impactions occurs when the moment of the particles is such
that they move in a straight direction, independently of the
airflow. Hence, impaction happens when the particles or
droplets collide on to the lung epithelium. The impact is
more likely to happen if the particles travel long distances,
since they will not stop due to the friction forces between
the particles and the air. The traveled distance is based on
the equation below
S = B·m·v
Where
S is the distance,B is the particle mechanical mobility,
m is the mass, and v is the particle velocity.

• The inertial deposition can also be related to the
stokes number(Stk) as it increase, the inertial
impaction efficiency increase. Since the Stk is
directly proportional to the square of the diameter, the
inertial deposition efficiency increases with particle
size.
Stk=ρ·²d·V ̸ 18Ƞ·R
Where
ρ is the particle density, d is the particle
diameter, V is the air velocity, and Ƞ is the air
viscosity, and R is the radius of the airway.

 Most of the particle deposition models assume a laminar
parabolic flow in all airway generations. Therefore, inertial
impaction is expected to occur preferentially in the upper
airways, at the airway bifurcations.
 Sedimentation occurs because of the gravity applied to
the particles stokes law governs the terminal settling
velocity (Vts)
 Vts = (ρ-ρɑ)d²·g 18Ƞ
Where
`ρɑ´ is the air density and g the gravitational
acceleration . However as the particle size decreases, the
stoke's law does not apply by itself and must be corrected with
a slip correction factor Cc, derived by cunningham.

Vts (slip)= Vts ·Cc
where Cc =1+kn(2.514+0.8·e 0.55/kn)
Where kn is the knudsen number in air.
Another parameter to consider when characterizingf
particle sedimentation behaviour is the reynolds
number,if it indicates laminar air flow, stokes law is
applicable otherwise, a turbulent drag correction
factor must be applied to model the appropriate Vts.

• The last particle deposition mechanism mentioned in this
chapter is diffusion. This phenomenon, also called brownian
motion, occurs when the particles undergo random motion
due to particle collisions in the fluid. The rate of diffusion is
proportional to the diffusion is proportional to the diffusion
coefficient given by the stoke-einstein equation.
Diƒ= k.T/3π·Ƞ·d
Where
k is the Boltzmann’s constant and T is the absolute
temperature.
• The diffusion driven deposition is only dependent on
particle size and not its density; it will increase as the particle
size decreases.

Particle engineering technologies
 Top down approach
1) Ball milling
2) Fluid energy milling
3) Cryogenic milling
High-pressure homogenization
1. Piston- Gap homogenization
2. Jet –stream homogenization

TECHNOLOGIES
CRYOGENIC TECHNOLOGIES
I. Spraying freeze drying
II. Spray freezing in to liquid (sfl)
III. Thin film freezing [tff]
Supercritical or compressed fluid technology
I. Gaseous anti-solvent precipitation
II. Supercritical or compressed fluid precipitation
III. Rapid expansion of supercritical solution (RESS)
IV. Modified ress process.

• Cryogenic technologies were developed to improve the
solubility and dissolution properties of poorly- water
soluble drugs by increasing the specific surface area of the
particle through nano structure & creating amorphous
materials.
1. Spray freeze drying: The particle engineering is generally
described as a three step process comprising the
atomization of a feed solutions, suspensions containing the
drug and potentially, pharmaceutical excipients, rapid
freezing of the atomized droplets above the surface of the
cryogenic liquid and sublimation of the solvent from the
frozen material to obtain a final, usually amorphous,
drypowder.

2. Spray freezing in to liquid: The cryogenic liquid
includes compressed fluid carbondioxide,helium,
propane, ethane, liquid nitrogen, liquid argon, or
hydrofluoroethers.
3. Thin film freezing: The tff technology is also known
as ultra rapid freezing, cold metal block freezing,
spray forming, thermal spray coating, splat cooling,
slat quenching solidification, powder spray
deposition.

• The feed solution is frozen drop wise on a rotating
cryogenic substrate pre-cooled to given temperature.
Usually below to lowest freezing temperature of the
solvent used to dissolve the drug and the excipients.
• The frozen thin pellets are then removed from the
cryogenic surface by a scraper and maintained in a
frozen state in liquid nitrogen.

Topical effects of the inhalation route
The main goal when delivery drugs to the lungs is
to achieve high drug concentrations to ensure the
therapeutic effect and onset of action.
NP targeting to the lungs has been investigated
for multiple lung disease states including asthma,
chronic obstructive pulmonary disease(COPD),
tuberculosis, cystic fibrosis, lung cancer, allograft,
rejection, pulmonary hypertension etc.
The nebulization itraconozole NPs made by the
sfl technique showed significantly improved.
Marketed product: Sporanox.

 The nasal absorption of polar substances is greatly
improved by the use of absorption enhancers co-
administered with active substance, such as bile salts,
chitosan (cs), cyclodextrins , saponins , phospholipids
etc.
 A morphine / cs powder solution have been
administered to human.

conclusion
• Pulmonary and nasal delivery of active
substances could significantly improve patient
outcomes and broader the therapeutic options
for local and systemic therapy.

Nanotechnology for pulmonary & nasal drug delivery

More Related Content

What's hot

Similar to Nanotechnology for pulmonary & nasal drug delivery

Recently uploaded

In this document

Nanotechnology for pulmonary & nasal drug delivery