Pharmaceutical

Aerosols

Pharmaceutical Aerosols
are pressurized dosage forms that, upon actuation,
emit a fine dispersion of liquid and/or solid materials
containing one or more active ingredients in a
gaseous medium .
Pharmaceutical aerosols differ from most other
dosage forms in their dependence upon the function
of the container, it valve assembly, and an added
component— the propellant—for the physical
delivery of the medication in proper form.

Categories of Aerosols
฀ Topical preparations

฀ Preparations for administration to body cavities

 Inhalation aerosols

 Lingual aerosols

 Nasal aerosols

 Rectal aerosol foams

 Vaginal aerosol foams

 Advantages of the aerosol
Dosage Form

1) A portion of medication may be easily withdrawn from the

package without contamination.

2) the aerosol container protects medicinal agents adversely

affected by atmospheric oxygen , moisture and light. If the

product is packaged under aseptic conditions, sterility may

also be maintained during the shelf life of the product.

3) Topical medication applied in a uniform thin layer to the skin without

anything touching the affected area, which may reduce irritation that

sometimes accompanies mechanical application. The rapid

volatilization of the propellant provides a cooling, refreshing effect.

4) By proper formulation and valve control, the physical form and the

particle size of product may be controlled, the spray characteristics may

be varied from a coarse wet spray to a fine dry mist, which may

contribute to the efficacy of a drug.

5) Convenience, speed and ease of application.

 Aerosol components
฀ The product concentrate: is the active ingredient of
the aerosol with additives as antioxidants, surface-
active agents, and solvents, to prepare a stable and
efficacious product.

฀ The propellant: is responsible for developing the

proper pressure with in the container.

฀ Container

฀ Valve & actuator

8
PROPELLANT:
It is responsible for developing the power pressure with in the
container and also expel the product when the valve is
opened and in the atomization or foam production of the
product.
Fororal and inhalation eg.
Fluorinated hydrocarbons Dichlorodifluro
methane (propellent 12)
Dichlorotetrafluro ethane (propellent 114)
Topical preparation
Propane
Butane
Isobutane
Compound gases
Nitrogen
C arbon dioxide
Nitrousoxide

Propellants
Types of propellants used:
฀ Liquefied gas or a mixture of liquefied gases: may serve the
dual role of propellant and vehicle for the product
concentrate. Liquefied gases under pressure in aerosol
devices revert to the gaseous state when the device is
activated and the liquid reaches atmospheric pressure.

 Fluorinated hydrocarbons: (chloro-fluorinated-carbons CFC

, hydro-fluoro-alkanes) are gases at room temperature and
may be liquefied by cooling below their boiling point or by
compression at room temperature.
 Hydrocarbons :propane, butane , isobutane
Calculation of vapor pressure of mixture of liquefied gases :
฀ These propellants are miscible ,thus suitable mixtures will provide an
infinite variety of pressures.

฀ In an ideal solution vapor pressure of a mixture of two liquefied

gases calculated according to Raoult’s Law by multiplying the sum
of the mole fraction of each component present by its vapor
pressure
p a =p a 0. xa

p a : partial vapor pressure of a component i in the vapor phase

xa : mole fraction in solution

p a 0 :vapor pressure of the pure component.

฀ Vapor pressure of mixed system is calculated by :

P=pa +p b

P:total vapor pressure of the system

p a , p b : partial vapor pressure of the system components

฀ The gas propellant mixtures can be formulated to

provide desired vapor pressures for enhancing the
delivery of the medication through the valve and
actuator in accordance with the purpose of the
medication.
฀ Compressed gases
 Insoluble gases: (Nitrogen & argon)
 upon use: head space increases and gas expands
which may lead to pressure fall. This result in changing
spray characteristics and even failure to deliver the
whole contents of the pack.

 Higher initial pressure is necessary and suitable

container required to withstand such pressure.

 This usually form a wet stream rather than a spray and

special break up spray actuators are necessary.

 Soluble gases: (Nitrous oxide & carbon dioxide)

are soluble in aqueous products.
 gas in solution is in equilibrium with gas in the
head space. As the head space increases this
equilibrium is re-established by gas coming out
of solution. There is a fall in pressure but it is less
pronounced than that observed with insoluble
gases.

 can produce coarse spray and by using a foam

actuator, foams may be produced .

Aerosol containers Various materials used in their

manufacture (a) glass, uncoated or plastic coated; (b)
metal, as tin-plated steel, aluminum, and stainless steel;
(c) plastics.
The selection of the container is based on:
 Adaptability to production methods
 Compatibility with formulation components
 Ability to sustain the pressure intended for the product
 Interesting design and appearance
 Cost
Valves Assembly:
Actuator: The design of the inner chamber and size of the
emission orifice of the actuator contribute to the physical
form (mist, coarse spray, solid stream, or foam) in which the
product is discharged. The type and quantity of propellant
used and the actuator design and dimensions control the
particle size of the emitted product.

Larger orifices (and less propellant) are used for products to

be emitted as foams and solid streams , than for those
intended to be sprays or mists.

Aerosol Systems
The pressure of an aerosol its to critialis
performance.

It can be controlled by:

(a) Type and amount of propellant

(b) Nature and amount of product concentrate.

฀ Two-phase system:

• Simplest system composed of:

• liquid phase consists of solution of propellant +

active ingredient (soluble in propellant).

• vapor phase consists of the vapor

propellant(s).

฀ Three-phase systems consist of( propellant liquid

phase +solution liquid phase +vapor phase).

 The active ingredient is insoluble in propellant,

cosolvents used to dissolve the active ingredient in
a suitable solvent which is immiscible with the
propellant (usually water).

 If the propellant is lighter than the solution, the dip

tube must reach to the bottom of the container.

 If it is heavier the dip tube must be shortened to

avoid spraying propellant and not product.
 The two liquid phases may also be emulsified to
produce an emulsion system which may be:

 oil-in-water or water-in-oil, the propellant

representing the oil phase.

 oil-in-water system produces a foam

 water-in-oil system produces a coarse wet spray

or stream.

Suspended powder aerosols are examples of

three-phase systems.

They consist of a :

 solid phase (the powder) suspended in

 liquid phase (the propellant),

 vapor phase (propellant vapor).

 Factors Affecting Spray Characteristics
1.Viscosity
Increase formulation viscosity increase particle size of
, the spray(coarser)
Further increase in viscosity stream instead of a spray.

2.Vapor pressure of the propellants

higher vapor pressure smaller particle finer spray

3. Solvent 4. Temperature (ambient)

5. Propellant /product ratio

 Greater propellant proportion in formulation

produces finer and drier the spray.

 Adjustment of: propellant / product ratio and

relative proportions of two propellants have

great effect on spray characteristics.

Manufacturing of Pharmaceuti2c7al Aerosols:

METHODS:
A) Pressure filling method:
B) Cold filling method:
C) Compressed gas filling:

A) COLD FILLING METHOD

In this method both the product concentrate and
propellent must be cooled to -3.5c to -40c.
This temp is necessary to liquefy the propellent
gas.this cooling system is mixture of dry ice and
acetone After chilled product concentrate
quantitatively metered into cold aerosol
container,the liquefied gas is added
B) Pressure filling method:
In this method product concentrate is quantitatively
placed in aerosol container, valve assembly is
inserted and crimped into place and liquefied gas
under pressure is metered into the valve system
from pressure burette the propellent is allowed to
enter the container under vapour pressure when
the pressure in the container equals that in the
burette, propellent stops flowing.

Additional propellant added by increasing the

pressure in the filling apparatus through use of
compressed gas

Inhalation therapy
Respiratory system Anatomy

฀ upper respiratory tract

฀ lower tract:trachea,

bronchi, bronchioles and

alveolar regions.

Provides surface area 100–

140 m2 in an adult male.

฀ The lung may be used as a route for delivering

drugs having systemic activity, because of its
large surface area, the abundance of
capillaries and the thinness of the air–blood
barrier.
 Inhalation aerosols and the importance of
size distribution
฀ drug/aerosol deposition in the airways may
depends on :

 Physicochemical properties of the drug

 Formulation

 Delivery/ liberating device

 Patient (breathing patterns and c linica l status).

mechanisms of deposition
฀ Impaction: for large particles >5 µm, is the principal
mechanism for deposition in the upper airways (nose,
mouth, pharynx, larynx and large conducting airways)
฀ Gravitational settling (Stokes’ Law ) is dependent on
its size and density. Sedimentation is a deposition
mechanism for particles in the size range 0.5–3 µm, in
the small airways and alveoli.
฀ Brownian diffusion: (Stokes-Einstein equation)Diffusion
is inversely proportional to particle size. It is mechanism
for smaller particles <0.5 µm
Types of Aerosol Delivery Devices

฀ Small-volume nebulizer (SVN)

฀ Pressurized metered-dose inhaler (pMDI)

฀ Dry powder inhaler (DPI)

฀Small-volume nebulizer (SVN) :

 are powered from a gas, electrical, or battery
source.
 convert drug solutions or suspensions into aerosols
that target the patient’s lower respiratory tract
with minimal patient cooperation.
฀ Pressurized Metered Dose Inhalers(pMDI)
 drug is either dissolved or suspended in liquid
propellant(s) together with other excipients.

 A predetermined dose is released as a spray on

actuation of the metering valve.

 The high-speed gas flow helps to break up the

liquid into a fine spray of droplets.
฀ Dry powder inhaler (DPI)
 Are propellant-free and do not contain
excipient, other than a carrier , which is usually
lactose .
 Are formulated as a powder mixture of coarse
carrier particles and micronized drug with
aerodynamic diameters of 1-5 μm.
 Are breath-actuated, avoiding the problems of
inhalation/ actuation coordination encountered
with pMDIs.

 can deliver larger drug doses than pMDIs (dose size are
limited by a) metering valve volume and b) maximum
suspension concentration that can be employed
without causing valve clogging) .