1. Aerosols
Aerosols; A system that depends on the power of a compressed or
liquefied gas to expel the content from a container. Or a package
which contains the product and propellant capable of expelling that
product through an open valve..
Types of aerosols
Aerosols are divided into 4 types;
1. Space aerosols (air born mist);
The product is dispensed as finely divided sprays with droplet
size less than 50 microns in diameter.
The droplets are intended to be suspended in air for sufficient
period of time
E.g. room deodorants, space insecticides
2. 2. Surface coating aerosols
The droplet size is larger than space aerosols. It is intended to
be deposited on the surface rather than suspended on air.
E.g.; Local anesthetics, hair spray, paints and paint removers.
3. In foam aerosols
the product is dispensed in the form of foam
E.g.; shaving creams
4. In stream aerosols;
The product is expelled from the pressurized package in the
form of a simple stream.
E.g., hand lotion
3. Advantages of Aerosol therapy
1. Convenience, speed and ease of application
2. efficient dispersion
3. Avoidance of manual contact with the medication
4. High concentration of the medication over a limited area.
5. Application without manual contact with the patient thus
producing minimum irritation of painful areas.
6. Rapid response to the medication
7. Controlled and uniform dosage produced by metered valve.
8. By changing the pressure in the pack or using special valves the
spray characteristics may be varied from a coarse wet spray to
a fine dry mist.
4. 9. No contamination of the product from the environment since the
system is pressurized.
10. The pressure with which the product is applied, increase the
penetration of the product into the affected area.
11. Absence of air from aerosol container increases the stability of
easily oxidized substances.
12. Hydrolysis of ingredients can be prevented since the propellants
contain no water.
5. Disadvantages of aerosols;
1. cost, the container, valves, propellants, and filling methods
are more expensive than traditional packs.
2. Aerosol packs must not be subjected to heat since high
pressure can develop.
3. formulation difficulties
4. Toxicity of propellant over prolonged use in inhalation
therapy.
5. The refrigerant effect of highly volatile propellants may
cause discomfort on injured skin.
6. Components of aerosols
It consists of 4 components
1. Container
2. Valve
3. Propellant
4. Product concentrate
7. 1. propellants;
The material which responsible for expelling the content of
aerosol container.
Propellant may act as solvent, suspending agent and diluent
and may affect the properties of the product.
Requirements for the Ideal propellants
1. Posses pressure sufficient for expelling the materials
(7 kg/cm).
2. Non-inflammable, Non-toxic, non-irritant and inert
3. Non-expensive
8. Types of propellant
There are 2 types of propellants are used in pharmaceutical
aerosols;
1. Liquefied gas propellant;
For many years, the liquefied gas propellants most used in
aerosols products were the chlorofluorocarbons (CFCs),
however, these propellants are being phased out and will be
prohibited due to the following recognition that they reduce the
amount of ozone in the stratosphere, which results in an
increase in the amount of UV radiation reaching the earth
which may increase the incidence of skin cancer.
Some exemption from this prohibition, in case of unavailability
of other alternative propellant and the product provides a
substantial health benefit unobtainable without the use of
CFCs.
9. Among the CFCs used as propellants in pharmaceuticals were;
dichlorteterafluoroethane (Freon 114 or propellant 114)
trichloromonofluoromethane (Freon 011)
dichlorofluoromethane (Freon 012).
N.B the numerical designation system (XYZ);
X = number of carbon atoms +1
Y = number of hydrogen atoms - 1
Z = number of fluorine atoms
E.g., propellant 113 has 2 C + no H + 3 F
Fluorinated hydrocarbons are gases at room temperature. They
may be liquefied by cooling below their boiling point or by
compression at room temperature.
10. They are used as single gas or as a mixture of gases if a single
propellant does not give the desired pressure.
They form 2 phase system i.e., they are completely miscible with
the rest of the formulation.
When a liquefied gas propellant is sealed in an aerosol container
a portion of the propellant vaporized and the remainder exist as
a liquid, until equilibrium, where the vapour phase exerts a
pressure in all direction above the liquid and this pressure forces
the liquid up the dip tube. When the valve is opened, the liquid
passes the valve into atmosphere.
The boiling point of the propellant is usually considerably lower
than the room temperature, so that the liquefied gas instantly
vaporize.
11. As the vapour phase leaves the container, the space above the
surface of the liquid increases causing a slight depression in the
pressure and at this moment some liquid propellant passes from
the solution to the vapour phase to compensate this drop in the
pressure and restoring the equilibrium between the vapour and
liquid phases. Therefore the system has a constant vapour
pressure as long as it still contains a liquid phase.
Advantages;
The product will have a constant pressure as long as there is
some liquid propellant in pressurized package.
12. Calculations of the vapor pressure:
Raoult`s law: Total vapour pressure in a container =
Σ (sum of) [Mole fraction X vapor pressure] for each
component.
Ex: Mix of Propellant 12/11 in 70/30 ratio where:
MW 11 = 137.38 Vp 11= 13.4 psig
MW 12 = 120.93 Vp 12 = 84.9 psig
Calculate total vapor pressure?
1- no of moles of p11= 30/137.38 = 0.218
2- no of moles of p12 = 70/120.93= 0.579
Ptotal= (0.218/0.218+0.579) X13.4 +
(0.579/0.218+0.579)X84.9 =
3.67+ 61.68= 65.35 psig.
13. 2. Compressed gas propellants
Compressed gases are used in preparation of aerosols,
where the pressure of the compressed gas in the head space
of aerosol container forces the product up the dip tube and
out of the valve. The gases used may be;
Insoluble gases in liquid phase of aerosol;
e.g., Nitrogen
It is odourless, tasteless and inert towards the other
components of aerosol and protects the product from
oxidation.
Slightly soluble gases in liquid phase of aerosol;
E.g., Carbon dioxide and nitrous oxide used in dispensing
foam product.
14. Unlike aerosols prepared with liquefied gas propellant,
compressed gas filled aerosols have no reservoir of propellant.
Thus higher gas pressures are required in these systems, where
the pressure in these aerosols diminishes as the product is used.
15. 2. Containers of aerosols
Various materials have been used in the manufacture of aerosol
container, including;
1. Glass, uncoated or plastic coated
Advantages;
Chemically inert.
Not subjected to corrosion, Easily shaped
Disadvantages;
Accidental breakage. For this reason, plastic coating are
commonly applied to the outer surface of glass container to
render them more resistant to accidental breakage, and in case
of breaking the plastic coat prevents the scattering of glass
fragments.
Glass containers are safely used for dispensing aerosol products
which are working at a pressure not exceed 25 psig and the
aerosol product contains not more than 50 % propellant.
16. 2. Metal containers
a) tin plated steel containers;
the most widely used metal containers for aerosols,
because they are manufactured from sheets of the metal,
these sheets are welded at the junctions which may
result in incomplete sealing of the container, this may
leads to leak of the container or may make a corrosion of
the container.
N.B; special protective coating are employed to the inner
surface of the container to prevent corrosion and interaction
between the container and formulation.
17. b) Stainless steel
Used for small amount of aerosol product in which a great
deal of chemical resistance is required.
The main limitation of stainless containers is their high cost.
c) Aluminum containers
Manufactured by extrusion or by other methods that make
them seamless. They have the advantage over the seam type
container of greater safety against leakage, incompatibility
and corrosion.
3- Plastic containers
Advantages
Low cost, light, unbreakable and no leakage.
Disadvantages
Adsorption of aerosol components
Drug-plastic interaction
Psychologically undesired.
18. 3. Valves
The function of the valve assembly is to permit expulsion
of the contents of aerosol in the desired form, at desired
rate, and in case of metered valves, in the proper amount
or dose.
The materials used in the manufacture of valves should be inert
to the formulation and approved by FDA. Among the materials
used in manufacture of valve are plastic, rubber, aluminum and
stainless steel.
19. The usual aerosol valve assembly is composed of the following
parts;
1.Actuator
2.Stem
3.Gasket
4.Spring
5.Mounting cup
6.Housing
7.Dip tube
20. 1. Actuator;
The button the user presses to activate the valve assembly
for emission of the product. It permits easy opening and
closing of the valve.
The size of the actuator orifices affect the physical form of
the product discharged (mist, coarse spray, solid stream or
foam)
The type and quantity of propellant used and the actuator
design control the particle size of the emitted product.
Where ;
Larger orifice and less propellant are used for
products to be emitted as foam
21. 2. Stem;
Support the actuator and deliver the formulation in the proper form
to the chamber of the actuator.
3. Gasket;
Prevent the leakage of the formulation when the valve is closed.
4. Spring;
Hold the gasket in place and when the actuator is depressed and
released, the spring will return the valve to its closed position.
5. Mounting cup;
Used to attach the valve to the aerosol container. Since it is
exposed to the formulation, it should be manufactured from an inert
material to prevent an undesired interaction.
6. Housing;
Located directly below the mounting cup, it links the dip tube and
the stem and actuator.
7. Dip tube;
Extends from the housing down into the product; brings the
formulation from the container to the valve.
22. Metered valve;
Are fitted to pharmaceutical preparations when a definite
volume of the product is released in one operation of the
valve button. Such valves contain a reservoir of definite
volume.
There are two types
1. Depression of the button may release the content of the
of reservoir which refills on release of the button
2. Depression of the button may fill the reservoir and the
content of which are ejected on release of the button.
23. 4. The concentrate (the active ingredients);
The concentrate may present in 4 states;
one liquid phase
two liquid phase (o /w emulsion spray or w /o emulsion spray
powder spray
One liquid phase;
The propellant is completely miscible with the product to
form a single liquid phase in addition to the vapour phase (2
phase aerosol system). This system gives homogenous spray
with constant pressure.
24. Two liquid phases
When the solution of active ingredient in a suitable solvent is
not miscible with the propellant gives rise to three phase
aerosol systems consisting of the propellant liquid phase, the
solution liquid phase and the vapour phase.
If the propellant is lighter than the solution, the dip-tube must
reach to the bottom of the container.
If the propellant is heavier than the solution, the dip-tube
must be shortened so that the tube dips in the aqueous phase
not in the propellant to avoid spraying the propellant and not
the product.
The 2 liquid phases may also be emulsified to produce an
emulsion system;
25. Oil in water emulsion
The propellant representing the oil phase which is immiscible
with the aqueous phase solution of the product or the
products containing water as carrier. So it is necessary to
emulsify the propellant in the product solution by using an
emulsifying agent. The ratio between the propellant and the
emulsifying agent used is 1: 4 or 1: 5 to ensure transparent
product.
Since the propellant is the internal phase, so when expanded
on release from the valve it tends to produce foam and foam
actuator must be fitted.
Water in oil emulsion
By using an emulsifying agent such as polyglyceride ester of
fatty acid (Emecol 14) or sorbitan monolourate (span 20)
Sine the propellant is the external phase the product can be
sprayed to produce coarse wet spray or stream.
26. powder spray
They consists of a solid phase (the powder) suspended in a
liquid phase (the propellant). The vapour phase consisting of
the propellant vapour, the inclusion of lubricant and control of
the particle size is necessary. Why? Because the too large
particles may clog the valve and the agglomeration of the
small particle may also cause clogging (the recommended
sizes of particles are 5 to 10 um and none greater than 50 um).
Due to the density difference between the solid particles and
the propellant the dispersed particles may be collected above
or below the propellant which may re-disperse by gentile
shacking, but in some cases the collected particles form a
hard cake on long standing, which can not re-disperse by
shacking, in this cases, small balls of stainless steel or
ceramic balls are included to break down the hard cake while
shacking of the container and re-dispersion can occur.