AerosolsAerosols

Aerosols;Aerosols; A system that depends on the power of a compressed or A system that depends on the power of a compressed or

liquefied gas to expel the content from a container. liquefied gas to expel the content from a container. Or a package Or a package

which contains the product and propellant capable of expelling which contains the product and propellant capable of expelling

that product through an open valve..that product through an open valve..

Types of aerosolsTypes of aerosols

Aerosols are divided into 4 types;Aerosols are divided into 4 types;

1.1. Space aerosols (air born mist);Space aerosols (air born mist);

The product is dispensed as finely divided sprays with The product is dispensed as finely divided sprays with

droplet size less than 50 microns in diameter.droplet size less than 50 microns in diameter.

The droplets are intended to be suspended in air for The droplets are intended to be suspended in air for

sufficient period of timesufficient period of time

E.g. room deodorants, space insecticidesE.g. room deodorants, space insecticides

2.2. Surface coating aerosolsSurface coating aerosols

The droplet size is larger than space aerosols. It is intended The droplet size is larger than space aerosols. It is intended

to be deposited on the surface rather than suspended on air.to be deposited on the surface rather than suspended on air.

E.g.; Local anesthetics, hair spray, paints and paint E.g.; Local anesthetics, hair spray, paints and paint

removers.removers.

3.3. In foam aerosolsIn foam aerosols

the product is dispensed in the form of foamthe product is dispensed in the form of foam

E.g.; shaving creamsE.g.; shaving creams

4.4. In stream aerosols;In stream aerosols;

The product is expelled from the pressurized package in the The product is expelled from the pressurized package in the

form of a simple stream.form of a simple stream.

E.g., hand lotionE.g., hand lotion

Advantages of Aerosol therapyAdvantages of Aerosol therapy

1.1. Convenience, speed and ease of applicationConvenience, speed and ease of application

2.2. efficient dispersionefficient dispersion

3.3. Avoidance of manual contact with the medicationAvoidance of manual contact with the medication

4.4. High concentration of the medication over a limited area.High concentration of the medication over a limited area.

5.5. Application without manual contact with the patient thus Application without manual contact with the patient thus

producing minimum irritation of painful areas.producing minimum irritation of painful areas.

6.6. Rapid response to the medicationRapid response to the medication

7.7. Controlled and uniform dosage produced by metered valve.Controlled and uniform dosage produced by metered valve.

8.8. By changing the pressure in the pack or using special valves By changing the pressure in the pack or using special valves

the spray characteristics may be varied from a coarse wet the spray characteristics may be varied from a coarse wet

spray to a fine dry mist.spray to a fine dry mist.

9.9. No contamination of the product from the environment since No contamination of the product from the environment since

the system is pressurized.the system is pressurized.

10.10. The pressure with which the product is applied, increase the The pressure with which the product is applied, increase the

penetration of the product into the affected area.penetration of the product into the affected area.

11.11. Absence of air from aerosol container increases the stability of Absence of air from aerosol container increases the stability of

easily oxidized substances.easily oxidized substances.

12.12. Hydrolysis of ingredients can be prevented since the Hydrolysis of ingredients can be prevented since the

propellants contain no water.propellants contain no water.

Disadvantages of aerosols;Disadvantages of aerosols;

1.1. cost, the container, valves, propellants, and filling cost, the container, valves, propellants, and filling

methods are more expensive than traditional packs.methods are more expensive than traditional packs.

2.2. Aerosol packs must not be subjected to heat since high Aerosol packs must not be subjected to heat since high

pressure can develop.pressure can develop.

3.3. formulation difficultiesformulation difficulties

4.4. Toxicity of propellant over prolonged use in inhalation Toxicity of propellant over prolonged use in inhalation

therapy.therapy.

5.5. The refrigerant effect of highly volatile propellants may The refrigerant effect of highly volatile propellants may

cause discomfort on injured skin.cause discomfort on injured skin.

Components of aerosolsComponents of aerosols

It consists of 4 componentsIt consists of 4 components

1.1. ContainerContainer

2.2. ValveValve

3.3. PropellantPropellant

4.4. Product concentrateProduct concentrate

1. propellants;1. propellants;

The material which responsible for expelling the content of The material which responsible for expelling the content of

aerosol container.aerosol container.

Propellant may act as solvent, suspending agent and Propellant may act as solvent, suspending agent and

diluent and may affect the properties of the product.diluent and may affect the properties of the product.

Requirements for the Ideal propellants Requirements for the Ideal propellants

1.1. Posses pressure sufficient for expelling the materials Posses pressure sufficient for expelling the materials

(7 kg/cm).(7 kg/cm).

2.2. Non-inflammable, Non-toxic, non-irritant and inertNon-inflammable, Non-toxic, non-irritant and inert

3.3. Non-expensiveNon-expensive

Types of propellantTypes of propellant

There are 2 types of propellants are used in pharmaceutical There are 2 types of propellants are used in pharmaceutical

aerosols;aerosols;

1.1. Liquefied gas propellant;Liquefied gas propellant;

For many years, the liquefied gas propellants most used in For many years, the liquefied gas propellants most used in

aerosols products were aerosols products were the chlorofluorocarbons (CFCs),the chlorofluorocarbons (CFCs),

however, these propellants are being phased out and will be however, these propellants are being phased out and will be

prohibited due to the following recognition that prohibited due to the following recognition that they reduce they reduce

the amount of ozone in the stratosphere, which results in an the amount of ozone in the stratosphere, which results in an

increase in the amount of UV radiation reaching the earth increase in the amount of UV radiation reaching the earth

which may increase the incidence of skin cancer.which may increase the incidence of skin cancer.

Some exemption from this prohibition, in case of Some exemption from this prohibition, in case of

unavailability of other alternative propellant and the product unavailability of other alternative propellant and the product

provides a substantial health benefit unobtainable without provides a substantial health benefit unobtainable without

the use of CFCs.the use of CFCs.

Among the CFCs used as propellants in pharmaceuticals were; Among the CFCs used as propellants in pharmaceuticals were;

dichlorteterafluoroethane (Freon 114 or propellant 114)dichlorteterafluoroethane (Freon 114 or propellant 114)

trichloromonofluoromethane (Freon 011)trichloromonofluoromethane (Freon 011)

dichlorofluoromethane (Freon 012).dichlorofluoromethane (Freon 012).

N.B the numerical designation system (XYZ);N.B the numerical designation system (XYZ);

X = number of carbon atoms +1X = number of carbon atoms +1

Y = number of hydrogen atoms - 1Y = number of hydrogen atoms - 1

Z = number of fluorine atomsZ = number of fluorine atoms

E.g., propellant 113 has 2 C + no H + 3 FE.g., propellant 113 has 2 C + no H + 3 F

Fluorinated hydrocarbons are gases at room temperature. Fluorinated hydrocarbons are gases at room temperature.

They may be liquefied by cooling below their boiling point or They may be liquefied by cooling below their boiling point or

by compression at room temperature. by compression at room temperature.

They are used as single gas or as a mixture of gases if a single They are used as single gas or as a mixture of gases if a single

propellant does not give the desired pressure.propellant does not give the desired pressure.

They form 2 phase system i.e., they are completely miscible They form 2 phase system i.e., they are completely miscible

with the rest of the formulation. with the rest of the formulation.

When a liquefied gas propellant is sealed in an aerosol When a liquefied gas propellant is sealed in an aerosol

container a portion of the propellant vaporized and the container a portion of the propellant vaporized and the

remainder exist as a liquid, until equilibrium, where the remainder exist as a liquid, until equilibrium, where the

vapour phase exerts a pressure in all direction above the vapour phase exerts a pressure in all direction above the

liquid and this pressure forces the liquid up the dip tube. liquid and this pressure forces the liquid up the dip tube.

When the valve is opened, the liquid passes the valve into When the valve is opened, the liquid passes the valve into

atmosphere.atmosphere.

The boiling point of the propellant is usually considerably The boiling point of the propellant is usually considerably

lower than the room temperature, so that the liquefied gas lower than the room temperature, so that the liquefied gas

instantly vaporize.instantly vaporize.

As the vapour phase leaves the container, the space above the As the vapour phase leaves the container, the space above the

surface of the liquid increases causing a slight depression in the surface of the liquid increases causing a slight depression in the

pressure and at this moment some liquid propellant passes from pressure and at this moment some liquid propellant passes from

the solution to the vapour phase to compensate this drop in the the solution to the vapour phase to compensate this drop in the

pressure and restoring the equilibrium between the vapour and pressure and restoring the equilibrium between the vapour and

liquid phases. liquid phases. Therefore the system has a constant vapour Therefore the system has a constant vapour

pressure as long as it still contains a liquid phase.pressure as long as it still contains a liquid phase.

Advantages;Advantages;

The product will have a constant pressure as long as there is The product will have a constant pressure as long as there is

some liquid propellant in pressurized package.some liquid propellant in pressurized package.

Calculations of the vapor pressure:Calculations of the vapor pressure:

Raoult`s law: Total vapour pressure in a container =Raoult`s law: Total vapour pressure in a container =

ΣΣ (sum of) [Mole fraction X vapor pressure] for each (sum of) [Mole fraction X vapor pressure] for each

component.component.

Ex: Mix of Propellant 12/11 in 70/30 ratio where:Ex: Mix of Propellant 12/11 in 70/30 ratio where:

MW 11 = 137.38 Vp 11= 13.4 psigMW 11 = 137.38 Vp 11= 13.4 psig

MW 12 = 120.93 Vp 12 = 84.9 psigMW 12 = 120.93 Vp 12 = 84.9 psig

Calculate total vapor pressure? Calculate total vapor pressure?

1- no of moles of p11= 30/137.38 = 0.2181- no of moles of p11= 30/137.38 = 0.218

2- no of moles of p12 = 70/120.93= 0.579 2- no of moles of p12 = 70/120.93= 0.579

Ptotal= (0.218/0.218+0.579) X13.4 + Ptotal= (0.218/0.218+0.579) X13.4 +

(0.579/0.218+0.579)X84.9 = (0.579/0.218+0.579)X84.9 =

3.67+ 61.68= 65.35 psig. 3.67+ 61.68= 65.35 psig.

2.2. Compressed gas propellantsCompressed gas propellants

Compressed gases are used in preparation of aerosols, Compressed gases are used in preparation of aerosols,

where the pressure of the compressed gas in the head where the pressure of the compressed gas in the head

space of aerosol container forces the product up the dip space of aerosol container forces the product up the dip

tube and out of the valve. The gases used may be;tube and out of the valve. The gases used may be;

Insoluble gases in liquid phase of aerosol; Insoluble gases in liquid phase of aerosol;

e.g., Nitrogene.g., Nitrogen

It is odourless, tasteless and inert towards the other It is odourless, tasteless and inert towards the other

components of aerosol and protects the product from components of aerosol and protects the product from

oxidation. oxidation.

Slightly soluble gases in liquid phase of aerosol;Slightly soluble gases in liquid phase of aerosol;

E.g., Carbon dioxide and nitrous oxide used in E.g., Carbon dioxide and nitrous oxide used in

dispensing foam product.dispensing foam product.

Unlike aerosols prepared with liquefied gas propellant, Unlike aerosols prepared with liquefied gas propellant,

compressed gas filled aerosols have no reservoir of propellant. compressed gas filled aerosols have no reservoir of propellant.

Thus higher gas pressures are required in these systems, where Thus higher gas pressures are required in these systems, where

the pressure in these aerosols diminishes as the product is the pressure in these aerosols diminishes as the product is

used.used.

2. Containers of aerosols2. Containers of aerosols

Various materials have been used in the manufacture of aerosol Various materials have been used in the manufacture of aerosol

container, including; container, including;

1.1. Glass, uncoated or plastic coatedGlass, uncoated or plastic coated

Advantages;Advantages;

Chemically inert. Chemically inert.

Not subjected to corrosion, Easily shapedNot subjected to corrosion, Easily shaped

Disadvantages;Disadvantages;

Accidental breakage. For this reason, plastic coating are Accidental breakage. For this reason, plastic coating are

commonly applied to the outer surface of glass container to commonly applied to the outer surface of glass container to

render them more resistant to accidental breakage, and in render them more resistant to accidental breakage, and in

case of breaking the plastic coat prevents the scattering of case of breaking the plastic coat prevents the scattering of

glass fragments.glass fragments.

Glass containers are safely used for dispensing aerosol Glass containers are safely used for dispensing aerosol

products which are working at a pressure not exceed 25 psig products which are working at a pressure not exceed 25 psig

and the aerosol product contains not more than 50 % and the aerosol product contains not more than 50 %

propellant.propellant.

2.2. Metal containersMetal containers

a)a) tin plated steel containers;tin plated steel containers;

the most widely used metal containers for aerosols, the most widely used metal containers for aerosols,

because they are manufactured from sheets of the because they are manufactured from sheets of the

metal, these sheets are welded at the junctions which metal, these sheets are welded at the junctions which

may result in incomplete sealing of the container, this may result in incomplete sealing of the container, this

may leads to leak of the container or may make a may leads to leak of the container or may make a

corrosion of the container. corrosion of the container.

N.B; special protective coating are employed to the inner N.B; special protective coating are employed to the inner

surface of the container to prevent corrosion and surface of the container to prevent corrosion and

interaction between the container and formulation.interaction between the container and formulation.

b)b) Stainless steelStainless steel

Used for small amount of aerosol product in which a great Used for small amount of aerosol product in which a great

deal of chemical resistance is required.deal of chemical resistance is required.

The main limitation of stainless containers is their high The main limitation of stainless containers is their high

cost.cost.

c)c) Aluminum containersAluminum containers

Manufactured by extrusion or by other methods that make Manufactured by extrusion or by other methods that make

them seamless. They have the advantage over the seam them seamless. They have the advantage over the seam

type container of greater safety against leakage, type container of greater safety against leakage,

incompatibility and corrosion.incompatibility and corrosion.

3- Plastic containers3- Plastic containers

AdvantagesAdvantages

Low cost, light, unbreakable and no leakage.Low cost, light, unbreakable and no leakage.

DisadvantagesDisadvantages

Adsorption of aerosol componentsAdsorption of aerosol components

Drug-plastic interactionDrug-plastic interaction

Psychologically undesired.Psychologically undesired.

3. Valves3. Valves

The function of the valve assembly is to permit The function of the valve assembly is to permit

expulsion of the contents of aerosol in the desired form, expulsion of the contents of aerosol in the desired form,

at desired rate, and in case of metered valves, in the at desired rate, and in case of metered valves, in the

proper amount or dose.proper amount or dose.

The materials used in the manufacture of valves should be The materials used in the manufacture of valves should be

inert to the formulation and approved by FDA. Among the inert to the formulation and approved by FDA. Among the

materials used in manufacture of valve are plastic, rubber, materials used in manufacture of valve are plastic, rubber,

aluminum and stainless steel.aluminum and stainless steel.

The usual aerosol valve assembly is composed of the following The usual aerosol valve assembly is composed of the following

parts;parts;

1.Actuator1.Actuator

2.Stem2.Stem

3.Gasket3.Gasket

4.Spring4.Spring

5.Mounting 5.Mounting cupcup

6.Housing6.Housing

7.Dip tube7.Dip tube

1.1. Actuator;Actuator;

The button the user presses to activate the valve assembly The button the user presses to activate the valve assembly

for emission of the product. It permits easy opening and for emission of the product. It permits easy opening and

closing of the valve.closing of the valve.

The size of the actuator orifices affect the physical form of The size of the actuator orifices affect the physical form of

the product discharged (mist, coarse spray, solid stream or the product discharged (mist, coarse spray, solid stream or

foam)foam)

The type and quantity of propellant used and the actuator The type and quantity of propellant used and the actuator

design control the particle size of the emitted product. design control the particle size of the emitted product.

Where ;Where ;

Larger orifice and less propellant are used for Larger orifice and less propellant are used for

products to be emitted as foamproducts to be emitted as foam

2.2. Stem;Stem;

Support the actuator and deliver the formulation in the proper Support the actuator and deliver the formulation in the proper

form to the chamber of the actuator.form to the chamber of the actuator.

3.3. Gasket;Gasket;

Prevent the leakage of the formulation when the valve is closed.Prevent the leakage of the formulation when the valve is closed.

4.4. Spring;Spring;

Hold the gasket in place and when the actuator is depressed and Hold the gasket in place and when the actuator is depressed and

released, the spring will return the valve to its closed position.released, the spring will return the valve to its closed position.

5.5. Mounting cup;Mounting cup;

Used to attach the valve to the aerosol container. Since it is Used to attach the valve to the aerosol container. Since it is

exposed to the formulation, it should be manufactured from an exposed to the formulation, it should be manufactured from an

inert material to prevent an undesired interaction.inert material to prevent an undesired interaction.

6.6. Housing;Housing;

Located directly below the mounting cup, it links the dip tube and Located directly below the mounting cup, it links the dip tube and

the stem and actuator.the stem and actuator.

7.7. Dip tube;Dip tube;

Extends from the housing down into the product; brings the Extends from the housing down into the product; brings the

formulation from the container to the valve.formulation from the container to the valve.

Metered valve;Metered valve;

Are fitted to pharmaceutical preparations when a Are fitted to pharmaceutical preparations when a

definite volume of the product is released in one definite volume of the product is released in one

operation of the valve button. Such valves contain a operation of the valve button. Such valves contain a

reservoir of definite volume.reservoir of definite volume.

There are two typesThere are two types

1.1. Depression of the button may release the content of Depression of the button may release the content of

the of reservoir which refills on release of the buttonthe of reservoir which refills on release of the button

2.2. Depression of the button may fill the reservoir and the Depression of the button may fill the reservoir and the

content of which are ejected on release of the button. content of which are ejected on release of the button.

4. The concentrate (the active ingredients);4. The concentrate (the active ingredients);

The concentrate may present in 4 states; The concentrate may present in 4 states;

one liquid phaseone liquid phase

two liquid phase (o /w emulsion spray or w /o emulsion two liquid phase (o /w emulsion spray or w /o emulsion

sprayspray

powder spraypowder spray

One liquid phase;One liquid phase;

The propellant is completely miscible with the product to The propellant is completely miscible with the product to

form a single liquid phase in addition to the vapour phase form a single liquid phase in addition to the vapour phase

(2 phase aerosol system). This system gives homogenous (2 phase aerosol system). This system gives homogenous

spray with constant pressure.spray with constant pressure.

Two liquid phasesTwo liquid phases

When the solution of active ingredient in a suitable solvent When the solution of active ingredient in a suitable solvent

is not miscible with the propellant gives rise to three phase is not miscible with the propellant gives rise to three phase

aerosol systems consisting of the aerosol systems consisting of the propellant liquid phasepropellant liquid phase, ,

the solution liquid phasethe solution liquid phase and the vapour phase.and the vapour phase.

If the propellant is lighter than the solution, the dip-tube If the propellant is lighter than the solution, the dip-tube

must reach to the bottom of the container. must reach to the bottom of the container.

If the propellant is heavier than the solution, the dip-tube If the propellant is heavier than the solution, the dip-tube

must be shortened so that the tube dips in the aqueous must be shortened so that the tube dips in the aqueous

phase not in the propellant to avoid spraying the propellant phase not in the propellant to avoid spraying the propellant

and not the product.and not the product.

The 2 liquid phases may also be emulsified to produce an The 2 liquid phases may also be emulsified to produce an

emulsion system;emulsion system;

Oil in water emulsionOil in water emulsion

The propellant representing the oil phase which is The propellant representing the oil phase which is

immiscible with the aqueous phase solution of the product immiscible with the aqueous phase solution of the product

or the products containing water as carrier. or the products containing water as carrier. So it is So it is

necessary to emulsify the propellant in the product necessary to emulsify the propellant in the product

solution by using an emulsifying agent.solution by using an emulsifying agent. The ratio between The ratio between

the propellant and the emulsifying agent used is 1: 4 or 1: the propellant and the emulsifying agent used is 1: 4 or 1:

5 to ensure transparent product.5 to ensure transparent product.

Since the propellant is the internal phase, so when Since the propellant is the internal phase, so when

expanded on release from the valve it tends to produce expanded on release from the valve it tends to produce

foam and foam actuator must be fitted.foam and foam actuator must be fitted.

Water in oil emulsionWater in oil emulsion

By using an emulsifying agent such as polyglyceride ester By using an emulsifying agent such as polyglyceride ester

of fatty acid (Emecol 14) or sorbitan monolourate (span 20)of fatty acid (Emecol 14) or sorbitan monolourate (span 20)

Sine the propellant is the external phase the product can Sine the propellant is the external phase the product can

be sprayed to produce coarse wet spray or stream.be sprayed to produce coarse wet spray or stream.

powder spraypowder spray

They consists of a solid phase (the powder) suspended in a They consists of a solid phase (the powder) suspended in a

liquid phase (the propellant). The vapour phase consisting of liquid phase (the propellant). The vapour phase consisting of

the propellant vapour, the inclusion of lubricant and control of the propellant vapour, the inclusion of lubricant and control of

the particle size is necessary. Why? the particle size is necessary. Why? Because the too large Because the too large

particles may clog the valve and the agglomeration of the particles may clog the valve and the agglomeration of the

small particle may also cause clogging (the recommended sizes small particle may also cause clogging (the recommended sizes

of particles are 5 to 10 um and none greater than 50 um).of particles are 5 to 10 um and none greater than 50 um).

Due to the density difference between the solid particles and Due to the density difference between the solid particles and

the propellant the dispersed particles may be collected above the propellant the dispersed particles may be collected above

or below the propellant which may re-disperse by gentile or below the propellant which may re-disperse by gentile

shacking, but in some cases the collected particles form a hard shacking, but in some cases the collected particles form a hard

cake on long standing, which can not re-disperse by shacking, cake on long standing, which can not re-disperse by shacking,

in this cases, small balls of stainless steel or ceramic balls are in this cases, small balls of stainless steel or ceramic balls are

included to break down the hard cake while shacking of the included to break down the hard cake while shacking of the

container and re-dispersion can occur. container and re-dispersion can occur.