AEROSOLS

(Pressurized package system)

Types of aerosol systems

Liquefied gas system
Compressed gas system
Barrier packs

Component of aerosol systems

1. Propellant
2. Container
3. Valve and actuator
4. Product Concentrate

Types of propellant

Hydrocarbon
(Propane, Butane, Isobutane)

Chlorofluorocarbon (EPA Banned )

(Trichloromonofluromethane,Dichlorodifluromethane)

Compressed gases: (Nitrogen, Nitrous oxide,Carbondioxide)

Types of containers
They must be stand at pressure as high as 140 to 180 psig(pounds per sq. inch
gauge) at 1300 F
1)Tinplated containers
Available in sheets
3 piece body
Coating is done after fabrication
2) Aluminum containers
Seamless
Great resistance to corrosion
Incompatible with pure water and ethanol

3) Stainless steel containers

Production hurdles
Costly
Use in inhalation aerosols
No internal coating

4) Glass containers
15-30ml Volume
Available without plastic coating
Good corrosion resistance
Freedom for design of containers
Not recommended for suspension

An aerosol is made up of several basic components:

An aerosol can
The product
The propellant
A valve with dip tube
An actuator

The product,
usually in the
form of a liquid,
is added.
This contains
active
ingredients,
except
propellant.

The propellant is
injected under
pressure, through the
valve.
The propellant may
be in the form of a
liquified gas, or a
compressed gas.

Valve and actuators

FDA approved valve
Valve made-up of
Actuator,Stem,Gasket,Spring,Mounting cup,
Housing, Dip-tube
Metering Valve
Actuator :
Integral part of aerosol
Spray actuator
Foam actuator
Solid stem actuator
Special actuator

Dispensing System: Actuators

Foam Actuator

Metered aerosol

Special actuator

Product concentrate
1.
2.
3.
4.
5.
6.

Active ingredient
Solvent
Antioxidant
Surfactant (Isopropyl myristate)
Sweetener (Aspartame)
Flavors (Strawberry )

Objective of Aerosol dosage form

Dose removed without contamination
Stability is enhanced for oxygen and moisture
sensitive drugs
Irritation by local administration is reduced
Ease and self administration
Uniform application of drugs
Ideal for the drug entity exhibits erratic
pharmacokinetic
Quick effect of drug

Aerosol solution

Preferred dosage form

Two phase system
Generally single propellant is used
Lowering of vapor pressure produced by
ethyl alcohol, propylene glycol, glycerine
and acetone
Amount of propellant 5% - 95%

Aerosol suspension

To avoid co-solvency

Dispersion of active ingredient

Used for oral administration

Surfactant is used ?

Physical stability of aerosols:

Reduction of particle size (2-5 Micron)

Adjustment of density

Use of dispersing agent

Aerosol Emulsion
Component
1.
2.
3.
4.

Active ingredient
Aqueous and nonaqueous vehicle
Surfactant
Propellant

Approx 7-10% Propellant

Stable foam
Quick breaking foam
Emulsion are available in foam forms, Edible
foams, Cough remedies , Antacids, vitamins

Drug deposition

System affected by- Particle size,

Aerosols velocity, Hygroscopicity

Device characteristic

Breathing pattern

Morphology of upper and lower airways

Intranasal application
Steroids, insulin, peptide and proteins are administered
Excellent depth of penetration
Lower doses compared to oral dose
Maintenance of sterility of dose
Aerosols suspension are preferred formulation for nasal
administration
Bypass Blood Brain Barrier
Nose to brain drug delivery system

Intra Nasal DDs

The FDA has cleared the NasalNeb for the delivery of aerosol to the upper
airway! And, in an unprecedented move, Healthline Medical has incorporated its
integrated filter, thereby protecting both caregiver and the environment!

Metered dose containers

Use in the treatment of asthma
Popular than nebulizer and DPI
60-90% of drug deposited in pharyngeal
area
Spacers are use

Drug substances for intranasal DDS

Local effect of drug
Less bioavailability
Quick effect of drug
Airway obstruction
Antispasmodic
Corticosteroids
Antidiabetic

Manufacturing of aerosols
Pressure filling apparatus
Cold filling apparatus
Compressed gas filling apparatus

Pressure filling apparatus

Consist of pressure burette
Desired amount of propellant is allowed to
flow
Additional propellant is added through the
hose or piston
Metered dose intranasal preparation are
not filled by this method

Cold filling apparatus

Insulated box fitted with copper tubing
Filled with dry ice/acetone prior to use
Use with meter as well as non metered
valve
Unsuitable for hydrocarbon aerosol

Compressed gas filling apparatus

Concentrate is filled in the container

The valve is crimped in the place
Air is evacuated by means of vacuum pump
Filling head is inserted into the valve opening
Gas is allow to flow in the container
The container is shaken manually during and
after filling

Evaluation of aerosols
1. Flammability and combustibility

Flash point (-25F,Tag open cup Apparatus)

Flame extension (Flame)

2.Physicochemical characteristic

Vapor pressure
Density (Hydrometer or Pycnometer)
Moisture content (Karl Fischer & GC )
Identification of propellant (GC&IR)
Concentrate propellant ratio

Evaluation of Aerosols
3. Performance
Aerosols valve discharge (gm/sec)
Spray pattern (Dye-talc power)
Dosage with metered dose (Assay technique)
Net content (Destructive method) (Eye drops)
Foam stability (Visual,Mass,Line)
Particle size determination (Light scattering viscometer)
Leakage (Heating at 130F)

4. Biologic characteristic
5. Therapeutic testing
6. Toxicity studies

Recent advances

Metered dose inhalers

Sublingual aerosols

Anti diabetic aerosols (Insulin liposome for

controlled drug delivery system)

Pressurized metered dose inhalers

Administration of proteins and peptides