PHARMACEUTICAL

AEROSOLS

Presented By,
Krishna Taretiya
Definition
 Packaging of therapeutic active
ingredients in a pressurized system.

 Aerosols are depends on the power of

compressed or liquefied gas to expel the
contents from containers.
 Advantages
• A dose can be removed with out contamination of
materials.

• The medication can be delivered directly to the affected

area in a desired form, such as spray, steam, quick
breaking foam or stable foam.

• Irritation produced by the mechanical application of

topical medication is reduced or eliminated.

• Ease of convenience of application.

• Application of medication in thin layer

 Components of aerosols

 Propellant

 Container

 Valve & actuator

 Product concentrate
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.
• For oral and inhalation eg.
Fluorinated hydrocarbons
Dichlorodifluromethane (propellant 12)
Dichlorotetrafluromethane (propellant 114)
• Topical preparation
Propane
Butane
Isobutane
• Compound gases
Nitrogen
Carbon di oxide
Nitrous oxide
• Containers
• They must be stand at pressure as high as 140 to 180
psig (pounds per sq. inch gauge) at 1300 F.
• A. Metals
• 1. Tinplated steel
• (a) Side-seam (three pieces)
• (b) Two-piece or drawn
• (c) Tin free steel
• 2. Aluminium
• (a) Two-piece
• (b) One-piece (extruded or drawn)
• 3. Stainless steel
• B. Glass
• 1. Uncoated glass
• 2. Plastic coated glass
• Physiochemical properties of propellants

• Vapor pressure

• Boiling points

• Liquid density
• Valves
– To delivered the drug in desired form.
– To give proper amount of medication.
– Not differ from valve to valve of medication
in pharmaceutical preparation.
• Types
• - Continuous spray valve
• - High speed production technique.
• - Metering valves
• Dispersing of potent medication at proper
dispersion/ spray approximately 50 to 150 mg ±10
% of liquid materials at one time use of same
valve.
Valve components
 Ferrule or mount cap

 Valve body or
housing

 Stem

 Gasket

 Spring

 Dip tube
 • Actuator
To ensure that aerosol product is delivered in
the proper and desired form.

Different types of actuators

Spray actuators
Foam actuators
Solid steam actuators
Special actuators
• Formulation of pharmaceutical aerosols
Contains two essential components
• Product concentrate
• Propellant
• Product concentrate
• Product concentrate contains ingredients or mixture of active
ingredients and other such as solvents, antioxidants and
surfactants.
• Propellant
• May be single or blend of various propellants
 Blends of propellant used in a p’ceutical formulation to
achieve desired solubility characteristics or various surfactants
are mixed to give the proper HLB value for emulsion system.
 To give the desired vapor pressure, solubility & particle size.
• Parameters consideration

 Physical, chemical and p’ceutical properties

of active ingredients.

 Site of application
• Types of system

Solution system
Water based system
Suspension or Dispersion systems
Foam systems
1. Aqueous stable foams
2. Nonaqueous stable foams
3. Quick-breaking foams
4. Thermal foams
Intranasal aerosols
• Manufacturing of Pharmaceutical
Aerosols

Apparatus

 Pressure filling apparatus

 Cold filling apparatus

 Compressed gas filling apparatus

• Quality control for pharmaceutical
aerosols

Propellants
Valves, actuator and dip tubes
Testing procedure
Valve acceptance
Containers
Weight checking
Leak testing
Spray testing
• Evaluation parameters of pharmaceutical aerosols
– A. Flammability and combustibility
1. Flash point
2. Flame extension, including flashback
– B. Physiochemical characteristics
1. Density
2. Moisture content
3. Identification of propellant(s)
4. Concentrate-propellant ratio
5. Vapor pressure
– C. Performance
1. Spray pattern
2. Aerosol valve discharge rate
3. Dosage with metered valves
4. Net contents
5. Foam stability
6. Particle size determination
7. Leakage
– D. Biologic characteristics
– E. Therapeutic activity
 Flame Projection
 This test indicates the
effect of an aerosol
formulation on the
extension of an open
flame.

 Product is sprayed for 4 sec. into flame.

 Depending on the nature of formulation, the

fame is extended, and exact length was
measured with ruler.
Flash point
• Determined by using standard Tag Open Cap
Apparatus.

Step involves are 

• Aerosol product is chilled to temperature of

- 25 0 F and transferred to the test apparatus.
• Temperature of test liquid increased slowly,
and the temperature at which the vapors ignite
is taken a flash point.
• Calculated for flammable component, which in
case of topical hydrocarbons.
Vapor pressure

• Determined by pressure gauge

• Variation in pressure indicates the presence of

air in headspace.

• A can punctuating device is available for

accurately measuring vapor pressure.
Density
Determined by hydrometer or a pycnometer.
Step involves are 
• A pressure tube is fitted with metal fingers
and hoke valve, which allow for the
introduction of liquids under pressure.
• The hydrometer is placed in to the glass
pressure tube.
• Sufficient sample is introduced through the
valve to cause the hydrometer to rise half
way up the length of the tube.
• The density can be read directly.
Moisture content
• Method used -- Karl Fischer method
 G. C has also been used
• Identification of propellants
 G.C,
 I.R Spectrophotometry
• Aerosol valve discharge rate
Determined by taking an aerosol known weight and
discharging the contents for given time using
standard apparatus.
By reweighing the container after time limit has
expired, the change in weight per time dispensed is
discharge rate,
Expressed as gram per seconds.
Dosage with metered valves
Amt. of medication actually received by the
patient.
Reproducibility has been determined by assay
technique,
Another method is that, involves accurate
weighing of filled container fallowed by
dispersing of several doses, container can
reweighed, and difference in weight divided
by No. of dose, gives the average dosage.
Reproducibility of dosage each time the valve
is dispersed
Net contents
• Weight method
• Filled full container, and dispensing the contents

Foam stability
• Visual evaluation
• Time for a given mass to penetrate the foam
• Times for given rod that is inserted into the
foam to fall
• The use of rotational viscometers
 Cascade impactor
Particle size determination

 Cascade impactor
 Light scatter decay method

Cascade impactor
• Operates on the projected through a series of nozzle
and glass slides at high viscosity, the large particles
become impacted first on the lower velocity stages, and
the smaller particles pass on and are collected at high
velocity stages.

• These particles ranging from 0.1 to 30 micron and

retaining on RTI.
• Modification made to improve efficacy
Light Scattering method
Porush, Thiel and Young used light
scattering method to determine particle size.
As aerosols settle in turbulent condition ,
the change in light intensity of Tyndall beam
is measured

Sciarra and Cutie developed method

based on practical size distribution.
• Metered dose inhaler

• To increased interest in
modifying metered dose
inhalers (MDIs) to
minimize the number of
• Administration error
and to improve the
drug delivery of aerosols
particles into the drug
delivery system of the
nasal passageways and
respiratory tract.
 Dry Powder Inhalers (DPIs)

• Drug is inhaled as a cloud of fine particles. The

drug is either preloaded in an inhalation device or
filled into hard gelatin capsule or foil blister discs
which are loaded in to a device prior to use.
• Dry powder inhalers are devices through which
dry powder formulation of an active drug is
delivered for local or systemic action via
pulmonary route.
• They are bolus drug delivery systems that contain
solid drug substance that is suspended or
dissolved in a non-polar propellant that is
fluidized when the patient inhales.
 Ideal DPI
• Effective dosing
• Uniform dose
• Targeted delivery
• Operable at low inhalation flow rates
• Efficient device
• Easy to use
 FORMULATION
• DPI formulations are generally engineered
composites, containing a drug material of
micron size formulated with or without a large
carrier material.
• The formulation is formulated around a device
that when actuated by patient is capable of
producing a respirable aerosol cloud that
penetrates the respiratory tract and reaches the
site of action.
 STEPS INVOLVED IN FORMULATION

• Active Pharmaceutical Ingredient

(API) production.
• Formulation of API with or
without carriers.
• Integration of the formulation into
device.
 DPI Design Issues
• Inhaler design, especially the geometry of the
mouth piece, is critical for patients to produce
an air flow sufficient to lift the drug from the
dose chamber, break up the agglomerates in
the turbulent air stream and deliver the drug
dose to the lungs as therapeutically effective
fine particles.
 Principle of operation
• When the patient actuates the DPI and inhales,
airflow though the device creates shear and
turbulence; air is introduced in to the powder
bed and the static powder blend is fluidized
and enters the patient airways. There the drug
particles separate from the carrier particles and
are carried deep into the lungs to exert the
effects.
 Evaluation
• Appearance
• Identity
• Microbial limits
• Water content
• Extractives
• Drug related impurities
• Particle analysis
• Drug content per unit dose/dose delivery
 Advantages
• Propellant free design
• Less need for patient coordination
• Less potential for formulation problems
• Environmental sustainability
• Less potential for extractable from device
components
 Disadvantages
• Dependency on patient inspiration flow rate
and profile
• Device resistance and other device issues
• More expensive than pressurized MDI
• Complex development and manufacture
• Not available world wide
• Greater potential problems in dose uniformity