aersols

• Defn-
• A system that depends on power of
compressed liquified natural gas to expel the
contents from container
 advantages
• A dose can be removed without
contamination
• Can be delivered directly to affected area in
forms of-
1. Quick breaking foam
2. Stream
3. Spray
4. Stable foam
• Irritation produced by mechanical application
is reduced or eliminated
• Rapid onset of action
• Avoidance of GI degradition is achieved
• Dose lovering in case of steroids therapy and
dose titration to individual needs by using
metered dose
 Components of aerosol
• Propellant
• Valve
• Actuator
• Product concentrate
 propellants
• Responsible for developing proper pressure
within container
• Expels the product when valve is opened
• Aids in automization or foam product
 Types of propellents
• Liquified gases
• Hydrocarbons
• Ether
• Compressed gases
 propellents
• Liqudified gases at room temperature
• When placed into a container separates into
liquid and gaseous phase
• Relative inert
• Non toxic
• Maintains constant pressure
• Florinated hydrocarbons- widespread used in
most aerosols-
1. Inhalation use
2. Topical aerosols
• Hydrocarbons are-
1. Less toxic
2. Less dense
3. More economic
4. More soluble
5. Chemically more stable
 containers

containers

metals glass

tin Stainless
aluminum coated uncoated
steel
 Tin plated containers
• A sheet of steel plate electroplated with tin
• Obtained In thin sheet
• Coted with organic material
• These sheets are lithiographed
• Cutted into proper sizes
• Body is shaped into cylinder by flaging and
soldering operating
 Valve
• Multifuctional
• Opens and closes
• Capable of delivering the content
• Do not usually differ from non pharmaceutical
valve
• Must be FDA approved
 Continuous spray valve
• Consist of many different parts
• Assembled using high speed technique
• Various materials are used for manufacturing
diffrent
 Ferrule or mounting cap
• Used to attach valve proper to container
• Are used with glass bottle or small aluminum
tubes
• Attached to the container either by rolling the
end under the lip of the bottle
 Valve body or housing
• Manufactured from nylon or derlin
• Contains an opening point of attachment of
dip tube
• Ranges from 0.013 inch to 0.080 inch
• May contain another opening refering as
vapour tap
 Vapour tap
• Vapour tap further produces fine particle size
• Allows for the escape of propellent with liquid
product
• Further prevents valve clogging
• Allow the product to be satisfactorly
dispensed
• Available in size ranging from 0.013 to 0.080
 stem
• Made from nylon or delrin
• Brass and stainless steel can also be used
• One or more orifaces
• one oriface- 0.013 inches - 0.30 inches
• Three orifaces- 0.040 each
 Gasket
• Buna-N and neoprene rubber are commonly
used
 spring
• Serves to hold the gasket in place
• When the actuator is depressed and relese it
returns the valve to its closed position
• Stainless steel can be used
 Dip tube
• Made from polyethylene or polypropylene
• Polypropylene tube is more rigid
• Inside diameter is about 0.120 to 0.125 inches
• Capillary dip tubes are about 0.05 inches
• Viscous products- 0.195 inches
 Metering systems
• Applicable to dispense potent medication
• Approximate 50 to 150 mg can be dispensed
 actuators
• Ensures the product to be delivered in proper
desired form
• Allows easy opening and closing of valve
• Integral part of almost every aerosol pack
• Serves to aid in producing the required type of
product discharge
 Spray actuators
• Actuators that are capable of dispersing the
stream of the product
• The product concentrate and propellant into
relatively small particles allowing the stream
to pass through varrous openings
• Large percent of propellent mixture
containing sufficient quantity of propellent
such as propellent 12 or propane.
• Actuators having orifice can be used
combination of actuator orifice and internal
channel can deliver the spray in particle size
range
• Low amounts of propellent produces stream
 Spray actuators
• Used for-
1. Local anesthatics
2. Spray onn bandages
3. Topical use
 Foam actuators
• Large orifices
• Orifice ranges from 0.07 inches to 0.125 inch
or greater.
 Solid stream actuators
• Used for dispensing semisolid products such
as ointments
• Large openings
• Passage of product through the valve
• Similar to foam type actuators
 Special actuators
• Many pharmaceutical and medical aerosols
requre specially designed actuators to
accomplish a specific purpose
• They are designed to deliver medication to
appropriate site
• Eg throat, nose, eye, vaginal tract
Formuation of pharmaceutical aerosols

• Consist generally of two components:

1. Propellent
2. Product concentrate
• The product concentrate cosist of active
ingredient, other necessary agents such as
anti oxidant , surfactant
• Poprellent may be single or a blend of various
propellent
• Various surfactant for proper HLB for emulsion
system
• The propellent is selected to give desired
vapour pressure solubility and particle size
• Propellent can be combined with active
ingredients in many ways producing products
of very varying characteristics
 Types of systems
• Solution systems
• Water based system
• Suspension system
• Foam system
 Solution system
• Large number of aerosol are manufactured in
these manner
• These system are refered to as two phase
system
• Consist of vapour phase and gaseous phase
• When active ingredients are soluble in
propellent no other systems are required
• Depending on type of spray required the
propellents are choosen
• The propellent used are propellant 12 or A-70
• A lovering of vapour pressure can be done by
adding solvents such as ethanol propylene
glycol ethyl acetate
• Concentration of propellant may vary from
5% (foam)to 95% inhalation poducts
• Useful for topical preparations since they coat
afected area with thin flim of active ingredients
• Packed in 15 to 30 ml aluminium , stainless
steel or glass container
 Water based system
• Relative large amounts of water
• To produce a spray formulation must consist of
active ingredient and other solvents in an
emulsified system in which propellants is an
external phases
• Since the propellent is not soluble in water
this system is known as three phase system
• We have three phases the propellent phase
the water phase, the vapour phase
• Ethanol can be used to solublize some
propellent in water but result in lowering of
surface tension
• Surfactents can be used in large extent to
produce homogenous dispersion
• Long chain fatty acid esters of poly hydroxy
compunds are used
• Propellents concentration used is from 25% to
60%
 Suspension system
• Various method are used to overcome difficulties
encountered using co- solvents
• Dispersion of active ingredients in propellents
• Various surfactants or suspending agents are
used
• Particles of certain materials tend to agglomerate
immidiately or shortly in following suspension
owing to solubility moisture or particle size
growth
• Agglomeration may result in valve clogging
inaccuracy of dose, and depending on nature
of the active ingredient , damage to liner
possibly to the metal container
• Various surfactant and lubricants have been
investigated in attempt to control the rate of
agglomeration
 Foam systems
• Emulsion and foam aerosols contains-
1. active ingredient
2. Surfactant
3. Propellent
• Dispensed as-
1. Aqueous stable foams
2. Non aqueous stable foam
3. Thermal foam
4. Quick breaking foam
• The liquefied propellant is emulsified in such
way that it s found in internal phase
• Non aerosol emulsions usually in lotion or
liquid form
• But the aerosol emulsion are dispensed as
foams
 Aqueous stable foam
• as high as 5 %
• As the propellent amount increases more
stiffer foam
• Propellant A-70 and propellant A- 46
• Several different steroids, antibiotics, and
other agents may be dispensed
• Surfactant that showed some solubility in
propellents were most effective
 Non aqueous stable foams
• May be formulated through use of various
glycols
• Emulsifying agent propylene glycol
monosterate
• Various medicinal agents can be incorporated
into the base
 Quick breaking foam
• Propellant is the external phase
• When dispensed the product is emitted in
foam which collapse into liquid
• Applicable for topical system
• The surfactant may e of anionic, cationic or
non ionic type
• 90 % concentrate 10 % propellant
 Manufacture of aerosols
• Pressurized filling appratus
• Cold filling appratus
• Compressed filling appratus
 Pressurized filling appratus
• Consist of pressure burette
• Capable of metering small volumes of liquified
gas
• Propellent is added through inlet valve at
bottom or top of burette
• Trapped air is allowed to escape through upper
valve
• The desired amount of propellent is allowed to
flow through aerosol valve under its own
pressure
• When the pressure is equalized between
burette and container the propellent stops
flowing
• Cannot be used to fill inhalation aerosols
 Cold filling appratus
• Somewhat simpler
• Insulated box fitted with copper tubing
• Must be filled with dry ice or acetone prior to
use
• Can be used wih metered valve
• Not to be use to fill hydrocarbons.
 Compressed gas filling appratus
• Compressed gasses can be handeled easily
• Flexible hose is attached to a delivery gauge
• Flexible hose is capable of witstanding about
150 pounds per square inch
• The concentrate is placed in a container
• The filling head is inserted into valve opening
• The valve is depressed the gas is allowed to
flow
• When the pressure within the container is
equal to delivery presser gas stops flowing
 Large scale equipments
• Concentrate filler
• Valve placer
• Purger crimper
• Pressure filler
• Leak test fillers
 Concentrate fillers
• Single stage single hopper filler
• Large straight line multiple head filler
 Valve placer
• Manually
• automatically
 Purger and vaccum crimper
• serves dual function
1. Evacuate air within the containers
2. Seal valve in place
 Manufacturing procdure
• In two stages-
1. Preparation of concentrate
2. Addition of propellent
• Part of manufacture take place during filling
• Aerosol concentrate is prepared according to
generally accepted procedure
• Sample is tested
• Once the propellent is added the product is
sealed with the valve
 Quality control tests
 Flammability and combustibility
• Flash point
• Flame extension, including flashback
 Physicochemical properties
• Vapour pressure
• Density
• Moisture content
• Identification of propellant
• Concentrate-propellant ratio
Performance
• Aerosol valve discharge rate
• Spray pattern
• Dosage with metered valve
• Net contents
• Foam stability
• Particle size
• Leakage
Biological characteristics
 Flash point
• Determined by Standard Tag Open Cup
Apparatus
• Aerosolized product is chilled to a
temperature about -25°F
• Transferred to test apparatus
• The test liquid is allowed slowly increase in
temperature the vapours ignite is termed as
flash point
 Flame extension
• The product is sprayed about 4 sec
• Depending on nature the flame is extended
• The exact length is mesured using ruler
 Vapour pressure
• Calculated using pressured gauge
• Measured simply using pressurized gauge and
water bath test gauge and special instruments
 density
• By using hydrometer or pycnometer