PULMONARY DRUG DELIVERY
SYSTEM
www.DuloMix.com
CONTENTS
AEROSOL
PROPELLANTS
ADVANTAGES
TYPES OF AEROSOL SYSTEM
PREPARATION
EVALUATION
CONCLUSION
REFERENCE
AEROSOL
An aerosol is a colloid of fine solid particles or liquid droplets, in air or another gas.
Aerosols can be natural or anthropogenic. Examples of natural aerosols are fog, dust,
forest exudates and geyser steam.
ADVANTAGES
➢ The drug sensitivity to the effect of oxygen or moisture is protected and stability is
enhanced.
➢ The drug can be directly applied to the affected areas.
➢ Administration of drug by aerosol is a rapid process.
➢ It protects the drug from gastrointestinal tract degradation.
➢ Hepatic first pass metabolism is avoided.
➢ Aerosols are used for both systemic and local application.
➢ Easy to apply.
COMPONENTS OF AEROSOL
Product concentrate
Propellant
Aerosol
Valves
Container
Actuator
PRINCIPLE OF RELEASING OUT OF PRODUCT
CONCENTRATES FROM CONTAINER
➢Liquefied propellant or propellant mixture exists in equilibrium with the product
concentrate in a sealed aerosol container.
➢ The liquefied propellant vaporizes and occupies the upper portion of the aerosol
container.
➢The liquefied propellant exists in equilibrium with the propellant in the vapour phase
in an aerosol container,
➢A constant pressure is maintained within the aerosol container. Hence, it is called as
a pressurized aerosol container.
➢The pressure exerted by the propellant is called as vapour pressure, measured in
psig; is the characteristic of specific propellant.
➢The actuation of the valve, the pressure exerted by the propellant is distributed
equally in all direction in the aerosol container, forcing the product concentrate up the
dip tube and out of the aerosol container.
➢As the vapour pressure of the propellant in air is lower than inside the aerosol
container, so the propellant evaporates on reaching the air and product concentrates
dries up as dry particles.
PROPELLANTS
➢The propellant or propellant mixture used in the MDI provides the energy necessary
to generate a fine aerosol of drug particles suitable for delivery to the lungs or nasal
cavity.
➢Liquefied compressed gases are preferred over non-liquefied compressed gases such
as nitrogen or carbon dioxide.
Types of propellant
1. Chlorofluorocarbon (CFC) propellants
2. Hydrocarbons Propellants
3. Compressed gas propellants
TYPES OF PROPELLANT
Application Name of propellant
Fluorinated hydrocarbon
Di chloro difluro methane(propellant 12)
Tri chloro monofluro methane(propellant 11)
For oral and inhalation Di- chloro tetrachloro methane(propellant 14)
Topical preparation Propane , butane, Isobutane
Compound gases Nitogen,carbon dioxide,Nitrous oxide
CHLOROFLUOROCARBON (CFC) PROPELLANTS
➢The basic characteristics of propellants are chemical inertness ,lack of toxicity ,lack
of flammability and explosiveness.
➢Due to the presence of these characteristics ,the chlorofluorocarbon (CFC)
propellants P-11, P-12, and P-14 were used in aerosol products for several years.
➢Now a day their uses have been declined as they cause the depletion of ozone layer.
➢But due to their relatively low toxicity, inflammability, they are still use in low
amount in the treatment of asthma and chronic obstructive pulmonary disease
(COPD).
➢ P-134a and P-227 are now been developed and are being incorporated in aerosol
formulations in place of P-12
HYDROCARBONS PROPELLANTS
➢The environmental acceptance, low toxicity and non reactivity are the characteristics
of hydrocarbons propellants allowing them to be used as the propellant.
➢Hydrocarbons are used in the preparation of water based aerosols as they are not
susceptible to hydrolysis due to the absence of chlorine.
➢They are immiscible with water, so they remain on the top of water.
➢They provide the force to push the contents out of the container.
Disadvantage
➢Flammability.
➢Explosiveness.
➢ It is being reduced by using a blend of propellant. Also the use of vapour tap valve
reduces flammability.
COMPRESSED GAS PROPELLANTS
➢Compressed gas like Nitrogen, Nitrogen dioxide and Carbon dioxide as propellant
dispenses products in the form of fine mists, foams or semisolid.
➢ It produces fairly wet sprays and the foams are not as stable as produced by the
liquefied gas propellant.
➢ The aerosol prepared with liquefied gas propellant, there is no propellant reservoir.
➢ The compressed gas propellant is contained in the headspace of the aerosol
container which forces the product concentrate out of the container.
➢ Higher gas pressure is required in this aerosol.
➢This aerosol finds its application to dispense food products, dental creams, hair
preparation and ointments.
CONTAINERS
Aerosol containers are generally made of
➢Glass
➢ metals
➢Tin
➢Plated steel
➢Aluminum
➢Stainless steel
➢Plastics
The aerosol containers must withstand pressure as high as 140 to 180 psig (pounds per
sq. inch gauge) at 130 0F.
PRESSURE LIMITATIONS OF AEROSOL CONTAINER
Contain material Temperature((0F)
Maximum Pressure(psig)
Tin -plated steel 130
180
Uncoated glass < 18 70
Coated glass < 25 70
Aluminum 180 130
Stainless Steel 180 130
Plastic < 25 70
GLASS
➢ Thus glass containers are used in lower pressure and when low amount of propellant
are in use such as if the pressure is less than 25psig propellant content is less than 15%.
➢ To protect the glass containers against breakage due to high pressure, it is to be coated
with plastic coating in two layers.
➢ Epoxy and vinyl resins can be used as linings.
➢ Vinyl resins are not resistant to high temperature of the steam about 200 0F.
➢ Epoxy resins are resistant to steam.
➢ Epoxy resins coatings are suitable for low pH water based products.
TINPLATED STEEL
➢It provides light and inexpensive aerosol container.
➢The both sides of the tin container are electroplated with sheets of steel plates.
➢To protect the inside of the container from corrosion and also to prevent the
interaction between the tin and the formulation.
➢Oleoresin, phenolic,vinyl, or epoxy coatings are used as the coating materials.
➢The tin plated steel containers are used in topical aerosols.
ALUMINIUM
➢ Light weight
➢ Less prone to corrosion than other metals.
➢ Aluminum used in most metered dose inhalers (MDIs) and many topical aerosols.
➢ Epoxy, vinyl, or phenolic resins coatings are done on aluminum containers to
reduce the interaction between the aluminum and the formulation.
➢ The seamless aerosol containers manufactured by an impact extrusion process have
greater safety against leakage, incompatibility, and corrosion.
➢ The container themselves available in sizes ranging from 10ml to over 1,000 ml.
STAINLESS STEEL
➢As it is strong and resistant to corrosion.
➢No coating is required.
➢ It can withstand high pressure.
➢The drawback is expensiveness which restricts its sizes to small sized containers.
PLASTIC
➢As plastics are highly permeable to vapours and air like oxygen.
➢They are interaction with the formulation may occur and also may lead to oxidative
degradation of the formulation.
➢ Polyethylene tetra phthalate (PET) container as used for some non pharmaceutical
products.
VALVE
➢A valve delivers the drug in desired form and regulates
the flow of product concentrate from the container.
➢The valve should be able to withstand the pressure
encountered by product concentrate.
➢The container, should be corrosion resistant.
1. Continuous spray valve
2. Metering valve.
ACTUATOR
➢It is the button which the users press to activate the valve assembly and controls
the easy opening and closing of valve, also directs the spray to the desired area.
➢ The actuator contains orifices of varying size and shapes as well as the expansion
chamber which determines the type and quantity of propellant used.
➢Actuator design and the physical characteristics of the emitted product
concentrate in the form of spray or foam.
➢In the case of inhalation aerosols where it is necessary to control the proper
particle size of the product concentrate.
ACTUATOR
TYPES OF ACTUATOR
Spray actuator
Types of actuator
Foam actuator
Solid stream actuator
Mist actuator
STEM
➢ The actuator is supported by the stem and the formulation is
delivered in the proper form to the chamber of the actuator by the
stem.
➢ It is made up of Nylon, Delrin,Brass and Stainless steel.
GASKET
➢The stem and valve are placed tightly in their place by the gasket
and the leakage of the formulation is prevented by gasket.
➢It is made up of Buna N and Neoprene rubber.
SPRING
➢The gasket is held in its place by the spring and also helps to keep
the valve in closed position when the pressure is released upon
actuation of the formulation.
HOUSING OR VALVE BODY:
➢ The Housing or Valve body located
directly below the Mounting cup or Ferrule
is made up of Nylon or Delrin work to
connect the dip tube and the stem and
actuator.
➢The rate of delivery of product and the
desired form in which the product is to be
emitted is determined by its orifice.
Mounting Cup or Ferrule:
➢The Mounting cup or Ferrule is generally made up
Mounting Cup or Ferrule:
of aluminum which serves to place the valve in its
position, and attached to the aerosol container.
➢The mounting cup or Ferrule is exposed to the
contents of the container, so it is to be compatible
with the contents so as to prevent any interaction.
➢ It may be coated with an inert material such as vinyl
coating as it prevents any interaction with the
contents also corrosion of aluminum is prevented.
Dip Tube:
➢The dip tube is made up of polyethylene or
polypropylene extends from the housing body or valve
body down into the product concentrate works to bring
the formulation from the container to the valve.
➢The inner diameter of the dip tube depends on the
viscosity and the desired rate of delivery of the product.
➢The inner diameter of the dip tube increases with an
increase in the viscosity of the formulation.
➢For less viscous solutions, the inner diameter ranges
from 0.12 inch to 0.125 inch.
➢While for viscous solution, inner diameter is as large as
0.195 inch.
TYPES OF INHALERS
Depending on the physical state of the dispersed phase and continuous medium,
inhaled drug delivery system is classified into three principle categories
1. Pressurized metered dose inhaler (PMDI)
2.Dry powder inhaler (DPI)
3.Nebulizer
METERED DOSE INHALER (PMDI)
➢Metered dose inhaler (PMDI) are composed of a canister, and actuator, and
sometimes a spacer. The canister is composed of a metering dose valve with an
actuating stem.
➢The formulation(containing the active ingredient i.e. drug, a liquefied gas
propellant, and a stabilizer) is present in the canister.
➢The drug may be suspended or dissolved in the liquefied gas propellant.
➢Upon actuation, the metering dose valve is opened which releases a single
metered dose of medication along with the liquified gas propellant to spray out of
a canister. This process is called cavitation.
➢The liquefied gas propellant is volatile in nature, breaks down into liquid
droplets which evaporates rapidly, and the dried micronized drug are inhaled to
the lung.
METERED DOSE INHALER (MDI)
DRAWBACK OF PMDI
➢ Till 1990s, various chlorofluorocarbons (CFC) were used as the propellant; it caused
depletion of ozone layer; so later it was replaced with hydro fluorocarbons. Hydro
fluorocarbons suffer from the drawback of greenhouse effect.
➢As PMDI is pressurized, it emits the dose at high velocity and gets deposited in the
oropharynx.
➢ The propellant and the co solvent may extract some of the organic compounds from
the device components and leads to chemical degradation.
➢A careful coordination of actuation and inhalation are required.
➢ High chances of pharyngeal depositions. Later on, the formulation related short
comings are reduced by Dry powder inhaler (DPI).
DRY POWDER INHALER
➢DPIs are composed of micronized powdered drug particles.
➢The micronized powdered drug particles (of sizes < 5µm) are mixed with much
larger sugar particles (of size < 30 µm) eg. Lactose monohydrate.
➢The smaller drug particles forms loose with lactose monohydrate.
ADVANTAGES
➢DPIs require little or no coordination of actuation and inhalation as they are
activated By patient’s Inspiratory airflow.
➢DPIs don’t extract organic compounds from the device components in contrast to
the PMDIs and the chances of chemical degradation are lesser than PMDI.
➢ The rate of drug delivery is better than PMDI.
➢ DPIs are efficient, more stable than PMDIs and easier to use than PMDI.
The DPIs are classified into two types
1. Unit dose devices
2. Multi dose devices
UNIT DOSE DEVICES
➢Unit dose devices are being developed as re-useable or disposable single-dose dry
powder inhalers.
➢They are designed to be easy to use and inexpensive to manufacture
➢It may be suitable for a wide range of conditions that require a rapid onset of effect
or that are for occasional use.
A wide range of unit dose dry powder inhalers are in use such as-
The Innova TM (Inhale Therapeutic Systems, San Carlos, California, and U.S.A.)
The Solo TM
MULTI DOSE DEVICES
➢It was the first developed multi dose DPIs by A.B. Draco (now a division of
AstraZeneca) capable of delivering carrier-free particles at moderate flow rates.
➢ Drawbacks of the Turbuhaler is that it has a variable rate of delivery due to different
flow rate.
➢To work out with the drawback and for replaced by Diskhaler developed by
Glaxosmith
A wide range of unit dose dry powder inhalers are in use such as-
Disk haler
Disk use
Click haler
Duo haler
NEBULIZER
➢Nebulizer is a device used to administer aerosolized medication in the form of a
mist inhaled into the lungs.
➢Nebulizers use oxygen, compressed air or ultrasonic power to break up medical
solutions and suspensions into small aerosol droplets called mists.
➢ That can be directly inhaled from the mouthpiece of the device.
➢ Nebulizer produce a mist of drug containing water droplets for inhalation.
➢The drug is present either in solution form or suspension form in the nebulizer.
It is usually of two types:
1. Electronic nebulizer
2. Jet or ultrasonic nebulizer
TYPES OF AEROSOL SYSTEM
Water based system or three
Solution system or two
phased system
phased system
Types of aerosol systems
Foam system
Suspension or
dispersion system
SOLUTION SYSTEM OR TWO PHASE SYSTEM
➢It is also called two-phase system as it contains both the vapour and the liquid. Based
On the desired spray, the propellant can be used single or a mixture of propellants can
be used.
➢Propellant 12 is added alone or in mixture. If propellants having vapour pressure lower
than propellant 12is added to propellant 12, a reduction of vapour pressure is achieved
but bigger sized aerosol particles are obtained.
➢Also bigger sized aerosol particles are obtained on addition of co solvents like ethyl
acetate, propylene glycol, ethyl alcohol , glycerin and acetone.
➢ The solution system is administered in topical application.
Some of the commonly used propellant combinations in solution systems are
propellant 12/11 (30:70),
propellant 12/14 (45:55),
propellant 12/14 (55:45).
WATER BASED SYSTEM OR THREE PHASE SYSTEM
➢In the water based or three phase system, large quantity of water is present to
solubilise the contents.
➢The water is immiscible with the propellant. Generally water based system is a three
phase system consisting of a water phase, vapour phase and the propellant.
➢The solubility of propellant in water can be increased by adding a cosolvent such as
ethanol and also by adding surfactants at a range of composition0.5% to 2.0 %.
➢The propellant composition ranges from 25 to 60%.
➢ The non polar surfactants such as esters of Oleic acid , palmitic acid, stearic acid
are more preferred than the polar surfactants.
➢ The surfactants act by reducing the interfacial tension existing between the water
phase and the propellant.
SUSPENSION OR DISPERSION SYSTEMS
➢Suspension or dispersion system is the dispersion of the active ingredients in the
propellant or the mixture of propellant by adding surfactants or the suspending
agents.
FOAM SYSTEM
➢The liquefied propellant is emulsified.
➢Aqueous or nonaqueous vehicles, propellant and the surfactants are its ingredients.
➢Foam system is further classified as aqueous stable, nonaqueous stable and the quick
breaking foam.
AQUEOUS STABLE FOAMS
➢The aqueous stable foam consists of propellant in the range of 3.0 to 4.0 %.
➢A dry spray is produced by the propellant
➢ The concentration of propellant goes on increasing, more and more contents are
delivered in dried form.
➢The propellant is present in the internal phase, so the concentration of propellant is
less.
➢It finds its application in steroid antibiotics
NON AQUEOUS STABLE FOAMS
➢The non aqueous stable foam contains glycol as the emulsion base and is used as the
emulsifying agent.
QUICK BREAKING FOAMS
➢The external phase is propellant.
➢The product will come out as foam which soon merges to form liquid.
➢ This type of system can be applied to small area or larger surface.
➢These are used for topical application.
➢Cationic or anionic or non-ionic surfactants are used in the formulation.
THERMAL FOAMS
➢The aerosol which is delivered in the form of foam upon the application of heat is called
thermal foam.
➢They are used in shaving creams.
MANUFACTURING OF PHARMACEUTICAL
AEROSOLS
The manufacturing of aerosol consists of three types of apparatus
1. Cold filling apparatus
2. Pressure filling apparatus
3. Compressed gas filling apparatus:
COLD FILLING APPARATUS
➢It consists of an insulated box fitted with copper tubing. The insulated tubing are filled
with dry ice or acetone.
➢The copper tubing increase the surface area and cause faster cooling.
➢The hydrocarbon propellant is not to be stored in the copper tubing as it might cause
explosion.
PRESSURE FILLING APPARATUS
➢Pressure filling apparatus consists of a metering burette capable of measuring the
amount of propellant to be filled to the aerosol container.
➢The propellant is added through the inlet valve present to the bottom of the valve under
its own vapour pressure.
➢A cylinder of nitrogen or compressed gas is attached to the top of the valve and the
pressure of nitrogen causes the propellant to flow to the container through the metering
burette.
➢The propellant flows to the container stops when the pressure of the flowing propellant
becomes equal to the pressure of the container.
COMPRESSED GAS FILLING APPARATUS:
➢A compressed gas propellant is used.
➢As the compressed gas is under high pressure, so the pressure is reduced by pressure
reducing valve.
➢A pressure of 150 pounds per square inch gauge is required to fill the compressed gas
propellant in the aerosol container.
➢The product concentrate is placed in the pressure gauge and the valve is crimped in its
place. The air is evacuated.
➢The filling head is inserted into the valve opening. Upon the depression of the valve,
the compressed gas propellant is allowed to flow into the container.
➢The compressed gas stops flowing when the pressure of the compressed gas flowing
to the container from the burette becomes equal to the pressure within the container.
➢In case of increasing the solubility of the gas in the product concentrate and also
when an increased amount of compressed gas is required, carbon dioxide and Nitrous
dioxide is used.
➢ The container is needed to be shaken during and after the filling operation to
enhance the solubility of the gas in the product concentrate.
The filling of aerosol product into the container is by two methods:
1. Cold filling method
2. Pressure filling method
COLD FILLING METHOD
➢In the first method, the product concentrates are chilled to a temperature of – 30 to – 400
F. The chilled product concentrates are added to the chilled aerosol container.
➢The chilled propellant is added through an inlet valve present under side of the valve of
the aerosol container.
➢ In the second method, both the product concentrate and the propellant are chilled to –
30 to – 400 F. Then the mixture is added to the chilled container.
➢After the aerosol containers are filled, the valves are set in its place and the filled
aerosol containers are passed through a water bath in which the contents of the containers
are heated to 130 0 F to test for leaks and strength.
➢Then the containers are air dried, capped and labelled.
➢Cold filling method is advantageous for the filling of metering valve containing aerosol
container.
PRESSURE FILLING METHOD
➢The product concentrate is filled to the aerosol container through the metering
pressure filling burette at room temperature.
➢The propellant is added through the inlet valve located at the base of the valve or
under the valve after the crimping of valve.
➢The flow of propellant to the aerosol container continues till the pressure of the filling
propellant becomes equal to the pressure within the container.
➢The aerosol container are capped and labelled.
➢The pressure filling methods have the following advantages over the cold filling
method
ADVANTAGES OF PRESSURE FILLING METHOD
➢ The emulsion, suspensions are unstable at very low temperature.
➢The pressure filling method is the preferred method than that of cold filling method.
➢The absence of moisture reduces the chance of contamination.
➢The rate of production is high.
➢ The chance of loss of propellant is low.
Concentrate filler, Valve placer, Purger and vacuum crimper , Pressure filler, Leak
test tank equipments are used for large scale of production.
QUALITY CONTROL OF PHARMACEUTICAL
AEROSOLS
Quality control and analytical tests
Individual component testing
➢Containers
➢Metering valve
➢ Mean weight per actuation and leakage rate
➢Input micronized drug
➢Propellant
➢Surfactant
➢Actuator
IN PROCESS CONTROL TESTING
➢Atmosphere condition
➢Drug suspension concentration
➢Drug suspension
➢Filled canisters
➢ Gross leakage and safety
➢Control of leakage rate
➢Metering valve function
ANALYTICAL TESTING APPLIED TO FINISHED PRODUCT
➢Identity
➢Microbial limit test
➢Spray pattern
➢Water content
➢Foreign particulate matter
DRUG PRODUCT SPECIFICATION TESTS FOR INHALATION PRODUCTS
➢Description
➢Assay
➢Moisture content
➢Mean delivered Dose
➢Delivered dose Uniformity
➢Content uniformity/ Uniformity of dosage Units
➢Fine particle mass
➢Leak rate
➢Microbial /Microbiological limits
➢Sterility
➢Leachable
➢Preservative Content
➢Number of actuations per container
Quality control of pharmaceutical aerosol includes the testing of propellant, valves,
actuator and dip tubes, containers , weight checking, leak testing and spray testing.
PROPELLANT
All quality control testings of propellants are accompanied by specification sheets:
➢A sample is taken out and vapour pressure is determined which then is compared to
specifications. The density is also checked when necessary.
➢ Identification of two or more blends of propellant by Gas chromatography.
➢very Purity of the propellant is checked by moisture, halogen , and non-volatile
residue determinations.
VALVES,ACTUATORS AND DIPTUBES
➢Both physical and chemical examinations are done. They are sampled according to
the standard procedures as found in“Military Standard Mil – STD-105D”.
➢A test method was developed for metered dose pharmaceutical aerosol by Aerosol
specifications committee, Industrial Pharmaceutical Technology section, Academy of
Pharmaceutical Science with an objective of determining the magnitude of valve
delivery and degree of uniformity between individual valves.
PREPARATION OF TEST SOLUTIONS
Ingredients % w/w Test solution A Test solution B Test solution
C
Isopropyl myristate 0.1 % 0.1 % 0.1 %
Dichlorodifluoromethane 49.95% 25% 50.25%
Dichlorotetrafluoroethane 49.95% 25% 24.75%
Trichloromonofluoromethane – – 24.95%
Alcohol USP – 49.9% –
Specific Gravity at 25 0 C 1.384 1.092 1.388
TESTING PROCEDURE
➢Take 25 valves and placed on suitable containers.
➢The containers are filled with specific test solutions.
➢A button actuator with 0.02 inch orifice is attached to the valves.
➢The filled containers are placed in a suitable atmosphere at a temperature of 25 ±
10C
➢ When the products have attained the temperature of 25 ± 10C, the filled containers
are actuated to fullest extent for 2seconds.
➢This procedure is repeated for a total of 2 delivered from each 25 test units.
➢The valve delivery per actuation in µl=Individual delivery weight in mg/Specific
gravity of test solution
LIMITS FOR ACCEPTANCE OF AEROSOL VALVES
Deliveries Limits
54 µl or less ± 15 %
55 to 200 µl ± 10 %
➢If 4 or more deliveries are outside limits, then valves are rejected.
➢If 3 or more deliveries are outside limits, another 25 valves are tested.
➢Lot is rejected if more than 1 delivery is outside specification.
➢ If 2 deliveries from 1 valve are beyond limits: another 25 valves are tested.
➢Lot is rejected if more than 1 delivery is outside specification.
CONTAINER
Containers are examined for defects in linings. Quality control aspects include degree of
conductivity of electric current as measure of exposed metals. Glass containers
examined for flaws.
WEIGHT CHECKING
➢It is done by periodically adding empty tared containers to filling lines which after
filling with product concentrate are removed and reweighed. Same procedure is used for
checking weight of the propellant.
LEAK TEST
➢It is done by measuring the crimp’s valve dimension and comparing. Final testing of
valve enclosure is done by passing filled containers through the water bath.
SPRAY TESTING
➢ It is done to clear up dip tube of pure propellant and concentrate and to check any
defects in the valve and the spray pattern.
PHYSICOCHEMICAL CHARACTERISTICS OF
PROPELLANTS AND PRODUCT CONCENTRATES
Characteristics Measuring device
Vapour pressure Can puncturing device, Pressure gauge
Density Hydrometer, Pycnometer
Moisture content Karl Fischer method,
Gas chromatography
Identification of propellant Gas chromatography,
Infrared spectrophotometry
EVALUATION TESTS OF PHARMACEUTICAL
AEROSOLS
FLAMMABILITY AND COMBUSTIBILITY
It includes Flame projection and Flame extension.
Flame projection:
The aerosol product is sprayed to an open flame for about 4 second and the extension
of the flame is measured with the help of a ruler.
Flash point:
Tag Open Cup apparatus is the standard test apparatus. The aerosol product is chilled
to a temperature of about – 25 0 F and transferred to the test apparatus. The
temperature of the test liquid is increased slowly and the temperature at which the
vapours ignite is taken as the flashpoint.
PERFORMANCE TEST
Aerosol Valve Discharge
➢Known weight is taken and its contents are discharged using standard apparatus for a
given period of time.
➢The container is reweighed.
➢Then the change in weight per time dispensed is the discharge rate.
➢The discharge rate can also be expressed as grams per second.
Spray patterns:
➢The method involves the impingement of sprays on a piece of paper that has been
treated with dye –talc mixture.
➢It gives a record of the spray pattern.
DOSAGE WITH METERED VALVES
➢ The doses are dispensed into the solvents or onto a material that absorbs the active
ingredients.
➢The assay of the solution gives the amount of active ingredients present.
➢Another method involves accurate weighing of the filled container followed by
dispensing of several doses.
➢The container is then reweighed, and the difference in weight divided by the number
of doses dispensed gives the average dose.
➢This process is repeated and the results are compared.
NET CONTENTS
➢The tared cans are placed onto the filling line are weighed, the difference in weight is
equal to the net contents.
➢The other method is a Destructive method and consists of weighing a full container and
then dispensing the contents.
➢The contents are then weighed.
➢The difference in weight gives the amount of contents present in the container.
Foam stability:
➢The life of a foam ranges from a few seconds (for quick breaking foam) to one hour or
more depending on the formulation.
➢To determine the foam stability includes visual evaluation,
➢Time for a given mass to penetrate the foam,
➢Time for a given rod that is inserted into the foam to fall
➢Rotational viscometer.
Particle size determination:
➢Cascade impactor and light scattering decay methods are used for particle size
determination.
➢It is based on the principle that for a stream of particles projected through a series of
nozzle and glass slides, the larger particles are impacted first on the lower velocity stage
and the smaller particles are impacted on the higher velocity stage.
BIOLOGICAL TESTING
Therapeutic activity and Toxicity are considered in Biologic testing.
THERAPEUTIC ACTIVITY:
FOR INHALATION AEROSOLS:
➢The determination of therapeutic activity is dependent on the particle size.
FOR TOPICAL AEROSOLS:
➢Therapeutic activity of aerosol products are determined by applying the
therapeutically active ingredients topically to the test areas and the amount of
therapeutically active substances absorbed is determined.
TOXICITY STUDY
FOR TOPICAL AEROSOLS:
➢ The topically administered aerosols are checked for chilling effect or irritation in
the skin.
➢When aerosol are topically applied, thermistor probe attached to the recording
thermometer are used to determine the change in skin temperature for a given period
of time.
FOR INHALATION AEROSOLS:
➢Inhalation toxicity study is done by exposing test animals to vapours sprayed from
the aerosol container.
LABELLING
Medicinal aerosols should contain at least the following warning information on the
label as in accordance with appropriate regulations according to USP:
WARNING— Avoid inhaling. Avoid spraying into eyes or on to other mucous
membranes.
NOTE—The statement “Avoid inhaling” is not necessary for preparations
specifically designed for use by inhalation. The phrase “or other mucous membranes”
is not necessary for preparations specifically designed for use on mucous
membranes.
CONCLUSION
➢Pharmaceutical aerosol is a noninvasive pulmonary drug delivery system which is
considered to be one of the best methods as compared to other routes of
administration.
➢Its advantages over the other route of administration enhance its wide range of
application in the treatment of illness including asthma, chronic obstructive
pulmonary diseases (COPD) etc.
➢ Some of its advantages include the possibility of directly targeting the drug to the
site of action, avoidance of first pass metabolism, rapid action and also reduction of
systemic side effects etc.
➢Hence pulmonary route of administration can be successful in the research field in
near future.
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