This document discusses pharmaceutical aerosols, including their history, components, and formulation. It provides details on the types of propellants, containers, valves, actuators used in aerosols. It describes the different systems for formulating aerosols such as solution, water-based, suspension, and foam systems. Key advantages of aerosols are rapid onset of action, avoidance of first-pass effect, dose titration, and alternate administration route. The document emphasizes the importance of selecting appropriate propellants and components based on the active ingredients and site of application.

1. Pharmaceutical Aerosols
By Ankita Burande
Assistant Professor
Nagpur College of Pharmacy
Nagpur

2. Introduction:
 Aerosol or pressurized package is defined as “a system that depends on the power of a
compressed or liquefied gas to expel the contents from the container.”
History:
 first aerosol insecticide was developed by the United States Department of Agriculture, that the
aerosol industry was begun.
 The principles of aerosol technology were applied to the development of pharmaceutical
aerosols in the early 1950s for topical administration for the treatment of burns, minor cuts and
bruises, infections, and various dermatologic conditions.
 In 1955, epinephrine was available in a pressurized package for local activity in the respiratory
tract.
 Based on their acceptability to both patient and physician, and their widespread use,
pharmaceutical aerosols represent a significant dosage form and should be considered along
with other dosage forms, such as tablets, capsules, solutions, etc.

3. Following specific advantages over other
dosage forms:
 When sterility is an important factor, it can be maintained while a dose is being dispensed. A dose
can be removed without contamination of remaining material
 Stability is enhanced for those substances adversely affected by oxygen and/or moisture.
 The medication can be delivered directly to the affected area in a desired form, such as spray,
stream,. quick-breaking foam, or stable foam
 Irritation produced by the mechanical application of topical medication is reduced or eliminated.
 Rapid onset of action, circumvention of the first pass effect and avoidance of degradation in the GI
tract is achieved.
 Dose lowering in case of steroid therapy and dose titration to individual needs can be achieved by
using metered dose and dry powder inhalers.
 Alternate route of administration is provided in case of drugs which shows erratic
pharmacokinetics upon oral or parenteral administration and which may interact chemically or
physically with other medicinals needed concurrently.

4. COMPONENTS OF AEROSOL PACKAGE
An aerosol product consists of the following component parts
(1) Propellant,
(2) Container,
(3) Valve and actuator and
(4) Product concentrate.

6. Propellant:
 It is responsible for developing the power pressure within the container and also expel
the product when the valve is opened and in the atomization or foam production of the
product.
Various types of propellants
 broadly classified as liquefied gases, hydrocarbons, hydrocarbon ether and compressed
gases.
1. Liquefied gases are gases at room temperature and atmospheric pressure and can be
liquefied easily by lowering the temperature or by increasing the pressure.
 Chlorofluorocarbons (CFCs), hydrochlorofluorocarbons
 Hydrochlorofluoro-carbons (HCFCs) and
 hydrofluorocarbons (HFCs) are commonly used liquefied gases.

7. Propellant:
2. hydrocarbons
 Are naturally occurring products, however, their purity varies.
 The pressure of each individual component varies somewhat, depending on the
degree of purity.
 E.g. Butane, Isobutane, Propane,
3. Hydrocarbon Esters: Dimethyl ether
4. Compressed gases: Carbon dioxide, Nitrous oxide, Nitrogen

8. Containers
 Various materials used for the manufacture of aerosol containers, must withstand
pressures as high as 140 to 180 psig at 130°F.
A. Metal
1. Tinplated steel
2. Aluminium
3. Stainless steel
B. Glass
1. Uncoated glass
2. Plastic-coated glass

9. Tinplate Containers
 The tinplated steel container consists of a sheet of steel plate that has been electroplated
on both sides with tin.
 The thickness of the tin coating is described in terms of its weight, for example, #25, #50
and #100.
 The size of the container is indicated by a standard system, which is a measure of the
diameter and height of the container. A container said to be 202 × 214 if, it is 2 inches in
diameter and 2 inches in height.
Aluminium Containers
 Many existing pharmaceuticals are packaged in aluminum containers, because of the
lessered danger of incompatibility due to its seamless nature and greater resistance to
corrosion.
 Aluminium can be corroded by pure water and pure ethanol.

10. Stainless Steel Containers
 These containers are limited to the smaller sizes, owing to production problems as well
as cost.
 They are extremely strong and resistant to most materials.
 Stainless steel containers have been used for inhalation aerosols.
 In most cases, no internal organic coating is required.
Glass Containers
 Glass aerosol containers have been used for a large number of aerosol pharmaceuticals.
 Glass containers are available with or without plastic coatings. The plastic coating may
be totally adhered (except for the neck ring) or non adhered.
 Glass aerosol containers are preferable from a compatibility viewpoint, since corrosion
problems are eliminated.
 The use of glass also allows for a greater degree of freedom in design of the container

11. Valves
 Valve is multifunctional, capable of being easily opened and closed and in addition,
is capable of delivering the content in the desired form.
 Valve delivered the drug in desired form and give proper amount of medication.
 Valves for pharmaceuticals usually do not differ from the valves used for non
pharmaceutical aerosol products, but the requirements for pharmaceuticals are
usually more stringent than for most other products.
 The materials used in the construction of the valve must be approved by the Food
and Drug Administration.
 Pharmaceutical aerosols may be dispensed as a spray, foam, or solid stream, and
they may or may not require dosage control.

12. Part of Valve:
Types –
Continuous spray valve - Consists of many different parts and is assembled using 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.

13. Part of Valve
1. Ferule or Mounting cap:
 used to attach the valve proper to the container.
 Ferrules are used with glass bottles or small aluminum tubes and are usually
made from a softer metal such as aluminum or brass.
 The ferrule is attached to the container either by rolling the end under the lip of
the bottle or by clinching the metal under the lip.
2. Valve Body or Housing
 Made up of Nylon or Delrin
 Has opening at the point of the attachment of the dip tube, which ranges from
about 0.013 inch to 0.080 inch.

14.  Valve body may or may not contain another opening referred to as the “vapour tap”.
The vapour tap allows for the escape of vapourized propellant and along with the
liquid product.
 The vapour tap further produces a fine particle size, prevents valve clogging with
products containing insoluble materials, allows for the product to be satisfactorily
dispensed.
 These vapour tap openings are available in sizes ranging from about 0.013 inch to
0.080 inch
3. Stem:
 made from Nylon or Delrin, but metals such as brass and stainless steel can also be
utilized.
 One or more orifices are set into the stem; they range from one orifice of about 0.013
inch to 0.030 inch, to three orifices of 0.040 inch each.

15. 4. Gasket:
 Buna-N and Neoprene rubber are commonly used for the gasket
 material and are compatible with most pharmaceutical formulations
5. Spring:
 The spring serves to hold the gasket in place, and when the actuator is depressed and
released, it returns the valve to its closed position.
 Stainless steel can be used with most aerosols.
6. Dip tube:
 Dip tubes are made from polyethylene or polypropylene.
 The inside diameter of the commonly used dip tube is about 0.120 inch to 0.125 inch,
and dip tubes for highly viscous products may be as large as 0.195 inch.
 Viscosity and the desired delivery rate play an important role in the selection of the
inner diameter of the dip tube.

16. Metering valves
 Metering valves are applicable to the dispensing of potent medication.
 These operate on the principle of a chamber whose size determines the amount of
medication dispensed
 Although these have been used to a great extent for aerosol products.
 Approximately 50 to 150 mg ±10% of liquid material can be dispensed at one
time with the use of such valves.

17. Actuators
 To ensure that the aerosol product is delivered in the proper and desired form,
a specially designed button or actuator must be fitted to the valve stem.
 The actuator allows for easy opening and closing of the valve and is an
integral part of almost every aerosol package.
Different types of actuators
(1)spray,
(2) Foam
(3) solid stream and
(4) special applications

18. Spray Actuators
 Spray actuators are capable of dispersing the stream of product concentrate and
propellant into relatively small particles by allowing the stream to pass through various
openings (of which there may be one to three on the order of 0.016 inch to 0.040 inch in
diameter).
 A spray type actuator can be used with pharmaceuticals for topical use, such as spray-
on bandages, antiseptics, local anesthetics, and foot preparations.
Foam Actuators
 These actuators consist of relatively large orifices ranging from approximately 0.070
inch to 0.125 inch and greater.
 The orifices allow for passage of the product into a relatively large chamber, where it
can expand and be dispensed through the large orifice in the form of foam.

19. Solid-Stream Actuators
 The dispensing of semisolid products as ointments generally requires these
actuators.
 Relatively large openings allow for the passage of product through the valve stem
and into the actuator. These are essentially similar to foam type actuators.
Special Actuators
 Many of the pharmaceutical and medicinal aerosols require a specially designed
actuator to accomplish a specific purpose.
 They are designed to deliver the medication to the appropriate site of action-throat,
nose, eye, or vaginal tract.

21. Formulation of Pharmaceutical Aerosols
An aerosol formulation consists of two essential components:
1. Product concentrate :
 The product concentrate consists of active ingredients, or a mixture of active
ingredients, and other necessary agents such as solvents, antioxidants, and
surfactants.
2. Propellant:
 The propellant may be a single propellant or a blend of various propellants; it can
be compared with other vehicles used in a pharmaceutical formulation.
 Just as a blend of solvents is used to achieve desired solubility characteristics, or
various surfactants are mixed to give the proper HLB value for an emulsion
system, the propellant is selected to give the desired vapour pressure, solubility and
particle size.

22. Formulation of Pharmaceutical Aerosols
 Formulator of aerosol preparations must be thoroughly familiar with propellants
and the effect the propellant will have upon the finished product.
 Propellants can be combined with active ingredients in many different ways,
producing products with varying characteristics.
 Depending on the type of aerosol system utilized, the pharmaceutical aerosol may
be dispensed as a fine mist, wet spray, quick-breaking foam, stable foam,
semisolid, or solid.
The type of aerosol system selected depends on many factors, including the following
(1) Physical, chemical, and pharmacologic properties of active ingredients and
(2) Site of application.

23. TYPES OF SYSTEMS
A. Solution System/Two-phase System:
 Large number of aerosol products can be formulated in this manner.
 Also referred to as a two-phase system and consists of a vapour and liquid phase.
 When the active ingredients are soluble in the propellant, no other solvent is
required.
 Depending on the type of spray required, the propellant may consist of propellant
12 or A-70 (which produce very fine particles), or a mixture of propellant 12 and
other propellants.
 These sprays are also useful for topical preparations, since they tend to coat the
affected area with a film of active ingredients.
 Ex. Of General formulations:

24. B. Water-based System
1. Three-phase System:
 Relatively large amounts of water can be used to replace all or part of the non
aqueous solvents used in aerosols.
 These products are generally referred to as “water-based” aerosols, and depending
on the formulation, are emitted as a spray or foam.
 To produce a spray, the formulation must consist of a dispersion of active
ingredients and other solvents in an “emulsion” system in which the propellant is
in the external phase.
 In this way, when the product is dispensed, the propellant vapourizes and disperses
the active ingredients into minute particles.
 Since propellant and water are not miscible, a three-phase aerosol forms
(propellant phase, water phase, and vapour phase).

25. 2. Aquasol System:
 The new Aquasol system allows for the
dispensing of a fine mist or spray of active
ingredient dissolved in water, which is not
possible with the usual three-phase system.
 It is designed to dispense pressurized products
efficiently and economically using relatively
small amounts of hydrocarbon propellant.
 This system, which is essentially a “three-
phase” aerosol, permits the use of fairly large
quantities of water in the formulation.

26. 3. Suspension or Dispersion Systems:
 This system, to overcome the difficulties due to the use of a co-solvent.
 One such system involves a dispersion of active ingredients in the propellant or a
mixture of propellants.
 To decrease the rate of settling of the dispersed particles, various surfactants or
suspending agents have been added to the systems.
 These systems have been developed primarily for use with oral inhalation aerosols.
 E.g. Oral steroid aerosol used in asthma, The oleic acid is present as a dispersing agent
for the steroid and is an aid in the prevention or reduction of particle growth or
agglomeration

27. 4. Foam Systems:
 Foam aerosols consist of active ingredients, aqueous or nonaqueous vehicle,
surfactant, and propellant, and are dispensed as a stable or quick-breaking foam,
depending on the nature of the ingredients and the formulation.
 The liquefied propellant is emulsified and is generally found in the internal
phase.
 Aerosol emulsions are dispensed as foams, and this can be advantageous for
various applications involving irritating ingredients, or when the material is
applied to a limited area.

28. 5. Aqueous Stable Foams:
These can be formulated as follows:
 While the total propellant content may be as high as 5% in certain cases, it usually is
about 8 to 10% v/v or 3 or 5% w/w.
 As the amount of propellant A-70, A-46, etc. increases, a stiffer and dryer foam is
produced.
 Lower propellant concentrations yield wetter foams.
 Several different steroids, antibiotics and other agents may be dispensed in this manner.
Both hydrocarbons and compressed gas propellants may be used.
 Fluorocarbons are no longer used for these products.
 The techniques used in preparing an aerosol emulsion are the same as those used for non-
aerosol emulsions.

29. 6. Non aqueous Stable Foams:
 Nonaqueous stable foams may be formulated through the use of various glycols such
as polyethylene glycol, which may be formulated according to the following:

30. 7. Quick-breaking Foams:
 In this system, the propellant is in the external phase. When dispensed, the product
is emitted as foam, which then collapses into a liquid.
 This type of system is especially applicable to topical medication, which can be
applied to limited or to large areas without the use of a mechanical force to
dispense the active ingredients.
 The surfactant can be of the nonionic, anionic, or cationic type. It should be soluble
in both alcohol and water.
 If the proportion of ingredients is varied, foams may be obtained having a wide
range in stability.

31. 8. Thermal Foams:
 Developed several years ago and were used to produce a warm foam for shaving.
 They were not readily accepted by the consumer and soon discontinued, owing to
inconvenience of use, expense, and lack of effectiveness.

32. Selection of Components
1. Propellant:
 Prior to 1978, fluorinated hydrocarbons were used almost exclusively as the
propellants for all types of pharmaceutical aerosols.
 Their chemical inertness, lack of toxicity, lack of flammability and explosiveness,
and their safe record of use made them ideal candidates for use.
 In 1978, Environmental Protection Agency (EPA), Food and Drug Administration
(FDA), ban of the use of fluorocarbon propellants in aerosols (with few exceptions)
because As per “ozone depletion theory” in the mid-1970s, alleged implication of
the fluorocarbons in depleting the ozone levels in the atmosphere.
 Inhalation aerosols for oral or nasal use have been exempted from the FDA ban, and
the fluorinated hydrocarbons—namely, propellants 12, 12/114, and in some cases
12/11 are still used.
 Hydrocarbon propellants, such as butane, propane, isobutane, and their mixtures,
safely used with aqueous products, and with solvent-based aerosols as well.
 Hydrocarbons can be used for all types of topical aerosols

33. Selection of Components
 The compressed gases-nitrogen, nitrous oxide, and carbon dioxide—can be used but
are of limited value.
 The pump system is used for liquid antiseptics, germicides, and nasal sprays
2. Containers:
 Both glass and metal containers have been used for pharmaceutical aerosols.
 Glass is preferred, but its use is limited, owing to its brittleness and the danger of
breakage should the container accidentally be dropped.
 When the total pressure of the system is below 25 psig and there is not more than
15% propellant, glass can be safely used.
 Pressures up to 33 psig can be utilized in conjunction with a glass container having a
double plastic outer coating.

34.  A mixture of 2% tin and 98% lead is used when the pressure is below 40 psig
 Most nonaqueous products can be placed into an tinplated metal container. E.g.
alcohol-based pharmaceuticals, e.g. spray on bandages.
 Products having a low pH and containing water utilize coating with organic linings of
epoxy and/or vinyl resins.
 A commonly used organic coating consists of an undercoat of vinyl and a top coat of
epoxy resin.
 Vinyl resin forms a tough film, it is poorly resistant to steam and cannot be used for
products that must be heat sterilized or filled hot (about 200°F).
 An epoxy resin can be used for heat sterilized product since it has a greater degree of
heat stability.
 Those products containing soaps, pure tin or combinations of tin, silver, and other
metals are used.
 Creams and ointments may be dispensed from a pressurized container by the use of an
aluminum container.

35. Manufacture of Pharmaceutical Aerosols
 To prepare and package pharmaceutical aerosols successfully, special knowledge,
skills and special equipment are required.
 Manufacturing operation (addition of propellant to concentrate) is carried out during
the packaging operation.
 In addition to the equipment used for the compounding of liquids, suspensions,
emulsions, creams, and ointments, specialized equipment capable of handling and
packaging materials at relatively low temperatures (about −40°F) or under high
pressure must be available.
Types of filling apparatus
 Pressure filling Apparatus
 Cold filling Apparatus
 Compressed Gas Filling Apparatus

36. 1. Pressure Filling Apparatus
 Pressure filling apparatus consists of a pressure burette
capable of metering small volumes of liquefied gas under
pressure into an aerosol container.
 The propellant is added through the inlet valve located at the
bottom or top of the burette.
 Trapped air is allowed to escape through the upper valve
 The desired amount of propellant is allowed to flow through
the aerosol valve into the container under its own vapour
pressure.
 When the pressure is equalized between the burette and the
container (this happens with low-pressure propellants), the
propellant stops flowing.

37. 2. Cold Filling Apparatus
 Cold filling apparatus is somewhat simpler than the pressure filling apparatus.
 Contains insulated box fitted with copper tubing that has been coiled to increase the area
exposed to cooling. This unit filled with dry ice/acetone prior to use.
 This system can be used with metered valves as well as with non-metered valves;
 This system, should not be used to fill hydrocarbon aerosols since an excessive amount
of propellant escaping and vapourizing may form an explosive mixture at the floor level
(or lowest level).
 Fluorocarbon vapours, although also heavier than air, do not form explosive or
flammable mixtures

39. 3. Compressed Gas Filling Apparatus:
 Compressed gases can be handled easily in the laboratory without the use of
elaborate equipment. Since the compressed gases are under high pressure, a pressure-
reducing valve is required.
 The filling head is inserted into the valve opening, the valve is depressed, and the
gas is allowed to flow into the container.
 When the pressure within the container is equal to the delivery pressure, the gas
stops flowing.

40. LARGE-SCALE EQUIPMENT
1. Concentrate filler:
 This can range from a single-stage single hopper to a large straight line multiple-head
filler or a rotary type multiple-head filler.
 Most of these fillers deliver a constant volume of product and they can be set to give a
complete fill in one or more operations.
 Usually, only part of the product is added at each stage, assuring a more accurate fill.
2. Valve placer: The valve can be placed over the container either manually or
automatically. High-speed equipment utilizes the automatic valve placer.
3. Purger and vacuum crimper:
 Aerosols are packaged in both metallic and glass containers, each requiring their own
style of crimper.
 Single-head crimpers or multiple-head rotary units capable of vacuum crimping up to
120 cans per minute are available. These usually require both air pressure (90 to 120
pounds per square inch) and vacuum.

41. 4. Pressure filler:
 These units are capable of adding the propellant either through the valve stem, body, and
dip tube, around the outside of the stem, or under the valve cup before crimping.
 They are either single or multiple-stage units arranged in a straight line or as a rotary
unit.
 Evacuation of air from the container, crimping the valve, and addition of the propellant
can be achieved in basically one operation through the use of an “under the cap” filler.
5. Leak test tank:
 This consists of a large tank filled with water and containing heating units and a
magnetized chain
 The length of the tank is such that the temperature of the product before it emerges from
the tank is 130°F.
 According to DOT regulations, each completed container filled for shipment must have
been heated until contents reached a minimum of 130°F, or attained the pressure it would
exert at this temperature, without evidence of leaking, distortion, or other defects”

42. Quality Control for Pharmaceutical Aerosols
1. Propellants:
 Identity: Gas chromatography is used to determine the identity of the propellant, and
when a blend of propellants is used, to determine the composition.
 Purity: Moisture, halogen, and non volatile residue determinations.
2. Valves, Actuators and Dip Tubes
These parts are subjected to both physical and chemical inspection.
 Valve acceptance: The test procedure applies to two categories of metered aerosol valves
having the following limits. For valves delivering:
 54 μl or less, the limits are ± 15%.
 55 to 200 μl, the limits are ± 10%.

43.  Of the 50 individual deliveries, if four or more are outside the limits for the specified
valve delivery, the valves are rejected.
 If three individual deliveries are outside the limits, another twenty-five valves are
sampled and the test is repeated. The lot is rejected if more than one delivery is
outside the specifications.
 If two deliveries from one valve are beyond the limits, another twenty five valves
should be taken. The lot is accepted if not more than one delivery is outside the
specifications.

44. 3. Container:
 Both uncoated and coated metal containers must be examined for defects in the lining.
 Degree of conductivity of an electric current as a measure of the exposed metal.
 Glass containers must be examined for flaws
 The dimensions of the neck and other parts must be checked to determine conformity to
specifications.
 The weight of the bottle also should be determined.
4. Weight Checking:
 This is usually accomplished by periodically adding to the filling line tared empty
aerosol containers, which after being filled with concentrate, are removed and then
accurately weighed.

45. 5. Leak test:
 Final testing of the efficiency of the valve closure is accomplished by passing the
filled containers through the water bath.
 Periodic checks are made of the temperature of the water bath, and these results are
recorded.
6. Spray Testing:
 Many pharmaceutical aerosols are 100% spray tested.
 This serves to clear the dip tube of pure propellant, to clear the dip tube of pure
concentrate and to check for defects in the valve and the spray pattern.

46. Testing of Pharmaceutical Aerosols
 Tests are necessary to ensure proper performance of the package and safety during use
and storage.
 All aerosol products that are shipped are subject to the regulations of the DOT
 Pharmaceutical aerosols can be evaluated by a series of physical, chemical, and biologic
tests, including:
A. Flammability and combustibility
1. Flash point:
 determined by use of the Standard Tag Open Cup Apparatus (STOCA).
 The aerosol product is chilled to a temperature of about 25°F and transferred to the test
apparatus. The test liquid is allowed to increase slowly in temperature and the
temperature at which the vapours ignite is taken as the flash point.
2. Flame Projection:
 Effect of an aerosol formulation on the extension of an open flame.
 The product is sprayed for about 4 sec into a flame. Depending on the nature of the
formulation, the flame is extended, the exact length being measured with a ruler.

47. Testing of Pharmaceutical Aerosols
B. Physicochemical characteristics
1. Vapour pressure:
 Measured using a pressure gauge
 It is important that the pressure variation from container to container be determined,
since excessive variation indicates the presence of air in the headspace.
2. Density: Determined through the use of a hydrometer or a Pycnometer
3. Moisture content:
 The Karl Fischer method has been accepted to a great extent.
 Gas chromatography has also been used.
4. Identification of propellant(s):
 Gas chromatography and infrared spectrophotometry have been used to identify the
propellants and also to indicate the proportion of each component in a blend.
5. Concentrate-propellant ratio: Gas chromatography and infrared spectrophotometry

48. Testing of Pharmaceutical Aerosols
C. Performance
1. Aerosol valve discharge rate:
 This is determined by taking an aerosol product of known weight and discharging the
contents for a given period of time using standard apparatus.
 By reweighing the container after the time limit has expired, the change in weight per time
dispensed is the discharge rate, which can then be expressed as grams per second.
2. Spray pattern:
 A method for comparing spray patterns obtained from different batches of material or
through the use of different valves is available
3. Net contents:
 Used to determine whether sufficient product has been placed into each container.
 The tared cans that have been placed onto the filling line are reweighed, and the
difference in weight is equal to the net contents.

49. Testing of Pharmaceutical Aerosols
4. Foam stability:
 The life of a foam can range from a few seconds to one hour or more depending on the
formulation.
 Several methods have been used, which include
a. Visual evaluation,
b. Time for a given mass to penetrate the foam,
c. Time for a given rod that is inserted into the foam to fall
d. Use of rotational viscometers.
5. Particle size determination: Cascade impactor and “light scatter decay” methods.

50. Testing of Pharmaceutical Aerosols
7. Dosage with metered valves:
Several points must be considered (1) reproducibility of dosage each time the valve is
depressed and (2) amount of medication actually received by the patient.
 Reproducibility of dosage may be determined by
1. Assay techniques: whereby one or two doses are dispensed into a solvent or onto a
material that absorbs the active ingredients. These solutions can then be assayed, and
the amount of active ingredients determined.
2. Another weighting method that can be used involves accurate weighing of filled
container followed by dispensing of several doses. The container can then be
reweighed and the difference in weight divided by the number of doses dispensed
gives the average dose.

51. Testing of Pharmaceutical Aerosols
D. Biologic characteristics:
 These tests are similar to tests performed on non aerosol pharmaceuticals.
 Biologic testing of aerosol products include
a. Therapeutic efficacy: determine the therapeutic activity of aerosol.
b. Toxicity:
 Toxicity testing should include both topical and inhalation effects.
 Aerosols applied topically may be irritating to the affected area and/or may cause a
chilling effect. The degree of chilling effect depends on the type and amount of propellant
present.
 Inhalation toxicity must also be considered and can be accomplished by exposing test
animals to vapours sprayed from an aerosol container.

52. AEROSOLS FOR PULMONARY DRUG DELIVERY
 The two possible mechanisms for delivery of drugs to the lung include an aerosol or
direct instillation.
 The main types of device used produce aerosols for pulmonary delivery are
1. Nebulizers,
2. Metered dose inhalers (MDI)
3. Dry powder inhalers (DPI),
 MDIs and DPIs have a relatively high gas flow rate resulting in high oropharyngeal
impaction. This problem is reduced in nebulizers since the airflow can be adjusted to
suit the patient’s inhalation rate.

53. Nebulizers
 Pharmaceutical nebulizers can be divided into two main groups,
1. An electric generator (ultrasonic) Nebulizer:
 operates from an electric source,
 The ultrasonic nebulizer consists of a piezoelectric crystal which
produces high frequency sound waves in the liquid in the
nebulizing unit.
 The surface waves produce small droplets which are conducted
away by an airstream for inhalation.
2. pneumatic generator (hydrodynamic and jet)nebulizers:
 derives its power from pressurized gas source.
 This high-velocity gas ruptures the thin film of water and
produces a continuous dispersion of fine, liquid particles.

54. Metered Dose Inhalers
 In these systems, the drug is usually a polar solid which has
been dissolved or suspended in a non-polar liquefied
propellant.
 If the preparation is a suspension, as is most commonly the
case, the powder is normally micronized by fluid energy
milling and the suspension is stabilized by the addition of a
surfactant.
 The canister consists of a metering valve crimped on to an
aluminum can.
 Individual doses are measured volumetrically by a metering
chamber within the valve.
 Each MDI canister can hold between 100 and 200 doses of
between 20 pg and 5 mg of drug, which is released within the
first 0.1 s after actuation.

55. Dry Powder Inhalers
 The environmental concerns surrounding the use of chlorofluorocarbons have led to
a resurgence of interest in dry powder inhaler devices. The dry powder inhalers rely
on inspiration to withdraw drug from the inhaler to the lung.
 This device contained finely micronized drug is thoroughly dispersed in the
airstream.
 It has been recommended that patients inhale as rapidly as possible from these
devices in order to provide the maximum force to disperse the powder.
 Rotahaler® used individual capsules of micronized drug which were difficult to
handle. Modern devices use blister packs (e.g. Diskus®)