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INTERNATIONALE PHARMACEUTICA SCIENCIA
AprilJune Vol. Issue Available online http//www.ipharmsciencia.com ISSN IPS
REVIEW ARTICLE
Review on Pharmaceutical Aerosol
ABSTRACT
Pulmonary drug delivery system is a needle free technique. The origin of inhaled therapies
seen in back years ago to India, where people smoked the leaves of the Atropa belladonna
plant to suppress cough. In the th and early th centuries, asthmatics smoked asthma
cigarettes that contained stramonium powder mixed with tobacco to treat the symptoms of
their disease. But administration of drugs by the pulmonary route is technically challenging
because oral deposition can be high, and variation in inhalation techniques can affect the
quantity of a drug delivered to the lungs. Pulmonary drug delivery remains the preferred
route for administration of various drugs. It is an important research area which impacts the
treatment of illnesses including asthma, chronic obstructive pulmonary disease and various
diseases. Due advancement in application nowadays Pulmonary drug delivery is useful to
treat Diabetes, angina pectoris, cancer , bone disorders , migraine, tuberculosis, acute lung
injury and others. In this article, we summarize the outline of this dosage form. Keywords
Unani system Anxiety Izterabe Nafsani
Mr. Hitesh. G. Pokar, Dr. K. R. Patel, Dr. N. M. Patel Department of Industrial Pharmacy Shri
B. M. Shah College of Pharmaceutical Education and Research, Modasa,Gujarat Date of
Submission Date of Acceptance Conflict of interest Nil Source of support None
Introduction 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. A dose can be removed without contamination of materials. Stability is enhanced
for these substances adversely affected by oxygen and or moisture. When sterility is an
important factor, it can be maintained while a dose is being dispensed. 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 It is responsible for developing
the power pressure within the container and also expel the product when the valve is opened
and in the
Address for correspondence
atomization or foam production of the product. For oral and inhalation Fluorinated
hydrocarbons Dichloro difluro methane propellant Dichloro tetrafluro ethane propellant
Topical preparation Propane Butane Isobutane Compound gases Nitrogen Carbon dioxide
Nitrous oxide Containers They must be stand at pressure as high as to psig pounds per sq.
inch gauge at F.The containers are generally made up of glass or metal. But brittleness
restricts the use of glass. If the pressure is less than psig and propellant content is less than
then glass can be used. Glass should be coated with plastic coating in two layers if pressure
is less than or equal to psig. Epoxy and vinyl resins can be used as linings. Vinyl resins can
form strong lining but
Internationale Pharmaceutica Sciencia AprJune Vol Issue
Pokar Hitesh. G /Bombay society, T. B. Road Vijapur, DistrictMehsana Email
hiteshpokargmail.com
The coating gives protection from impact. They also provide proper amount of medication.
Stainless steel It is resistant to corrosion and no coating is required. G et al Review on
Pharmaceutical Aerosol it will get damaged by steam. .Pokar Hitesh. Special . However they
are expensive. b The three piece container has aside seam the base being attached as for
two piece container. Valve components Actuator The actuator or adaptor which is fitted to the
aerosol valve stem is a device which on depression or any other required movement opens
the valve and directs the spray to the desired area. Fig. Dispersing of potent medication at
proper dispersion/ spray approximately to mg of liquid materials at one time use of same
valve. It is steel that has been plated on both side with tin. Glass Glass containers are often
coated with plastics. B. Polyethylene tetra phthalate PET container as used for some non
pharmaceutical products. Glass has advantage of being transparent so contents can be
viewed. A vinyl coating on which the epoxy coating is most suitable for products having less
PH. Aluminium container are made by an extrusion process and hence have no seam. Solid
steam actuators actuators are used. Foam actuators. Metals . But epoxy resins can be used
as they are resistant to steam. A proportion of the active ingredients is usually deposited on
the inner surface of the actuator. It can withstand high pressure.Pressure of the system.
Aluminium Aluminium containers are more resistant to corrosion than tinplated steel.
Tinplated steel It is used for most aerosol as it is light inexpensive and durable. consisting of
adrawn cylinder. Glass is virtually inert. Tin plated steel containers are of two typesa Two
pieces container body.there are two types of valves are available which are continuous spray
valve and metering valve. particularly in the case of inhalation aerosols. PH of the
product.different types of actuators like Spray actuators. whether product is aqueous or not.
where the active ingredients must be delivered in the proper particle size range. is held in
place with double seam. . the base of the container. Plastic Types of inhalers Dry powder
inhalers Internationale Pharmaceutica Sciencia AprJune Vol Issue Not widely used for
aerosol container. the amount available is therefore less than the amount released by
actuation of the valve. physicochemical properties of preparation. A. Aluminium is subjected
to corrosion by water and alcohol. Choice of the material is depend on. The design of the
actuator which incorporates an orifice of varying size and shape and expansion chamber is
very important in influencing the physical characteristics of the spray or foam. the top has a
inch opening and is joined to body by double seaming. Valves Valves delivers the drug in
desored form. C.
This typically would be treatment for one to two days. Formulation of solutions for
nebulisation Internationale Pharmaceutica Sciencia AprJune Vol Issue . the aluminum blister
is pierced. This product had limited commercial success and was superseded in the late s by
the Diskuse. The formulation resides within the canister and is made up of the drug. This
device is truly a metereddose powder delivery system. The use of nebulisers generally
reserved for the treatment of is acute conditions e. respiratory infection or in those patients
who havedifficulties using other respiratory dosage forms. and the contents of the pouch are
dropped into the dosing chamber. The capsule is opened within the device and the powder is
inhaled.g. creating an aerosol containing micronized drug that is inhaled into the lungs. The
drug particles must be of sufficiently small aerodynamic diameter to make it to and deposit
on the airways.g. having doses in a foil foil aluminum strip that is opened only at the point
just prior to patient inspiration. The MDI device consists of a canister. Dry powder
formulations either contain the active drug alone or have a carrier powder e. and actuator.
lactose mixed with the drug.The volatile propellant breaks up into droplets which then
evaporate. The capsule residue must be discarded after use and a new capsule inserted for
the next dose. acute asthma. The drug is contained within a storage reservoir and can be
dispensed into the dosing chamber by a simple backand forth twisting action on the base of
the unit. which are then inspired by the patient through a facemask. or preferable an
automated image analyzer.The dose delivered by an MDI can be analyzed using a
microscope. Consistent performance and broad patient acceptance has allowed the Diskuse
to become the gold standard of multi dose powder delivery devices. G et al Review on
Pharmaceutical Aerosol UnitDose Devices Singledose powder inhalers are devices in which
a powdercontaining capsule is placed in a holder. 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.Pokar Hitesh. A bronchodilator MDI was examined using
the PSA image analysis system. An asthma attack and requires immediate delivery of drug
Disadvantage Multi dose Devices The development of multi dose DPIs was pioneered by A.
The doses are maintained in separate aluminum blister reservoirs until just before
inspiration.However. This device uses a circular disk that contains either four or eight powder
doses on a single disk. The canister itself consists of a metering dose valve with an actuating
stem. To address issues associated with a need for multiple dosing and consistent
performance. Metered dose inhaler Nebulisers Solutions for nebulisation Nebulisation
involves the application of energy either a highvelocity gas or by the use of ultrasonic
systems to a solution of a therapeutic agent and results in the formation of droplets of
solution.. which was used to deliver a range of drugs. and sometimes a spacer. and often
stabilizing excipients. Glaxo developed the Diskhaler . one of the drawbacks of the
Turbuhaler has been the fact that it has a highly variable delivery at different flow rates.
Fig.The device is capable of working at moderate flow rates and also delivers carrierfree
particles. a liquefied gas propellant. Draco now a division of Astra Zeneca with their
Turbuhaler. On priming the device. This device is a true multi dose device. B. including
salbutamol and beclomethasone. Actuation of the device releases a single metered dose of
liquid propellant that contains the medication. The energy source is provided by a nebuliser
most commonly a jet or ultrasonic nebuliser.
generally three phase system results. surfactants can be used and those surfactants which
are soluble to large extent in non polar solvents and soluble to smaller extent in water are
more preferred. The surfactants composition ranges between . G et al Review on
Pharmaceutical Aerosol Vehicle The vehicle for solutions designed for nebulisation is water
for injections nebuliser solutions are sterile. Based on the type of spray required. care should
be taken when selecting the concentration of these to ensure that there is no toxicity to the
respiratory epithelia. it should be noted that sulphites may cause brochospasm preservatives
some multidose nebuliser solutions contain preservatives. It is also called twophase system.
glycerol and polyhydroxylic acid like oleic. modification of the osmolality of nebuliser
solutions may be performed by adding the appropriate ionic concentration e. sodium
chloride. ethanol. Then the propellant layer is present on the top water layer. To produce a
uniform dispersion. Dried particle is obtained on the use of A and wetten particles on use of
A and A. When less volatile substances are added to the system. three phase system is
produced based on the amount of water present. Examples of cosolvents that may be used
include propylene glycol. glycerol.parameters like physical. phosphate. Water based system
If only water or large amount of water is present to solubilize the contents then it is called
water based system. however. .chemical and pharmaceutical properties of active ingredients
and site of application are considered. Osmolalitymodifying agents The use of hypo.g. If
spray form is required. Cosolvents Cosolvents may be used in nebuliser solutions to increase
the solubility of the drug. However. either propellant is added or other propellants are also
added. The solubility of the propellant increases as the amount of alcohol Internationale
Pharmaceutica Sciencia AprJune Vol Issue May be single or blend of various propellants are
used. In aquasol dispenser system. as in other applications. palmitic stearic acids can be
used as surfactants.and hyperosmotic solutions within the respiratory tract has been linked to
bronchoconstriction and therefore solutions designed for nebulisation should be formulated
to be isoosmotic. antioxidants and surfactants. the drug is dissolved in the water or the
mixture of water and alcohol. The recent advancement is the aquasol valve. solubility amp
particle size. Miscellaneous agents Other components that may be present in nebuliser
solutions include antioxidants watersoluble examples. and propellant composition ranges
from to . ethyl alcohol can be added to the system. Due to the possibility of acidic solutions
pH causing bronchoconstriction. then active ingredient is dispersed and other solvents
should be present in the form of emulsion and propellant will be external phase. This may be
modified via the use of buffers e. No other solvent is required if the drug is soluble in the
propellant. to . As described previously Chapter . mannitol. do not require the addition of
preservatives. as such. the pH of nebuliser solutions is greater than . Propellant Types of
system Solution system It consists of the vapour and the liquid. As the water is not miscible
in propellant. the vast majority of formulations do not contain these excipients. Ester formed
between glycol.g. To increase the solubility of propellants in water.Blends of propellant used
in a pharmaceutical formulation to achieve desired solubility characteristics or various
surfactants are mixed to give the proper HLB value for emulsion system. Propellant gives the
desired vapor pressure.Pokar Hitesh. however. Formulation of pharmaceutical aerosols
Contains two essential components Product concentrate Product concentrate contains
ingredients or mixture of active ingredients and other such as solvents. citrate. potassium
chloride. Generally nebuliser solutions are packaged as singledose vials/ampoules and.
Manufacturing Aerosols Concentrate filler. vehicle. suspension system is developed. In this
system. To overcome this. Aqueous stable foams This consists of propellant in the range of
to v/v. Quick breaking foams Here the external phase is propellant. Agglomerates will be
formed in case of certain substances. G et al Review on Pharmaceutical Aerosol increases
and will become completely soluble if only alcohol is present. This is generally used for
steroid antibiotics. Add suspending agents. Non aqueous stable foams Glycols are used in
the formulation of these foams and their esters are used as emulsifying agents.Purger and
crimper. Suspension or dispersion systems There comes a number of problems by the use of
co solvent. Concentrate preparation . the drug particles are suspended. the particles will get
attached to the walls. the mucosal irritation will be reduced. more will be the agglomeration.
As the temperature increases this condition will be increase. which results in the production
of less number of smaller particles. Foam system Here the propellant which is present in the
liquid acts as internal phase. . This type of system can be applied to small area or larger
surface. Propellant is mixed With help of the procedures that are previously accepted. The
filling of aerosols in to the containers can be done by two methods namely . As the
concentration of A. Here the randomization takes place which gives an uniform spray.
Aquasol aerosol Water based systems produces the dried spray. At extreme conditions. .
Here the ingredients include aqueous or non aqueous surfactant. Intranasal aerosols The
design of the adaptor varies from the inhalation aerosols. Cold filling method . in the
propellant or the blend of propellants. More the moisture content. Valve placer . it results in
drier spray. It has number of advantages like contamination free. Fig. if the number of
agglomerates increases then caking results. very less quantity of drug moves into the lungs.
The adaptors will be of less height and narrow. the vaporized propellant and product via
different ducts reaches the actuator. Pressure filling method of Pharmaceutical Internationale
Pharmaceutica Sciencia AprJune Vol Issue . . These are used when the warmness is
required. The product will come out as foam which soon merges to form liquid. propellant
and Thermal foams These are not used much these days. . To increase the physical stability
. Manufacturing procedure It includes two steps. Surfactants are added to reduce the settling
rate. The particle size should be maintained less than microns. Pressure filler. A propellant
increases. Moisture content must be monitored . Leak test tank equipments are used for
large scale of production.Pokar Hitesh. In aquasol. Cationic or anionic or nonionic surfactants
are used in the formulation. By decreasing the density difference. And wetter spray is
produced as the concentration of propellant decreases. the product is manufactured and
then tested. The particles should have less solubility.
. The object of this test is to determine magnitude of valve delivery amp degree of uniformity
between individual valves. Halogen. This method is more prominent than cold filling method
as most of the formulations cannot be cooled to very low temperatures Quality aerosols . The
propellant is then added under pressure through the valve stern or through the actuator and
around the sealing gaskets. . . Diptubes Sampling is done according to standard procedure
as found in Military Standards MILSTDD. . Individual delivery wt in mg. or the concentrate
and propellant can be chilled together and mixture added to container. inch orifice is
attached. . The valve crimped into place.Pokar Hitesh. A valve is then crimped. Method
Under the cap method position. Filled with specific test solution Actuator with . For metered
dose aerosols test methods was developed by Aerosol Specification Committee
Internationale Pharmaceutica Sciencia AprJune Vol Issue . Test Solutions C . . . Valve is
actuated to fullest extent for sec. This method is not suitable for aqueous product or for
preparations that are adversely affected by low temperatures. Testing Procedure product
concentrate is Take valves amp placed on containers. The valve is then crimped into the
place. Pressure filling A. Repeat this for total individual delivery from each test units. Valve
delivery per actuation in L Specific gravity of test soln added to the container and valve place
in a Valve Acceptance Deliveries L or less to L Limits control for pharmaceutical For delivery
If or more are outside limits valves are rejected If delivery are outside limits another valves
are tested lot is rejected if more than delivery outside specification If delivery from valve are
beyond limits another valves are tested lot is rejected if more than delivery outside
specification . Container passed through a heated test bath as a check for leakage and
container strength. Containers Identification Purity Gas Chromatography Moisture. A seal is
formed around the shoulder of the container and using a vacuum. Method The product
concentrate is added to container at room temperature.Product concentrate is chilled and
added to open container followed by chilled prpellant. the valve cup is raised slightly from the
can and propellant is added. Test Solutions Ingredients w/w Iso Propyl Myristate Dichloro
Difluoro methane Dichloro tetrafluoro ethane Trichloro monofluoro methane Alcohol USP
Specific Gravity c Test Solutions A . Actuator. NonVolatile Residue Determination . B.
Propellents All Propellants are accompanied by Specification sheet. . G et al Review on
Pharmaceutical Aerosol Cold filling method Low temperature range c to c required. . Valves.
Standard test solutions were proposed to rule out variation in valve delivery. . Test Solutions
B . . Parameter Tested by Industrial Pharmaceutical Technical Section Academy Of
Pharmaceutical Sciences.
A can punctuating Density It is Determined by hydrometer or a pycnometer. container can
reweighed. To clear dip tube of pure propellant amp concentrate and To check for defects in
valves amp spray pattern. . By reweighing the container after time limit has expired. Dosage
with metered valves Reproducibility of dosage each time the valve is dispersed. Vapor
pressure Determined by pressure gauge. the fame is extended. and dispensing the contents.
These practical ranging from . Evaluation parameters of pharmaceutical aerosols Flame
Projection This test indicates the effect of an aerosol formulation on the extension of an open
flame. Aerosol valve discharge rate It is determined by taking an aerosol known weight and
discharging the contents for given time using standard apparatus. Foam stability Visual
evaluation. the large particles become impacted first on the lower velocity stages. In which A
pressure tube is fitted with metal fingers and hoke valve. which allow for the introduction of
liquids under pressure. . Variation in pressure indicates the presence of air in headspace.
involves accurate weighing of filled container fallowed by dispersing of several doses. Same
procedure is used for checking weight of Propellants. Another method is that. Reproducibility
has been determined by assay technique. Flash point Determined by using standard Tag
Open Cap Apparatus. This method is use for non aerosol. Q. velocity stages.C aspects
includes degree of conductivity of electric current as measure of exposed metals. into flame.
The use of rotational viscometers. Times for given rod that is inserted into the foam to fall.
Final testing of valve closure is done by passing filled containers through water bath. Net
contents Weight method. and the smaller particles pass on and are collected at high F and
transferred to the test apparatus. Temperature of test liquid increased slowly. Moisture
content Karl Fischer method or Gas chromatography method has also been used
Identification of propellants Gas chromatography or I. Sufficient sample is introduced through
the valve to cause the hydrometer to rise half way up the length of the tube. Amount of
medication actually received by the patient. Filled full container. Leak Test Leak test is done
by measuring the Crimps dimension amp comparing. of dose. Time for a given mass to
penetrate the foam. gives the average dosage. and exact length was measured with ruler.
Depending on the nature of formulation.The hydrometer is placed in to the glass pressure
tube.it is expressed as gram per seconds.Pokar Hitesh. In which Aerosol product is chilled to
temperature of . . G et al Review on Pharmaceutical Aerosol Containers are examined for
defects in lining. Glass containers examined for Flaws. It is calculated for flammable
component. and difference in weight divided by No. modification to accommodate liquefied
gas preparation.R spectrophotometry methods are used for identification of propellants.
Particle size determination Cascade impactor Operates on the projected through a series of
nozzle and glass slides at high velocity. to Internationale Pharmaceutica Sciencia AprJune
Vol Issue . Weight Checking Weight checking is done by periodically adding tared empty
aerosol container to filling lines which after filling with concentrate are removed amp
weighed. the change in weight per time dispensed is discharge rate. The density can be read
directly. device is available for accurately measuring vapor pressure. Spray Testing It is done
for . Product is sprayed for sec. and the temperature at which the vapors ignite is taken a
flash point. which in case of topical hydrocarbons.
Avoid spraying into eyes or onto other mucous membranes. should be identified and
minimized wherever possible. G et al Review on Pharmaceutical Aerosol micron and
retaining on RTI. As aerosols settle in turbulent condition . leak rate. behavior aerosol
dispersion. Inhalation gives the most direct access to drug target. plasticizers. Warning
Contents under pressure. Warning Use only as directed. Warning Avoid inhaling. is
statement Avoid inhaling is not The not phrase or other for mucous necessary for
preparations specifically designed for use membranes necessary preparations specifically
designed for use on mucous membranes.. Do not puncture or incinerate container. the
change in light intensity of Tyndall beam is measured. which may include poly nuclear
aromatics. pulmonary delivery can minimize systemic side effects. to ensure reproducible
quality and purity of the drug product. Modification made to improve efficacy. In addition to
the aforementioned warnings. The extractables profiles of a representative sample of each of
the elastomeric and plastic components of the valve should be established under specified
conditions and should be correlated to the extractable profile of the aged drug product or
placebo. etc. where required under regulations of the FDA. NOTEThe by inhalation. Labeling
Medicinal aerosols should contain at least the following warning information on the label as in
accordance with appropriate regulations. Their compatibility with formulation components
should be well established so as to prevent distortion of the valve components and to
minimize changes in the medication delivery. stem. CONCLUSION Drug delivery to the
respiratory tract has been characterized in the past decade by an increase in knowledge of
drug droplets or particle manufacture. nitrosamines. deliberate inhalation of contents can
cause death. lung deposition and clearance. antioxidants.Pokar Hitesh. Keep out of reach of
children. In the treatment of obstructive respiratory diseases. Internationale Pharmaceutica
Sciencia AprJune Vol Issue .g. and impurity profile of the drug product over time. Extractable
Substances Since pressurized inhalers and aerosols are normally formulated with organic
solvents as the propellant or the vehicle. For Topical Aerosols Toxicity For Inhalation
Aerosols For Topical Aerosols are determined. Pulmonary drug delivery is an important
research area which impacts the treatment of illnesses including asthma. Light scattering
decay Porush. etc. Therapeutic Activity For Inhalation Aerosols size. intentional misuse by
deliberately concentrating and inhaling the contents can be harmful or fatal. Thus.
vulcanization accelerators. must be carefully selected and controlled. the composition and
the quality of materials used in the manufacture of the valve components e. Extractable.
housing. chronic obstructive pulmonary disease and various diseases. bear either of the
following warnings Warning Do not inhale directly. Thiel and Young used light scattering
method to determine particle size. leaching and of extractables components from into the the
elastomeric plastic exposing test animals to Irritation amp Chilling effects vapor sprayed from
Aerosol container.. is applied to test areas amp adsorption of therapeutic ingredient is
determined. is depends on the particle Specifications and limits for individual and total
extractables from different valve components may require the use of different analytical
methods. provide rapid response and minimize the required dose since the drug is delivered
directly to the conducting zone of the formulation is a potentially serious problem. gaskets.
the label of a drug packaged in an aerosol container in which the propellant consists in whole
or in part of a halocarbon or hydrocarbon shall. monomers. Do not expose to heat or store at
temperatures above F C.
co. Specialized drug delivery systems manufacturing amp production technology. G et al
Review on Pharmaceutical Aerosol lungs .Aulton nd edition pg . pg .co. . pg .. Vol.
Remingtons The Science amp Practice Of Pharmacy rd Edition.Liberman. VolumeI.P
.google. USP.E. and Joseph L.cchs. Pceutical dosage form Disperse
system.in/booksidagEAAAAAMBAJ amppgPAamplpgPAampdqaquasolvalvefrompop
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Edition. page no . www.kpaerofill. Vol. Herbert Publishing A. House.medicombangolufsen.
Kaing.com www.optinose..shieldmedicare. Varghese Pub. Liberman. amp Basel. Third
edition.jp/mfen/products/unipore. onepageampqampffalse accessed on march th pm The
Theory amp Practice Of Industrial Pharmacy by Leon Lachman. pharmaceutics. Marcel
dekker.. to improve the Quality of pulmonary drug delivery system without affecting their
integrity.html http//www.It is a needle free several techniques have been developed in the
recent past.kitz.Y. References The theory and practice of Industrial Pharmacy by Leon
Varghese page no to http//books. Kaing.com Internationale Pharmaceutica Sciencia AprJune
Vol Issue . Joseph L.Pokar Hitesh. N.com Lachman. page no. by M. page no. pg Pceutics
The science of Dosage Form Design. Because of advancement in applications of pulmonary
drug delivery it is useful for multiple diseases.com/pages/sales/enquire.A. Joseph Kanig. Inc.
pg . VolII. So pulmonary drug delivery is best route of administration as compare to other
routes. by Praveen Tyle.dosag for and design by david jones.com www.html www.
www.net/health/healthinfo/doc www.chiesigroup. I.