INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
Review Article
AEROSOLS: PULMONARY DRUG DELIVERY SYSTEM
Nimesh P. Patel*, Arpan A. Patel and Moin K. Modasiya
A.P.M.C. College of Pharmaceutical Education and Research, Motipura, Himatnagar, Gujarat,
India.
____________________________________________________________________________
ABSTRACT
Pulmonary drug delivery system is a needle free technique. The origin of inhaled therapies seen in back
4000 years ago to India, where people smoked the leaves of the Atropa belladonna plant to suppress
cough. In the 19th and early 20th 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: Asthma, pulmonary route, inhalation therapy, propellants.
INTRODUCTION potential side effects. Drug delivery by
An inhalation therapy that is effective and Nasal route is inefficient in terms of the
safe depends not only on a amount of drug actually delivered to the
pharmacologically active molecule, but also body and to improve its efficiency
on a delivery system and its application. penetration enhancers must be added that
The respiratory tract is exposed to a may cause local irritation. But in case of
relatively large number of biological and non pulmonary route research has shown that
biological particulates. These are contained many molecules are absorbed through the
in the 20,000 L of air that must be inhaled deep lung into the bloodstream naturally
daily to accomplish gas exchange. It is a with relatively high bioavailability and
characteristic of the effectiveness of lung without the need for enhancers used by
defense mechanisms that in healthy other noninvasive routes. Intra dermal route
people’s lungs are sterile below the larynx. offers an even less naturally permeable
By pulmonary route drug goes gives direct boundary to macromolecules than the
to a target organ1. In the treatment of gastrointestinal tract. The devices, which
obstructive respiratory diseases, pulmonary inject proteins like insulin, have been
delivery can minimize systemic side effects, available for years, however they have not
provide rapid response and minimize the very well accepted by doctors as well as
required dose since the pulmonary route is patients due to the discomfort and the
better alternative to other routes because if potential for ‘‘splash back’’ to transmit blood
we compare it with parental route injection borne diseases associated with it .Thus
is associated with pain2,3. pulmonary route is better route as compare
Secondly, chronic injection is an unpleasant to other routes.
prospect with a host of hygiene issues and
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 19
INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
The dosage forms used for this purpose are 2. Three-phase system. (Gas, liquid,
known as AEROSOLS. They are the solid/liquid).
dosage forms containing therapeutically
active ingredients that are packaged under Propellants
pressure in a sealed container and are For pressurized metered dose inhalations
released as a fine mist of spray upon propellants perform the essential function of
activation of a suitable valve system4. expelling the material from the container by
Basic components supplying the necessary pressure within the
1. The container aerosol system. They are liquefied or
2. Propellants compounded gases having vapor pressures
3. Product concentrate(containing API) exceeding employed to obtain the
4. Valve and Actuators. necessary delivery and spray characteristics
Types of the aerosol.
1. Two-phase system. (Gas & liquid)
Table 1: Commonly used propellants in aerosol systems
0
Propellants Molecular weight(g/mol) Vapor pressure(PSI at 25 C) Boiling point Density
0
( Cat 1 atm) (g/cm3)
011(CCl3F) 137.4 13.4 23.8 1.48
012(CCl2F2) 120.9 94.5 -29.8 1.31
114(C2Cl2F4) 170.9 27.6 3.8 1.46
134(CH2FCF3) 102.0 96.0 -26.5 1.20
227(CHF2C2F5) 170.0 72.6 17.3 1.92
The commonly used propellants in aerosol to improve safety characteristics or to coat
systems are hydrocarbons, especially the metal containers to improve corrosion
fluorochloro derivatives of methane and resistance and enhances the stability of
ethane (Table 1), the butanes and pentanes formulation. Suitable metals include
and compressed gases are used. stainless steel, aluminum and tin-plated
steel. Aerosol containers are made of metal
Containers (stainless steel, aluminum or tin-plated
Aerosol containers are usually made up of steel), glass or plastic or a combination of
glass, plastic, metal or combination of these these materials. The containers must be so
materials. Glass containers must be designed that they provide the maximum in
precisely engineered to provide maximum in pressure safety and impact resistance.
pressure, safety and impact resistance.
Plastics must be employed to coat the glass
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 20
INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
Metered dose inhalers have been popular
because of ease of usage, small and
compact size and the relative cost-
effectiveness. On the other hand, the
commonest error in the usage of an MDI is
the lack of coordination between the
actuation of the device and the initiation of
inspiration. Many other problems can also
be associated with the use of MDI. The
physician who prescribes these devices
should keep these things in mind and the
same should be conveyed to the patient as
well.
Fig.1: Metered dose inhalers
2) Dry Powder Inhalers (DPIs)
Dry powder inhalers (DPI) consist of
pharmacologically active powder as an
aggregate of fine micronized particles in an
inhalation chamber (Figure 2). These
aggregates are converted into an aerosol by
inspiratory airflow through the inhaler
generated by the patient. This basic fact
excludes the problem of coordination
between the delivery of the drug and the
initiation of inspiration. But the very same
fact also makes it unsuitable for patients
who are unable to generate high inspiratory
Fig. 2: Dry powder inhalers flow rates. Lack of requirement of propellant
is an advantage of DPIs over MDIs. The
fraction of the drug delivered to the site of
1) Metered Dose Inhalers (MDIs)
action by a DPI varies from 9% to 30% and
Metered dose inhalers are the most
varies among different commercially
commonly used devices for generation of
available products. The DPIs tend to fail in
aerosol (Figure 1). They consist of a
patients who cannot generate moderate to
micronized form of the drug in a propellant
high inspiratory flow rates since unlike the
under pressure with surfactants to prevent
MDI, they are driven by the patient’s own
clumping of drug crystals. Lubricants for the
effort. In a DPI, the aerosol needs to be
valve mechanism and other solvents are the
generated from the powder formulation by
other constituents. When the device is
patient’s own effort5-9.
actuated, the propellant gets exposed to
atmospheric pressure, which leads to
Valves
aerosolisation of the drug. As it travels
The valve regulates the flow of the active
through the air, the aerosol warms up
ingredient(s) and propellant from the
leading to evaporation of the propellant that
container and determines the spray
reduces the particle size to the desirable
characteristics of the aerosol. It must be
range. The fraction of drug to the airways
manufactured from materials which are inert
ranges from 5 percent to 15 percent.
to the contents of the aerosol. The
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 21
INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
commonly used materials are rubber, by inflammation and narrowing of airways.
plastic, aluminum and stainless steel. Asthma causes recurring periods of
Products for oral or nasal inhalation require wheezing, chest tightness, shortness of
metered-dose valves which ensure delivery breath, and coughing. The coughing often
of a uniform quantity of spray and an occurs at night or early in the morning.
accurate dose of the active ingredient(s), Asthma affects people of all ages, but it
both within specified tolerances, with each most often starts in childhood. In the United
activation of the valve. States, more than 22 million people are
known to have asthma. Nearly 6 million of
Actuators these people are children. Aerosol systems
The actuator or adaptor which is fitted to the that deliver bronchodilators to relax airways
aerosol valve stem is a device which on and corticosteroids to control inflammation
depression or any other required movement in asthma and COPD are widely used today
opens the valve and directs the spray to the and carry a proven track record. Today’s
desired area. The design of the actuator inhaled drug delivery market is dominated
which incorporates an orifice of varying size by the three main classes of drug such as
and shape and expansion chamber is very bronchodilators, corticosteroids, and ant
important in influencing the physical cholinergic. Nowadays all above three
characteristics of the spray or foam, classes of drugs given by pulmonary route.
particularly in the case of inhalation For management of asthma advances done
aerosols, where the active ingredient(s) in drugs such levosalbutamol inhalers which
must be delivered in the proper particle size having superior efficacy as compare to
range. A proportion of the active salbutamol. COPD means chronic
ingredient(s) is usually deposited on the obstructive pulmonary diseases. COPD is
inner surface of the actuator; the amount linked to smoking, comprises chronic
available is therefore less than the amount bronchitis and emphysema and causes one
released by actuation of the valve. million deaths annually. Some of the
marketed products are listed in Table 2.
Advantages of Pulmonary Drug
Delivery10-13 2) Pulmonary delivery in cystic fibrosis.
1. It is needle free pulmonary delivery. Nowadays cystic fibrosis is very common
2. It requires low and fraction of oral disease. Pulmonary delivery played an
dose. important role in the management of CF for
3. Pulmonary drug delivery having very decades. The main aim of aerosol system is
negligible side effects since rest of to deliver drugs to infants and children.
body is not exposed to drug. Recently following drugs are given by
4. Onset of action is very quick with pulmonary route for cystic fibrosis.
pulmonary drug delivery. Tobramycin-spray dried, Tobramycin
5. Degradation of drug by liver is powders containing nano particles for
avoided in pulmonary drug delivery. pulmonary delivery. Tobramycin is widely
used to treat patients with CF. Overall,
Current Applications of Pulmonary Drug evidence suggests improved lung function
Delivery15-18 and probably reduced hospitalization when
1) Application of pulmonary drug delivery in tobramycin is part of maintenance therapy
Asthma and COPD. Asthma is a chronic in CF.
long term lung disease that is characterized
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 22
INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
Table 2: Some marketed products
Name of Product API of drug Manufacturer
Epaq Salbutamol 3M Pharmaceuticals
Ventolin Albuterol Sulphate GSK
Flixotide Fluticasone Propionate GSK
Qvar Beclomethasone dipropionate 3M Pharmaceuticals
Asmol Salbutamol 3M Drug Delivery systems
CONCLUSION J Appl Physiology. 1998;85(2):379-
Drug delivery to the respiratory tract has 385.
been characterized in the past decade by 4. Indian Pharmacopeia, Aerosol
an increase in knowledge of drug droplets therapy. 2007;1:25.
or particle manufacture, behavior aerosol 5. Miller WF. Aerosol therapy in acute
dispersion, lung deposition and clearance. and chronic respiratory disease.
Pulmonary drug delivery is an important Arch Intern Med. 1973;131:148-55.
research area which impacts the treatment 6. Freedman T. Medihaler therapy for
of illnesses including asthma, chronic bronchial asthma: a new type of
obstructive pulmonary disease and various aerosol therapy. Postgrad Med J.
diseases. Inhalation gives the most direct 1956;20:667-73.
access to drug target. In the treatment of 7. US Pharmacopeial Convention, Inc.
obstructive respiratory diseases, pulmonary The United States Pharmacopeia.
delivery can minimize systemic side effects, 23rd ed. Rockville, MD: US
provide rapid response and minimize the Pharmacopeial Convention, Inc.;
required dose since the drug is delivered 1995.
directly to the conducting zone of the lungs 8. Loyd V. Allen, Jr. Nicholas G.
.It is a needle free several techniques have Popovich, Howard C. Ansel;
been developed in the recent past, to Aerosols, 2005;681:426-438.
improve the Quality of pulmonary drug 9. Leon Lachman, Herbert A.
delivery system without affecting their Lieberman, Joseph L. Kanig.
integrity. Because of advancement in Pharmaceutical Aerosols.
applications of pulmonary drug delivery it is 1987;3:589.
useful for multiple diseases. So pulmonary 10. Sciarra JJ. Aerosols; Remington’s
drug delivery is best route of administration Pharmaceutical Sciences.
as compare to other routes. 1980;16:1614.
11. Ji JH, Bae GN and Hwang J. Journal
REFERENCES of Aerosol Science.
1. Clark AR. Medical aerosol inhalers. 2004;35(11):1347-1358.
Past, present and future. Aerosol Sci 12. www.rddonline.com
Technol. 1995;22:374–391. 13. www.thecochranelibrary.com
2. Newman SP and Clarke SW. 14. Bahraini R, Dunlea EJ, Matthew BM,
Inhalation devices and techniques. Simons C, DochertyKS, DeCarlo PF,
In: Clark TJH, Godfrey S, Lee TH, Jimenez JL, Brock CA and
editors. Asthma. 3. London: Middlebrook AM. Design and
Chapman & Hall; 1992:469–505. operation of a pressure-controlled
3. David A. Edwards, Abdelaziz Ben- inlet for airborne sampling with an
Jebria and Robert Lange. Recent aerodynamic aerosol lens. Aerosol
advances in pulmonary drug delivery Science and Technology.
using large, porous inhaled particles. 2008;42(6):465-471.
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 23
INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES
15. Docherty KS and Ziemann PJ.
Effects of stabilized Criegee
intermediate and OH radical
scavengers on aerosol formation
from reactions of beta-pinene with
O3. Aerosol Science and
Technology. 2003;37(11):877-891.
16. Cheng YS, Zhou Y and Chen BT.
Particle deposition in a cast of
human oral airways. Aerosol
Science and Technology.
1999;31(4):286-300.
17. Yu G, Zhang Z and Lessmann R.
Fluid flow and particle diffusion in
the human upper respiratory system.
Aerosol Science and Technology.
1998;28(2):146-158.
18. Patel AR and Vavia PR. Indian
Journal of Experimental Biology.
2007;45:166-174.
Vol. 1 (1) Jan – Mar 2012 www.ijpcsonline.com 24
