Targeted drug delivery to the respiratory system- An article
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Targeted drug delivery to the respiratory system- An article
TARGETED DRUG DELIVERY TO THE
Submitted by - Satyaki A. Mishra
Regd No - 1561611001
School of Pharmaceutical Sciences, Bhubaneswar
Pulmonary drug delivery or drug delivery to the respiratory system is primarily
used to treat conditions of the airways, delivering locally acting drugs directly to
their site of action. Growing attention has been given to the potential of
pulmonary route as an alternative for non-invasive systemic delivery of
therapeutic agents. It can be used as an alternative to oral delivery.
These systems can be best utilized for both local and systemic actions. Pulmonary
drug delivery is an important research area which impacts the treatment of
illnesses including asthma, chronic obstructive pulmonary disease and various
other diseases. Inhalation gives the most direct access to drug target. These routes
of drug delivery may give the advantages like small amount of drug, less adverse
reaction and rapid onset of action.
The latest and probably one of the most promising applications of pulmonary drug
1) Its use to achieve systemic absorption of the administered drug substances.
2) Particularly for those drug substances that exhibit a poor bioavailability when
administered by the oral route, as for example peptides or proteins, the respiratory
tract might be a convenient port of entry.
Devices used to deliver drugs by pulmonary route are based on one of three
platforms. They are pressurized metered dose inhaler, nebulizer and dry powder.
In the treatment of obstructive respiratory diseases, pulmonary delivery can
minimize systemic side effects, and it provides rapid response, and it minimizes the
When developing a pulmonary drug delivery system, one of the important
parameter to be considered is the particle size. Optimum particle size is very
important for targeting of drug to lungs. If the particle size is too small they will
exhale and if it is too large, they may affect the oropharynx and larynx. Drug can
be delivered by using carriers like cyclodextrins, micro particles, liposomes,
FACTORS AFFECTING PULMONARY DRUG DELIVERY
Mechanisms of particle deposition in the airways
Effective resistance mechanisms involved may reduce the burden of external
particles enter the airways, and clearing those it may achieve something in being
stored. Therapeutic aerosols are two-phase colloidal systems in which the drug is
contained in a dispersed phase. They may have a solid, liquid or combination of the
two, based on the method and formulation of aerosol generation. The respiratory
resistance mechanisms of mucociliary clearance and phagocytosis by macrophages
may act upon insoluble particles. Aerosol particle dissolution may slow down and
the drug may then subsequently to be subjected to enzymatic deprivation before it
reaches to its specific site of pharmacological action. Aerosols for such are
transported from the mouth.
This is the main deposition mechanism for particles >1 μm in the upper tracheo-
bronchial regions. A particle having a larger momentum may not be able to follow
the altering direction of the inspired air as it transfers the bifurcations and it will
show result to collide with the airway walls as it continues on its original course.
By settling under gravity the particles get deposited. It becomes highly important
for particles that reach airways where the airstream velocity is relatively low, e.g.
the bronchioles and alveolar region. The fraction of particles depositing by this
mechanism may depend upon the time and the particles used in these regions.
This is of minor significance for particles >1 μm. Particles smaller than this size
are displaced by a sequentially bombardment of gas molecules, which may result in
particle collision with the airway walls.
The chances of particle deposition by diffusion increases with the decrease in
particle size. Brownian diffusion is also more common in regions where airflow is
very low or absent, e.g. in the alveoli. Another method of deposition, that of
interception, is of important for fibres but it may not for drug delivery. Generally:-
• Particles bigger than 10 μm will have impact in the upper airways and are
rapidly removed by swallowing, coughing and mucociliary processes.
• The particles in the size range 0.5–5 μm may break away from impaction in the
upper airways and may deposit by sedimentation and impaction in the lower TB
and A regions. If the aerosol particle size is between the 3 and 5 μm and deposition
it mainly occurs in the TB region. If the particles are smaller than the 3 μm then
appreciable deposition in the A region is likely to occur.
DRUG DELIVERY DEVICES
For pulmonary route, drug delivery devices play an important role equivalent to
that of formulation aspects. It is difficult to administer a formulation through
pulmonary route without suitable drug delivery devices. The drug delivery devices
are given below.
1. Dry Powder Inhalers
2. Metered Dose Inhalers
Dry Powder Inhalers (DPI)
DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix
(DPI) that is fluidized when the patient inhales. Dry powder formulations either
contain the active drug alone or have a carrier powder (e.g. lactose) mixed with the
drug to increase flow properties of drug.
Metered Dose Inhalers (MDI)
Used for treatment of respiratory diseases such as asthma and COPD. They can be
given in the form of suspension or solution. A metered-dose inhaler (MDI) is a
complex system designed to provide a fine mist of medicament, generally with an
aerodynamic particle size of less than 5 microns, for inhalation directly to the
Nebulizers are widely used as aerosolize drug solutions or suspensions for drug
delivery to the respiratory tract and are particularly useful for the treatment of
• Delivered the drug in the form of mist.
• There are two basic types:
1) Air jet
2) Ultrasonic nebulizer
In ultrasonic nebulizers, ultrasound waves are formed in an ultrasonic nebulizer
chamber by a ceramic piezoelectric crystal that vibrates when electrically excited.
The aerosol produced by an air jet nebulizer is generated when compressed air is
forced through an orifice; an area of low pressure is formed where the air jet exists.
Nebulizers are particularly useful for the treatment of hospitalized or non-
Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In
Vitro and in Vivo Evaluation by Hao Wang et.al
The stability data of DTX microspheres showed that during stored at 4°C or
room temperature 25 °C for 3 months, surface morphology and content of DTX
had no notable changes (Table 1). However, at 37 °C and RH (relative humidity)
75% the agglutinative phenomenon was observed, the mean diameter increased to
Docetaxel-loaded, glutaraldehyde-crosslinked chitosan microspheres were
prepared using a w/o emulsification method. The prepared microspheres were
found to possess suitable physico-chemical properties and the particle size range.
The microspheres were found to release the drug to a maximum extent in the
target tissue (lungs). This work adds to the already significant domain of targeted
drug delivery systems, which holds a promising alternative over the conventional
RECENT ADVANCES IN FORMULATION OF PULMONARY DRUG
Effective inhalable medications are formed by drug formulation. Formulation
stability is another challenge in producing pulmonary drug delivery. Formulation
is responsible for keeping drug in pharmacologically active state, it must be
efficiently delivered into the lungs, to the appropriate site of action and remain in
the lungs until the desired pharmacological effect occurs. Several factors have been
included in support of developing nasal formulations containing liposomes,
microspheres and nanoparticles for intranasal drug delivery.
ADVANTAGES OF PULMONARY DRUG DELIVERY
• It requires low and fraction of oral dose i.e. drug content of one 4 mg tablet
of salbutamol equals to 40 doses of meter doses.
• Pulmonary drug delivery having very negligible side effects since rest of
body is not exposed to drug.
• Onset of action is very quick with pulmonary drug delivery.
• Inhaling helps to avoid gastro intestinal tract problems such as poor
solubility, low bioavailability, gut irritability, unwanted metabolites, food
effects and dosing variability.
• In asthma and diabetes, long term treatment is required if it’s given by
pulmonary drug delivery. Safety is maximum because rest of the body is not
exposed to drug.
• Degradation of drug by liver is avoided in pulmonary drug delivery.
• Stability of drug in vivo.
• Targeting specificity.
• Drug irritation and toxicity.
• Drug retention and clearance
Pulmonary drug delivery is one of the oldest drug delivery systems. But still now
it is widely used due to its potential advantages. The drugs which produce GI
irritation can be administered by pulmonary route. One of the major hurdles in
this system is achieving the optimum particle size, which determines the targeted
delivery of drug to lungs. Inhalable nano carrier systems offer numerous
advantages, the decrease in particle size leads to an increase in surface area leading
to enhanced dissolution rate, as well as relatively uniform distribution of drug
dose among the alveoli. But still it requires further study to select the suitable
methods and additives based on the nature of the drugs. Carriers like micro
particles, nanoparticles, liposomes etc. can be used in pulmonary delivery.
Although advanced technologies are available, in some cases, the product may fail
to achieve its goal. Pulmonary route can be best utilizes by the researcher if they
have thorough knowledge of the disease behind treated, lungs anatomy, deposition
mechanism, delivering device used.
1. R. Sunitha; Drug Delivery And Its Developments for Pulmonary System:
Review Article. International Journal of Pharmaceutical, Chemical and
Biological Sciences .2011, 1(1), 66-82.
2. Chaturvedi N.P., Solanki H.; Pulmonary drug delivery system : A Review;
International Journal of Applied Pharmaceutics; Vol 5 (Issue 3) 2013
3. Karhale AA, Chaudhari HS, Ughade PL, Baviskar DT, Jain DK; Pulmonary
Drug Delivery System; International Journal of PharmTech Research; Vol.4,
No.1, Page 293-305, Jan-Mar 2012
4. Hao W, Yongdong X, Xiao Z; Docetaxel-Loaded Chitosan Microspheres as a
Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation;
International Journal of Molecular Sciences; Page 3519-3532