Pulmonary drug delivery (PDD) systems were recently introduced into the pharmaceutical field to treat both the local and the systemic types of lung diseases. PDD systems are known to be able to simply deliver the drug to the required site in the body directly or to other distant sites through the bloodstream.

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Presented by-
Mr. Sachin M.Chandankar
M. Pharm
Department of Pharmaceutics

2. • Introduction
• Anatomy of lungs
• Advantages
• Disadvantages
• Challenges
• Factors affecting
• Barriers
• Formulation approches
• Containers
• Evaluations
• Applications
• Marketed Products
• Newer Developments
• Conclusion
• References
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3. • Pulmonary drug delivery is primarily used to treat conditions of the airways,delivering
locally acting drugs directly to their site of action.
• The inhalation therapies involved the use of leaves from plants, vapours from aromatic
plants, balsams, and myhrr.
• The drug used for asthma and COPD e.g..- β2-agonists such as salbutamol (albuterol),
Terbutalin formoterol, corticosteroids such as budesonide, beclomethasone and mast-cell
stabilizers such as sodium cromoglycate or nedocromi.
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5. • The dose needed to produce a pharmacological effect can be reduced.
• Low concentrations in the systemic circulation are associated with reduced
systemic side-effects.
• Rapid onset of action.
• Avoidance of gastrointestinal upset.
• Avoidance of intestinal and hepatic first-pass metabolism.
• Deliver high drug concentrations directly to the disease site.
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6. • Complex delivery devices are required to target drugs to the airways and
these devices may be inefficient.
• Aerosol devices can be difficult to use.
• Various factors affect the reproducibility of drug delivery to the lungs,
including physiological (respiratory maneuver) and pharmaceutical (device,
formulation) variables.
• Drug absorption may be limited by the physical barrier of the mucus layer and
the interactions of drugs with mucus.
• Mucociliary clearance reduces the retention time of drugs within the lungs.
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7. • Low efficiency of inhalation system
particle size-0.5-1mm
• Less drug mass per puff
less than 1000 mcg
• Poor formulation stability for drug
• Improper dosing reproducibility
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8. Physiological factors
1. Thickness of Mucous layer
2. Lung morphology
3. Pulmonary surfactant
4. PH of microenvironment
5. Surface area
6. Tidal volume
7. Blood flow
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Physico-chemical factors
1. Lipid solubility
2. Pka
3.Particle size (1-3 um)
4. Density -0.4 g cm3
5.Electric charge
6.Shape
7. Hygroscopy
Formulation factor
1. Use of excipient
2. Type of formulation
3.Combination thereapies
4.Aerosol velocity

9. Mechanical barriers
• Coughing
• Sneezing
• Mucous
• Ciliary cells
• Pulmonary epithelium ( Thick layer 5-10um)
Chemical barrier
• Surfactant
• Pulmonary metabolism
Immunological barriers
• Alveolar macrophages
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10. • Pulmonary delivered drugs are rapidly absorbed except large macromolecules drugs, which
may yield low bioavailability due to enzymatic degradation and/or low mucosal permeability.
• Pulmonary bioavailability of drugs could be improved by including various permeation
enhancers such as surfactants, fatty acids, saccharides, chelating agents and enzyme
inhibitors such as protease inhibitors.
Recent advances in Formulations-
• Micronization via jet milling,
• Precipitation,
• Spray drying using various excipients, such as lipids and polymers,Carrier systems like
lactose.
• Liposomes,
• Nanoparticles.
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•Definition- A suspension of very fine liquid or solid particles in
a gas.
•Respirable range:1-5 micron
•80%drugs deposited in oropharynx
•10% in walls of inhaler
•10% in the lungs
• The drugs, delivery
• by aerosols is deposited in the airways by:
1.Inertial impaction-greter than
1um
2.Gravitational sedimentation-
0.5um
3.Diffusion-lesst han 1um

12. Recent technologies of pulmonary drug delivery-
1. NEBULISERS
a) Jet Nebulisers
b)ultrasonic nebulizers
2. DRY-POWDER INHALER (DPI)
a)Unit dose Devices
b)Multidose Devices
3.METERED–DOSE INHALER (MDI)
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13. • A nebulizer is a device used to administer medication to patient in the form of a mist inhaled
into the lungs.
• Used in treating cystic fibrosis, asthma, and other respiratory diseases.
• There are two basic types of nebulizers:
• The jet nebulizer functions by the Bernoulli principle by which compressed gas (air or oxygen)
passes through a narrow orifice, creating an area of low pressure at the outlet of the adjacent
liquid feed tube. This results in the drug solution being drawn up from the fluid reservoir and
shattering into droplets in the gas stream.
• The ultrasonic nebulizer uses a piezoelectric crystal, vibrating at a high frequency (usually 1–3
MHz), to generate a fountain of liquid in the nebulizer chamber; the higher the frequency, the
smaller the droplets produced.
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14. Nebulizers-
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15. • DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix that is fluidized when the
patient inhales.
• They typically formulated as one-phase, solid particle blends. The drug with particle sizes of less than 5µm
is used.
• Either they contain the active drug alone or have a carrier powder (e.g. lactose) mixed with the drug to
increase flow properties of drug.
• They are a widely accepted particularly in Europe, where they are currently used by approximately 40% of
asthma patients.
There are two types of devices-
1. Unit dose Devices
Single dose powder inhalers are devices in which a powder containing capsule is placed in a holder. The
capsule is opened within the device and the powder is inhaled.
2.Multidose Devices
This device is truly a metered-dose powder delivery system. The drug is contained within a storage
reservoir and can be dispensed into the dosing chamber by a simple back and forth twisting action on the
base of the unit.
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16. Principal of dry powder inhaler design
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17. •The pMDI containers must withstand high pressure generated by the propellant. Stainless steel has
been used as pMDI container material. Aluminium is now preferred because, compared to glass, it is
lihgter, more compact, less fragile, and light proof.
• In pMDI’s, drug is either dissolved or suspended in liquid propellants together with other
excipients and presented in pressurized cantainer fitted with metering valve.
• The predetermined dose is released as a spray on actuation of the metering valve.
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19. Containers:- Aerosol container must withstand pressure as high as 140-180 psig at
130°F.
Aerosols conatiners-
A.Metals
1.Tinplated steel
2.Aluminium
3.Stainless steel
B.Glass.
1.Uncoated glass
2.Plastic Coated
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20. C. Valves Assembly Consists of;
1.Ferrule or mounting cup
2.Valvebody or housing
3.Stem
4.Dip tube
5.Rubber ring
D. Actuatores-
1.Sprey actuators
2.Foam actuators
3.Solid steam actuators
4.Special actuators
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21. Containers Looking
Ultra sonic nebulizer Jet nebuliser Dry powder inhaler
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22. Properties Methods
1.Biological testing 1.Therapeutic Activity
2.Toxicities Study
B. Biological Characteristics
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Properties Methods
1.Vapor Pressure 1.Pressure gauge
2.Density 1.Hydrometer
2.Pycnometer
3.Identification of Propellents 1.IR Spectroscopy
2.Gas Chromatography
4.Visual Evaluation 1.Rotational Viscometer
5.Particle Size Determination 1.Cascade Impactor
2.Light Scattering Decay
A.Physiochemical Characteristics and Performance

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Particle Size Determination -
1.Cascade Impactor
2. Light Scattering Decay.
a). Cascade Impactor- Principle- Stream of particles projected through a series of nozzles and glass slides at
high velocity, larger particle are impacted first on lower velocity stage and smaller particles are collected at higher
velocity stage.
b). Light Scattering Decay- Principle- As aerosol settles under turbulent conditions, the change in the light
intensity of a Tyndall beam is measured.

24. • In Asthma and COPD-eg. bronchodilators corticosteroids.
•Recent role pulmonary delivery in patients on ventilators.
• In cystic fibrosis I- eg. N-Acetylcysteine.
•In migraine- eg. Ergotamine.
• In the Gene therapy via pulmonary route-eg. Cationic-lipid-mediated CFTR gene transfer can
significantly influence the underlying chloride defect in the lungs of patients with CFC.
•In angina pectoris –eg. Nitroglycerine.
•In diabetes mellitus-eg. Insulin nanoparticals.
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25. Dr Reddy's launches 'Dose Counter Inhalers' in India Friday, April 16, 2010
Dr.Reddy's Laboratories (DRL) has launched an innovation in the metered dose inhaler
(MDI) space with launch of 'Dose Counter Inhalers (DCI) for the first time in India.
This the first MDI in India that gives patients an advance indication of when the inhaler is going to
be empty. DCI is a new drug delivery device with a single device having 120 metered doses.
There is a window in the inhaler that changes colour
from green to red.
Green indicates the inhaler is full,
and red indicates the inhaler is empty.
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26. Active ingredient Brand Name Manufacturer Country
Terbutaline 0.25mg Bricanyl AstraZeneca UK
Beclomethasone
dipropionate 250mcg
Becloferte Cipla India
Salbutamol Salbutamol Dry
Powder capsules
Cipla India
Active ingredient Brand Name Manufacturer Country
Salbutamol pressurized
inhalation (100mcg)
Asthalin Cipla India
Albuterol Ventolin Gsk India
Levalbutarol Xopenex 3D Pharmaceuticals U.S.A.
Metered Dose inhaler
Dry Powder Inhaler
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27. • Pulmonary drug delivery is an important research area which impacts the treatment of illnesses
including asthma, chronic obstructive pulmonary disease and various diseases.
• Regional drug targeting is now possible.
• Local application is advantageous by pulmonary route.
• Inhalation gives the most direct access to drug target.
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28. • John J. Sciarra, Christopher J. Sciarra, Aerosols. In: Alfonso R. Geearo, editor. Remington: Science and practice
of pharmacy, second edition.vol-1.New York: Lippincott Williams and Wilkins publication; 2001.p.963-979.
• Anthony J. Hickey, Physiology of airway. In: Anthony J. Hickey, editor. Pharmaceutical inhalation aerosols
technology, second edition.vol-54.New York: Marcel Dekker;1992.p.1-24.
• Jain N. K, “Advances in Controlled and Novel Drug Delivery” 1st ed.(2010), CBS Publishers and Distributors
Pvt.Ltd. New Delhi, p.120-156.
• Lachman L, Liberman HA, Kaing JL, and Cuttie AJ. The theory and practice of Industrial Pharmacy, 3rd edition,
Varghese Publishing House;1976. p.589 618.
• Indian Pharmacopiea, 2014, Vol-1; p.24.
• Pharmaceutical dosage form; Disperse system. Vol-3, p.495-498.
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