INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005

Review Article
Dry Powder Inhaler: An Advance Technique for
Pulmonary Drug Delivery System
SP. Sahane*, AK. Nikhar, S. Bhaskaran and DR. Mundhada

Department of Pharmaceutics, Agnihotri College of Pharmacy, Sindhi (Meghe), Wardha,

Maharashtra, India.
_________________________________________________________________________

ABSTRACT
A growing attention has been given to the potential of a pulmonary route. Pulmonary Drug Delivery
represents an attractive, needle free, rapid and patient-friendly route used for drugs with poor to no
bioavaibility when administered via the oral route which can pass the alveolar membrane. It is mainly
classified into three classes; Nebulizer, pMDI, DPI. DPIs are an alternative to pMDI that delivers
medication to the lungs in the form of a dry powder. Particle Size of API must be present in size range
about 1-10 μm which also guarantee that the patient gets the same dose every time at different airflow
rate. DPI are formulated using four types of formulation strategies such as; Carrier Free, Drug Carrier,
Drug Additive, Drug Carrier Additive. Dry powder for inhalation is often composed of fine drug
particles and inert coarse carrier particles such as lactose. The dispersion of a dry powder aerosol is
conducted from a static powder bed. When the patient takes breathe, air is introduced into the powder
bed creates turbulence and leads to fluidization of static powder blend and enters the patient’s airways
where the drug particles separate from the carrier particles and are carried deep into the lungs, while the
larger carrier particles impact in the oropharynx and are cleared. Lung Deposition Study is carried out
by Twin Stage Impingner. The inhalation device is important in achieving adequate delivery of inhaled
drug to lung which mainly classified based on dose type into Single-unit and Multi-dose reservoirs.

Keywords: pMDI, DPI, Inhalation Device.

INTRODUCTION 1, 2 3. Respiratory tract provide a large

Pulmonary Drug Delivery System serves surface area which is highly
as major route of drug administration for permeable for absorption of drug
thousand of year. Ancient inhalation into the blood so gives quick onset
therapies include the use of leaves from of action.
plants, vapors from aromatic plants, 4. The large protein molecules which
balsams, and myrrh. It is mainly used for might degrade in gastrointestinal
systemically acting drugs such as peptide tract and eliminated by first pass
and protein, as well as for drugs that are metabolism are given by
designed to act locally on the lungs pulmonary route which avoid the
themselves for the treatment of asthma, first pass metabolism.
Chronic Obstructive Pulmonary Diseases Pulmonary drug delivery system is mainly
(COPD) or Cystic Fibrosis (CF). classified into three classes;

Advantages of Pulmonary Drug 1. Nebulizer: 4

Delivery System. 1, 2, 3 In this system, aerosols are generated
1. Needle free and non invasive drug from solution or suspension of drug in an
delivery system. appropriate solvent. Nebulizers are very
2. Drug is directly deposited in the efficient at creating mists of extremely fine
lung, so minimizes the dose droplets with good pulmonary deposition.
requirement and has negligible
side effect as the rest of body is a. Advantages of Nebulizer5
not exposed to drugs. 1. High doses of medication can be
used.

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2. Multiple drugs can be used in as Lactose Monohydrate. The

single system. development of DPIs has been motivated
3. Easy formulation handling and by the desire for alternatives to pMDIs, to
requires less co-ordination of reduce emission of ozone-depleting and
patient. greenhouse gases chlorofluorocarbons
and hydrofluoroalkanes respectively that
b. Disadvantages of Nebulizer6 are used as propellants. DPIs are
1. Equipment is large which is difficult commonly used to treat respiratory
to transport. diseases such as asthma, bronchitis,
2. Variability in performance between emphysema and COPD although DPIs
different nebulizers. have also been used in the treatment of
3. Need for external power source. diabetes mellitus.

2. pressurized Metered Dose Inhaler a. General Requirements of DPI. 8, 9

(pMDI)6,7 DPIs have to meet the following
pMDI are the device in which medication requirements;
is mixed into the canister with a propellant i. Particle Size of API: Active Compound
and the performed mixture is expelled in must be size about 1 to 10 μm. Such
precise measured amounts upon micro fine particles can be obtained by
actuation of the device. micronization, controlled precipitation
from suitable solvent or by spray
a. Advantages of pMDI: 1, 4, 5 drying if the process conditions are
1. Easy to handle. suitable.
2. Accurate metering ii. Drug content uniformity: It is important
performance. that each capsule or blister in a single-
3. Capacity of large number of dose system contain the same amount
does at low cost. of powder and medication while in a
multi-dose system; the reservoir must
b. Disadvantages of pMDI: 1, 4, 5 release the same amount of powder
1. Limited to the treatment of upper and drug every time.
airway conditions because of it iii. Content uniformity at different airflows:
emits the dose at high velocity, The dose has to be released in exactly
which makes premature deposition the same way at low breathing and at
in the oropharynx. a high breathing rate.
2. Require careful co-ordination of iv. Stability of powder against humidity
actuation and inhalation. and temperature: Major ingredient of
3. Drug content/dose is problematic if DPI is lactose which must be protected
pMDI not shaken in case of against particle size growth. The main
suspensions. property responsible for particle size
4. Contains propellant such as growth is an undesired combination of
Chlorofluorocarbon (CFC) which temperature and relative humidity
depletes the ozone layer which is controlled by storage in the
5. pMDI is limited to certain drugs correct packaging is important for
that are stable in a propellant. stability.
v. Flowability: Almost all active
3. Dry Powder Inhaler ingredients have poor flowability; the
Dry powder inhalers have advanced good flow has to be supplied by the
significantly over the past 10–15 years. A carrier.
Dry powder inhaler (DPI) is a device that
delivers medication to the lungs in the b. Advantages of Dry Powder Inhaler3,
4, 10
form of a dry powder. The dry powder
platform comprises devices that generate As DPIs has been motivated by
an aerosol directly from 1-5 μm size drug the desire for alternatives to pMDIs, so
powder, or mixtures with excipients such

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INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005

advantages of DPI over pMDI is given as agglomerate. There are three types of
follows; interparticle forces, the van der Waals
1. Require little or no coordination of force, the electrostatic force and the
actuation and inhalation: Incorrect use capillary force. The van der Waals force
of pMDIs found that poor coordination becomes noticeable when the particles
of actuation and inhalation caused are sufficiently close (0.2–1.0 nm) to one
decreased asthma control in a another and when the particles are small
substantial proportion of patients (20 μm or less). Surface roughness,
treated with corticosteroid pMDIs. geometrical structure and deformation of
Whereas DPIs are activated by the individual particles can significantly
patient’s inspiratory airflow, they change the van der Waals force.
require little or no coordination of Electrostatic force can occur by the
actuation and inhalation. potential difference when particles of
2. Formulation Stability: Since DPIs are different work functions are brought into
typically formulated as one-phase, contact. The resulting Coulomb attraction
solid particle blends, so they are makes the powder adhesive. Capillary
preferred as stable formulation. Dry force comes from fluid condensation in the
powders are at a lower energy state, gaps between particles in close contact,
which reduces the rate of chemical resulting in the formation of liquid bridges
degradation and the likelihood of between particles. High capillary force
reaction with contact surfaces. By comes at the expense of electrostatic
contrast, pMDI formulations, which force, which diminishes with increasing
include propellant and co solvents, moisture.
may extract organic compounds from To overcome these difficulties different
the device components. types of formulation strategies for DPI
3. Propellant-free design: pMDI contains (Fig. 1) are used as follows
propellants such as i. Carrier Free: In carrier free
chlorofluorocarbons and strategy, active therapeutic
hydrofluoroalkanes which are ozone- ingredient is in the form of a single
depleting and greenhouse gases compound, multi-compound
respectively. Production of CFC composite or encapsulated
propellants was banned from 1st particles. The inhalation drug
January 1996 in order to stop the particle must have aerodynamic
depletion of ozone layer. So pMDI particle size less than 5 µm.
were replaced by DPI which do not ii. Drug Carrier: It is difficult to
contains propellant. So DPI’s are dispense 1μg to 1 mg of doses of
environmental friendly formulation. drug into the small blisters for dry
Other advantages of DPI are as follows; powder inhalers. So the drug
1. High drug dose carrying capacities molecules are mixed with larger
range from less than 10 mg to particle to make them flow better
more than 20 mg and also to increase the volume of
2. Minimal extrapulmonary loss of each dose. Coarse particles in the
drug due to low oropharyngeal bed of fine particles, if mobilized,
deposition, low device retention can act as an additional agitator or
and low exhaled loss. turbulence promoter to aid the
3. Less potential for extractable from fluidization of fine particles.
Disadvantage of this strategy
device components.
includes; carriers generally deposit
c. Formulation Strategies for Dry in the mouth along with many drug
Powder Inhaler1 particles adhered to them which
Efficacy of DPI is mainly depends on flow leads to less drug reaching the
property of powder which is mainly lungs.
iii. Drug Additive: The addition of finer
affected by strong interparticle forces
which make the cohesive bulk powder particles can also improve the

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INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005

fluidization quality of drug fine a spinning rotor and stationary stator

powders. Additives such as plate. Powder is fed to the milling chamber
submicron silica (0.5–3 wt. %), and transported through the milling
alumina (29 nm), aerosol 200 (12 chamber by centrifugal force. Final milled
nm) were used. product is collected from bottom. The ball
iv. Drug Carrier Additive: An mill is a rotating cylinder loaded with drug
additional particle type may be and balls that grind the drug between
added to the formulation to each other as they tumble inside the mill.
improve drug delivery. This In spray-drying, the drug is dissolved in
additive may be a fine particle water or solvent and sprayed as fine mist
such as a fine particle of the same into a heated expansion chamber. The
composition as the carrier, which droplets dry, leaving behind tiny particles
could function as a physical of drug that are collected at the bottom of
spacer, or possibly by occupying the chamber.
high-energy sites such as clefts in
the carrier surface. ii. Formulation of API with or
without carriers
d. Formulation. 6, 11, 12 The role of carrier in DPI is enhancing the
Formulation of DPI mainly includes three flow property of powder and also aerosol
steps; performance of the cohesive drugs and
i. API Production fine lactose. After drug and carrier (s)
Particle size of drug should be less than 5 have individually been brought to their
μm. It should be in the range of 2-5 μm. desired forms, they are combined in the
Generally the drug particle size is not well blending process. Mixer selection, rotation
controlled during bulk drug production. speed, capacity, and fill level are all
The drug particle size must be reduced in parameter for optimization which affects
a separate unit operation. There are the blend homogeneity. Different powders
various size reduction techniques such as may have different mixing requirements,
milling, spray drying, and supercritical fluid depending on the forces present between
extraction. the various particles. For low
There are various types of mills used for concentration (drug-carrier ratio) blends,
size reduction of drugs but few of them geometric dilutions are necessary
are suitable for DPI to reduce the size in preblending steps.
the range of 2-5 μm such as fluid-energy
mills, such as the jet mill; high-peripheral- iii. Integration of the formulation
speed mills, such as the pin-mill; and the into device
ball mill. After the formulation has been blended, it
Jet mill reduces particle size via high- is filled into capsules, multi-dose blisters,
velocity particle-particle collisions. or reservoirs for use with the inhaler
Unmilled particles are introduced into the device. The filling process is automated
milling chamber. High-pressure nitrogen is and depends on the nature of the
fed through nozzles and accelerates the metering system.
solid particles to sonic velocities. The
particles collide and fracture. While flying iv. Carriers used in DPI1, 13, 14
around the mill, larger particles are Dry powder formulations for inhalation are
subjected to higher centrifugal forces and often composed of fine drug particles and
are forced to the outer perimeter of the inert coarse carrier particles. The fine drug
chamber. Small particles exit the mill particles adhere to the carrier surface. API
through the central discharge stream. usually present in a low concentration,
A pin mill uses mechanical impact to grind with a drug to carrier ratio of 1:67.5 (w/w).
material, both by particle-particle and Interactions between Carrier and Drug
particle-solid collisions which can produce particles are mainly dependent on the
1 µm particles. It is equipped with a series physicochemical characteristics of the
of concentrically mounted pins located on interacting particles such as; particle size,

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shape, surface morphology, contact area, For aerosol generation, several power-
hygroscopicity of drug and carrier particle. assisted devices (pneumatic, impact force,
Lactose is the most widely used carrier. and vibratory) have been developed or are
Several other compounds such as currently under development. These are
mannitol, sucrose and sorbitol, glucose, called as active-dispersion DPIs which are
and more recently cyclodextrin, raffinose, no commercially available.
trehalose and xylitol have been suggested
as possible alternatives to lactose. vi. Lung Deposition Study
Alternatives are required if the drug is Five mechanisms govern particle
chemically incompatible with lactose. deposition in lung airways as follows
i. Inertial impaction: defined as inertial
i. General Requirements for deposition of a particle onto an airway
Carrier.27, 28 surface. It happens principally close to
Two contradictory requirements must be the airway bifurcations of the large
fulfilled for dry powder formulation. On the conducting airways.
one hand, adhesion between carrier and ii. Gravitational sedimentation: occurs in
drug must be sufficient for the blend drug the small conducting airways where
and carrier to be stable. On the other hand the velocity of the air is low and for
adhesion of drug and carrier has to be particle below 5µm in size.
weak enough to enable the release of iii. Diffusion: occurs in small airways and
drug from carrier during patient inhalation. alveoli where the airflow is very low
Other requirements are given as follows; and for sub micrometer-sized particles
1. Carrier should not react with drug (below 0.5) and are subject at
and device. Brownian motion.
2. Carrier should be compatible with iv. Interception: is important only for fibers
drug. (asbestos) and aggregates. For such
3. Improving transport and the particles, deposition may occur when a
proportion of drug that reaches to particle contacts an airway wall, even
the lungs. though its centre of mass might remain
4. Improving stability of the drug in on a fluid streamline.
vivo. v. Electrostatic attraction: electrostatic
5. Increasing the specific delivery of charges enhance deposition by
drug to target tissues. increasing attractive forces to airway
surfaces, in particular for fresh
v. Principle of dry powder inhaler generated particles.
design. 6, 11 Lung deposition study is carried out by
The dispersion of a dry powder aerosol is Twin Stage Impingner apparatus.
conducted from a static powder bed. To
generate the aerosol, the particles have to vii. DPI Device15, 16
be moved. Movement can be brought The primary inhaler parts are same for all
about by several mechanisms viz.; Passive type of devices on the market and many in
and Active. Passive inhalers employ the development. Dry Powder Inhaler device
patient’s inspiratory flow. When the patient consists of; powder formulation, dose
activates the DPI and inhales, airflow measuring system, powder
through the device creates shear and deagglomeration principle and mouthpiece
turbulence; air is introduced into the (Fig. 3)
powder bed and the static powder blend is
fluidized and enters the patient’s airways. Ideal Characteristics for DPI Device16
There, the drug particles separate from the 1. Device should be easy to use and
carrier particles and are carried deep into convenient to carry.
the lungs, while the larger carrier particles 2. Contain multiple doses
impact in the oropharynx and are cleared 3. Protect the drug from moisture.
(Fig. 2)

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4. Accurate and uniform delivery of generally consist of drug having size

doses over wide range of range 1-5µm and carrier particles having
inspiratory flow rate. 50-150 µm. Generally Lactose is mostly
5. Consistent dose delivery preferable carrier. Lung deposition
throughout the life of the inhaler. occurred by Active and Passive
6. Minimum adhesion between drug mechanism can be studied by using Twin
formulation and devices. Stage Impingner apparatus.

ACKNOWLEDGEMENT
CONCLUSION Authors are thankful to D. R. Mundhada,
Dry Powder Inhaler is promising route for Principal, Agnihotri College of Pharmacy,
Pulmonary Drug Delivery System which is Wardha and Dr. Shyamala Bhaskaran,
given by oral inhalation as DPI having Director, Agnihotri College of Pharmacy,
numerous advantages over pMDI. DPIs Wardha for their valuable guidance.

Fig. 1: Different types of formulation strategies for Dry Powder Inhaler1

Fig. 2: Principle of dry powder inhaler design.6

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Fig. 3: Primary functional design elements of dry powder inhaler10

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