All about DRY POWDER INHALER(DPI)

1. Mr. Krishna Sudhakar Jadhav
Department of Pharmaceutics
National Institute of Pharmaceutical Education and Research,
Mohali(S.A.S Nagar),Punjab

2. • DPI are device through which a dry powder formulation
of an active drug is delivered for local or systemic effect
via the pulmonary route.
• Used to treat respiratory disease such as asthma, COPD,
Bronchitis etc.
• Dry powder for inhalation are formulated either as loose
agglomerates of micronized drug particle with
aerodynamic particles size less than 5µm.
• Whereas for systemic effects particle size of less than
2µm is needed for drug deposition in the small peripheral
airways.
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3.  Propellants free design.
 Provides rapid drug action.
 High drug dose carrying capacities, reproducibility
(Monodisperse).
 low device retention and low exhaled loss.
 Provides local action within the respiratory tract and
are non-invasive.
 Better patient compliance, simple to use and
convenient to carry and do not require spacers.
 Less potential for formulation problems.
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4.  Deposition efficiency depends on patients inspiratory
airflow.
 Greater potential problems in dose uniformity.
 Less protection from environmental effects,
Humidity may cause powders to aggregate and
capsules to soften.
 Dose lost if patient inadvertently exhales into the DPI
 More expensive than pressurized metered dose
inhalers
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6.  The mechanisms by which particles deposit in the
respiratory tract includes
1. Impaction(inertial deposition),
2. Sedimentation(gravitational deposition)
3. Brownian diffusion
4. Interception,
5. Electrostatic precipitation .
 All mechanisms act simultaneously, but the first two mechanisms
are
most important for large-particle deposition within the airways
(1 mm, AD, 10 mm).
 Diffusion, however, is the main determinant of deposition of
smaller particles in peripheral regions of the lung.
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7. Different biophysical parameters determine regional drug
deposition in the human lungs:
 Aerodynamic particle behavior (e.g. size, density,
hygroscopicity, shape, electrical charge)
 Breathing pattern of the patients (e.g. flow rate, ventilation
volume, end-inspiratory breath holding)
 Time of aerosol pulse injection into the breathing cycle
 Anatomy of the respiratory tract.
Of these factors, aerosol particle size and size distribution are
the most influential on aerosol deposition.
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9.  Most DPIs contain micronized drug blended with larger
carrier particles, which prevents aggregation and helps flow.
 Movement can be brought about by several mechanisms:
1) Passive inhalers employ the patient’s inspiratory flow.
patient activates the DPI airflow through the device creates shear and
turbulence; air is introduced into the powder bed and the static powder
blend is fluidized and enters the patient’s airways. the drug particles
separate from the carrier particles the larger carrier particles impact
in the oropharynx Smaller are carried deep into the lungs and
cleared.
2) Active inhaler :shear and turbulence could be produced by
using a dispersion mechanism that is independent of the
patient’s breath, high delivery efficiency and reproducibility
might be might provide formulation independent delivery.
.
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10. Formulation of DPI can be classified into three The categories:
 API production
 Formulation of API with or without carrier
 Integration of formulation into device.
1) API Production: To introduce the drug particle into the lungs, they must
be <5μm in aerodynamic diameter. This is achieved by milling the
powder prior to formulation.
Development of various approaches to the controlled production of fine
particle :
 Controlled crystallization or precipitation
 Micronization
 Blending
 Pelletization
 Spray Drying
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11. 2) Formulation of API with or without carrier.
 Carrier Free system: the drug particle which is to be inhaled must have
aerodynamic diameter less than 5 μm and present either in the form of
single compound or as an encapsulated particles.
 Carrier Based system: Lactose is the most common and frequently used
carrier in DPI formulations.
Carrier particles offers several advantages :
1)improve drug particle flow ability.
2)improved dosing accuracy.
3)minimum dose variability.
4)ease of handling during manufacturing operations.
5)inhalation efficiency increases.
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12. Different types of formulation:
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13.  Based on the metering system, they can be
 Unit dose inhaler
 Multi dose inhaler
Multi-unit dose inhaler
Reservoir type.
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14.  supplied in individual capsules, then inserted into the inhaler
for a single dose and removed.
 capsule body containing the dose falls into the device, while
the cap is retained in the entry port for subsequent disposal.
 Example: Rotahaler(GlaxoSmithKline),
Aerolizer(Novartis), Handihaler (BoehringerIngelheim).
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15. Multi-unit dose devices Multi-dose reservoir devices
 Individual doses packaged in blister packs
on a disk cassette.
 piercing, inspiratory flow induces drug
dispersion of the powder.
 aerosol stream is mixed with flow entering
through holes in the mouthpiece that, gives
rise to turbulence and promotes
deagglomeration.
 Example .Diskhaler (GlaxoSmithKline),
Diskus (GlaxoSmithKline)
 multiple doses of small pellets of micronized
drug that disintegrate into their primary
particles during metering and inhalation.
 One dose can be dispensed into the dosing
chamber by a simple back-and-forth twisting
action on the base of the reservoir.
 Scrapers actively force drug into conical holes
which cause the pellets to disintegrate.
 Fluidization and the deagglomeration
 Example: Turbuhaler (AstraZeneca)
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16.  provide an environment where the drug can maintain
its physicochemical stability and produce
reproducible drug dosing.
 The device should be designed to deliver high fine
particle fraction (FPF) of drugs from the
formulations.
 devices with higher resistance need a higher
inspiratory force by the patients to achieve the
desired air flow. This could be difficult for patients
with severe asthma and for children and infants.
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17.  device design is an important factor in deciding its
efficiency because the dimensions and internal
anatomy of the device introduce resistance to airflow.
 success of passive DPI depends on patient’s ability to
generate an inspiratory flow rate (IFR) that is strong
enough to overcome the resistance of the inhaler and
set particles in motion.
 Device resistance plays an important role in
successful therapy.
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18. 1. Appearance and Color
2. Particle size analysis: The optimum aerodynamic particle
diameter for most inhalation products has generally been recognized as
being in the range of 1–5microns.
Equipment use for Particle size analysis
1)Cascade impactor
2)light scattering decay method .
Sieve analysis and laser diffraction are used for the particle size
analysis for lactose used in inhalation products.
3. Moisture Content: The Karl Fisher method has been accepted to a
greater extent .
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19. 4. Flow properties of Powder: The flow properties of a DPI were
measured by the Carr’s method which involves
a)Angle of repose Compressibility
b)Uniformity coefficient
c)Hausner’s Ratio (HR)
d)Angle of spatula.
5. Packing Properties of Dry Powder Inhalation:
Determined with the tapping method by utilization of Kawakita’s
equation for indicating porosity.
6. Drug Content (Assay)
7. Net Content
8. Impurities and Degradation Products : By means of stability
indicating methods the levels of degradation products and impurities
should be determined.
9. Microbial Limits
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20. 10. Spray Pattern:. The method of comparison is based on the
impingement of the spray on a piece of paper that has been treated with
a dye-talc mixture.
11. Extractable/Leachable: For plastic and for rubber container closure
components that are in contact with the formulation during storage (e.g.,
valves), a study should be conducted to determine the extractible profile.
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21.  DPI can be considered as an attractive drug delivery system, both for drug
that are to be administered for local therapy in the lung, as well as for
drugs that act systemically and for which the lung is only port of entry to
the body.
 Currently, the inhalation performance of DPIs is being improved by
changing formulation strategy, drug and carrier particle engineering.
 The future research in DPIs will thus aim to assimilate drug in a matrix
particle to achieve specific pulmonary drug deposition and probably to
achieve intracellular drug delivery especially, proteins, peptides, plasmids,
DNA etc.
 A better understanding of the influencing properties of powder on the
performance of DPI will help to address the challenges in the development
of DPI formulation and inhaler devices for optimum therapeutic benefits.
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