Innovations in Aerosol Drug

Delivery System
INTRODUCTION
• Liquid aerosol inhalation has been an accepted means of drug delivery
since the beginning of modern pharmaceutical therapy.
• Beginning with the development of the first nebulizer in the early 20th
century, aerosol-generating devices have continued to progress to provide
higher efficiencies, lower variability, and better patient compliance.
• Aerosol delivery is used in almost every stage of health care: acute, long-
term, and home health care, each of which demands variations on liquid
aerosol generation method.
• While trying to adapt to patient needs in a multitude of settings, pulmonary
delivery devices are constantly being improved and modified to create
aerosols that effectively traverse the human airway.
INTRODUCTION
•Compact devices designed for patients have been dominated in recent years
by two types of devices: pressurized metered dose inhalers (pMDIs) and
dry powder inhalers (DPIs). Whereas these methods of pulmonary delivery
have seen considerable success, recent technological innovations have lead
to renewed interest in aqueous aerosol drug delivery.
•New technology involving liquid aerosolization has been focused
predominately on delivery of a precisely metered dose to the deep lung, which
may fill a well-known need for devices capable of delivery of systemic drugs
via the pulmonary route.
•Aqueous aerosol delivery devices can also greatly simplify the formulation
process and allow for new pulmonary therapies to be implemented more
readily.
•Devices for aqueous aerosol generation seen in currently marketed products
can be classified into four main categories: air-jet nebulizers, vibrating
nebulizers, “smart” nebulizers, and metered dose liquid inhalers (MDLIs).
Metered Dose inhalers
• It is composed of four essential
components: the base formulation (Drug,
propellant, excipients, etc.), the container,
the metering valve and the actuator (or
mouth piece)
• The drug is delivered through a valve in a
metered volume from a volatile propellant,
pressurized container.
Types
• Non pressurized Metered dose
inhaler
• Pressurized metered dose inhaler
(pMDI)
• MDI with spacers or holding
chambers
• Breath actuated MDI
NONPRESSURIZED SYSTEM
• Micronised drug is dissolved or dispersed in liquefied
propellant (CFC). Before the propellant exits from the
atomized nozzle, it is partially (15-20%) evaporated and
droplets are broken up by the violent evaporation
generating droplets with wide distribution (1-5µm).
• But due to alarms raised for stratospheric ozone
depletion, a more environment friendly substitutes like
Hydrofluoroalkane (HFA) came in light. They have the
limitation of poor solvency which can be overcome by
addition of co-solvents like ethanol.
• Some patients cannot fulfill the co-ordination
requirements which is essential for maximum therapeutic
benefits, breath actuated powder inhalers are developed.
 Pressure
resistant
container

Liquid solution or
suspension

Metering
chamber

Valve stem

Actuator
Mouthpiece Air inlet

Spray jet
Pressurized MDI
Propellants
Provides the force to generate the aerosol cloud and is also the
medium in which the active component must be suspended or
dissolved. Propellants in MDIs typically make up more than 99% of
the delivered dose
• Chlorofluorocarbons (CFCs)
most commonly used propellants were the
chlorofluorocarbons CFC-11, CFC-12 and CFC-114.
Banned due to adverse effect on ozone layer

• Hydrofluoroalkanes (HFA)
HFA 134a (1,1,1,2,-tetrafluoroethane)
These new devices are more effective. The HFA
propellant produces an aerosol with smaller particle size,
resulting in improved deposition in the small airways and
greater efficacy at equivalent doses compared with CFC
MDIs.
• When the valve is actuated propellant
and drug leave the inhaler at high
velocity
• Majority of drug impacts in
oropharynx
• Less than 25% reaches the lung
Most efficient way of using MDI- steps
Advantages of MDIs
• Compact, portable ,convenient
• Multidose delivery capability
• Lower risk of bacterial contamination
• Suitable for emergency situation
Disadvantages of MDIs
• Needs correct actuation and inhalation
coordination- difficult for children and
elderly patients
• Cold freon effect
• High pharyngeal drug deposition
• Flammability possibility of new HFA
propellants
• Remaining dose –difficult to determine
MDI with Spacer
Steps for Using a Spacer with an MDI

• Insert the inhaler/canister into spacer and

shake.
• Breathe out.
• Put the spacer mouthpiece into your
mouth.
• Press down on the inhaler once.
• Breathe in slowly (for 3-5 seconds).
• Hold breath for 10 seconds.
Advantages of MDI with spacer
• Compensate for poor technique/coordination
with MDI
• Spacers slow down the speed of the aerosol
coming from the inhaler, meaning that less of
drug impacts on the back of the mouth and
somewhat more may get into the lungs.
Because of this, less medication is needed for
an effective dose to reach the lungs, and there
are fewer side effects from corticosteroid residue
in the mouth.
Disadvantages
• Large size and volume of device
• Bacterial contamination is
possible; device needs to be
cleaned periodically
• Electrostatic charges may reduce
drug delivery to the lungs
Breath actuated MDI
• Recent Innovations in MDI
AERx®
• AERx pulmonary drug delivery platform demonstrated
performance that is highly efficient and precise
compared to other inhalation systems.
• The performance of the AERx platform is due to its
unique fine mist aerosol generation systems combined
with patented breath control technology.
• For each therapeutic application, the AERx platform can
be customized to deliver drugs and biologics to treat lung
diseases topically or to transport therapeutics through
the lung and into the bloodstream.
 The AERx dosage form.

The AERx device (with dosage forms).

AERx nozzle array.
AERx®
 AERx®
• It is built around a microprocessor controlled hand-held device
that delivers a unit bolus dose by extruding a drug-containing
solution through small laser drilled holes.
• The extruded jets of fluid will break up into droplets when
appropriate pressure, surface tension, and pore diameter are
present.
• Each unit dose is packaged in a disposable strip with the nozzle
built in.
• The nozzle pore size, aerosol production rate, required patient
flow rate, and integrated patient instruction may be changed
depending on the treatment desired.
• The slow-velocity aerosol produced has a narrow droplet size
distribution; 90% of the droplets are within the 2–3 μm diameter
range, contributing to the high-deposition efficiency of this device.
 Respimat®
• The Respimat® inhaler combines the advantages of pMDIs and
nebulizers.
• It is a small, portable, hand-held inhaler with no need for power supply
(like pMDIs) that slowly aerosolizes propellant free-drug solutions as a
soft mist (like nebulizers), thus decreasing the chance for oropharyngeal
deposition.
• Administration of one-half of the cumulative dose of ipratropium bromide
and fenoterol hydrobromide by Respimat® achieved the same
therapeutic outcome as that of the full dose administered by pMDI to
asthmatic patients.
 Respimat®
• Soft mist inhalation offers several advantages over current metered dose
inhalation therapies including easier patient coordination, less
oropharyngeal deposition, and formulation simplification without the use
of ozone depleting propellants.
• Spacers, commonly used to slow down high-velocity pMDI aerosols, are
not necessary or recommended for use with this, or any, MDLI device
because of the unique method of aerosolization used.
• In this device aerosolization occurs when two liquid jets of formulation
collide to produce a slow-velocity mist containing a FPF of 65–80% able
to achieve a twofold-to-fourfold reduction in oropharyngeal impaction
when compared with a pMDI.
• Potential energy stored in a compressed spring supplies required force
for multiple actuations. Dose delivered has been shown to remain
uniform over several actuations (Figure 5)
Respimat®
 Mystic®
• A unique concept of producing an aerosol through electrohydrodynamic
disruption has led to the development of the Mystic® (Battelle,
Columbus, OH).
• After passing through a capillary, the liquid formulation forms a conical
shape due to the electrical field. At the crest of the liquid conical,
electrically excited droplets aerosolize. The result is the production of
fine respirable mist with an electrical charge that is subsequently
neutralized. This method of aerosolization is not new in spray technology
but has only recently been adapted for pharmaceutical applications.
Initial device designs include the ability for multiple dosing
(approximately 200) and an actuation cycle lasting 2 s. In a phase I
clinical study, the proportion of the total emitted dose (for an intended
dose of 400 μg) to reach the lung was 78%. While not much information
is published regarding studies conducted with this device, the claim of a
nearly monodisperse aerosol cloud and superior deep lung deposition in
in vivo tests (Williams, 2007) provides promise for this product’s future.
Mystic®
Dry powder inhaler (DPI)
 Single dose Devices
Had to be reloaded with capsule containing
micronized drug in a large particle carrier
powder ,usually lactose
Multiple DoseDevices
Advantages
• Breath-actuated
• Less patient coordination required
• Spacer not necessary
• Compact Portable
• No propellant
• Usually higher lung deposition
than a pMDI
Disadvantages of DPI
• Work poorly if inhalation is not forceful enough
• Many patients cannot use them correctly (e.g.
capsule handling problems for elderly
• Most types are moisture sensitive
Humidity potentially causes powder clumping
and reduced dispersal of fine particle mass
• Need to reload capsule each time
 Nebulizers

Jet nebulizer Ultrasonic nebulizer

Pneumatic Jet Nebulizer
• Delivers compressed gas through a jet, causing an area
of negative pressure and drawing the liquid up the tube
by the Bernoulli effect. The solution is entrained into the
gas stream and then sheared into a liquid film that is
unstable and is broken into droplets by surface tension
forces. The fundamental concept of nebulizer
performance is the conversion of the medication solution
into droplets in the respirable range of 1-5 micrometers
Ultrasonic Nebulizer
• Generates high-frequency ultrasonic waves
(1.63 MHz) from electrical energy via a
piezoelectric element in the transducer. These
ultrasonic waves are transmitted to the surface
of the solution to create an aerosol. Aerosol
delivery is by a fan or the patient’s inspiratory
flow; particle sizes may be larger with this
device. A limitation of ultrasonic nebulizers is
that they do not nebulize suspensions efficiently
Advantages Of Nebulizers
• Provide therapy for patients who cannot
use other inhalation modalities (eg, MDI,
DPI)
• Allow administration of large doses of
medicine
• Patient coordination not required
• Effective with tidal breathing
• Dose modification possible
• Can be used with supplemental oxygen
Disadvantages Of Nebulizers
• Decreased portability
• Longer set-up and
administration time
• Higher cost
• Electrical power source
required
• Contamination possible
Thank you !!