AEROSOLS

Q) Explain dry powder and metered dose inhalers?

A) Dry powder inhalers (DPIs) are mechanical devices through which dry powder formulations are
delivered for the treatment of local or systemic effect via the pulmonary route. Drug/excipients
powders are delivered to the lungs by dry-powder-inhalers. Dry powder inhalers are bolus drug
delivery devices containing solid drug, suspended or dissolved in a non-polar volatile propellant or
in dry powder inhaler that is fluidized when inhaled by patient. In the treatment of respiratory
diseases such as asthma, bronchitis, emphysema and COPD, dry powder inhalers are widely used.
These are also used in the treatment of diabetes mellitus.
Dry powder inhaler contains a device which produces aerosols directly from powders of 1 to 5 m
size, or mixtures with excipients.

Formulation of dry powder inhaler mainly includes following three steps;

Preparation of active pharmaceutical ingredient: Most essential requirement in the active
pharmaceutical ingredient preparation is their particle size, which must be ideally less than 5 um.
For size reduction, various sorts of mills are used such as fluid-energy mills, jet mill, high-
peripheral-speed mills, pin-mill and the ball mill.
Formulation of API with or without carriers: Flow properties of powder as well as aerosol
performance cohesive drugs and fine lactose is increased by adding carriers. Once the drug and
carrier are separately brought to their desired forms, they are combined in the blending process.
Integration of the formulation into device: After the blending of above-mentioned ingredients,
they are filled into capsules, multi-dose blisters, or reservoirs for use with the inhaler device. The
filling process is automated and depends on the nature of the metering system.

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Metered dose inhalers
In these systems, the drug is usually a polar solid which has been dissolved or suspended in a non-
polar liquefied propellant. If the preparation is a suspension, as is most commonly the case, the
powder is normally micronised by fluid energy milling and the suspension is stabilized by the
addition of a surfactant. Lecithin, oleic acid and the Span and Tween series surfactants have been
widely used for this type of formulation. Metered dose inhalers (MDIs) are the most commonly
used drug delivery system for inhalation . The propellants have a high vapour pressure of around
400 kPa at room temperature, but since the device is sealed, only a small fraction of the propellant
exists as a gas. The canister consists of a metering valve crimped on to an aluminum can. Individual
doses are measured volumetrically by a metering chamber within the valve.

Formulation of Pressurized Metered Dose Inhalers

A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs,
in the form of a short burst of aerosolized medicine that is inhaled by the patient. Bronchodilator,
corticosteroid or a combination of both are most commonly used for the treatment of asthma,
chronic obstructive pulmonary disease (COPD) and other respiratory diseases.
Pressurized metered aerosols may be formulated as either solutions or suspensions of drug in the
liquefied propellant. MDIs can be formulated with the drug completely dissolved in the formulation,
rendering a solution formulation, or with the drug practically insoluble in the formulation, rendering
a suspension formulation.
Compared with suspension formulations, solution MDIs offer the benefits of homogenous
formulation, a finer residual aerosol.
When formulating solution MDIs, the total amount of fine particle drug delivered cannot simply be
increased by increasing the drug concentration in a formulation. Many drugs are not readily soluble

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in HA propellants, which frequently limit the amount of drug that can be dosed using MDIs.
Previously, surfactants or complexation aids were used in MDIs to increase drug solubility in CFC
systems. However, many of the conventional excipients used in CFC formulations and approved for
human use, are insoluble in HFA system.
The method for preparing drug particles for MDI formulations needs to be selected based on the
chemical stability of the drug. Proteins, for instance, require additional care when micronizing, due
to being heat-labile and need to preserve any three-dimensional conformation. Frequently, spray-
drying with another agent, such as sodium carboxymethylcellulose, polyvinyl alcohol, or polyvinyl
pyrrolidone is utilized for protein drugs due to the need to preserve the three-dimensional
conformation and biological activity of the protein.
Advantages
The major advantages of pMDIs are their portability, low cost and disposability. Many doses (up to
200) are stored in the small canister, which may also have a dose counter, and dose delivery is
reproducible. The inert conditions created by the propellant vapour, together with the hermetically
sealed container, protect drugs from oxidative degradation and microbiological contamination.
Disadvantages
However, pMDIs have disadvantages. They are inefficient at drug delivery. On actuation, the first
propellant droplets exit at a high velocity, which may exceed 30 m s.Consequently, much of the
drug is lost through impaction of these droplets in the oropharyngeal areas. The mean emitted
droplet size typically exceeds 40 mm, and propellants may not evaporate sufficiently rapidly for
their size to decrease to that suitable for deep lung deposition.
Q) Write a note on evaluation of aerosol?
A) Pharmaceutical aerosols can be evaluated by a series of physical, chemical, and biologic tests,
including: 1.Flammability and combustibility
 Flash point
 Flame extension, including flashback
2.Physicochemical characteristics
 Vapour pressure
 Density
 Moisture content
 Identification of propellant(s)
 Concentrate-propellant ratio

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3. Performance
 Aerosol valve discharge rate
 Spray pattern
 Dosage with metered valves
 Net contents
 Foam stability
 Particle size determination
 Leakage
4. Biologic characteristics
Flash Point
This is determined by use of the standard Tag Open Cup Apparatus. The aerosol product is chilled
to a temperature of about 25°F and transferred to the test apparatus. The test liquid is allowed to
increase slowly in temperature and the temperature at which the vapours ignite is taken as the flash
point.
Flame Projection
This test indicates the effect of an aerosol formulation on the extension of an open flame. The
product is sprayed for about 4 sec into a flame. Depending on the nature of the formulation, the
flame is extended, the exact length being measured with a ruler.
Vapour Pressure
The pressure can be measured simply with a pressure gauge or elaborately through use of a water
bath, test gauges and special equipment.
Density
The density of an aerosol system may be accurately determined through the use of a hydrometer or
a pycnometer.
Moisture Content
Many methods have proven useful for this purpose. The Karl Fischer method has been accepted to a
great extent. Gas chromatography has also been used.
Identification of Propellants
Gas chromatography and infrared spectrophotometry have been used to identify the propellants and
also to indicate the proportion of each component in a blend.
Aerosol Valve Discharge Rate

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This is determined by taking an aerosol product of known weight and discharging the contents for a
given period of time using standard apparatus.
Spray Patterns
A method for comparing spray patterns obtained from different batches of material or through the
use of different valves. The method is based on the impingement of the spray on a piece of paper
that has been treated with a dye-talc mixture. Depending on the nature of the aerosol, an oil-soluble
or water-soluble dye is used. The particles that strike the paper cause the dye to go into solution and
to be absorbed onto the paper. This gives a record of the spray, which can then be used for
comparison purposes.
Particle Size Determination
Many methods have been advanced for the measurement of particle size of aerosols. Among, those
that have been used to a great extent are the Cascade impactor and “light scatter decay” methods.
Biologic Testing
The final phase involved in a comprehensive research and development program for pharmaceutical
aerosols must involve biologic testing. A limited number of these tests have been used to evaluate
the efficiency of many products, including various antibacterial agents.

REFERENCE:
“The Theory & Practice Of Industrial Pharmacy” by Leon Lachman, H.A.Liberman, Joseph Kanig,
3rd Edition, Varghese Pub., page no. 613-618.