86566257 24332651 6 Pharmaceutical Aerosols

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6. Pharmaceutical Aerosols

Berhanemeskel W.G, Asst. Prof.

Department of Pharmaceutics

School of Pharmacy

College of Medicine and Health Sciences

University of Gondar

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Wednesday, October 01,

2014


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Presentation Outline

Introduction

Components of aerosol Package

Stability testing

Equipment used

Quality control

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Introduction

Definition: A suspension of small solid particles ordropletssuspended in a gas or vapor.

Aerosol or pressurized package is a system that

depends on the power of a compressed or

liquefied gas to expel the contents from thecontainer

Pressurized packages existed during the early1900s

Aerosol industry begin in 1942, aerosol insecticidedeveloped by Good hue and Sullivan of the USDepartment of Agriculture.

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The principle of aerosol technology wereapplied to the development of pharmaceuticalaerosols in the early 1950s

In 1950s- intended for topical administration

In 1955- intended for local activity in therespiratory tract

Introduction (2)

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Advantages of Pharmaceutical

Aerosols

Dose can be removed without contaminationof remaining material

Medication can be delivered directly to the

affected area in a desired form Irritation produced by the mechanical

application of topical medication is reduced or

eliminated Ease and convenience of application and

application of medication in thin layer

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Limitations

Expensive Performance of package can deteriorate

during life of product

Limited safety hazard Flammable

Pressurized

Inadvertent inhalation

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Types of drug delivery systems

Nebulizers used to administer medication to people in the form of a

mistinhaled into the lungs.

Meter dose Inhaler (MDI)

are pressurized, hand-held devices that use propellants to

deliver doses of medication to the lungs of a patient

Propellant driven

Aqueous pump sprays

Dry powder inhaler (DPI)

delivers medication to the lungs in the form of a dry

powder.

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Components of Aerosol Package

An aerosol product consists of the

following component parts:

1. Propellant2. Container

3. Valve and actuator (Button)

4. Product concentrate

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Propellant It is responsible for developing the proper pressure within the

container

It expels the product when the valve is opened and aids in the

atomization or foam production of the product

Types of Propellant

1. Fluorinated hydrocarbons e.g.

Trichloromonfluoromethane (Prop 11)

Dichlorodifluoromethane (Prop 12)

Dichlorotetrafluoroethane (Prop 114)

2. Hydrocarbons e.g.

Propane, Butane, and Isobutane

3. Compressed gases e.g.

Nitrogen, Carbon dioxide, and Nitrous oxide

4. Hydrofluoroalkanes

In practice blends are used to provide various vapor pressure. The

ultimate interest is to have vapor pressure 11


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Hydrocarbon Propellants

Advantages Inexpensive

Minimal ozone depletion

Negligible greenhouse effect Excellent solvents

Disadvantages

Flammable Aftertaste

Unknown toxicity following inhalation

Low liquid density12


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Chlorofluorcarbons (Used only in

inhalation aerosols)

Advantages

Low inhalation toxicity

High chemical stability

High purity

CFC-11 is a good solvent

Disadvantages

Destructive to atmospheric Ozone

Contribute to greenhouse effect

High cost13


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Hydrofluoroalkanes (aka

Hydrofluorocarbons) Advantages

Low inhalation toxicity


High purity

Not ozone depleting

Disadvantages

Poor solvents

Minor greenhouse effect

High cost

e.g. 1,1,1,2,3,3,3Heptafluoropropane (HFA-227), 1,1,1,2Tetrafluoroethane(HFA-134a)14


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Compressed gas propellants

Advantages Low inhalation toxicity


High purity Inexpensive

No environmental problems

Disadvantages Require use of a nonvolatile co-solvent

Produce course droplet sprays

Pressure falls during use 15


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Containers Containers must withstand pressure as high as

140 to 180 psig

Types of containers:

1.Tin plate containers

consists of sheet of steel plate that has been

electroplated on both sides with tin

2. Aluminum containers

greater resistance to corrosion

Light weight, not fragile

Good for light sensitive drugs

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3. Stainless steel container

Limited for smaller size

Extremely strong and resistant to most materials

Pressure stand

4. Glass containers

Available with plastic or without plastic coating

Compatible with many additives

No corrosion problems

Can have various shape because of molding

Fragile

Not for light sensitive drugs17


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Valves

Deliver the content in the desired form

Generally designed to work in inverted position

Primary functionreproducibly delivery an aliquot

of liquid phase in which drug is dissolved or

suspended There are mainly two types of valves

Continuous spray valve

Metering valves

Has various components:

Mount cap, Valve housing, Stem, Gasket

(rubber), Spring, Deep tube18


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Are specially designed buttons

Ensure proper delivery of the aerosols by

allowing the opening and closing of the valve

When actuators depressed valve open

They produce different forms of final product

Actuators

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Formulations

Pharmaceutical aerosol

Product concentrate + Propellant

Filling first product concentrate to the

container and then fill propellant during

package = two steps

Product concentrate is composed of

Active ingredients

Solvent

Additives

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Types of systems

1. Solution system

Consist of two phases liquid and vapor

If the active ingredient is soluble in propellant

it has one system The ratio of propellant and solvent could

range from 5% (foaming) to 95% (inhalation).

To lower vapor pressure we can add solventsof non volatile e.g. Propylene glycol, acetone,

alcohol

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2. Water based systems

Are increasing in use nowadays

Have relatively large amount of water

There is three phase system: water, propellant and vapor

In aquasol system it has two phases i.e. water and vapor

3. Dispersed systems (suspension)

It needs surfactants

Particle size is important

4. Foam systems

Have foaming agent

Aqueous or non aqueous

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Stability testing Stability is tested during the product development

Parameters for product concentrate and propellant are: Vapor pressure - Spray rate (pattern valve)

pH - Specific gravity

Viscosity - Total weight with time

Purity of propellant Total weight of active ingredient with time

Color and odor

Containers stability

Pressure withstand

Corrosion

Stability of valves and actuators functions

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Equipments used

Those fill at pressurized and low temperature

1. Pressure filling (gauge-burette)

2. Cold filling (low temp.)3. Compressed gas filling (after concentrate has

been filled)

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Quality control (QC)

Leak test

Passing the filled container to hot water. If there is

bubble it has leak

Q.C on propellant

Q.C on concentrate and their stability

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86566257 24332651 6 Pharmaceutical Aerosols

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