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Pharmaceutical Aerosols
Berhanemeskel W.G, Asst. Prof. Department of Pharmaceutics School of Pharmacy College of Medicine and Health Sciences University of Gondar

Saturday, March 24, 2012

Presentation Outline
Introduction

Components of aerosol Package

Stability testing Equipment used Quality control

Introduction
Definition: A suspension of small solid particles or
droplets suspended 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 the container Pressurized packages existed during the early 1900s Aerosol industry begin in 1942, aerosol insecticide developed by Good hue and Sullivan of the US Department of Agriculture.
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Introduction (2)
The principle of aerosol technology were applied to the development of pharmaceutical aerosols in the early 1950s In 1950s- intended for topical administration In 1955- intended for local activity in the respiratory tract

Advantages of Pharmaceutical Aerosols

Dose can be removed without contamination of 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

Types of drug delivery systems

Nebulizers
used to administer medication to people in the form of a mist inhaled 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. 2. 3. 4. Propellant Container Valve and actuator (Button) Product concentrate

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 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)

Propellant

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

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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 density
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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 cost
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 Advantages

Hydrofluoroalkanes (aka Hydrofluorocarbons)

Low inhalation toxicity High chemical stability High purity Not ozone depleting

Disadvantages
Poor solvents Minor greenhouse effect High cost
e.g. 1,1,1,2,3,3,3 Heptafluoropropane (HFA-227), 1,1,1,2 Tetrafluoroethane 14 (HFA-134a)

Compressed gas propellants

Advantages
Low inhalation toxicity High chemical stability High purity Inexpensive No environmental problems

Disadvantages
Require use of a nonvolatile co-solvent Produce course droplet sprays Pressure falls during use

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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 drugs
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Valves
Deliver the content in the desired form Generally designed to work in inverted position Primary function reproducibly 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 tube
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Actuators
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

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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 solvents of 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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