6. Pharmaceutical Aerosols

Berhanemeskel W.G, Asst. Prof.Department of Pharmaceutics

School of Pharmacy College of Medicine and Health Sciences

University of Gondar

1Saturday, April 8, 2023

Presentation Outline

Introduction

Components of aerosol Package

Stability testing

Equipment used

Quality control

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IntroductionDefinition: 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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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

Introduction (2)

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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

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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. Propellant2. Container3. 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 pressure11

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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Hydrofluoroalkanes (aka Hydrofluorocarbons)

• Advantages– 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

(HFA-134a)14

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 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 systems1. 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 vapor3. Dispersed systems (suspension)• It needs surfactants• Particle size is important4. 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 temperature1. 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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