6 pharmaceutical aerosols
DESCRIPTION
Lecture note for PharmacistsTRANSCRIPT
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
2
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.
3
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)
4
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
5
Limitations Expensive Performance of package can deteriorate
during life of product Limited safety hazard – Flammable– Pressurized– Inadvertent inhalation
6
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.
7
8
Components of Aerosol Package
An aerosol product consists of the following component parts:1. Propellant2. Container3. Valve and actuator (Button)4. Product concentrate
9
10
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
12
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
13
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
15
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
16
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
17
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
19
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
20
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
21
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
22
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
23
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
24
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)
25
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
26