AEROSOLS
(Pressurized package system)
Types of aerosol systems
Liquefied gas system Compressed gas system Barrier packs
Component of aerosol systems
1. Propellant
2. Container
3. Valve and actuator
4. Product Concentrate
Types of propellant
Hydrocarbon (Propane, Butane, Isobutane) Chlorofluorocarbon (EPA Banned ) (Trichloromonofluromethane,Dichlorodifluromethane) Compressed gases: (Nitrogen, Nitrous oxide,Carbondioxide)
Types of containers
They must be stand at pressure as high as 140 to 180 psig(pounds per sq. inch gauge) at 1300 F 1)Tinplated containers Available in sheets 3 piece body Coating is done after fabrication 2) Aluminum containers Seamless Great resistance to corrosion Incompatible with pure water and ethanol
3) Stainless steel containers
Production hurdles Costly Use in inhalation aerosols No internal coating
4) Glass containers
15-30ml Volume Available without plastic coating Good corrosion resistance Freedom for design of containers Not recommended for suspension
An aerosol is made up of several basic components:
An aerosol can The product The propellant A valve with dip tube An actuator
The product, usually in the form of a liquid, is added. This contains active ingredients, except propellant.
The propellant is injected under pressure, through the valve. The propellant may be in the form of a liquified gas, or a compressed gas.
Valve and actuators
FDA approved valve Valve made-up of Actuator,Stem,Gasket,Spring,Mounting cup, Housing, Dip-tube Metering Valve Actuator : Integral part of aerosol Spray actuator Foam actuator Solid stem actuator Special actuator
Dispensing System: Actuators
Foam Actuator
Metered aerosol
Special actuator
Product concentrate
1. 2. 3. 4. 5. 6. Active ingredient Solvent Antioxidant Surfactant (Isopropyl myristate) Sweetener (Aspartame) Flavors (Strawberry )
Objective of Aerosol dosage form
Dose removed without contamination Stability is enhanced for oxygen and moisture sensitive drugs Irritation by local administration is reduced Ease and self administration Uniform application of drugs Ideal for the drug entity exhibits erratic pharmacokinetic Quick effect of drug
Aerosol solution
Preferred dosage form Two phase system Generally single propellant is used Lowering of vapor pressure produced by ethyl alcohol, propylene glycol, glycerine and acetone Amount of propellant 5% - 95%
Aerosol suspension
To avoid co-solvency Dispersion of active ingredient Used for oral administration Surfactant is used ?
Physical stability of aerosols: Reduction of particle size (2-5 Micron)
Adjustment of density
Use of dispersing agent
Aerosol Emulsion
Component
1. 2. 3. 4. Active ingredient Aqueous and nonaqueous vehicle Surfactant Propellant
Approx 7-10% Propellant Stable foam Quick breaking foam Emulsion are available in foam forms, Edible foams, Cough remedies , Antacids, vitamins
Drug deposition
System affected by- Particle size, Aerosols velocity, Hygroscopicity Device characteristic Breathing pattern Morphology of upper and lower airways
Intranasal application
Steroids, insulin, peptide and proteins are administered
Excellent depth of penetration
Lower doses compared to oral dose Maintenance of sterility of dose Aerosols suspension are preferred formulation for nasal administration
Bypass Blood Brain Barrier
Nose to brain drug delivery system
Intra Nasal DDs
The FDA has cleared the NasalNeb for the delivery of aerosol to the upper airway! And, in an unprecedented move, Healthline Medical has incorporated its integrated filter, thereby protecting both caregiver and the environment!
Metered dose containers
Use in the treatment of asthma Popular than nebulizer and DPI
60-90% of drug deposited in pharyngeal
area
Spacers are use
Drug substances for intranasal DDS
Local effect of drug
Less bioavailability
Quick effect of drug
Airway obstruction
Antispasmodic
Corticosteroids
Antidiabetic
Manufacturing of aerosols
Pressure filling apparatus Cold filling apparatus Compressed gas filling apparatus
Pressure filling apparatus
Consist of pressure burette Desired amount of propellant is allowed to flow Additional propellant is added through the hose or piston Metered dose intranasal preparation are not filled by this method
Cold filling apparatus
Insulated box fitted with copper tubing
Filled with dry ice/acetone prior to use
Use with meter as well as non metered
valve
Unsuitable for hydrocarbon aerosol
Compressed gas filling apparatus
Concentrate is filled in the container The valve is crimped in the place Air is evacuated by means of vacuum pump Filling head is inserted into the valve opening Gas is allow to flow in the container The container is shaken manually during and after filling
Evaluation of aerosols
1. Flammability and combustibility
Flash point (-25F,Tag open cup Apparatus) Flame extension (Flame) Vapor pressure Density (Hydrometer or Pycnometer) Moisture content (Karl Fischer & GC ) Identification of propellant (GC&IR) Concentrate propellant ratio
2.Physicochemical characteristic
Evaluation of Aerosols
3. Performance
Aerosols valve discharge (gm/sec)
Spray pattern (Dye-talc power)
Dosage with metered dose (Assay technique) Net content (Destructive method) (Eye drops) Foam stability (Visual,Mass,Line) Particle size determination (Light scattering viscometer) Leakage (Heating at 130F)
4. Biologic characteristic 5. Therapeutic testing 6. Toxicity studies
Recent advances
Metered dose inhalers Sublingual aerosols Anti diabetic aerosols (Insulin liposome for controlled drug delivery system) Pressurized metered dose inhalers Administration of proteins and peptides
