Definition : A suspension of small solid particles or droplets suspended in a gas or vapor. • Pharmaceutical aerosols are usually unstable. • Common perception : Products that depend on the pressure of a compressed or liquefied gas to expel the contents from a container

Advantages of Pressurized Delivery Systems • Portable • Regarded as easy to use and convenient • Remaining product is not contaminated during use Aerosol can be filled aseptically • Tamper- proof • Protect unstable drugs from light, oxygen and water • Target site need not be touched. Provides access to hard- to-reach sites • Provides access to systemic circulation Expands to fill available space and provide complete surface coverage Minimal Dripping

Disadvantages of Pressurized Delivery Systems • Expensive • Performance can deteriorate during life of product • Flammable Pressurized • Sometimes prone to incorrect use

Uses of Pharmaceutical Aerosols Topical Local anesthetics (e.g.Benzocaine) • Wound washing • Rubiferants (e.g.Methylsalicylate) • Spray on bandages • Proprietary burn applications • Antibacterials(e.g. Neomycin) • Antifungal sprays (Miconazole) • Anti- inflammatory steroids (e.g.Dexamethasone) Oral and Lingual • Antacids (e.g. Aluminum and magnesium silicate) • Local anesthetics (e.g. Lidocaine) • Antiseptics (e.g. Chloroseptic) • Anti –anginals (e.g. Nitroglycerin) Vaginal and Rectal • Contraceptive Foams (e.g. Nonoxyenol-9) • Local anesthetics (e.g. Pramoxine) • Anti –inflammatory steroids (e.g.Hydrocortisone)

Nasal • Decongestants (e.g. Phenylephrine) • Anti -inflammatory steroids (e.g.Beclomethasone) • Antiallergics (e.g. Cromolyn sodium) • Moisturizers (e.g. Normal saline) Ocular • Contact lens cleaning solutions (not applied directly to eye) Respiratory • Bronchodilators (e.g. Albuterol) • Anti -inflammatory steroids (e.g. Beclomethasone) • Antivirals (e.g. Ribavirin) • Smoking cessation (e.g. Nicotine) Migraine (e.g. Ergotamine tartrate)

HYDROCARBON Propellants Advantages • Inexpensive • Minimal ozone depletion • Negligible “greenhouse effect” • Excellent solvents Disadvantages • Flammable • Aftertaste • Unknown toxicity following inhalation • Low liquid density

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

HYDROFLUOROALKANES Advantages • Low inhalation toxicity • High chemical stability • High purity • Not ozone depleting Disadvantages • Poor solvents • Minor “greenhouse effect” • High cost Examples: 1,1,1,2,3,3,3 – Heptafluoropropane (HFA-227) 1,1,1,2 – Tetrafluoroethane (HFA-134a)

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

Packaging Components Containers Plastic Coated Glass • Allows level of contents to be seen • Compatible with most formulations • Plastic coating absorbs "neckshock" during crimping and provides barrier to broken glass • Poor aesthetic finish / difficult to label / heavy • Used for inhalation aerosols containing dissolved drug Aluminum • Lightweight and seamless • Can be screen printed, therefore visually appealing • Easy to fill and crimp • Incompatible with some propellants and solvents – Can be anodized or epoxy coated • Opaque • Used for inhalation and topical aerosols

Three Piece Tinplate • Corrosion inhibitors typically included in formulation – Not suitable for all products • Incompatible with some propellants and solvents • Visible seams make them less cosmetic appealing • Can be pressurized from the base with compressed gasses Polyethyleneterephthalate (PET) • Plastic containers under development VALVES Continuous (used for most topical aerosols) • Product is released as long as pressure is maintained on the actuator. Metered (Used for all inhalation, & some topical aerosols) • A finite Volume of product is released when the actuator is pressed. No more product is released unless the actuator is returned to its rest position and repressed – 25 -150ml for inhalation aerosols – up to 5 ml for topical aerosols

Dip-tubes and Canister Orientation • Diptubes are essential when the product is sprayed “valve up” • Diptubes are never used when a product is only sprayed “valve down” – Difficult to homogeneously disperse product inside a dip-tube • Canister orientation should be described as “valve-up” or “valve- down”, not “upright” or “up-side-down” Multi Spray-Orientation Canisters • Valve bodies with filling holes and a dip- tube (Vapor Tap valves) • “Bag in can” pressurized formulations Actuators, Adapters & Dust Caps • Dust caps keep the actuator clean • Allow the valve stem to be easily depressed to release product • Direct the aerosol to where it is required • Partially control the physical form of the aerosol output

Quality Control Tests on Manufactured Pressurized Formulations Standard Pharmaceutical Tests – Identity and purity of drug – Drug concentration and product fill weight – Stability • Integrity test – no bubbles released under water at 55oC • Propellant leakage rate test • Product delivery rate (continuous valves only). • Flame projection test (continuous valve only) • Specific tests for inhalation aerosols