 Definition: products that depend on the power of a compressed or liquefied gas to expel the contents from the container.  Aerosols are termed also pressurized package.  Pharmaceutical aerosols: aerosol products containing therapeutically active ingredients dissolved, suspended or emulsified in a propellant or a mixture of solvent and propellant and intended for topical administration, for administration into one of the body cavities (ear, rectum and vagina) or intended for administration orally or nasally as fine solid particles or liquid mists through the pulmonary airways, nasal passages or oral cavity.

 The product is administered easily and quickly.  A dose can be removed with out contamination of materials.  Stability is enhanced for these substances adversely affected by oxygen and or moisture.  When sterility is an important factor, it can be maintained while a dose is being dispensed.  Rapid onset of action, avoidance of degradation of the drug in the GIT and first pass effect.  Lower dose of drug can be used and hence minimize adverse and side effects.

 The medication can be delivered directly to the affected area in a desired form, such as spray, steam, quick breaking foam or stable foam.  Irritation produced by the mechanical application of topical medication is reduced or eliminated.  Application of medication in thin layer

Components of aerosols:  Propellant  Container  Valve and actuator  Product concentrate

 Propellant: It is responsible for developing the power pressure within the container and also expel the product when the valve is opened and in the atomization or foam production of the product. For oral and inhalation: eg. Fluorinated hydrocarbons Dichlorodifluromethane (propellent 12) Dichlorotetrafluromethane (propellent 114) For Topical preparation: Propane Butane Isobutane

A- Liquefied gas - these are materials that at room temperature and atmospheric pressure exist in the gaseous or vapor state and are capable of being liquefied at relatively low pressures or temperatures. - E.g. Chloroflurocarbon (CFCs) Hydrocarbons - Because the aerosol is under pressure the propellant exists mainly as a liquid, but it will also be in the head space as a vapour. - As the product is used up as the valve is opened, some of the liquid propellant turns to vapour and keeps the head space full of vapour - In this way the pressure in the can remains constant and the spray performance is maintained throughout the life of the aerosol.

B- Compressed Gas Propellants  Compressed gas propellants only occupy the head space above the liquid in the can.  When the aerosol valve is opened the gas 'pushes' the liquid out of the can.  The amount of gas in the headspace remains the same but it has more space, and as a result the pressure will drop during the life of the can.  E.g. nitrogen, nitrous oxide, carbon dioxide

 They must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge). A. Metals 1. Tinplated steel 2. Tin free steel 3. Aluminium 4. Stainless steel B. Glass 1. Uncoated glass 2. Plastic coated glass

Tinplated steel : - Used in topical pharmaceutical aerosols - Coating decreases the compatibility problems - Light - Inexpensive Aluminum: - Used in oral aerosols ** Metal containers may be further coated with organic coating, e.g. oleoresin, phenolic, vinyl or epoxy coating for additional protection.

 Glass - Advantage: Absence of incompatibility - Its use is limited for products having lower pressure and lower percentage of propellant - There are two types of glass containers: Uncoated glass: - Low cost - High clarity Plastic coated glass: - Prevent the glass from shattering in the event of breakage - Used for some topical and MDI aerosols

 Why a Curved Bottom? In most aerosol cans, the bottom curves inward. This serves two functions: 1-The shape strengthens the structure of the can. If the can had a flat bottom, the force of the pressurized gas might push the metal outward. A curved bottom has greater structural integrity. 2-The shape makes it easier to use up all the product.

 To deliver the drug in desired form.  To give proper amount of medication.  Types: 1- Continuous spray valve - High speed production technique. 2- Metering valves - Dispersing of potent medication at proper dispersion - spray approximately 50 to 150 mg ±10 % of liquid materials at one time use of same valve.

 Valve Cup :- typically constructed from tinplated steel, or aluminium.  Outer Gasket :- this is the seal between the valve cup and the aerosol can.  Valve Housing :- contains the valve stem, spring and inner gasket.  Valve Stem :- in effect, the tap through which the product flows.  Inner Gasket :- covers the hole in the valve stem.  Valve Spring :- usually stainless steel.  Dip Tube :- allows the liquid to enter the valve.  Actuator (not shown) :- fits onto the valve stem.

 To ensure that aerosol product is delivered in the proper and desired form.  Different types of actuators: Spray actuators, Foam actuators, Solid steam actuators, Special actuators

 Contains two essential components:  Product concentrate - contains ingredients or mixture of active ingredients and other such as solvents, antioxidants and surfactants  Propellant. - Propellant May be single or blend of various propellants

 Solution system - Consist of a solution of active ingredients in pure propellant or a mixture of propellant and solvents. - Easy to formulate, provided that the ingredients are soluble in the propellant

 Suspension or Dispersion systems - Active ingredients are suspended or dispersed throughout the propellant or propellant and solvent phase. - Problems associated with the formulation: Agglomeration, caking, particle-size growth and valve clogging (closing). - To overcome these problems: 1-lubricants: isopropyl myristate, oleic acid - Provide slippage between particles - Lubricate components parts of the valve 2- Surfactants: to disperse particles

3- Dispersing agents: oleic acid, lecithin - Keep the suspended particles from agglomeration 4- The particle size of metered-dose inhalant should be between 2 – 8 um, while those for topical aerosols should be 50 – 100 um.

Metered dose inhalers Consists of a pressurized container with metered-dose valve and placed in an oral adapter (mouthpiece). When the unit is dispensed, the exact amount of the drug is expelled in the proper particle size to achieve maximum deposition in the lungs. Formulated as solution or suspension.

Effect of particle size on drug deposition in the lung

3- Emulsion: - Suitable for topical aerosols - Two types of emulsions can be formulated- o/w OR w/o - If the product concentrate is dispersed throughout the propellant …………..W/O emulsion………the product is dispersed as wet stream - If the propellant is in the internal phase……..O/W emulsion………foam is emitted

 Cold filling apparatus - Lowering the temperature of the concentrate (solution or suspension) below room temperature (-30ºC to - 60ºC) - The cold concentrate is added to chilled (cooled) container - The propellant is added - The valve is crimped in place - The container is passed into a water path (55ºC) to ensure there is no leakage or distortion in the container.

 Pressure filling apparatus - The concentrate may be chilled slightly (15 -20ºC) to reduce vaporization of any volatile solvent or propellant. - The concentrate is added to an open container - The valve is crimped in place - The propellant is added under pressure through the valve. - The filled container is passed through the water path.

 A. Flammability and combustibility 1-Flame Projection This test indicates the effect of an aerosol formulation on the extension of an open flame. - Product is sprayed for 4 sec. into flame. - Depending on the nature of formulation, the fame is extended, and exact length was measured with ruler. -

2- Flash point Determined by using standard Tag Open Cap Apparatus. - Aerosol product is chilled to temperature of - 25º F and transferred to the test apparatus. - Temperature of test liquid increased slowly, and the temperature at which the vapors ignite is taken a flash point. - Calculated for flammable component, e.g. topical hydrocarbons.

 B. Physiochemical characteristics 1- Vapor pressure Determined by pressure gauge Variation in pressure indicates the presence of air in headspace. 2-Density Determined by hydrometer or a pychnometer. 3-Moisture content By Karl Fischer method 4- Identification of propellants I.R spectrophotometry

 C. Performance 1- Aerosol valve discharge rate - Determined by taking an aerosol known weight and discharging the contents for given time using standard apparatus. - By reweighing the container after time limit has expired, the change in weight per time dispensed is discharge rate, Expressed as gram per seconds.

2- Dose uniformity - To determine amount of medication actually received by the patient. - The method involves accurate weighing of filled container followed by dispersing of several doses. - Container can reweighed - Difference in weight divided by No. of dose, gives the average dosage.

3- Net contents - Weight filled full container - Dispensing the contents, then reweight the container - The difference in weight, will be the net weight 4- Leakage Used to estimate the weight loss over a 1-year period.

5- Particle size distribution - By using Cascade Impactor - Carrying particles in a stream of air through a series of consecutively smaller jet openings. - The heavier and larger diameter particles are impacted on a slide under the larger opening. - As the openings get smaller, the velocity of the stream increases and the next larger particles are deposited on the next slides.  E. Therapeutic activity