Overview Of Pharmaceutical Aerosol
Aerosol is the state of the intermediate matter between the liquid and the gaseous state. Therefore, it is composed of particles neither as dispersed as the gas nor as concentrated as of the liquid. Pharmaceutical aerosols means fine particles of one or more drugs or medicine (either solid or liquid or both) that are kept in a container under pressure and that are released as a fine spray when a button is pressed. They are used for both systemic and local applications.
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An aerosol consists of extremely fine solid or liquid particles that remain suspended in a gas or air, called propellant. Propellant is an inert substance. Fog and smoke are examples of natural aerosols.
Types Of Aerosol
1. Space spray: these types of aerosols produce dispersion of particles which remain in the air for prolonged periods. The particles of spray are usually less than 50 µm in size.
2. Surface coating spray: such aerosols used for producing a film on the surface treated this type of aerosols is relatively coarse. The particles range in size from 50 to 200 µm.
3. Foams: They are formed when expansion of propellant within an emulsion results in production of small bubbles.
Types Of Aerosols Device
Generally, pharmaceutical aerosols are stored in two types of inhalers viz: metered-dose inhalers (MDIs) and dry powder inhalers (DPIs).
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Desired Characteristics Of Aerosol
1. Less explosive
2. Uniform and constant dose delivery
3. Non allergic
4. Economic/low cost
5. Easy to handle
6. Non breakable
7. Eco-friendly
8. Chemical inertness
9. Lack of toxicity
10. Non flammability
Features And Components Of Pharmaceutical Aerosol
The components of pharmaceutical aerosols are product concentrate and propellant.The product concentrate contains therapeutically active Ingredients. The propellant having vapour pressure greater than atmospheric pressure at 40°C (105°F) is responsible for the development of proper pressure in the container to expel the product concentrate in the desired form like spray, mist, solid, foam, stream, etc. The propellant can also act as the solvent or vehicle for the product concentrate.
The delivery of contents of aerosol is dependent on a few features of the container which includes the valve assembly, containers, and actuators as well as on the propellant.
Propellant
Responsible for developing proper pressure within the container. Provide driving force to expel the product from the container.
Types Of Propellants
I) Type-I propellant A- liquefied gas
1) For oral and inhalation (Fluorinated hydrocarbons)
2) Topical pharmaceutical aerosols (hydrocarbons) II) Type-II Propellant B - compressed gas
1) Compound gases
Containers
They must be able to withstand pressures as high as 140 to 180 psig (pounds per sq. inch gauge) at 130 ° F.
Type Of Aerosol Containers
A . Metals
1. Tin Plated Steel: It consists of a sheet of steel plate. This sheet is coated with tin by electrolytic process. The coated sheet is cut into three pieces (top, bottom and body). The top and bottom are attached to the body by soldering. When required it is coated with organic material usually oleoresin, phenolic, vinyl or epoxy coating. Welding eliminates the soldering process, saves considerable manufacturing time and decreases the product/container interactions.
2. Aluminum: Used for inhalation and topical aerosols. Manufactured by impact extrusion process. Light in weight, less fragile, less incompatibility due to its seamless nature. Greater resistance to corrosion. Pure water and pure ethanol cause corrosion to aluminium containers. Added resistance can be obtained by coating inside of the container with organic coating like phenolic, vinyl or epoxy and polyamide resins.
3. Stainless steel: Used for inhalation aerosols. It is extremely strong and resistant to many materials. No need for internal coating but it is very expensive.
B. Glass
These containers are preferred because of its Aesthetic value and absence of incompatibilities. These containers are limited to the products having a lower pressure (33 psig) and lower percentage of the propellant. Used for topical and MDI aerosols. Two types of glass aerosol containers;
i) Uncoated glass container: Less cost and high clarity and contents can be viewed at all times
ii) Plastic coated glass containers: These are protected by plastic coating that prevents the glass from shattering in the event of breakage
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Valves
A good valve should be easy to open and close and capable of delivering the content in the desired form such as spray, foam, solid stream etc. It can deliver a given amount of medication.
Types Of Valves
1. Continuous spray valve: Used for topical aerosols. Valves assembly consists of;
i. Ferrule Or Mounting Cup: Used to attach valves to containers. Made from Tin plated steel, aluminium , brass . The underside of the valve cup is coated with single or double epoxy or vinyl resins.
ii. Valve Body Or Housing: Made up of Nylon or Derlin and contains an opening at the point of attachment of the dip tube. (0.013 to 0.080 inch).
iii. Stem: Made from nylon or delrin, brass and stainless steel can also be used. (orifice - 0.013 to 0.030 inch).
iv. Gasket: Made from Buna-N and neoprene rubber
v. Spring: Made from Stainless steel. Used to hold gasket in place
vii. Dip Tube: Made from Polyethylene or polypropylene. Inner diameter 0.120 – 0.125 inch. However for capillary dip tube inner diameter is 0.050 inch and for highly viscous products it is 0.195 inch.
2. Metering valves: Used for dispensing of potent medication. Operates on the principle of a chamber whose size determines the amount of medication dispensed. Approximately 50 to 150 mg ±10 % of liquid materials can be dispensed at one time with the use of such a valve.
Actuators
These are specially designed buttons which helps in delivering the drug in desired form i.e., spray, wet stream, foam or solid stream
Types Of Actuators
1.
Spray actuators: It can be used for topical preparation, such as antiseptics, local anesthetics and spray on bandages etc. It allows the stream of product concentrate and propellant to pass through various openings and dispense as spray
2. Foam actuators: It consist of large orifice which ranges from 0.070—0.125 inch
3. Solid steam actuators: These actuators are required for dispensing semi solid products such as ointments
4. Special actuators: These are used for a specific purpose. It delivers the medication to the appropriate site of action such as the throat, nose, dental and eyes etc
Read Also: Classification of pharmaceutical liquid dosage form
Types Of Aerosol Systems
1. Solution System
This system is also referred to as a two phase system consisting of vapor and liquid phase. If an active ingredient is soluble in propellant, no other solvent is required. The vapor pressure of the system is reduced by the addition of less volatile solvents such as ethanol, acetone, propylene glycol, glycerin, ethyl acetate. This results in production of larger particles upon spraying. Amount of propellant may vary from 5% (for foams) to 95% (for inhalations).
2. Water Based System
Surfactants with low water solubility and high solubility in nonpolar solvents will be most useful e.g. Long chain fatty acid esters of polyhydric compounds including glycol, glycerol and sorbitan esters of oleic, stearic, palmitic and lauric acids. Propellant concentration varies from about 25 to 60%.
Aquasol system (Aquasol valve) – dispensing fine mist or spray of active ingredients dissolved in water. No chilling effect, since only active ingredients and water are dispensed, propellant is in vapor state. Difference between aquasol system and three phase system is aquasol dispenses fairly dry spray with very small particles, non flammability of the product.
3. Suspension Or Dispersion Systems
It involves dispersion of active ingredients in the propellant or mixture of propellants. To decrease the rate of settling of dispersed particles, surfactants or suspending agents can be added. Primarily used for inhalation aerosols.
Physical stability of a dispersed system depends on the rate of agglomeration of the suspensoid. Agglomeration is accelerated at elevated temperatures and it is also affected by particle size of the drug (1-5µ , never > 50 µ). Agglomeration results in valve clogging, inaccuracy of dosage and depending on the nature of active ingredients, it may cause damage to the liner and metal container. Isopropyl myristate and mineral oil are used to reduce agglomeration. Surfactants of HLB value less than 10 are utilized for aerosol dispersions (sorbitan monooleate, monolaurate, trioleate, sesquioleate). Surfactants are effective in a concentration of 0.01 to1 %.
Physical stability of aerosol dispersion can be increased by:
1. Control of moisture content. (< 300 ppm)
2. Reduction of initial particle size to less than 5 µm
3. Adjustment of density of propellant and suspensoid so that they are equalized
4. Use of dispersing agents
5. Use of derivatives of active ingredients with minimum solubility in the propellant system
4. Foam Systems
Emulsion and foam aerosols consist of active ingredients, aqueous or non aqueous vehicle, surfactant, propellant and are dispensed as a stable or quick breaking foam depending on the nature of the ingredients and the formulation.
A. Aqueous stable foam
B. Non-aqueous stable foam
C. Quick breaking foam
D. Thermal foam: warm foam for shaving
E. Intranasal aerosols: Intended to deposit medication into nasal passages for local or systemic effect
Advantages
1. Deliver measured dose of drug
2. Require lower doses compared to other systemic products
3. Excellent depth of penetration into the nasal passageway
4. Decreased mucosal irritability
5. Maintenance of sterility from dose to dose
6. Greater flexibility in the product formulation
Production Of Aerosol
Pressure Filling Method
In this method, the product's concentrate is placed in the container and closed with the valve. The product is maintained below critical temperature/slightly below boiling point (critical temperature is defined as the temperature above which the liquid can no longer exist as liquid or in easy term, temperature above which liquid shows properties which are intermediate between gas & liquid). The propellant gets liquefied in the container.
Advantages
1. Solutions, emulsions, suspensions can be filled by this method as chilling does not occur
2. Contamination due to moisture is less
3. High production speed can be achieved
4. Loss of propellant is less
Disadvantages
1. Certain types of metering valves can be handled only by the cold filling process or through use of an under the cap filler and valve crimper
2. Process is slower than the Cold filling method
Read Also: Overview of Inhalation
Cold Filling Apparatus
The product concentrate is chilled to a temperature of - 40°F and filled into an already chilled container. Then the chilled propellant is added completely in 1 or 2 stages, depending on the amount. Another method is to chill both the product concentrate and propellant in a separate pressure vessel to - 40 °F and then filling them into the container. The valve is placed and crimped on to the container. Then a test for leakage and strength of the container is carried out by passing the container into a heated water bath, where the contents of the container are heated to 130°F. After this, the containers are air dried, capped and labelled. The cold filling method is no longer being used, as it has been replaced by the pressure filling method.
Advantage
1. Easy process
Disadvantages
1. Aqueous products, emulsions and those products adversely affected by cold temperature cannot be filled by this method
Compressed Gas Filling
The product concentrate is filled into the container. Valve is placed and crimped on the container. With the help of a vacuum pump the air is removed from the container. Filling head is put in the opening of the valve and the valve is depressed and the gas is allowed to flow into the container. The gas stops flowing if the delivery pressure and the pressure within the container become equal. Carbon dioxide and nitrous oxide is used if more gas is required. High solubility of the gas in the product can be achieved by shaking the container manually or with the help of mechanical shakers.
Quality Control Tests
It includes the testing of;
1. Propellants
2. Valves, Actuators and Dip Tubes
3. Containers
4. Weight Checking
5. Leak Testing
6. Spray Testing
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