How are Aerosols manufactured?
A.The manufacture of aerosol products takes place in two stages:
1.Manufacture of the concentrate and
2.Filling of the propellant
The aerosol concentrate consists of drug or combination of drugs, solvents, antioxidants and surfactants formulated as solution, suspension or foam systems. The aerosol concentrate is first prepared and filled into the container. The propellant is then filled into the container. Therefore, part of the manufacturing operation takes place during the filling operation which requires special quality control measures to ensure that both concentrate and propellant are brought together in the proper proportion. Filling operation is a unique step specific for aerosol products.
The equipments used for manufacture of aerosols can be classified into two classes:
1.Equipments used for compounding of liquids, suspensions, emulsions, creams and ointments. 2.Specialized equipments capable of handling and packaging materials at relatively low temperatures (above -40º F) or under high pressure.
Firstly, the aerosol concentrate is prepared according to the generally accepted procedure and a sample tested. Then it is filled into the container with or without the propellant. Lastly, the propellant is filled into the container. Three methods have been developed for filling of aerosol products:
1.Cold filling 2.Pressure filling 3.Compressed gas filling
Cold filling method:
The principle of cold filling method requires the chilling of all components including concentrate and propellant to a temperature of -30 to -40 º F. The propellant liquefies when chilled. First, the product concentrate is chilled and filled into already chilled container followed by the chilled liquefied propellant.
Process
Single head or multiple head rotary unit capable of vacuum crimping up to 120 can / min are available. The rotary unit requires air pressure (90 to 120 lbs / inch2) and vacuum.
1.The product is chilled to -30 ° to -40 ° C. 2.Propellant is also chilled to -30 ° to -40 ° C. The propellant is added to the chilled product in one or two stages depending on the amount. 3.A valve is placed either manually or automatically depending on the production rate required. The air is purged after which the valve is crimped in place ( about 24 inch of mercury and then seal the valve ) 4.The container passes through a heated water bath in which the contents of the container are heated to 130 º F to test for leaks and strength of the container. 5.The container is air dried, spray – tested, capped and labeled.
FIG 9:
Advantages
1.Easy process
Disadvantages
1.Chilling of the product, container and propellant is required. Aqueous products, emulsions and those products adversely affected by cold temperature cannot be filled by this method. This method is restricted to non-aqueous product and those products not affected by low temperature in the range of -40º F 2.Loss of propellant during air evacuation.
The cold filling aerosol line consists of: 1.Un-scrambler 2.Air-cleaner 3.Concentrate filler (capable of being chilled) 4.Propellant filler 5.Valve placer 6.Valve purger 7.Valve crimper 8.Heated water-bath 9.Labeler 10.Coder and packaging table
Pressure Filling Process
Pressure filling is carried out at R.T. under high pressure. The apparatus consists of a pressure burette capable of metering small volumes of liquefied gas under pressure into an aerosol container. The propellant is added through the inlet valve located at the bottom or top of the burette. Trapped air is allowed to escape through the upper valve. The desired amount of propellant is allowed to flow through the aerosol valve into the container under its own vapor pressure. When the pressure is equalized between the burette and the container (thus happens with low pressure propellant), the propellant stops flowing. To help in adding additional propellant, a hose leading to a cylinder of nitrogen or compressed is attached to the upper valve and the added nitrogen pressure causes the propellant to flow.
Process
1.The concentrate is added to the container at room temperature the valve is crimped in place, before crimping air in the container is purged out. 2.The propellant is added through the valve or ‘under the cap’. Since the valve contains extremely small openings (0.018 inch to 0.030inch) this step is slow and limits production. 3.Rotary filling machines and newer filling heads have developed, which allow propellant to be added around or through the valve stem and thus the speed has been increased. 4.After adding the propellant, the container passes through a heated water bath in which the contents of the container are heated to 130ºF to test for leaks and strength of container. 5.The container is air-dried, spray tested, capped and labeled.
Advantages
1.It is the preferred method because some solutions, emulsions, suspensions and other preparations cannot be chilled. 2.Lesser danger of contamination of product with the moisture 3.Less propellant is lost 4.With ‘under the cap’ filling process, higher production speed can be achieved. 5.No refrigeration is required, can be carried out at RT
Disadvantages
Incase of certain types of metering valves, filling can be done only by cold filling
Typical pressure filling aerosol line consists of: 1.Un-scrambler 2.Air cleaner 3.Concentrate filler (capable of being chilled) 4.Valve placer 5.Valve plunger 6.Valve crimper 7.Pressure filler 8.Heated water-bath 9.Labeler 10.Coder and packaging table
Where ‘under the cap’ filling is used, the purger, vacuum crimper and pressure filler are replaced with a single unit.
Compressed Gas Filling
Compressed gases are present under high pressure in cylinders. These cylinders are fitted with a pressure reducing valve and a delivery gauge. The delivery gauge in turn fitted with flexible hose capable of withstanding about 150 lbs per square inch gauge pressure and a filling head.
Process
1.The concentrate is placed in the container 2.The valve is crimped in place 3.Air is evacuated by means of vacuum pump 4.The filling head is inserted into the valve opening, valve depressed and gas is allowed to flow into the container. 5.When the pressure inside the container is equal to the delivering pressure, the gas stops flowing. For those products requiring an increased amount of gas or those in which the solubility of gas in the product is necessary, carbon dioxide and nitrous oxide can be used. To obtain maximum solubility of the gas in the product, the container is shaken manually during and after the filling operation by mechanical shakers.
Advantages
1.Easy process 2.Can be carried out at RT
Disadvantages
Compressed gas is used as a propellant in topical preparations and not used in oral inhalation products used for pulmonary delivery.
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