The Pharmaceutics and Compounding Laboratory

Two methods are used to manufacture aerosols: the cold fill process and the pressure fill process. The cold fill process takes advantage of the property that some ingredients will liquefy when cooled, and the pressure fill process uses the property that some ingredients will liquefy when placed under pressure.

In the cold fill process, both the product concentrate and the propellant must be cooled to temperatures between 30°C to 60°C where they will remain liquefied. The cooling system may be a mixture of dry ice and acetone or an elaborate refrigeration system. The chilled product concentrate is quantitatively added to the equally cold aerosol container and then the liquefied gas is added. The heavy vapors of the cold liquid propellant will generally displace the air present in the container. When filling is complete, the valve assembly is inserted into the container and crimped into place. The container is then passed through a water bath of about 55°C to check for leaks or distortion in the container.

Aqueous solutions cannot be filled by this process since the water will turn to ice in the low temperatures. For nonaqueous systems, some moisture usually appears in the final product due to the condensation of atmospheric moisture within the cold containers.

Pressure filling is carried out essentially at room temperature. The product concentrate is placed in the container, the valve assembly is inserted and crimped into place, and then the liquefied gas, under pressure, is added through the valve. The entrapped air in the package might be ignored if it does not interfere with the stability of the product, or it may be evacuated prior to or during filling. After the filling operation is complete, the valve is tested for proper function. This spray testing also rids the dip tube of pure propellant prior to consumer use. Pressure filling is used for most pharmaceutical aerosols. It has the advantage that there is less danger of moisture contamination of the product and also less propellant is lost in the process.