Pressure-filling method

Typically CFC products utilize both the cold-fill and the pressure-fill processes. Whether a product is filled by pressure or cold, is determined by the manufacturing equipment available at a particular company and by the nature of the active drag. For example, since Albuterol is moisture-sensitive, it cannot be filled by the cold process. Hydrofluorocarbon products are typically filled using the pressure-filling method. Figure 3 depicts the process flow, indicating both types of fillings. 

In the manufacture of MDIs, liquid filling procedures have been developed based on either a cold-filling method or a pressure-filling method. Both methods are suitable for either solution or suspension formulations and regardless of the process, it is important to maintain a low atmospheric relative humidity in the filling area to minimize condensation and possible absorption of water by the product. 

Fig. 24 Schematic diagram of EPP molding production cycle using the pressurized filling method...

Mousses pose Httle manufacturing problem, but because they are aerosolized they must be filled with special equipment. The pressure fill technique requites the container to be filled with mousse concentrate, then a valve is crimped on and a vacuum of approximately 2.4 kPa (18 mm Hg) is pulled. The propellants are added through the valve. Another technique, the under-the-cup method, fills the container under pressure with propellant and crimps the valve, all in one step. 

The old, tedious, but quite reliable method is to measure the supply flow by the bag method. A tightly rolled plastic bag empty of air at the commencement of the test is pressed on the terminal with all the supply air passing into the bag. The filling time of the bag is measured and the flow rate calculated based on this information. The bag volume has to be determined in advance by a special measurement. Finally, the characteristic pressure difference method, menrumed above, can also be applied to supply terminals. 

Describe the pressure-vacuum method of filling an IR cell equipped with inlet and outlet ports. 

Two methods for filling aerosol MDIs are used today—cold filling and pressure filling [5,7]. These methods describe the manner in which the propellant is added to the can or plastic-coated glass bottle. Solution or suspension formulations may be filled by either method. 

Studies of high-pressure NMR spectra have been carried out in by one of two ways, known, respectively, as the high-pressure probe method and the high-pressure cell method. High-pressure probes usually show a better sensitivity, due to the better filling factor. 

Accurate thermal data can be obtained, even at low pressures. This method is therefore recommended for studying the energetics of micropore filling or adsorption on high energy sites. 

Pressure Filling. The propellant is introduced under high pressure into the container through the valve, as shown in Fig. 26. Most valve manufactures design their valves for this method. 

Another alternative, particularly for high-pressure measurements, is the isochoric method. A cell of known volume is filled with the fluid, and then the pressure is measured as the temperature of the cell is changed. This provides data along curves of approximately constant density, known as isochors. Corrections are made for the expansion of the vessel due to temperature and pressure. This method is most useful for supercritical fluids and other situations where the fluid is fairly compressible. Uncertainties with this method can be on the order of 0.1%, but are often higher at elevated temperatures and pressures. 

Initial formulation work, when tens of cans are required, is often carried out by cold filling, where the propellants are cooled to below their boiling point, and can then be processed as liquids without any pressure implications. This method was often used for full-scale production for CFCs, since propellant 11 has a boiling point of 23°C. However, both HFA-134a and HFA-227 have low boiling points therefore, pressure filling is more common for the HFA propellants. 

Another experimental example of the use of the drop and bubble shape technique is given in Figure 12.11. The latter shows the dynamic surface tensions of blood serum as measured by the maximum bubble pressure (filled symbols) and drop shape techniques (open symbols). It becomes evident that both methods complement each other perfectly when the data from the MPT2 studies are plotted as a function of /efi- The results impressively demonstrate that during the radiotherapy process the dynamic surface tension parameters return to the normal values (2), i.e. approach those characteristic of healthy females from the respective control group. 

Fig. 1. Principle of the pressure-generating method with opposed diamond anvils. The enlargement on the right side shows the central hole of the gasket filled with rubies, a sample, and a pressure-transmitting medium.

If a Type I isotherm exhibits a nearly constant adsorption at high relative pressure, the micropore volume is given by the amount adsorbed (converted to a liquid volume) in the plateau region, since the mesopore volume and the external surface are both relatively small. In the more usual case where the Type I isotherm has a finite slope at high relative pressures, both the external area and the micropore volume can be evaluated by the a,-method provided that a standard isotherm on a suitable non-porous reference solid is available. Alternatively, the nonane pre-adsorption method may be used in appropriate cases to separate the processes of micropore filling and surface coverage. At present, however, there is no reliable procedure for the computation of micropore size distribution from a single isotherm but if the size extends down to micropores of molecular dimensions, adsorptive molecules of selected size can be employed as molecular probes. 

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