Abstract:
A system and method for controlling the temperature of the fluid in a volumetric dispensing apparatus, without the need for a controlled ambient environment. The reservoir used to hold the fluid prior to dispensing is maintained at a constant temperature through the use of a temperature-controlled surround, such as a water jacket. This ensures uniform fluid properties, such as viscosity and density, thereby guaranteeing that accurate volumes will be dispensed. Methods for controlling the temperature within the encased reservoir are also disclosed.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     There are various types of dispensing apparatuses for filling bottles and other containers. One such type is positive displacement fillers. These devices employ a cylinder and piston arrangement, which contacts and dispenses the fluid. Typically, fluid enters the cylinder as the piston is in its upward motion, which creates a vacuum into which the fluid enters through an inlet port. The downward motion of the piston expels the fluid through an outlet port. The process can then be repeated. Other embodiments of positive displacement fillers also exist, such as those using rotary pumps.  
         [0002]     While these fillers are popular due to their speed and accuracy, their application is limited, especially in the pharmaceutical field. These devices are very difficult to clean, and typically must be disassembled to be sterilized. Also, since the device actually contacts the fluid, contamination is a constant risk.  
         [0003]     Another type of dispensing apparatus is the time/pressure filler. These typically include a fluid chamber that is held under constant pressure. Fluid is dispensed through a discharge line, which is controlled by a pinch type valve. The valve is opened for a precise amount of time to dispense fluid. Since the pressure is held constant, and the time interval is constant, the amount of fluid dispensed should also be constant. However, due to variances in the equipment and deformation of the discharge tube over time, these systems are less accurate than required for many applications.  
         [0004]     A third type of dispensing apparatus is the volumetric dispensing apparatus, as shown in U.S. Pat. No. 5,480,063, which is hereby incorporated by reference. These devices measure and dispense a predetermined volume of fluid. These systems are highly accurate and avoid problems of contamination common with positive displacement apparatus, since there are no moving parts in contact with the fluid.  
         [0005]     These systems are well suited for use in the pharmaceutical field, due to their accuracy and no risk of contamination. However, they do have shortcomings. They are highly accurate, as long as the viscosity of the fluid remains constant throughout the dispensing period. If the viscosity of the fluid changes, the volume dispenses may vary. While this variation may only be 1%, this may be unacceptable in the pharmaceutical field.  
         [0006]     In typical usage, these apparatus are kept in a controlled environment, such as a “clean room”, which maintains a relatively constant temperature and humidity. In so doing, the viscosity of the fluid also remains constant, thereby yielding highly accurate results. In addition, many pharmaceutical fluids need to be processed at specific temperatures or temperature ranges to maximize their effectiveness. This is also accomplished by the use of a constant environmental setting.  
         [0007]     However, setting up and maintaining a “clean room” can be expensive and impractical. Some facilities may not have the required space or equipment to install such an environment. Others may find that the cost of such an environment is prohibitive. However, without this controlled temperature environment, the two shortcomings cited above, i.e. variable viscosity and de-optimized effectiveness of the pharmaceutical fluid, become apparent.  
       SUMMARY OF THE INVENTION  
       [0008]     The problems of the prior art have been overcome by the present invention, which provides a system and method for controlling the temperature of the fluid in a volumetric dispensing apparatus, without the need for a controlled ambient environment. The reservoir used to hold the fluid prior to dispensing is maintained at a constant temperature through the use of a temperature-controlled surround, such as a water jacket. This ensures uniform fluid properties, such as viscosity and density, thereby guaranteeing that accurate volumes will be dispensed. Methods for controlling the temperature within the encased reservoir are also disclosed. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]      FIG. 1  is a schematic diagram illustrating the pharmaceutical fluid dispensing system of the prior art;  
         [0010]      FIG. 2  is a schematic diagram illustrating a first embodiment of the present invention; and  
         [0011]      FIG. 3  is a schematic diagram illustrating a second embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0012]     Pharmaceutical fluid dispensing systems require extremely tight tolerances to dispense appropriate amounts of fluid.  FIG. 1  is a schematic diagram illustrating such a pharmaceutical fluid dispensing system of the prior art.  
         [0013]     A reservoir  12  holds the fluid to be dispensed by the system. To minimize variation in the volume dispensed, the fluid is held under constant pressure. Typically, there is no venting of these systems. Rather, an inert gas, such as nitrogen can be used to fill the remaining capacity in the reservoir to prevent any reaction between the gas and the fluid. As liquid is dispensed from the reservoir, it is replenished from fluid source  18 . Reservoir level control  22  is used to monitor the level of fluid in reservoir  12 . When the level drops below a threshold, reservoir level control  22  signals to the controller (not shown) that additional fluid must be added. The controller signals supply solenoid  21  to open supply valve  20 . Once open, fluid is free to move from the fluid source  18  to the reservoir  12  through supply port  14 . When the proper fluid level in the reservoir is reached, the reservoir level control  22  again signals the controller, which then causes the solenoid  21  and supply valve  20  to close. In this way, the fluid in the reservoir  12  is maintained under constant pressure.  
         [0014]     Reservoir  12  is in communication with drain line  26  through drain port  24  and with fill tube  36  through fill vent  38 . When the controller signals the fill solenoid  31  to open fill valve  30 , fluid from the reservoir flows into drain line  26  and up into fill tube  36 . Located along fill tube  36  are several sensors, preferably optical sensors, which can detect the presence of fluid in the fill tube  36 . The upper level sensor  34  is used to set the upper fluid level in the fill tube, while lower level sensor  32  is used to set the lower fluid level. Operationally, when fill valve  30  is opened, fluid enters drain line  26  and fill tube  36 . Once the fluid reaches the level of the upper level sensor  34 , the sensor signals the controller to close the fill valve. As the fluid exits the reservoir and fills the fill tube  36 , the gas previously in the fill tube is pushed back into the reservoir, since the fill tube forms a closed loop with the reservoir  12 .  
         [0015]     Once the fluid has reached the level of the upper level sensor  34  and the fill valve is closed, the controller then opens the drain valve  28  by signaling drain solenoid  29  to open. While the drain valve  28  is open, the fluid exits the fill tube through drain line  26  and drain valve  28 . Once the level of the fluid in the fill tube reaches the lower level sensor  32 , the controller is signaled to close the drain valve  28  by actuating drain solenoid  29 . In this way, a precise amount of fluid, equal to the volume of the fill tube between the upper and lower level sensors, is dispensed.  
         [0016]     This process then continues, with the reservoir  12  being filled by fluid source  18  through supply valve  20  and being emptied by opening fill valve  30  and drain valve  28 . This process is highly effective in dispensing precise amounts of liquids. Furthermore, there are no moving parts in communication with the fluid, thereby eliminating mechanical wear and contamination of the fluid.  
         [0017]     While this system is highly effective, there are limitations to its operation with respect to pharmaceutical products. First, pharmaceutical products must be dispensed with great accuracy. Variations in volume of even 1% may be unacceptable. Fluid properties, such as viscosity and density can change as a function of the fluid temperature. Therefore, in order to guarantee accurate dispersion of a specific volume of fluid, the fluid must be maintained at a constant temperature while being processed. Second, many pharmaceutical products must be processed within a given temperature range, or their effectiveness may be compromised. This temperature can vary, depending on the product, and typically is between 4° and 37° C.  
         [0018]     However, as shown in  FIG. 1 , the nature of the dispensing system is that the fluid must be kept in the reservoir for proper operation. Therefore, fluid can remain in the reservoir for extended periods of time, depending on the usage of the dispensing system. In an extreme situation, the system may only be used during one work shift during a standard five-day workweek. Fluid in the reservoir at the end of one day&#39;s work shift will remain there until the start of the next day&#39;s work shift. This period of time can be even longer when the fluid is left in the reservoir during a weekend. More typically, fluid will remain in the reservoir during periods of inactivity during the day, such as shift changes, and coffee and lunch breaks.  
         [0019]     Therefore, either the fluid within the reservoir must be used quickly in order to insure that it is at the proper temperature, or the ambient environment around the reservoir must be kept at the desired temperature. One method of achieving this result is to keep the dispensing system in a controlled environment, such as a temperature-controlled clean room. In actual practice, neither of these options may be possible, or economically feasible. For example, some fluids must be kept refrigerated. If the temperature-controlled environment is not at the same temperature as the refrigerator, the fluid will undergo temperature changes over time, thereby affecting its properties, such as viscosity and density. Therefore, a mechanism is needed to keep the fluid within the reservoir at the appropriate temperature, even during long periods of system inactivity without requiring the environment surrounding the system to be controlled.  
         [0020]      FIG. 2  shows an expanded view of a first embodiment of the reservoir of the current invention. Reservoir  12  is partially filled with fluid. As described above, additional fluid enters the reservoir  12  through supply port  14 , and exits the reservoir  12  through drain port  24 . Fill vent  38  provides a closed loop path from drain port  24 .  
         [0021]     To maintain the fluid at a constant uniform temperature, a thermally controlled surround, such as a water jacket  100  encases the reservoir  12 . The water jacket, preferably made of plastic, has an inlet port  102  and an outlet port  104 . Water is maintained at a constant temperature, such as by conventional regulating means outside the fluid jacket (not shown), including heating or cooling, depending on the specific requirements and properties of the pharmaceutical fluid. This regulated water is then circulated through the water jacket  100 , entering the jacket through the inlet port  102  and exiting through the outlet port  104 .  
         [0022]     In the preferred embodiment, the thermally controlled surround encases the entire reservoir, however, in another embodiment, the surround covers a substantial portion of the surface area of the reservoir to ensure proper thermal transfer. Similarly, while a uniform thickness of the surround is preferred, the surround can be designed to have a non-uniform thickness. For example, the surround may contain more water at the bottom than at the top. Optionally, the thermal surround and the reservoir can be fabricated as a single component.  
         [0023]     The optimal rate of flow of water through the thermal surround is determined by understanding the thermal transfer characteristics of the reservoir and the surround, as well as the temperature gradient between the water and the ambient environment, the amount of fluid in the reservoir, and the fluid&#39;s properties. Typically, a higher flow rate will insure a more uniform temperature for the fluid in the reservoir.  
         [0024]     There is a plurality of mechanisms that can be employed to insure that the fluid in the reservoir is at the proper temperature. In one embodiment, heat transfer calculations based on the properties of the fluid in the reservoir, the flow rate of the water, the ambient temperature, and the heat transfer properties of the reservoir and the surround are conducted to determine the appropriate temperature for the water in the thermal surround. In a second embodiment, the temperature of the water circulating in the thermal surround is calculated empirically. In a third embodiment, a temperature sensor, located within the reservoir, supplies information to a controller, which then adjusts the temperature of the water in the thermal surround accordingly.  
         [0025]     The use of a water jacket may interfere with the operation of the reservoir level control  22 , depending on the type of sensor technology that is used. For example, if a mechanism employing a float is installed in the reservoir, as shown in  FIG. 1 , the use of the water jacket will not interfere with its operation. However, if an optical or capacitance sensor is used as the level control, the water jacket may interfere with proper operation of the sensor unless suitable accommodations are made to the jacket design.  
         [0026]      FIG. 3  illustrates a second embodiment of the present invention, adapted to permit proper operation of an optical or capacitance sensor in conjunction with the water jacket. A closed loop  200  is in fluid communication with both the fill vent  38  and the drain port  24 . The level of fluid in closed loop  200  will be at the same height as that within the reservoir  12 . Thus, capacitance or optical sensors  201  can be employed for use with the closed loop to perform the functions currently implemented within the reservoir. Alternatively, closed loop  200  can utilize inlet and outlet ports that are separate from those used for the dispensing of fluid. In either case, the level of fluid in the closed loop will equal that within the reservoir.  
         [0027]     While water is the preferred medium used within the water jacket, the invention is not so limited. Any other appropriate fluid, including gases, may be used to produce the required effect, so long as they are relatively inert and are sanctioned by the appropriate government agency (such as the FDA) for use in such systems. Such fluids include, but are not limited to, food grade oils such as corn or canola oils, mineral oils, and the like. Gases may include cooled or heated air, Freon® and Freon®-like refrigerants and the like. (Freon® is a registered trademark of DuPont Corporation.) Accordingly, those skilled in the art will appreciate that the use of the water jacket is merely exemplary and not to be interpreted as limiting the fluid in the jacket to water.  
         [0028]     In an alternate embodiment, the temperature of the fluid in the reservoir is electronically controlled. Electrical devices, such as thermistors and thermoelectric coolers (solid state heat pumps), are used to create the temperature-controlled surround. These devices can be placed directly on the reservoir, or alternatively within a surround which encases the reservoir. These devices are in communication with a controller, which regulates the temperature of the fluid in the reservoir by actuating the devices as required.