Abstract:
A method of filling pharmaceutical syringes with fluid in a machine having a reservoir, vacuum source, pump an actuator that holds a vacuum adapter, sealing element and filling needle over a syringe. The method includes drawing a vacuum during a critical step while maintaining a constant fluid level in the filling needle to avoid overfilling or under filling.

Description:
FIELD OF THE INVENTION 
       [0001]    This invention relates to a method of filling a syringe with a pharmaceutical product wherein the method uses a vacuum and a compensating vacuum pumping stroke to avoid undesirable explosive discharge of fluid during the subsequent stopper injection process when air rises out of the syringe injection needle. The process also provides a more accurate syringe needle fill volume. 
       BACKGROUND OF THE INVENTION 
       [0002]    Machinery for filling and closing pharmaceutical syringes must comply with the FDA cleanliness and volume accuracy guidelines. In addition they need to be fast to provide a product that is competitive in the marketplace. To meet these requirements the industry has developed machines that can fill and close syringes at a rate of 50 syringes per minute or more and other machines that can fill volumes with an accuracy of 0.05%. The filling ranges possible are between 0.15 and 100 milliliters. To fill the small volumes it therefore becomes important to be extremely accurate for the fill volume due the high price of the filling fluid which can approach $1200 or more for each syringe fill. One syringe tray would be worth $180000 alone. A preferred method is one that minimizes volumetric error by avoiding splashing and wetting of a filling needle which is injecting the fluid. It is the purpose of this invention to disclose the apparatus and method of filling syringes that provides this careful and precise method. This method also provides a procedure that insures filling of the syringe injection needle that has a very narrow cross section that can entrap air. 
       SUMMARY OF THE INVENTION 
       [0003]    The machine to perform this method consists typically of a filling apparatus and a closing (stoppering) apparatus. The invention consists of the filling apparatus method. This apparatus comprises an actuator arm that supports a vacuum adapter, filling needle and a sealing element above the syringe. Connecting by flexible hose to the vacuum adapter is a rotatable piston pump and a reservoir that connects to the pump suction. The rotatable piston in the pump, in one position opens a port to the reservoir to draw in fluid while the piston raises. In a second rotated position the pump piston uncovers a port to the vacuum adapter to allow the lowering piston to inject fluid into the syringe when the adapter is lowered to engage the sealing element with the top of the syringe. The careful sequencing of critical steps using this pump and the use of a vacuum source create a method that provides a closely controlled volume of fluid in a syringe. The method can be used in a machine that fills multiple syringes simultaneously or one or two syringes simultaneously. The method will be described for a single syringe filling apparatus. 
         [0004]    The apparatus to perform this method consists of a reservoir of fluid, a vacuum source, a rotatable piston pump, and a movable actuator arm that supports a vacuum adapter, syringe sealing element and fluid filling needle over a syringe. The method comprises:
       a) filling the pump with fluid by raising the pump piston;   b) rotating the piston to open a flow path from pump to fill needle;   c) drawing a vacuum on the vacuum adapter and syringe from the vacuum source and simultaneously raising the piston thereby maintaining a constant fluid level in the filling needle and removing air from the syringe injection needle;   d) lowering the piston and discharging fluid into the syringe and syringe needle;   e) releasing the vacuum and continuing the discharge of fluid into the syringe; and   f) raising the actuator arm and vacuum adapter as the liquid level rises in the syringe until the proper volume has been filled in the syringe and the cycle is completed. This method eliminates air from the syringe injection needle and avoids fill needle undesirable drips into the syringe upsetting control of the fill volume.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]      FIG. 1  is a side section schematic view of the apparatus used to fill a syringe showing the rotatable piston pump, vacuum adapter and syringe of the present invention. 
           [0012]      FIG. 2  is a section view of the apparatus at the start of a fill cycle. 
           [0013]      FIG. 3  is a section view showing the pump piston rotation. 
           [0014]      FIG. 4  is a section view showing the pump compensation stroke. 
           [0015]      FIG. 5  is a section view showing the fluid injection stroke. 
           [0016]      FIG. 6  is a section view showing the continued injection and release of vacuum. 
           [0017]      FIG. 7  is a section view showing the end of the filling stroke 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0018]    The invention will be first described by referring to the apparatus illustrated in  FIG. 1 . The syringe  10  shown as partially filled with fluid  12  is held in position below the vacuum adapter  14  which holds the filling needle  16  and the sealing element  18 . Injection needle  19  is attached at the bottom of syringe  10 . The vacuum adapter  14  is raised and lowered by actuator arm  20 . A vacuum port  22  is connected to a sequentially controlled vacuum source (not shown). The flexible filling tube  24  connects to the discharge of pump  26  which has both vertical motion as shown at arrow  28  and rotary motion as shown at arrow  30  depending on the programmed action of pumping, changing ports or drawing a vacuum. Connecting to the inlet side of the pump is a reservoir  32  containing the pharmaceutical fluid  12 . In a typical machine for filling syringes there can be multiple apparatus like  FIG. 1  that operate in unison to fill multiple syringes simultaneously. The following operation will be described for only one device by referring to  FIGS. 2-7 . The cycle starts at  FIG. 2 . The pump piston  34  is rising to draw by vacuum, fluid  12  from reservoir  32 . At this point the piston  34  has sealed the opening at the filling tube  24  at pump discharge  36 . The air surrounding the device at P 1  and within the syringe  10  at P 2  is at normal atmospheric pressure and the actuating arm  20  has lowered the vacuum adapter  14  so the sealing element  18  seals against the top of the syringe  10 . 
         [0019]    In  FIG. 3  the pump piston  34  has reached an upper position and the pump is filled with fluid  12 . At this point the piston  34  rotates 180 degrees closing the suction  38  and opening the pump discharge  36 . The filling needle  16  has remained in the same position as in  FIG. 2  and the pressures remain the same. 
         [0020]      FIG. 4  illustrates the important step incorporating the “outgassing compensation stroke”. A vacuum source connected at vacuum port  22  creates a vacuum P 2  within the syringe  10  thereby causing air in injection needle  19  to expand and be discharged from the top of needle 19 . At the same time the pump piston  34  rises creating a vacuum in the pump discharge  36  so as to maintain a constant fluid level  40  within the filling needle  16  while air is evacuated at vacuum port  22 . It is this air evacuation step with the outgassing compensation stroke that eliminates a loss of fluid from the fill needle  16  that would otherwise upset the control of volume in the syringe  10 , i.e. too much fluid. 
         [0021]    In  FIG. 5  once the proper vacuum is obtained in the syringe at P 2  and air is removed from the injection needle  19 , the piston  34  starts down discharging the fluid  12  into the syringe  10  which is still maintained at a vacuum compared to atmospheric pressure P 1 . This step fills the injection needle  19  as shown by fluid  12  since the vacuum has been maintained. 
         [0022]    In  FIG. 6  the piston  34  continues down discharging fluid  12  and the vacuum is released at port  22  and the pressure at P 2  is equal to atmospheric pressure P 1  so that the fluid  12  does not start to boil. 
         [0023]    Once equal pressures are reached when P 1  equals P 2  in  FIG. 7  the filling needle  16  moves continuously up as the fluid level in the syringe  10  rises due to the downward motion of piston  34 . The piston  34  is now at it&#39;s lowest position and the filling cycle is complete. The fill needle  16  and vacuum adapter  14  are now raised so that the syringe can pass on to the next station for stopper insertion. The fill cycle is completed. 
         [0024]    The critical evacuation step as shown in  FIG. 4  has eliminated a possible air bubble from remaining in the injection needle  19  and it&#39;s subsequent discharge during a later stopper injection step. Additionally, this step includes the upward compensation stroke that maintains a constant level in fill needle  16  thereby preventing loss of fluid from that needle and consequent incorrect measure of fluid volume on completion of the filling process.