Abstract:
A method for lubricating a sealing member and a medicament chamber in a drug delivery device includes providing lubricating silicone on the surface of the stopper and within the plastic material of the chamber. The stopper preferably is first washed and rinsed in hot deionized water followed by drying. The dried sealing member is then tumbled with polymeric silicone and then irradiated at a target dose between 2.5 to 4.0 Mrads to cause the silicone molecules to bond with the elastomeric material of the stopper. The irradiated sealing members are then loaded in any of a series of chambers including syringes, pre-filled syringes, drug cartridges, and needleless injector ampules. The chamber preferably is made from a plastic material that has been mixed with a lubricating solution such as silicone when the plastic is compounded.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    This invention generally relates to a method of lubricating the components of a drug delivery system and, more particularly, to a method of lubricating a sealing member and a drug holding chamber with a polymeric silicone.  
           [0002]    Many drug delivery systems, like syringes, pre-filled syringes, drug cartridges and needleless injectors include an interior chamber for receiving a medicament and a sealing member. The sealing member is usually slidable within the interior chamber and in a fluid-tight relationship with the walls forming the interior chamber.  
           [0003]    The sealing member can take many forms, with two conventional forms being a stopper and an O-ring. The sealing members are often made of rubber or elastomeric materials. The interior chamber of many drug delivery systems is made of plastic. The fluid-tight relationship between the sealing member and the wall forming the interior chamber provides a large resistance to movement of the sealing member within the interior chamber. Typically, this resistance has been reduced by pre-treating the walls of the interior chamber and the sealing member with a lubricating solution such as silicone. In the typical coating method, the sealing member is agitated with a solution of the silicone and then the sealing member is removed from the silicone solution and placed in the interior chamber of a drug delivery system. Typically, the surface of the walls of the interior chamber have also been pre-treated with a silicone solution.  
           [0004]    There are several disadvantages with the typical lubricating method. The major disadvantage is that the lubricant typically is only loosely adhered to the sealing member or the interior chamber. This loose adherence permits the lubricating solution to become deposited into a medicament loaded in the drug delivery system. In some instances, spheres of silicone have been found suspended within the medicament solution.  
           [0005]    Therefore, a drug delivery system that is lubricated in a manner that prevents the lubricant from becoming deposited in the medicament is desirable. This invention includes lubricating the sealing member and the chamber material using techniques that prevent the lubricant from accumulating in the medicament.  
         SUMMARY OF THE INVENTION  
         [0006]    In general terms, this invention is a medicament delivery device having two basic components. A chamber has a body made from a plastic material that includes a lubricating substance within the plastic. The chamber includes an inner surface for receiving the medicament. A sealing member is slidably received within the chamber and has an exterior surface that sealing engages the inner surface of the chamber. The sealing member outer surface includes a lubricating silicone substance on the outer surface. The lubricating silicone substance is adhered to the outer surface of the sealing member by cross linking bonds between molecules of the lubricating silicone. The cross linking bonds preferably are formed by irradiating the sealing member after the lubricating silicone has been applied to the outer surface.  
           [0007]    In the most preferred embodiment, the lubricating silicone on the sealing member comprises a polydimethyl siloxane having a viscosity of approximately 100,000 centistokes.  
           [0008]    The delivery device of this invention preferably is made by the method having the following basic steps. The chamber is formed by mixing a lubricating substance into a plastic material during the process of compounding the plastic material. The chamber is formed from the compounded plastic material that contains the lubricating substance within it. An outer surface of the sealing member is coated with a lubricating substance. The lubricating substance used within the plastic material for the chamber can be, but is not necessarily, the same lubricating substance used on the outer surface of the sealing member. Once the sealing member is coated, the sealing member and the lubricating substance are irradiated to induce cross linked bonds between the molecules of the lubricating substance so that the substance adheres to the outer surface of the sealing member. Then the sealing member is inserted into the chamber so that the outer surface of the sealing member sealingly engages the inner surface of the chamber.  
       
    
    
       [0009]    These and other features and advantages of this invention will become more apparent to those skilled in the art from the following detailed description of the presently preferred embodiment. The drawings that accompany the detailed description can be described as follows.  
       BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    [0010]FIG. 1 is a flowchart illustrating the steps of lubricating a sealing member according to the method of this invention.  
         [0011]    [0011]FIG. 2 is a schematic illustration of the processing steps of manufacturing a prefilled syringe assembly designed according to the present invention.  
         [0012]    [0012]FIG. 3 is a side, cross-sectional view of a drug delivery cartridge.  
         [0013]    [0013]FIG. 4 is an exploded, side view of a syringe and a needle cannula.  
         [0014]    [0014]FIG. 5 is a cross-sectional, side view of a stopper and a plunger.  
         [0015]    [0015]FIG. 6 is an exploded, side view of a medicament cartridge that can be used with a needleless injector.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0016]    A flow chart of the method of this invention of lubricating a stopper member is provided in FIG. 1. In step  20 , the sealing members are washed. Preferably the sealing members are washed with hot deionized water. Most preferably, the sealing members are washed in deionized water at a temperature between 154 and 181° F. for 1.5 minutes.  
         [0017]    In step  22  the sealing members are rinsed. Preferably, the sealing members are rinsed in deionized water. Most preferably, the sealing members are rinsed in deionized water at a temperature between 154 and 181° F. for 7.5 minutes.  
         [0018]    In step  24  the sealing members are dried. Most preferably, the sealing members are dried for 30 minutes at 200° F.  
         [0019]    In step  26 , the sealing members are tumbled with polymeric silicone to coat the sealing members. Most preferably, the sealing members are tumbled with polymeric silicone for 60 minutes to coat the sealing members. A conventional tumbling device can be used.  
         [0020]    In step  28 , the coated sealing members are packaged in a container. Most preferably, the coated sealing members are packaged and sealed in the container. In step  30 , the packaged and coated sealing members are irradiated. Most preferably, the packaged and coated sealing members are irradiated with Cobalt radiation at a target dose of 2.5 to 4.0 Mrads. The radiation provides cross linking between the silicone molecules and adheres the silicone to the stopper. Thus, steps  20  through  30  produce a lubricated, sterile, sealing member.  
         [0021]    This invention also includes forming a medicament receiving chamber from a plastic that has been mixed with a polymeric silicone to produce a pre-lubricated plastic material. The method preferably includes mixing a selected polymeric silicone with a plastic material during the compounding of the plastic material. Apart from the addition of the selected polymeric silicone, the compounding process is conventional. Preferably, the polymeric silicone used has a viscosity of approximately 100,000 centistokes. The plastic material containing a polymeric silicone can be formed into a variety of drug delivery devices as will be described more fully below. Prelubrication of the plastic material further reduces the resistance between the medicament chamber interior wall and a coated sealing member produced according to the method described above. Moreover, prelubrication of the plastic material during the plastic compounding procedure effectively eliminates the possibility for the lubricant to become deposited in the medicament. Further, since the plastic chamber is prelubricated, the assembly/manufacturing step of applying a lubricant to the inside of the chamber is eliminated.  
         [0022]    A schematic diagram of the processing steps of manufacturing a prefilled syringe using a lubricated sealing member designed according to the present invention is generally indicated at  40  in FIG. 2. As shown at  42 , a plastic, prelubricated syringe  44  having a needle shield  46  receives a fill tube  48 . The fill tube  48  dispenses a medicament  50  into the syringe  44  to fill the syringe  44 . In the stage illustrated at  52 , a coated, lubricated, and irradiated sealing member  54 , preferably made according to the method described above, is inserted into the syringe  44  in a fluid-tight relationship over the medicament  50 . At  56 , a plunger  58  is inserted into the sealing member  54 . Put another way, step  42  involves filling the syringe  44  with a medicament  50 , step  52  involves placing a lubricated sealing member  54  into the syringe  44 , and step  56  involves connecting the plunger  58  and the sealing member  54 . Of course, the sealing member  54  and plunger  58  can be preassembled before step  52  is performed.  
         [0023]    The particular polymeric silicone used to lubricate the sealing member  54  preferably is selected in order to be compatible with the particular medicament in the drug delivery system and the material composition of the sealing member. In addition, it is necessary to comply with federal regulations regarding acceptable materials for use in a drug delivery system.  
         [0024]    Polymeric silicones that may be used with the method of this invention include: phenyl substitute silicones, vinyl substitute silicones, hydrogen substituted silicones, and others. One especially preferred silicone is known as Med-361, which is a polydimethyl siloxane, produced by Nusil and the most preferred viscosity of Med-361 is 100,000 centistokes. All of these silicones can be used at viscosities between 1,000 and 100,000 centistokes. Acceptable phenyl substituted silicones include: dimethyldiphenylpolysiloxane copolymers; dimethyl, methylphenylpolysiloxane copolymers; polymethylphenylsiloxane; and methylphenyl, dimethylsiloxane copolymers. The higher the phenyl content of the substituted silicone the lower the amount of radiation-induced crosslinking that occurs. The phenyl substituted silicones can be used in a variety of viscosities especially between 12,500 centistokes and 100,000 centistokes.  
         [0025]    When compounding the silicone with a plastic, to form the chamber as described above, it is most preferred to use a silicone having a viscosity of 100,000 centistokes.  
         [0026]    Vinyl substituted silicones that have been found to be advantageous in the method of this invention include: vinyldimethyl terminated polydimethylsiloxanes; vinylmethyl, dimethylpolysiloxane copolymers; vinyldimethyl terminated vinylmethyl, dimethylpolysiloxane copolymers; divinylmethyl terminated polydimethylsiloxanes; polydimethylsiloxane, mono vinyl, mono n-butyldimethyl terminated; and vinylphenylmethyl terminated polydimethylsiloxanes. The vinyl substituted silicones also can be made in a variety of viscosities as noted above. Higher vinyl content provides more efficient radiation induced crosslinking.  
         [0027]    The hydrogen substituted silicones that have been found to be advantageous in the method of this invention include: dimethylhydro terminated polydimethylsiloxanes; methylhydro, dimethylpolysiloxanecopolymers; methylhydro terminated methyloctyl siloxane copolymers; and methylhydro, phenylmethyl siloxane copolymers. The hydrogen substituted siloxanes can be used in a variety of viscosities as noted above.  
         [0028]    Other substituted silicones that may be used in the method of this invention include: polyfluoroalkylmethyl siloxanes; fluoralkyl, dimethyl siloxanecopolymers; and polymethylalkylsiloxanes.  
         [0029]    [0029]FIGS. 3 through 6 illustrate example drug delivery assemblies that incorporate a lubricated sealing member and a prelubricated plastic medicament chamber made according to this invention. A plastic, pre-lubricated medicament cartridge is shown generally at  66  in FIG. 3. The medicament cartridge  66  comprises a generally cylindrical barrel  68  having a first end  70 , a second end  72 , and an interior chamber  74 . A neck portion  76  is located adjacent the first end  70 . A seal  78  surrounds an end of the neck portion  76  and seals the neck portion  76 . A lubricated stopper  80 , made according to the method described above, is received in a fluid-tight relationship into the interior chamber  74  through the second end  72  of the medicament cartridge  66 . The stopper  80  includes a first side  82  and a second side  84 . A medicament  86  is located between the first side  82  of the stopper  80  and the seal  78 . As will be understood by those skilled in the art, such medicament cartridges  66  are designed to be received in a wide variety of delivery devices (not shown). The delivery devices include a needle cannula for penetrating the seal  78  and a plunger mechanism for moving the stopper  80  from the second end  72  toward the first end  70  to expel the medicament  86  from the interior chamber  74  during an injection.  
         [0030]    An exploded side view of a plastic, pre-lubricated syringe and a needle cannula is generally indicated at  90  in FIG. 4. The syringe  91  includes a cylindrical barrel  92  made from a prelubricated plastic material containing one of the silicones listed above and having a first end  94  and a second end  96  and an interior chamber  98 . A neck portion  100  is located adjacent the first end  94 . A flange  102  is located adjacent the second end  96 . A lubricated stopper  104 , formed according to the method of this invention is received in a fluid-tight relationship into the interior chamber  98 . The stopper  104  has a first side  106  and a second side  108 . A plunger  110  is received in the second side  108  of the stopper  104 . A needle cannula  112  includes a hub  114  and a needle  116 . The neck portion  100  includes a fluid channel  118 . A medicament  120  is located in the interior chamber  98  between the first side  106  of the stopper  104  and the neck portion  100 . The needle cannula  112  is received on the neck portion  100 . The fluid channel  118  is in fluid communication with the needle  116 .  
         [0031]    [0031]FIG. 5 is a cross-sectional side view of a portion of the plunger  110  and the lubricated stopper  104 . The stopper  104  preferably includes a plurality of ribs  130 . An interior space  132  extends from the second side  108  of the stopper  104  into the stopper  104 . A set of internal threads  134  lines the interior space  132 . A set of external threads  136  are located on the plunger  110  adjacent a plunger base  138 . The internal threads  134  are adapted to receive the external threads  136 .  
         [0032]    An exploded side view of a pre-lubricated plastic cartridge for use with a needleless injector is shown at  140  in FIG. 6. The cartridge  140  includes a cylindrical barrel  142  having a first end  144 , a second end  146 , and an interior chamber  148 . A luer lock arrangement  150  preferably is located adjacent the second end  146  for securing the cartridge  140  into a needleless injector. A tapered tip  152  is located adjacent the first end  144  and includes a fluid orifice  154 .  
         [0033]    A plunger  156  is slidably received in the interior chamber  148 . The plunger  156  includes a tip portion  158  and a lubricated sealing member  160 , formed according to the method of this invention, adjacent the tip portion  158 . The sealing member  160  is in a fluid-tight relationship with the interior chamber  148  when the plunger  156  is received into the chamber  148 . Preferably, the sealing member  160  is an O-ring. The plunger  156  further includes a first cutout  162  and a second cutout  164 . A plunger portion  166  includes a series of spaced tabs  168  that facilitate cooperation between an injector driver member (not shown) and the plunger  156 . A tab lip  170  is located on each of the spaced tabs  168 . A boss  172  is located centrally to the spaced tabs  168 . The plunger  156  further includes a pair of slots  174 .  
         [0034]    As will be understood by those skilled in the art, the needleless injector cartridge  140  is designed to be utilized with a variety of commercially available injector devices (not shown). The injector device driver mechanism is used to drive the plunger  156  from a position adjacent the second end  146  toward the first end  144  and expel a medicament (not shown) out of the interior chamber  148 , through the fluid orifice  154  to accomplish a needleless injection.  
         [0035]    As will be understood by those skilled in the art, all of the sealing members and stoppers are in fluid-tight relationship with the walls of the interior chambers. The sealing members and stoppers preferably are made of rubber or elastomeric materials. The specific embodiments described above are for illustration purposes only. A plurality of applications or uses for the lubrication methods of this invention have been shown.  
         [0036]    The foregoing description is exemplary rather than limiting in nature. Variations and modifications to the disclosed embodiments may become apparent to those skilled in the art that still come within the scope of this invention. Accordingly, the scope of legal protection afforded this invention can only be determined by studying the following claims.