Abstract:
A method for lubricating a sealing member in a drug delivery device includes the steps of washing and rinsing the sealing members in hot deionized water following by drying the sealing members. The dried sealing members are tumbled with polymeric silicone and then irradiated at a target dose between 2.5 and 4.0 Mrads. The irradiated sealing members are then utilized in a variety of drug delivery devices including syringes, pre-filed syringes, drug cartridges, and needleless injector ampules.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
   This application is a divisional of application Ser. No. 09/265,677, filed Mar. 10, 1999, now U.S. Pat. No. 6,200,627, issued Mar. 13, 2001, which claims Benefit of Provisional Application Ser No. 60/078 266 filed Mar. 17, 1998. 

   BACKGROUND OF THE INVENTION 
   This invention relates generally to a method of providing lubrication in a drug delivery system and, more particularly, to a method of lubricating a sealing member of a drug delivery system with a polymeric silicone. 
   Many drug delivery systems, like syringes, prefilled 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. 
   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 glass. 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 walls of the interior chamber have also been pre-treated with a silicone solution. 
   There are several disadvantages with the typical lubricating method. The first disadvantage is that it requires coating both the sealing member and the interior chamber with a lubricating solution. A second 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, for instance silicone, to be deposited into a medicament loaded in the drug delivery system. In some instances, spheres of silicone have been found suspended within the medicament solution. 
   Therefore, a drug delivery system that prevents the lubricant from becoming deposited in the medicament is desirable. This invention includes lubricating only the sealing member and prevents the lubricant from accumulating in the medicament. 
   SUMMARY OF THE INVENTION 
   In general terms, this invention includes a method for coating a sealing member of a drug delivery system with polymeric silicone to provide a lubrication layer on the sealing member. The polymeric silicone in the lubricating layer is crosslinked by radiation and adheres to the sealing member. 
   The method of this invention includes the steps of coating a sealing member with a polymeric silicone having a plurality of polymer molecules and then exposing the coated sealing member to irradiation. Cobalt radiation is most preferred, at a target dose between 2.5 to 4.0 Mrads. Irradiating the coated sealing member forms crosslinks between the molecules of the polymeric silicone and causes the crosslinked molecules to adhere to the sealing member, thus forming a lubricating layer. The preferred embodiment of this invention includes using polymeric silicone having a relatively high viscosity when forming the lubricating layer. 
   The inventive method prevents the polymeric silicone from being deposited into the medicament. The method of the invention further permits the manufacture of a drug delivery system wherein only one of the sealing member or the interior chamber is lubricated. 
   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 briefly described as follows. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a flowchart illustrating the steps of lubricating a sealing member according to the method of this invention. 
       FIG. 2  is a schematic illustration of the processing steps of manufacturing a prefilled syringe using a lubricated sealing member designed according to the present invention. 
       FIG. 3  is a side cross-sectional view of a drug delivery cartridge. 
       FIG. 4  is an exploded side view of a syringe and a needle cannula. 
       FIG. 5  is a cross-sectional side view of a stopper and a plunger. 
       FIG. 6  is an exploded side view of a medicament cartridge that can be used with needleless injector. 
   

   DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
   A flow chart of the method of this invention is provided at  10  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. 
   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. 
   In step  24  the sealing members are dried. Most preferably, the sealing members are dried for 30 minutes at 200° F. 
   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. 
   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 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 produce a lubricated, sterile, sealing member. 
   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 glass 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 , 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 plunger  58  and the sealing member  54  can be preassembled before step  52  is performed. 
   The particular polymeric silicone used in the present method 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. 
   Polymeric silicones that may be used in 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 irradiation induced crosslinking that occurs. The phenyl substituted silicones can be used in a variety of viscosities especially between 12,500 centistokes to 100,000 centistokes. 
   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. 
   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. 
   Other substituted silicones that may be used in the method of this invention include: polyfluoroalkylmethyl siloxanes; fluoralkyl, dimethyl siloxanecopolymers; and polymethylalkylsiloxanes. 
     FIGS. 3 through 6  illustrate example drug delivery assemblies that incorporate a lubricated sealing member made according to this invention. A glass 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. 
   An exploded side view of a syringe and a needle cannula is generally indicated at  90  in FIG.  4 . The syringe  91  includes a cylindrical barrel  92  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 . 
     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  to secure the plunger  110  to the stopper  104  so the two will move in unison. 
   An exploded side view of a cartridge for use with a needleless injector is generally 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 . 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 . 
   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 driver mechanism of the device is used to drive the first 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. 
   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 specifics described above are for illustration purposes only. A plurality of applications or uses for the lubrication method of this invention have been shown. 
   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.