Patent Publication Number: US-2018043102-A1

Title: O-Ring Plunger for a Prefilled Syringe and Method

Description:
BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The invention relates, in general, to a plunger for use with a syringe, such as a prefilled syringe containing a therapeutic agent to be injected to a patient, and, more particularly, to a multi-piece plunger including a head portion and one or more elastomeric annular seals. 
     Description of Related Art 
     Current syringe designs generally include a tubular barrel having an access opening formed at one end, and a smaller discharge opening (e.g., a nozzle) formed at the opposing end. A lead end of an elongated plunger is received within the access opening of the barrel so as to be slidable within the barrel. Attached to or integral with the lead end of the plunger is a flexible sealing member or stopper that snugly seals against the interior surface of the barrel. A needle, a threaded member, or a non-threaded member is usually attached to the discharge opening on the barrel. The needle can be used to penetrate a surface while the threaded member can be used to attach the syringe to another medical device, such as a catheter. The flexible stopper is usually manufactured from an elastomeric material, such as a rubber or a cross-linked or thermoplastic elastomer. 
     During use, the discharge end of the syringe is initially placed in contact with a fluid. For example, the needle on the syringe can be inserted into a source of liquid medication such as a medical vial. As the plunger is retracted within the barrel, a process known as aspiration, a negative pressure is formed within the end of the barrel so as to cause the fluid to be drawn into the barrel. The syringe can then be moved to a second location where advancing the plunger within the barrel causes the fluid to be pushed or expressed out the discharge end of the barrel. In some examples, syringes are provided prefilled with a fluid to be administered to a patient and, accordingly, fluid does not need to be drawn into the syringe barrel immediately prior to use. 
     Conventional elastomeric plungers and stoppers generally include an open proximal end configured to engage a plunger rod, a distal surface, often referred to as a roof, configured to come into contact with the fluid contained in the syringe barrel, and a sidewall extending therebetween. The sidewall can include protrusions, such as ribs, fins, or flanges, for creating variable contact with the inner surface of the syringe barrel. Due to the high contact forces and high friction coefficient between the protrusions and the inner wall of the barrels, current elastomeric plunger designs are often lubricated with a liquid lubricant, such as silicone oil, so that break-loose and break-out forces required to operate the syringe are not too high. An exemplary method for coating a sealing member with a lubricant by tumbling is disclosed in U.S. Pat. No. 7,141,042, entitled “Low silicone glass prefillable syringe”, which is incorporated by reference herein in its entirety. Elastomeric stoppers formed, for example, by injection molding can be tumbled and/or immersed in a silicone bath thereby covering the entire surface of the plunger or stopper with the lubricant. Since only the protrusions or ribs of the plunger sidewall actually contact the syringe barrel, a large portion of the surface area of the coated or lubricated plunger or stopper does not actually contribute to the sliding properties of the syringe and stopper. As such, the amount of lubricant required for each plunger and associated manufacturing costs could be reduced if only the interface between the plunger and syringe barrel were lubricated. 
     Current rubber stoppers are often manufactured from a specialized cross-linked rubber (e.g., polyisoprene) that requires a specialized compression molding/curing process. Such a process can significantly increase the cost of manufacturing the syringe. Furthermore, significant waste materials are also produced during the compression molding process. For example, in a typical manufacturing process, up to 30% of the rubber is discarded during manufacturing of the conventional elastomeric stopper. 
     For these reasons, a need exists for a stopper that can be efficiently manufactured, thereby reducing manufacturing costs and the amount of waste materials, including elastomeric materials and lubricants, produced during the manufacturing of the syringe. The plunger and syringe assembly disclosed herein are designed to address these issues. 
     SUMMARY OF THE INVENTION 
     According to an aspect of the disclosure, a plunger configured to be slidably advanced through a syringe barrel to expel fluid therefrom is provided. The plunger includes a head portion having a proximal end, a distal end, and an annular sidewall extending therebetween. The sidewall can define a first annular groove and a second annular groove. The plunger also includes a first annular seal disposed within the first annular groove, and a second annular seal disposed within the second annular groove, such that at least a portion of each of the annular seals protrudes radially beyond an outer surface of the sidewall to form a slideable seal with an inner sidewall of the syringe barrel. 
     In some examples, the head portion can include a first material, and the annular seals can include a second material that is different from the first material. For example, the first material can include one or more of polypropylene, polyethylene, cyclic olefin polymer or copolymer, polycarbonate, and polyester. The second material can include one or more of a thermoset rubber and a thermoplastic elastomer. The thermoset rubber can be butyl rubber, styrene-butadiene rubber (SBR), and/or poly-isoprene rubber. The thermoplastic elastomer can be one or more of thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. 
     In some examples, the annular seals can include a lubricant disposed on an outer surface thereof. The lubricant can be silicone. The head portion of the plunger can be lubricant free. 
     In some examples, the head portion defines a cavity configured to receive a receiving portion of a plunger rod. The cavity may extend inwardly from the proximal end of the plunger head. The cavity can include a sidewall defining a plurality of threaded grooves configured to engage corresponding threads of the distal end of the plunger rod. The head portion may be configured to receive a portion plunger rod in a snap-fit configuration. The cavity may also include one or more longitudinal supports extending in a distal direction from a distal end thereof. The longitudinal supports can be configured to support the closed distal end of the head portion. The distal end of the head portion can be a conical contact surface. 
     In some examples, the at least two annular grooves are spaced apart in a longitudinal direction by a gap having a length that is greater than or equal to a thickness of the annular seals. In other examples the gap may have a length that is smaller than the thickness of the annular seals. The at least two annular grooves can be a concavely curved surface having a curvature that corresponds to the curvature of the annular seals. 
     According to another aspect of the disclosure, a syringe is provided. The syringe includes a substantially cylindrical barrel having an open proximal end, a distal end including a nozzle, and a sidewall extending therebetween. The syringe also includes a plunger slideably disposed within the syringe barrel and configured to be advanced through the barrel in a distal direction to expel fluid through the nozzle. The plunger can include a head portion including a proximal end, a distal end, and an annular sidewall extending therebetween. The sidewall can define at least two annular grooves. The plunger further includes annular seals disposed within each of the at least two annular grooves, such that at least a portion of each of the annular seals protrudes radially beyond the sidewall to form a slideable seal with an inner sidewall of the syringe barrel. 
     In some examples, the syringe further includes a plunger rod. A distal end of the plunger rod can be removeably inserted in a cavity extending inward from the proximal end of the plunger head. The distal end of the plunger rod may include threaded grooves configured to engage corresponding threaded grooves on an inner sidewall of the cavity. The plunger rod and the head portion may include a first material and the annular seals may include a second material different than the first material. For example, the first material can be one or more of polypropylene, polyethylene, cyclic olefin polymer or copolymer, polycarbonate, and polyester. The second material can be one or more of butyl rubber, styrene-butadiene rubber, poly-isoprene rubber, thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. 
     According to another aspect of the disclosure, a manufacture of a prefilled syringe is provided. The method includes molding a head portion of a multi-piece plunger, wherein the head portion includes a proximal end, a distal end, and an annular sidewall extending therebetween. The method also includes providing at least one annular seal around at least a portion of the sidewall of the plunger, thereby forming the multi-piece plunger. The method further includes inserting the multi-piece plunger into a syringe barrel thereby forming a prefilled syringe. In some instances, when inserted in the barrel, at least a portion of the at least one annular seal contacts an inner sidewall of the syringe barrel to form a slideable seal therewith. 
     In some examples, the head portion of the plunger includes a first material and the at least one annular seal includes a second material that is different from the first material. For example, the first material can be one or more of polypropylene, polyethylene, cyclic olefin polymer or copolymer, polycarbonate, and polyester. The second material can be one or more of butyl rubber, thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. 
     In some examples, providing the at least one annular seal can include forming the annular seal by overmolding the seal on the head portion. In other examples, providing the at least one annular seal can include molding the at least one annular seal from an elastomeric material different from the material used to mold the head portion and assembling the plunger by inserting the at least one annular seal in a groove on the sidewall of the head portion. 
     In some examples, the method also includes filling the syringe barrel with a fluid prior to insertion of the multi-piece plunger. Inserting the plunger into the syringe barrel can include inserting the plunger by a vented placement method. 
     According to another aspect of the disclosure, a plunger configured to be slideably advanced through a syringe barrel to expel fluid therefrom is provided. The plunger includes a head portion having a proximal end, a distal end, and an annular sidewall extending therebetween and an annular seal disposed about at least a portion of the sidewall. The annular seal can include at least two annular ribs protruding radially outward from the seal and configured to form a slideable seal with an inner sidewall of the syringe barrel. 
     In some examples, the head portion can include a first material and the annular seal can include a second material that is different from the first material. The first material can be one or more of polypropylene, polyethylene, cyclic olefin polymer or copolymer, polycarbonate, and polyester. The second material can be one or more of butyl rubber, styrene-butadiene rubber, poly-isoprene rubber, thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. 
     In some examples, the head portion can include at least two annular grooves on the sidewall thereof. A portion of the annular seal can be disposed within each of the at least two annular grooves. The at least two annular ribs may have a polygonal shaped cross section. In other examples, the at least two annular ribs can be convexly curved. 
     These and other features and characteristics of the present invention, as well as the methods of operation and functions of the related elements of structures and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention. As used in the specification and the claims, the singular form of “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a multi-piece plunger according to an aspect of the disclosure; 
         FIG. 2  is a perspective cross-sectional view of the plunger of  FIG. 1  taken along line A-A in  FIG. 1 ; 
         FIG. 3A  is a side view of a head portion of the plunger of  FIG. 1 ; 
         FIG. 3B  is a top view of the head portion of  FIG. 3A ; 
         FIG. 4A  is a top view of an annular seal of the plunger of  FIG. 1 ; 
         FIG. 4B  is a side view of the annular seal of  FIG. 4A ; 
         FIG. 5A  is a cross-sectional view of the plunger of  FIG. 1  prior to insertion in a syringe barrel; 
         FIG. 5B  is a cross-sectional view of the plunger of  FIG. 1  inserted in a syringe barrel; 
         FIG. 6  is a schematic drawings of a syringe assembly including the plunger of  FIG. 1  according to an aspect of the disclosure; 
         FIG. 7  is a perspective cross-sectional view of another example of a multi-piece plunger according to another aspect of the disclosure; 
         FIG. 8  is a perspective cross-sectional view of another example of a multi-piece plunger according to an aspect of the disclosure; 
         FIG. 9  is a perspective cross-sectional view of another example of a multi-piece plunger according to an aspect of the disclosure; 
         FIG. 10  is a perspective cross-sectional view of another example of a multi-piece plunger according to an aspect of the disclosure; 
         FIG. 11  is a perspective cross section view of an example of a two-piece plunger according to an aspect of the disclosure; 
         FIG. 12  is a perspective cross-sectional view of another example of a two-piece plunger according to an aspect of the disclosure; 
         FIG. 13  is a perspective cross-sectional view of another example of a two-piece plunger according to an aspect of the disclosure; and 
         FIG. 14  is a flow chart illustrating a method of manufacture of a prefilled syringe according to an aspect of the disclosure. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. The term “proximal” is used to refer to a portion of a device or object that is closest to or manipulated by a user. The term “distal” refers to the portion of the device or object farthest away from the portion manipulated by a user. For example, the end of a syringe grasped by a user is the proximal end, and fluid is expelled from the distal end of the syringe. However, it is to be understood that the invention may assume various alternative variations except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting. 
     According to an aspect of the disclosure, a multi-piece plunger is discussed herein. The multi-piece plunger can be configured to be slideably advanced through a substantially tubular structure, such as a syringe barrel, to expel fluid therefrom. In some examples, the plunger includes a head or head portion formed from a substantially rigid plastic material, such as one or more of polyolefins (e.g., polyethylene (PE), polypropylene (PP), and their copolymers), cyclic olefin polymers or copolymers, polyamides (e.g., nylons), polyesters (e.g., PET), polystyrene, polyurethane, polycarbonate, acrylonitrile-butadiene-styrene, fluoropolymers, ionomers, and polyacrylates. The plunger can also include a plurality of annular seals disposed around the head portion. For example, the annular seals can be O-rings having a substantially circular cross section. The annular seals can be formed from an elastomeric material, such as rubber or a thermoplastic elastomer. For example, the annular seals can be formed from one or more of thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. Optionally, the annular seals may be formed from one or more of butyl rubber, styrene-butadiene rubber, poly-isoprene rubber, thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. 
     Desirably, material and manufacturing costs for the multi-piece plunger are lower than costs associated with conventional elastomeric stoppers and plungers. For example, a multi-piece plunger having a plastic head or head portion and elastomeric annular seals can include about 80% less elastomeric material (by weight) compared to a similarly sized conventional elastomeric plunger. Since elastomeric materials are more expensive than rigid plastics, such as polypropylene, reduction in an amount of elastomeric material in the plunger reduces manufacturing costs. However, since the seal between the plunger and syringe barrel is formed by the elastomeric annular seals, it is believed that the multi-piece plunger provides an improved or at least comparable seal quality and stability compared to conventional elastomeric plungers. Accordingly, the multi-piece plunger meets functional requirements for use in prefilled syringes in a satisfactory manner but with reduced cost compared to conventional elastomeric plungers. 
     In some examples, the multi-piece plunger is configured to form at least two annular seals with the syringe barrel. Forming multiple annular seals offers a number of benefits compared with stoppers and plungers that only form a single seal with the barrel. For example, a plunger which provides multiple sealing points of contact with the syringe barrel provides a more robust seal, comparable to seals formed from conventional elastomeric stoppers with two or more protrusions or ribs. A seal formed from two or more annular seals is more stable and less susceptible to side loads created as the plunger is advanced or retracted through the syringe barrel, compared to stoppers with a single annular seal. The presence of multiple annular seals also provides a larger sealing area with the barrel which, in conjunction with barrel retaining disks or rings on the plunger rod, acts to prevent loss of sterility when the syringe plunger is pulled back beyond the storage position (e.g., to prevent break-loose contamination). The presence of two or more annular seals or O-rings can also ensure that the multi-piece plunger does not inadvertently invert during insertion into the syringe barrel, as may occur with a plunger having only a single annular seal or point of contact with the syringe barrel. 
     It is believed that the multi-piece plunger disclosed herein is particularly suitable for use in prefilled syringes due to the quality of the seal between the plunger and syringe barrel and material properties of the head portion and annular seals. For example, the multi-piece plunger can be configured to be inserted in a syringe barrel by conventional high speed assembly techniques used with conventional elastomeric stoppers. Accordingly, prefilled syringes having multi-piece plungers can be manufactured rapidly in high speed production facilities. High speed assembly often involves a vented insertion process in which the syringe is filled with a selected fluid through the open proximal end of the syringe barrel. After filling, stoppering with the multi-piece plunger is performed by a vented placement process, which permits faster manufacturing speeds with a smaller footprint compared to other techniques, such as tip-filling and vacuum stoppering. Vented placement of the stopper or plunger generally involves inserting the plunger in a tube or brace having an outer diameter that is slightly smaller than the inner diameter of the syringe barrel and an inner diameter that is slightly larger than the diameter of the head portion of the plunger. The multi-piece plunger is contracted when inserted in the tube or brace. The tube or brace and contracted plunger are inserted to the barrel and, once in a desired position, the tube or brace is removed. Once the tube or brace is removed, the annular seals of the multi-piece plunger expand radially outward to contact the syringe barrel, thereby forming a fluid tight seal between the plunger and barrel. 
     Since the contact surface or roof of the multi-piece plunger is formed from the hard plastic material, the multi-piece plunger also reduces the amount of elastomer or rubber material that contacts the solution (e.g., therapeutic agent) compared with conventional elastomeric plungers and stoppers. This result is desirable since rubbers tend to have more complex formulations including a larger number of additives and agents (e.g., curing agents) compared with rigid polymers, such as polypropylene or polystyrene. The greater number of additives and agents may increase the likelihood that leachables and extractables will pass from the plunger to the fluid solution over time. Contamination concern is heighted for prefilled syringes in which the fluid is in contact with the plunger for substantial and/or indefinite periods of time. In order to account for the increased likelihood of contamination in prefilled syringes, conventional elastomeric plungers and stoppers are often coated with expensive surface coatings to protect the prefilled solution (drug, biomolecule, etc.), from the rubber material. Coating the stopper with such barrier coatings further increases manufacturing costs for prefilled syringes including conventional elastomeric stoppers. Since the multi-piece plunger disclosed herein replaces the rubber front or roof of the stopper with a more inert rigid plastic material, which is less prone to producing leachables and extractables, such protective coatings may not be needed for multi-piece plungers. 
     In some examples, the multi-piece plunger can also be designed to reduce an amount of lubrication needed to advance or retract the plunger through the syringe barrel. For example, conventional elastomeric stoppers are often coated and/or immersed in a lubricant, such as silicone oil, to effectively lubricate the interface between radially extending ribs of the plunger and the syringe barrel. While lubricant free stoppers are also known, such lubricant free stoppers may be unsuitable for use with prefilled syringes. Often, the lubrication process effectively applies lubricant to an entire surface of the plunger including the roof or contact surface, meaning that the lubricant comes into contact with the solution contained in the syringe. The contact of stopper lubricants with the solution can have adverse effects for some drugs and biomolecules used as prefilled solutions. However, for the multi-piece stopper, only the annular seals (e.g., O-rings) need to be subjected to the lubrication process. The head or head portion does not need to be lubricated since it does not contact or seal the syringe barrel. Since the head or head portion is not lubricated, the lubricated surface area in contact with the solution is substantially reduced. In addition, reducing the amount of lubricant needed for each syringe further reduces manufacturing costs compared with conventional elastomeric stoppers and plungers. 
     In some examples, the multi-piece plunger can be designed to demonstrate improved barrier properties compared with elastomeric stoppers and plungers. For example, rigid polymer materials, such as polypropylene, which form the head or head portion of the multi-piece plunger generally form better barriers to oxygen and water vapor compared to soft elastomers. Accordingly, the multi-piece plunger, which replaces a major portion of the elastomer or rubber with rigid plastic, may be expected to form an improved barrier for the prefilled syringe which may prevent contamination and/or degradation of the fluid solution (e.g., the therapeutic agent) and improve shelf life for therapeutic agents and materials in prefilled syringes. 
     In some examples, the multi-piece plunger disclosed herein also offers certain structural advantages compared with conventional stoppers and plungers. For example, elastomers and rubbers are elastic and characterized by high resilience (e.g., the ability to bounce back after a stress is released). In some instances, the bounce back of a conventional rubber plunger or stopper after the pressure on the plunger (e.g., pressure exerted by a plunger rod when expelling fluid from the syringe) is released, can cause fluid to be drawn back into the syringe barrel after the injection is performed. Such a bounce back is referred to as syringe reflux, in which the plunger bounces backwards (e.g., in a proximal direction away from the end of the syringe) thereby drawing patient fluid (e.g., blood) back into the syringe barrel. However, rigid plastics that form the head or head portion of the multi-piece plunger are not as resilient as elastomeric materials. Therefore, replacing the flexible rubber plunger with a more rigid plastic roof may reduce plunger bounce back and syringe reflux. 
     In some examples, the multi-piece plunger can be configured to be connected to a plunger rod for advancing and/or retracting the multi-piece plunger through the syringe barrel. The plunger rod can be formed from the same rigid plastic material as the head portion of the multi-piece plunger. The plunger rod can be attached to the multi-piece plunger by, for example, a snap mechanism or threaded connection. The plunger rod can include one or more retaining disks for preventing syringe pull out, as can occur when the multi-piece plunger is retracted through the syringe barrel. These and other features of the multi-piece plunger and prefilled syringe will be discussed in detail herein, in connection with the following examples. 
     Exemplary Multi-Piece Plunger 
     With reference to  FIGS. 1, 2, and 5A-6 , an exemplary multi-piece plunger  10  configured to be slideably advanced through a syringe barrel  112  (shown in  FIGS. 5A, 5B, and 6 ) is illustrated. The plunger  10  includes a head or head portion  12  having an open proximal end  14 , a closed distal end  16  having a roof or contact surface configured to contact fluid contained in the syringe barrel  112 , and an annular sidewall  18  extending therebetween. Optionally, the head portion  12  can have an outer diameter of about 0.50 inches and a length of about 0.376 inches not including the distal end  16  or tip. The head portion  12  can be formed from a suitable rigid plastic material including, for example, one or more of polyolefins (e.g., PE, PP, and their copolymers), cyclic olefin polymer or copolymer, polyamides (e.g., nylons), polyesters (e.g., PET), polystyrene, polyurethane, polycarbonate, acrylonitrile-butadiene-styrene, fluoropolymers, ionomers, polyacrylates, or any other similar material. The plunger  10  further includes a plurality of annular seals, such as a proximal seal  30  and a distal seal  32 , disposed around the sidewall  18  of the head portion  12 . 
     With specific reference to  FIGS. 2, 3A, and 3B , in some examples, the closed distal end  16  of the head portion  12  includes a first angled portion  20  and a second angled portion  22 , which are both part of a single conical surface that extends toward a tip  24 , thereby providing the closed distal end  16  with a substantially conical appearance. As shown in  FIG. 3A , the conical angle α can be about 35°, however, various alternative conical angles α are also contemplated herein. Optionally, the conical distal end of the head portion  12  can have a thickness D 1  (shown in  FIG. 2 ) of about 0.048 inches. An exemplary geometry of a distal end of a stopper, which can be used for the head portion  12  of the presently disclosed multi-piece plunger, is described in U.S. Pat. No. 7,331,942, entitled “Flush syringe having anti-reflux stopper”, which is hereby incorporated by reference in its entirety. However, this shape of the flexible roof is not to be considered as limiting the present invention as the roof may be flat. 
     In some examples, the sidewall  18  can define a plurality of annular grooves, such as a proximal groove  26  and a distal groove  28 , extending radially inward from the outer surface of the sidewall  18 . The grooves  26 ,  28  can be sized and shaped to receive the annular seals  30 ,  32  (shown in  FIG. 2 ). In some examples, the sidewall  18  can also define a middle groove  27  disposed between the proximal groove  26  and the distal groove  28 . However, the middle groove  27  may not receive a corresponding annular seal. The grooves  26 ,  27 ,  28  can have a variety of different shapes including, for example, a substantially square or rectangular cross section with opposing vertical walls and a substantially flat bottom surface, as shown, for example, in  FIG. 3A . In other examples, the annular grooves  26 ,  27 ,  28  can have a triangular shaped cross section with angled opposing walls or a curved cross section. The annular grooves  26 ,  28  can also be provided on the sidewall in various arrangements. For example, the annular grooves  26 ,  28  may be separated by a space or gap, which defines the distance between the annular seals of the multi-piece plunger  10 . In some examples, the gap can be about the thickness T of one of the annular seals, as shown in  FIG. 2 . The distance D 2  (shown in  FIGS. 2 and 3A ) between the annular seals  30 ,  32  can be about 0.262 inches. As discussed herein, the height/diameter ratio of the seal is selected to impart sufficient stability to the plunger  10  and, in particular, to prevent the plunger  10  from flipping inside out during insertion in a tube, such as an insertion tube used for vented tube placement. In other examples, as discussed herein, the grooves  26 ,  28  and annular seals  30 ,  32  can be enlarged, thereby reducing the distance D 2  between the seals. In some examples, the grooves  26 ,  28  are substantially equidistant from a central latitudinal or radial axis X of the plunger head  12 . In other examples, the grooves  26 ,  28  may be disposed closer to the distal end  16  of the plunger head  12  to impart particular sliding characteristics for the plunger  10  and/or prefilled syringe. 
     With specific reference to  FIG. 2 , the annular seals  30 ,  32  can be mounted in respective annular grooves such that at least a portion of each of the annular seals  30 ,  32  protrudes radially beyond the outer surface sidewall  18  to form the slideable seal with an inner sidewall of the syringe barrel  112  (shown in  FIGS. 5A, 5B, and 6 ). In this way, the annular seals  30 ,  32  replace or supplement annular ribs or protrusions found in conventional elastomer or rubber stoppers and plungers. For example, the annular seals  30 ,  32  may protrude a distance D 3  (shown in  FIG. 2 ) beyond the outer surface of the plunger sidewall  18 . In some examples, the distance D 3  is about one half of the thickness T (shown in  FIGS. 2 and 4B ) of the annular seal  30 ,  32 . In other examples, the protrusion distance D 3  can be less than 30% or less than 20% of the thickness T of the annular seals  30 ,  32 . 
     In some examples, the head portion  12  can define a plunger rod receiving portion or cavity  34  extending inwardly from the open proximal end  14  of the head portion  12  and being configured to receive a distal end of a plunger rod  114  (shown in  FIG. 6 ). The cavity  34  can define a substantially circular distal surface  36  and a straight or tapered cylindrical sidewall  38  extending between the proximal open end  16  of the head portion  12  and the surface  36 . In some examples, the cavity sidewall  38  includes threaded grooves configured to engage corresponding threads of the distal end of the plunger rod  114 . In other examples, the distal end of the plunger rod can be mounted into the cavity  34  with a snap fit mechanism or other connector, as is known in the art. 
     With specific reference to  FIGS. 4A and 4B , in some examples, the annular seals  30 ,  32  are elastomeric O-rings formed from suitable elastomeric materials including, for example, one or more of thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. While the size and shape of the annular seals  30 ,  32  are largely dependent on the syringe size and volume, the seals  30 ,  32  can have an inner diameter ID of about 0.410 inches, an outer diameter OD of about 0.590 inches, and a thickness of about 0.090 inches. In some examples, a lubricant, such as silicone or silicone oil, is provided on the surface of each annular seal  30 ,  32  to improve sliding characteristics. As discussed above, the silicone lubricant can be applied by a tumbling process, in which the annular seals are immersed in a lubricant bath to form a coating on an outer surface of the annular seals  30 ,  32 . 
     In use, the multi-piece plunger  10 , is configured to be inserted into the syringe barrel  112  (shown in  FIGS. 5A, 5B, and 6 ). As shown in  FIG. 5A , prior to insertion, the annular seals  30 ,  32  are in an expanded position having a generally curved outer surface. The outer diameter of the annular seals is selected to be slightly larger than the inner diameter of the syringe barrel  112 . Accordingly, when inserted in the syringe barrel  112 , the radially outer portion of the annular seals  30 ,  32  is slightly compressed thereby forming a sufficient seal with the inner surface of the syringe barrel  112 . The degree of compression of the annular seals is selected to permit the plunger  10  to easily slide through the barrel  112 , but also to provide robust sealing properties, which prevent leaks and/or contamination of fluid contained in the prefilled syringe. The plunger  10  inserted in the syringe barrel  112  with the annular seals  30 ,  32  in a compressed position is shown, for example, in  FIG. 5B . 
     Exemplary Syringe Assembly 
     With reference to  FIG. 6 , the multi-piece plunger  10  can be used with a syringe assembly  100 , such as a prefilled syringe. In addition to the multi-piece plunger  10  and syringe barrel  112  described hereinabove, the assembly  100  includes a plunger rod  114  configured to be removeably coupled to the plunger  10 . The plunger rod  114  is an elongated structure extending along longitudinal axis A from a proximal end having a thumb press flange  126  and a distal end including a receiving portion  116 . The receiving portion  116  may be configured to be screwed into the cavity  34  (shown in  FIGS. 2 and 3B ) of the plunger  10  such that threads on the receiving portion  116  of the plunger rod  114  engage corresponding threads on the cavity sidewall  38  (shown in  FIG. 2 ). In some examples, the plunger rod  114  is formed from the same rigid plastic material as the head portion  12  of the plunger  10 . For example, the plunger rod  114  can be formed from one or more of polypropylene, polyethylene, cyclic olefin polymer or copolymer, polycarbonate, and polyester. 
     The plunger rod  114  can further include one or more retaining rings or disks  118  proximal to the receiving portion  116  and configured to engage a corresponding portion of the plunger  10 , such as a notch or groove located near the proximal open end  14  of the cavity  34 . The engagement between the retaining disk  118  and cavity  34  is configured to prevent a user from inadvertently pulling the plunger rod  114  out of the plunger  10  during aspiration. Specifically, when the disk  118  is engaged to the groove or notch, the plunger  10  and plunger rod  114  are locked together and cannot be disconnected merely by pulling the plunger rod  114  and/or plunger  10  in a proximal direction P. 
     The assembly  100  further includes the syringe barrel  112 . The syringe barrel  112  may be formed of glass, or may be injection molded from thermoplastic material, such as polypropylene and polyethylene, according to techniques known to those of ordinary skill in the art. However, it is to be appreciated that syringe barrel  112  may be made from other suitable materials and according to other applicable techniques as well. Often the material is transparent or translucent so that position of the plunger  10  and/or amount of fluid remaining in the barrel  112  can be easily ascertained. The syringe barrel  112  is generally a substantially cylindrical tubular structure, though syringe barrels having an oval, square, or rectangular cross section may also be used within the scope of the present disclosure. In some examples, the syringe barrel  112  includes a distal or frontal end  120 , which includes an outlet opening, such as a nozzle  122 . The nozzle  122  can include a mechanism for attachment of a needle cannula or a separate medical device (such as a catheter). For example, the attachment mechanism can be a luer connector, threaded connector, snap fit connector, or similar connection mechanism. The syringe barrel  112  also includes an open proximal or rearward end  124  for receiving the multi-piece plunger  10  and plunger rod  114  assembly. In some examples, the rearward end  124  can include a flange  128  positioned to permit a user to grasp the rearward end of the syringe barrel  112  with his/her forefingers when advancing the plunger rod  114  through the barrel  112 . 
     In use, a user may obtain an empty syringe assembly  100  in which the multi-piece plunger  10  is disposed adjacent to the distal end  120  of the syringe barrel  112 . The user can draw fluid into the syringe barrel  112  by moving the plunger  10  in a proximal direction P (e.g., a process often referred to as aspiration). Once a desired amount of fluid is drawn into the syringe barrel  112 , the user can advance the plunger  10  through the barrel  112  by pushing on a thumb-press flange  126  of the plunger rod  114  to advance the plunger  10  through the barrel in a distal direction D. Advancing the plunger through the barrel  112  causes fluid contained therein to pass through the nozzle  122  and, in some cases, through a needle cannula or another fluid conducting structure, such as medical tubing, for administration to a patient. In the case of a prefilled syringe, the syringe assembly  100  is often provided from the manufacturer filled with a single dose of fluid to be administered to a patient. In one configuration, the user attaches the plunger rod  114  to the multi-piece plunger  10  by, for example, inserting the receiving portion  116  of the rod  114  into the plunger cavity  34 , such that the threads or another connection mechanism lock the plunger  10  and plunger rod  114  together. In another configuration, the syringe may be provided in a pre-assembled configuration in which the syringe is provided with the plunger rod  114  already attached to the multiple piece plunger  10 . The user then performs the injection by pushing the plunger  10  through the barrel in the distal direction D. 
     Alternative Exemplary Multi-Piece Plungers 
     With reference to  FIG. 7 , another example of a multi-piece plunger  10   b  configured to be advanced through a syringe barrel to expel fluid therefrom is illustrated. As in previously described examples, the multi-piece plunger  10   b  includes a head or head portion  12   b  having an open proximal end  14   b , a closed distal end  16   b  having a roof or angled contact surface configured to contact fluid contained in the syringe barrel, and an annular sidewall  18   b  extending therebetween. The sidewall  18   b  defines a plurality of annular grooves, such as a proximal groove  26   b  and a distal groove  28   b , extending radially inward from the outer surface of the sidewall  18   b . Each of the grooves  26   b ,  28   b  can be sized and shaped to receive an elastomeric annular seal, such as a proximal annular seal  30   b  and a distal annular seal  32   b . Unlike in previously described examples in which the annular grooves had a square or rectangular cross section, the annular grooves  26   b ,  28   b  can define a substantially concavely curved surface, having a curvature substantially similar to the curvature of the annular seals  30   b ,  32   b . The head portion  12   b  may also include a central groove  27   b  defining a curved surface; however, an annular seal is not inserted in the central groove  27   b . The grooves  26   b ,  27   b ,  28   b  are separated by a small flat annular surface  29   b . In other examples of the head portion  12   b , the flat annular surface  29   b  can be removed and/or replaced by a pointed ridge between each of the one or more grooves  26   b ,  27   b ,  28   b.    
     As in previously described examples, the head portion  12   b  of the plunger  10   b  defines a cavity  34   b  extending inwardly from the open proximal end  14   b  thereof. The cavity  34   b  is configured to receive the receiving portion of a plunger rod to removeably connect the plunger  10   b  to the plunger rod. 
     With reference to  FIG. 8 , another exemplary multi-piece plunger, generally labelled  10   c , is illustrated. As with the embodiment of  FIG. 7 , the plunger  10   c  includes a head portion  12   c  with annular grooves  26   c ,  27   c ,  28   c  defining curved surfaces and separated by annular flat surfaces  29   c . The multi-piece plunger  10   c , shown in  FIG. 8 , also includes a cavity  34   c . However, unlike in previously described examples, a distal end  36   c  of the cavity  34   c  includes one or more longitudinal supports  40   c  extending toward the roof or angled contact surface of the plunger  10   c . The supports  40   c  can be arranged in various configurations including, for example, x-shaped or cross patterns, in which a first support is orthogonal to a second support, and/or in a circular or cylindrical orientation. In other examples, two or more supports  40   c  can be arranged parallel to one another. The supports  40   c  are positioned to prevent or reduce deflection of the roof or angled contact surface of the plunger  10   c , which can occur when the plunger  10   c  contacts fluid contained in the syringe barrel. The supports  40   c  can also prevent or reduce syringe reflux by limiting deformation of the angled contact surface, thereby reducing the distance that the plunger  10   c  bounces in a proximal direction after contacting the distal end of the syringe barrel. 
     With reference to  FIG. 9 , another exemplary multi-piece plunger, generally labelled  10   d , configured to be advanced through a syringe barrel to expel fluid therefrom is illustrated. As in previously described examples, the plunger  10   d  includes a head or head portion  12   d  including a sidewall  18   d , which defines a plurality of annular grooves, such as a proximal groove  26   d  and a distal groove  28   d , extending radially inward from the outer surface of the sidewall  18   d . Each of the grooves  26   d ,  28   d  can be sized and shaped to receive an elastomeric annular seal, such as a proximal annular seal  30   d  and a distal annular seal  32   d . The annular grooves  26   d ,  28   d  can define a substantially concavely curved surface, having a curvature substantially similar to the curvature of the annular seals  30   d ,  32   d . The head portion  12   d  also includes a central groove  27   d  defining a curved surface; however, an annular seal is not inserted in the central groove  27   d . Unlike in previously described examples, which included only small annular surfaces or pointed ridges between adjacent grooves, as shown in  FIG. 9 , the grooves  26   d ,  27   d ,  28   d  are separated by enlarged flat annular surfaces  29   d . Increasing the width of the flat surfaces  29   d  between the grooves  26   d ,  27   d ,  28   d  increases the distance between the annular seals  30   d ,  32   d , thereby increasing the total length D 2  of the seal compared with previously described examples. While not intending to be bound by theory, it is believed that increasing the total width of the seal improves stability of the multi-piece plunger even though the surface area of contact between the annular seals  30   d ,  32   d  and syringe barrel is not increased. 
     With reference to  FIG. 10 , another example of a multi-piece plunger  10   e  configured to be advanced through a syringe barrel to expel fluid therefrom and including thicker annular seals is illustrated. As in previously described examples, the multi-piece plunger  10   e  includes a head or head portion  12   e  having an open proximal end  14   e , a closed distal end  16   e  having a roof or angled contact surface configured to contact fluid contained in the syringe barrel, and an annular sidewall  18   e  extending therebetween. The sidewall  18   e  defines a plurality of annular grooves, such as a proximal groove  26   e  and a distal groove  28   e , extending radially inward from the outer surface of the sidewall  18   e . The grooves  26   e ,  28   e  have a substantially square-shaped or rectangular cross section with opposing vertical walls and a flat bottom surface. Unlike in previously discussed examples, the head portion  12   e  does not include a central groove between the grooves  26   e ,  28   e . Each of the grooves  26   e ,  28   e  is sized and shaped to receive an enlarged elastomeric annular seal, such as a proximal annular seal  30   e  and a distal annular seal  32   e . In some examples, the seals  30   e ,  32   e  have a thickness T of about 0.195 inches, which is about double the thickness of the annular seals show in  FIGS. 1-9 . The grooves  30   e ,  32   e  are separated by a small flat annular surface  29   e . The thicker seals  30   e ,  32   e  have a larger area of contact with syringe barrel compared to previously described examples. Increasing the area of contact between the seals  30   e ,  32   e  and the syringe barrel increases the stability and fluid-tight properties of the seal. However, increasing the surface area of the seal may increase the force needed to slide the plunger  10   e  through the syringe barrel and/or may increase the amount of lubricant required to impart suitable sliding characteristics to the plunger  10   e.    
     Exemplary Two-Piece Plungers 
     According to another aspect of the disclosure, examples of two-piece plungers  210 ,  210   b  are illustrated in  FIGS. 11-13 . With specific reference to  FIGS. 11 and 12 , the two-piece plunger  210  includes a head or head portion  212  having an open proximal end  214 , a closed distal end  216  having a roof or contact surface configured to contact fluid contained in a syringe barrel, and an annular sidewall  218  extending therebetween. The head portion  212  can be formed from a suitable rigid polymer material including, for example, one or more of polyolefins (e.g., PE, PP, and their copolymers), cyclic olefin polymer or copolymer, polyamides (e.g., nylons), polyesters (e.g., PET), polystyrene, polyurethane, polycarbonate, acrylonitrile-butadiene-styrene, fluoropolymers, ionomers, polyacrylates, or any other similar material. 
     The plunger  210  further includes a single annular seal  230  disposed about the sidewall  218 . The annular seal  230  can be formed from an elastomeric material including, for example, one or more of thermoplastic olefins, styrenic block copolymers, thermoplastic polyurethanes, and thermoplastic polyamides. The head portion  212  and annular seal  230  can be made by any suitable method including injection molding by two-shot molding. In other examples, the annular seal  230  can be overmolded on a molded head or head portion  212 . In other examples, the annular seal  230  can be formed separately. In that case, the plunger  210  can be assembled by pulling the annular seal  230  over the head portion  212 . 
     In some examples, the plunger head portion  212  can include a number of shallow annular grooves, such as a proximal groove  226  and a distal groove  228 . Portions of the annular seal  230 , such as a proximal protrusion  242  and a distal protrusion  244 , can be configured to be inserted in the respective grooves  226 ,  228 . The annular seal  230  also includes at least two radially protruding ribs or ridges, such as a proximal ridge  246  and a distal ridge  248  extending radially outward beyond the sidewall  218  of the head portion  212 . The ridges  246 ,  248  are configured to contact an inner surface of the syringe barrel to form a suitable seal therewith. As shown in  FIG. 11 , the ridges  246 ,  248  can have a polygonal or tetrahedral cross section with a substantially flat annular outer surface configured to contact the syringe barrel. In other examples, the ridges or ribs can have a square-shaped cross section, a triangular cross section, or can be curved. For example, a two-piece plunger  210  having radially extending ribs or ridges  246 ,  248  with a curved outer surface is shown in  FIG. 12 . 
     With specific reference to  FIG. 13 , another example of two-piece plungers  210   b  is illustrated. As in the previously described examples, the two-piece plunger  210   b  includes a head or head portion  212   b  having an open proximal end  214   b , a closed distal end  216   b  having a roof or conical contact surface configured to contact fluid contained in a syringe barrel, and an annular sidewall  218   b  extending therebetween. The plunger  210   b  further includes a single annular elastomeric seal  230   b  disposed about the sidewall  218   b . The annular seal  230   b  includes at least two radially protruding ribs or ridges, such as a proximal annular ridge  246   b  and a distal ridge  248   b  extending radially outward beyond the sidewall  218   b  of the head portion  212   b . As shown in  FIG. 13 , the ridges  246   b ,  248   b  may have a curved outer surface and a semi-circular cross section. The ridges  246   b ,  248   b  can be tapered or angled, thereby providing a substantially continuous sidewall surface without vertical walls or other discontinuities. In some examples, a distal portion  250   b  of the annular seal  230   b  can extend around the conical contact surface of the head portion  212   b  at the distal end  216   b  thereof. The distal portion  250   b  of the annular seal  230   b  can be angled or tapered in the same manner as the conical contact surface of the head portion  212   b , thereby creating a two-piece plunger  210   b  having a distal contact surface formed from both the head portion  212   b  and the annular seal  230   b.    
     Exemplary Manufacturing Method 
     With reference to  FIG. 14 , steps for manufacture of a multi-piece plunger including a head portion and one or more annular seals, such as the multi-piece plungers shown in  FIGS. 1-13 , are discussed. As shown at box  310 , the head portion of the plunger is provided. The head portion can include, for example, a proximal end, a distal end, and an annular sidewall extending therebetween. The annular sidewall of the head portion can include structures for receiving elastomeric annular seals, such as the annular grooves discussed hereinabove. The head portion can be molded by conventional molding processes, as are known in the art. For example, the head portion can be molded by an injection molding, in which fluid polymer material is injected into a mold and cured to form the head portion. As discussed herein, the head portion can be formed from a suitable rigid polymer material including, for example, one or more of polyolefins (e.g., PE, PP, and their copolymers), cyclic olefin polymer or copolymer, polyamides (e.g., nylons), polyesters (e.g., PET), polystyrene, polyurethane, polycarbonate, acrylonitrile-butadiene-styrene, fluoropolymers, ionomers, polyacrylates, or any other similar material. 
     As shown at box  312 , the method further includes providing the one or more annular seals. As discussed herein, the annular seals can be elastomeric structures, such as O-rings, formed from a suitable elastomeric material. In some examples, the head portion and seals can be formed substantially simultaneously, as occurs during two-shot molding processes. In some examples, providing the annular seals can include overmolding the seals to the head portion. In other examples, the annular seals can be formed separately from the head portion. For example, the one or more annular seals may be formed by injection molding in individual molds or may be pressed or stamped from sheets of elastomeric material. In some examples, as shown at box  314 , a lubricant, such as silicone oil, can be applied to the annular seals to improve sliding characteristics of the seals through a syringe barrel. For example, prior to being attached to the head portion, the annular seals can be tumbled or immersed in a lubricant bath to coat the outer surface thereof with the lubricant. As shown at box  316 , after the head portion and annular seals are prepared, the plunger can be assembled by attaching the annular seals to the head portion. For example, assembly can include manually or automatically sliding the annular seals over the head portion and allowing the seals to contract into the respective annular grooves on the head portion. 
     As shown at box  318 , a prefilled syringe can be assembled by filling a syringe barrel with a fluid, such as a fluid containing a therapeutic agent, and inserting the assembled plunger into the syringe barrel. For example, as discussed herein, a prefilled syringe can be produced by filling the syringe barrel with fluid through the open proximal end thereof. After the syringe barrel is filled, the multi-piece plunger can be inserted through the open proximal end of the barrel by a vented placement method as is known in the art. In other examples, the plunger can be inserted by a vacuum stoppering method. 
     While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of invention which is to be given the full breadth of the claims appended and any and all equivalents thereof.