Patent Publication Number: US-2016243308-A1

Title: Convertible plungers, film coated plungers and related syringe assemblies

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application Ser. No. 61/887,899, filed Oct. 7, 2013; 61/912,734, filed Dec. 6, 2013; 61/938,011, filed Feb. 10, 2014 and 62/048,675, filed Sep. 10, 2014. 
    
    
     FIELD OF INVENTION 
     The present invention relates generally to plungers and their use in drug delivery devices, such as (pre-filled, filled before use or empty) syringes, cartridges or auto-injectors. More particularly, the present invention relates to convertible plungers that provide and maintain container closure integrity in an expanded state or storage mode, during the shelf-life of a pre-filled syringe, and which are reducible to a constricted state or dispensing mode, when in use, to provide for relatively low and smooth plunger force when dispensing syringe contents. 
     BACKGROUND 
     The present disclosure predominantly describes use of plungers and plunger assemblies according to the present invention in connection with pre-filled syringes. However, a skilled artisan would readily appreciate that the invention is not limited to pre-filled syringes, but may include other drug delivery devices, such as (pre-filled, filled before use, or empty) syringes, cartridges and auto-injectors. 
     Pre-filled parenteral containers, such as syringes or cartridges, are commonly prepared and sold so that the syringe does not need to be filled by the patient or caregiver before use. The syringe, and more specifically the barrel of the syringe, may be prefilled with a variety of different injection products, including, for example, saline solution, a dye for injection, or a pharmaceutically active preparation, among other items. 
     Pre-filled parenteral containers are typically sealed with a rubber plunger, which provides closure integrity over the shelf life of the container&#39;s contents. To use the prefilled syringe, the packaging and cap are removed, optionally a hypodermic needle or another delivery conduit is attached to the proximal end of the barrel, the delivery conduit or syringe is moved to a use position (such as by inserting it into a patient&#39;s blood vessel or into apparatus to be rinsed with the contents of the syringe), and the plunger is advanced in the barrel to inject contents of the barrel to the point of application. 
     Seals provided by rubber plungers in the barrel typically involve the rubber of the plunger being pressed against the barrel. Typically the rubber plunger is larger in diameter than the internal diameter of the barrel. Thus, to displace the rubber plunger when the injection product is to be dispensed from the syringe requires overcoming this pressing force of the rubber plunger. Moreover, not only does this pressing force provided by the rubber seal typically need to be overcome when initially moving the plunger, but this force also needs to continue to be overcome as the rubber plunger is displaced along the barrel during the dispensing of the injection product. The need for relatively elevated forces to advance the plunger in the syringe may increase the difficulty at which a user may administer the injection product from the syringe. This is particularly problematic for auto injection systems where the syringe is placed into the auto injection device and the plunger is advanced by a fixed spring. Accordingly, primary considerations concerning the use of a plunger in a pre-filled parenteral container include: (1) container closure integrity (“CCI”, defined below); and (2) plunger force (defined below) required to dispense syringe contents. 
     In practice, CCI and plunger force tend to be competing considerations. In other words, absent other factors, the tighter the fit between the plunger and the interior surface of the container to maintain adequate CCI, the greater the force necessary to advance the plunger in use. In the field of medical syringes, it is important to ensure that the plunger can move at a substantially constant speed and with a substantially constant force when advanced in the barrel. In addition, the force necessary to initiate plunger movement and then continue advancement of the plunger should be low enough to enable comfortable administration by a user. 
     Plunger force is essentially a function of the coefficients of friction of each of the contacting surfaces (i.e., the plunger surface and interior syringe wall surface) and the normal force exerted by the plunger against the interior wall of the syringe. The greater the respective coefficients of friction and the greater the normal force, the more force required to advance the plunger. Accordingly, efforts to improve plunger force should be directed to reducing friction and lowering normal force between contacting surfaces. However, such efforts should be tempered by the need to maintain adequate CCI, as discussed above. 
     To reduce friction and thus improve plunger force, lubrication may be applied to the plunger, the interior surface of the container, or both. Liquid or gel-like flowable lubricants, such as free silicone oil (e.g., polydimethylsiloxane or “PDMS”), may provide a desired level of lubrication to optimize plunger force. Optionally, use of free silicone oil to reduce plunger force, especially in small amounts, may in certain embodiments, be within the scope of the invention. However, for some applications, including preferred embodiments of the invention, use of large amounts of flowable lubricant is not desired. For example, a flowable lubricant can mix and interact with the drug product in a syringe, potentially degrading the drug or otherwise affecting its efficacy and/or safety. Such lubricants may in some cases be problematic if they are injected into the patient along with the drug product. In addition, flowable lubricants, when used with pre-filled syringes, may migrate away from the plunger over time, resulting in spots between the plunger and the interior surface of the container with little or no lubrication. This may cause a phenomenon known as “sticktion,” an industry term for the adhesion between the plunger and the barrel that needs to be overcome to break out the plunger and allow it to begin moving. 
     As an alternative (or in addition) to flowable lubricants, plungers may be made from materials having lubricious properties or include friction-reducing coatings or laminates on their exterior surfaces. Examples of such plungers include, for example: the i-COATING by TERUMO, which is disclosed in Canadian Patent No. 1,324,545, incorporated by reference herein in its entirety; W.L. Gore extended ETFE film on a rubber plunger; and the CZ plunger by WEST. While these commercially available plungers may complement a lubricated barrel to provide a desired level of plunger force, it has not been found that they provide desirable plunger force absent a lubricious coating or flowable lubricant on the barrel of coated or uncoated plastic parenteral containers. 
     As an alternative to free liquid lubricants, lubricious coatings may be applied to the interior wall of a container barrel. Lubricity coatings, e.g., according to methods disclosed in U.S. Pat. No. 7,985,188 (incorporated by reference herein in its entirety), are particularly well suited to provide a desired level of lubricity for plungers in parenteral containers. Such lubricity coatings are preferably applied using plasma enhanced chemical vapor deposition (“PECVD”) and may have one of the following atomic ratios, Si w O x C y  or Si w N x C y , where w is 1, x is from about 0.5 to 2.4 and y is from about 0.6 to about 3. Such lubricity coatings may have a thickness between 10 and 500 nm. Advantages of such plasma coated lubricity layers may include lower migratory potential to move into the drug product or patient than liquid, sprayed or micron-coated silicones. It is contemplated that use of such lubricity coatings to reduce plunger force is within the broad scope of the invention. However, for some applications, including preferred applications of the invention, use of such lubricity coatings may not be optimal. For example, due to relatively low cross-link density, the lubricity layer may sometimes interact with the contents of the syringe, resulting in the presence of silicon ions being extracted from the lubricity layer into the syringe. In addition, application of a lubricity coating introduces an additional step in container manufacturing, thus increasing the complexity and cost of the manufacturing process. 
     Thus, there is a need for optimizing plunger force in a parenteral container while maintaining adequate CCI to prevent drug leakage, protect the drug product and attain sufficient product shelf life. In addition, there is a need to provide adequate lubricity to achieve a desired plunger force while minimizing extractables and interaction with the drug product held by the container. There is a further need to optimize these factors while reducing the manufacturing cost and complexity that may be associated with applying a discrete lubricity coating to a medical barrel. 
     SUMMARY OF THE INVENTION 
     Accordingly, in one optional aspect of the invention, there is provided a convertible plunger having an internal portion and a generally cylindrical exterior surface. At least a portion of the exterior surface is maintained in an initial expanded state by a property of the internal portion. The expanded state is reducible to a constricted state by an operation that is applied to the internal portion of the plunger to alter the property. The property may include, but is not limited to, gas pressure, mechanically produced outward radial pressure or outward radial pressure produced by a liquid or gelatinous compression material disposed within the plunger. 
     Another optional aspect of the invention is a convertible plunger. The convertible plunger includes a generally cylindrical exterior surface configured to be seated against a generally cylindrical interior surface of a barrel wall in a storage mode and to advance along the barrel wall in a dispensing mode. A cavity in the plunger defines an interior surface of the plunger. The interior surface and exterior sealing surface defines between them a generally annular portion of the plunger. A compression material (e.g., a solid article (which may be, e.g, generally spherical in shape), or a charge of gas, liquid or gel) is disposed at least partially in the cavity and configured to apply outward radial pressure on at least a portion of the interior surface in the storage mode to provide a sealing force between the exterior sealing surface and a syringe barrel wall. The plunger may be configured to convert to the dispensing mode by reducing the applied outward radial pressure, thus reducing the sealing force between the exterior surface and a syringe barrel wall. 
     Another optional aspect of the invention is a plunger assembly that includes a plunger rod and a plunger. The plunger rod includes an exterior shaft and an interior shaft. The exterior shaft has an inner portion that is configured for the slideable insertion of at least a portion of the interior shaft. The interior shaft is configured to be displaced from a first position to a second position relative to the exterior shaft. Further, the plunger is operably connected to the plunger rod and is configured to receive the insertion of at least a portion of the interior shaft. 
     Another optional aspect of the invention is a dual actuated plunger that includes a sleeve having a first cavity, a second cavity, and at least one rib. The at least one rib is generally aligned with the first cavity. Further, the first cavity is in communication with the second cavity. The term “in communication with” as used in the foregoing sentence means that the structure within the sleeve facilitates passage of an insert between the cavities, e.g., through an opening or passage between the cavities, and/or by providing a thin breakable membrane between the cavities that is broken when the plunger is actuated. The insert is configured to be displaced from the first cavity to the second cavity, such as, for example, by the displacement of the interior shaft to the second position. Additionally, the insert is configured to provide support for the compression of the at least one rib when the insert is positioned in the first cavity. However, according to certain embodiments, the support for the compression of the at least one rib provided by the insert may be reduced and/or removed when the insert is positioned in the second cavity. 
     Further, another optional aspect of the invention is a dual actuated plunger having an insert, a sleeve, and a connector body. At least a portion of the connector body is positioned within the sleeve between the sleeve and the insert and is configured to provide support for the compression of the sleeve against an inner surface of a sidewall of a barrel. Additionally, according to certain embodiments, the insert is configured to be displaced from a deactivated position to an activated position in the plunger. Further, the sleeve is configured to have a length of the sleeve elongated and outer width of the sleeve reduced when the insert is in the activated position. Such a reduction in width may reduce the compressive force or radial pressure that at least a portion of the sleeve, such as at least one rib on the sleeve, exerts against an adjacent surface such as, for example, the interior surface of a sidewall of a barrel. 
     Additionally, another optional aspect of the invention is a method for forming a film coated plunger. The method includes forming, from a film of a thermoplastic elastomer, a preform coating. Additionally, the preform coating is pressed against a sidewall and/or base of a mold cavity to generally conform an outer shape of the preformed coating to a shape of the plunger. The method also includes injecting a plunger material into the mold cavity. The injected plunger material may be positioned against an adjacent inner surface of the preform coating to form the film coated plunger. 
     Another optional aspect of the invention is a film coated plunger configured for insertion into a barrel, the barrel having a product containing area. The film coated plunger includes a plunger that is configured to provide a compressive force against an inner surface of a sidewall of a barrel to form a compressive seal between the plunger and the sidewall of the barrel. The film coated plunger further includes a film coating that is positioned about at least a portion of the plunger. The film coating is configured to reduce a friction between the film coated plunger and the inner surface of the sidewall of the barrel and/or to provide a barrier between the plunger and a product contained in the product containing area of the barrel. 
     Other aspects of the invention will be apparent from this disclosure and the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a perspective view of a plunger assembly. 
         FIG. 2  illustrates an axial sectional view of a plunger assembly according to an illustrated embodiment. 
         FIG. 3  illustrates an isolated partial sectional view of the plunger shown in  FIG. 2 , with the connector body transparent to reveal internal structure. 
         FIG. 4  illustrates a partial sectional view of the plunger of  FIG. 3  positioned within a barrel of a syringe. 
         FIG. 4A  is an enlarged sectional view of a first alternative embodiment of the inner surface of the syringe of  FIG. 4 , comprising a trilayer coating set disposed thereon. 
         FIG. 4B  an enlarged sectional view of a second alternative embodiment of the inner surface of the syringe of  FIG. 4 , comprising an organo-siloxane coating disposed thereon. 
         FIG. 5  illustrates an axial sectional view of a plunger assembly according to an illustrated embodiment. 
         FIG. 6  illustrates a partial sectional view of the plunger shown in  FIG. 5  positioned within a barrel of a syringe. 
         FIG. 7  illustrates an isolated partial sectional view of the plunger shown in  FIGS. 5 and 6 . 
         FIG. 8  illustrates an axial sectional view of a plunger having a film coating according to an illustrated embodiment. 
         FIG. 9  illustrates a schematic axial sectional view of a forming die and forming plug used to transform a portion of a film into a coating preform for a film coating. 
         FIG. 10  illustrates the coating preform of the film coating formed by the forming die and forming plug of  FIG. 9 . 
         FIG. 11  illustrates the coating preform subjected to a vacuum in a mold cavity and in which a material for a plunger has been injected into the mold cavity and is against the coating preform. 
         FIG. 12  illustrates a cross sectional view of a formed plunger and film coating prior to a trim tool cutting or trimming the coating from a film. 
         FIG. 13  illustrates an axial sectional view of a plunger assembly according to an illustrated embodiment. 
         FIG. 14  illustrates a perspective view of a substantially spherical mesh insert. 
         FIG. 15  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 2 , with the connector body transparent to reveal internal structure, the plunger having disposed within it the substantially spherical mesh insert shown in  FIG. 14 . 
         FIG. 16  illustrates a perspective view of a substantially cylindrical insert. 
         FIG. 16A  illustrates a perspective view of the substantially cylindrical insert of  FIG. 16  after it has been inwardly collapsed. 
         FIG. 17  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 2 , with the connector body transparent to reveal internal structure, the plunger having disposed within it the substantially cylindrical insert shown in  FIG. 16 . 
         FIG. 18  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 13 . 
         FIG. 19  illustrates an isolated sectional view of a tapered insert having partially inserted therein a protrusion axially extending from an interior shaft of a plunger rod. 
         FIG. 20  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 13 , the plunger having disposed within it the tapered insert shown in  FIG. 19 . 
         FIG. 21  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 13 . 
         FIG. 22  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 13 . 
         FIG. 23  illustrates an isolated sectional view of an alternative plunger assembly configured similarly to the assembly shown in  FIG. 13 , the convertible plunger&#39;s exterior surface being in an expanded state. 
         FIG. 23A  is the same embodiment and view illustrated in  FIG. 23 , except that the convertible plunger&#39;s exterior surface is in a constricted state. 
         FIG. 24  illustrates an isolated sectional view of an alternative plunger disposed within a syringe. 
         FIG. 25  illustrates an isolated sectional view of an alternative plunger disposed within a syringe. 
         FIG. 26  illustrates an isolated partial sectional view of an exemplary embodiment of a film coated convertible plunger. 
         FIG. 26A  illustrates an enlarged sectional view of the sidewall of the film coated convertible plunger of  FIG. 26 . 
         FIG. 27  illustrates an isolated partial sectional view of an exemplary embodiment of a cap covered convertible plunger. 
         FIG. 28  is a chart illustrating break loose force and glide force measured from plunger test samples similar to the embodiment of the film coated convertible plunger of  FIG. 26 . 
         FIG. 29  is a chart illustrating the effect of plunger compression on pressure drop for purposes of testing CCI. 
         FIG. 30  is a chart illustrating break loose force and glide force measured from plunger test samples similar to the embodiment of the film coated convertible plunger of  FIG. 26  on four different syringe embodiments. 
     
    
    
     The following reference characters are used in the drawing figures:
           10 ,  210  Plunger assembly     12 ,  212  Plunger     12   a - 12   i  Convertible plunger     14 ,  214  Plunger rod     16 ,  216  Interior shaft     16 ′ Tip     18 ,  218  Exterior shaft     20 ,  220  Distal end     22 ,  222  Proximal end     24 ,  224  Locking tab     25 ,  225  Tapered surface     26 ,  226  Actuator     28 ,  228  First end     30 ,  230  Second end     32 ,  232  First recess     34 ,  234  Second recess     36 ,  236  Inner portion     38 ,  238  Thread (of exterior shaft  18 ,  218 )     40 ,  240  Thread (of plunger  12 ,  212 )     42  Insert     44  Sleeve     45  Connector body     46  Outer portion     48  First cavity     48   a - g  Cavity     50  Second cavity     51  Storage Sealing Section     52  Rib of Storage Sealing Section     53  Liquid Sealing Section     54  Interior area     55  Rib of Liquid Sealing Section     56  Barrel     57  Valley     58  Sidewall     59  Product containing area     60  Inner surface     61  Proximal end (of barrel  56 )     62  Insert     63  Connector body     64  Sleeve     65  First section (of connector body  63 )     66  Cavity     67  Second section (of connector body  63 )     68  Shaft     69  Third section (of connector body  63 )     70  Outer surface (of insert  62 )     72  Recesses (of insert  62 )     74  Protrusions (of insert  62 )     76  Inner surface (of sleeve  64 )     77  Recesses (of connector body  63 )     78  Protrusions (of sleeve  64 )     79  Protrusions (of connector body  63 )     80  Recesses (of sleeve  64 )     82  Bottom portion (of outer surface  70 )     84  Lower portion (of inner surface  76 )     86  Exterior surface     88  Film coating     90  Sidewall (of plunger  12 )     92  Nose cone (of plunger  12 )     94  Film     96  Forming die     98  Forming plug     100  Base wall (of forming plug  98 )     102  Bottom portion (of forming die  96 )     104  Sidewall (of forming die  96 )     106  Coating preform     107  Mold     108  Mold cavity     110  Sidewall (of mold cavity  108 )     112  Bottom wall (of mold cavity  108 )     113  Mold core     114  Trim tool     152  Rib     194  Cap     300  Spherical mesh insert     302  Cylindrical insert     303  Central portion     304  Protrusion     304   a  Cavity     304   b  Protrusion     305  Opening     305   a,b  Opening     306  Insert     307  Wings     308  Porous material     309  Stopper     310  Sealed inner cavity     310   a  Compression material     311  Tip     312  Membrane     314  Juts     316  Valve     318  Sliding shaft     400  Coating set     402  Tie coating or layer     404  Barrier coating or layer     406  pH Protective coating or layer     500  Sample A     502  Sample B     504  Sample C     510  Set A     512  Set B     514  Set C     516  Bare COP syringe results     518  Trilayer syringe results     520  Bare glass syringe results     522  Glass syringe with PDMS results       

     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The present invention will now be described more fully with reference to the accompanying drawings, in which several embodiments are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth here. Rather, these embodiments are examples of the invention, which has the full scope indicated by the language of the claims. Like numbers refer to like elements throughout. 
     DEFINITIONS 
     In the context of the present invention, the following definitions and abbreviations are used: 
     For purposes of the present invention, an “organosilicon precursor” is a compound having at least one of the linkages: 
     
       
         
         
             
             
         
       
     
     which is a tetravalent silicon atom connected to an oxygen or nitrogen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom). A volatile organosilicon precursor, defined as such a precursor that can be supplied as a vapor in a PECVD apparatus, is an optional organosilicon precursor. Optionally, the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors. 
     Values of w, x, y, and z are applicable to the empirical composition Si w O x C y H z  throughout this specification. The values of w, x, y, and z used throughout this specification should be understood as ratios or an empirical formula (for example for a coating or layer), rather than as a limit on the number or type of atoms in a molecule. For example, octamethylcyclotetrasiloxane, which has the molecular composition Si 4 O 4 C 8 H 24 , can be described by the following empirical formula, arrived at by dividing each of w, x, y, and z in the molecular formula by 4, the largest common factor: Si 1 O 1 C 2 H 6 . The values of w, x, y, and z are also not limited to integers. For example, (acyclic) octamethyltrisiloxane, molecular composition Si 3 O 2 C 8 H 24 , is reducible to Si 1 O 0.67 C 2.67 H 8 . Also, although SiO x C y H z  is described as equivalent to SiO x C y , it is not necessary to show the presence of hydrogen in any proportion to show the presence of SiO x C y . 
     The term “barrel” refers to a medical barrel, as may be used, e.g., as part of a medical device for containing and dispensing liquid product, such as a syringe. 
     “Frictional resistance” can be static frictional resistance and/or kinetic frictional resistance. 
     The “plunger sliding force” (synonym to “glide force,” “maintenance force”, or F m , also used in this description) in the context of the present invention is the force required to maintain movement of a plunger tip in a syringe barrel, for example during aspiration or dispense. It can advantageously be determined using the ISO 7886-1:1993 test known in the art. A synonym for “plunger sliding force” often used in the art is “plunger force” or “pushing force”. 
     “Container closure integrity” or “CCI” refers to the ability of a container closure system, e.g., a plunger disposed in a prefilled syringe barrel, to provide protection and maintain efficacy and sterility during the shelf life of a sterile product contained in the container. 
     The “plunger breakout force” (synonym to “breakout force”, “break loose force”, “initiation force”, Fi, also used in this description) in the context of the present invention is the initial force required to move the plunger tip in a syringe, for example in a prefilled syringe. 
     Both “plunger sliding force” and “plunger breakout force” and methods for their measurement are described in more detail in subsequent parts of this description. These two forces can be expressed in N, lbs or kg and all three units are used herein. These units correlate as follows: 1N=0.102 kg=0.2248 lbs (pounds). 
     “Slidably” means that the plunger tip, closure, or other removable part is permitted to slide in a syringe barrel or other vessel. 
     The term “syringe” is broadly defined to include cartridges, injection “pens,” and other types of barrels or reservoirs adapted to be assembled with one or more other components to provide a functional syringe. “Syringe” is also broadly defined to include related articles such as auto-injectors, which provide a mechanism for dispensing the contents. 
     The term “outward radial pressure” refers to pressure applied or exerted in a direction outward from (or away from) the plunger&#39;s central axis. 
     Convertible Plungers and Film-Coated Plungers 
       FIGS. 1-2  illustrate a two-position plunger assembly  10  according to an embodiment of the present invention. The plunger assembly  10  may have a variety of different shapes and sizes. For example, according to an illustrated embodiment, the plunger assembly  10  may be approximately 79 millimeters long. The plunger assembly  10  includes a plunger  12  and a plunger rod  14 . The plunger rod  14  may include an interior shaft  16  and an exterior shaft  18 . The interior shaft  16  includes a distal end  20 , a proximal end  22 , and a locking tab  24 . According to certain embodiments, the distal end  20  of the interior shaft  16  may be configured to form an actuator  26  that, during use of the plunger assembly  10 , is to be pressed upon by a user, such as, for example, by the thumb of the user. The exterior shaft  18  may include a first end  28 , a second end  30 , a first recess  32 , a second recess  34 , and an inner portion  36 . According to certain embodiments, the first end  28  may be configured for a threaded engagement with the plunger  12 . For example, as shown, the first end  28  may include an external thread  38  that is configured to mate with an internal thread  40  of the plunger  12 . 
     At least a portion of the interior shaft  16  is configured for slideable displacement along the inner portion  36  of the exterior shaft  18 . Additionally, the locking tab  24  may protrude from at least a portion of the interior shaft  16 . In the illustrated embodiment, the locking tab  24  has a tapered surface  25  that may assist in controlling the direction and timing of the displacement of the interior shaft  16  along the inner portion  36  of the exterior shaft  18 . For example, at least  FIG. 2  illustrates the interior shaft  16  in a first position relative to the exterior shaft  18 , with the locking tab  24  protruding into at least a portion of the first recess  32  of the exterior shaft  18 . The orientation of the tapered surface  25  of the locking tab  32  allows, when sufficient force is exerted upon the actuator  26 , for the locking tab  32  to be at least temporarily compressed or deformed in size so that the locking tab  24  may at least temporarily enter into the inner portion  26  as the locking tab  25  is moved from the first recess  32  to the second recess  34 . However, in the absence of sufficient force, the locking tab  32  may remain in the first recess  32 , thereby maintaining the interior shaft  16  in the first position. 
     The distance that the locking tab  24  is to travel from the first recess  32  to the second recess  34 , and thus the distance the interior shaft  16  is displaced relative to the exterior shaft  18  when moving from the first position to the second position may vary for different plunger assemblies. For example, according to certain embodiments, the interior shaft  16  may be displaced approximately 3 to 5 millimeters. Additionally, as shown in  FIGS. 2 and 5 , according to certain embodiments, the proximal end  22  of the interior shaft  16  may or may not be housed in the interior portion  36  of the exterior shaft  18  when the interior shaft  16  is in the first position. 
     Further, the orientation and size of the tapered surface  25  of the locking tab  24  may provide the locking tab  24  with sufficient width to prevent the locking tab  24  from being pulled into the inner portion  36  in the general direction of the second end  30  of the exterior shaft  18 . Accordingly, when the locking tab  24  is in the second recess  34 , and thus the interior shaft  16  is in the second position, the orientation and size of the tapered surface  25  of the locking tab  24  may provide the locking tab  24  with sufficient width to resist the locking tab  24  from being pulled back into the first recess  32 . 
     As shown in at least  FIGS. 2-4 , the plunger  12  is configured to be received in an interior area  54  of a barrel  56  (e.g., of a syringe). The interior area  54  may be generally defined by a sidewall  58  of the barrel  56 , the sidewall  58  having an inner surface  60 . Additionally, the interior area  54  may include a product containing area  59  between the plunger  12  and the proximal end  61  of the barrel  56 . 
     According to certain embodiments, as best shown in  FIG. 3 , the plunger  12  includes an insert  42 , a sleeve  44 , and a connector body  45 . The connector body  45  may be operably connected to the sleeve  44 , such as, for example, through the use of over molding, a plastic weld, an adhesive, and/or a mechanical fastener, such as a screw, bolt, pin, or clamp, among other connections. As previously discussed, the connector body  45  may be configured to be connected to the exterior shaft  18 , such as, for example, by the threaded engagement of the internal thread  40  of the connector body  45  and the external thread  38  of the exterior shaft  18 . Additionally, according to certain embodiments, the connector body  45  may be molded from a relatively stiff and/or rigid material, such as, for example, polyethylene or polypropylene, among other materials. 
     The sleeve  44  may be configured to provide a first cavity  48  and a second cavity  50 . Additionally, the first and second cavities  48 ,  50  are in communication with each other and are configured to receive the movable insertion of the insert  42 . The outer portion  46  of the sleeve  44  generally comprises a nose cone  92  (generally facing the syringe contents), and a sidewall  90  (generally facing the sidewall  58  of the barrel  56 ). The term “nose cone”  92  refers to the syringe contents-facing surface of the plunger  12 , and may be of any suitable geometry (e.g., rounded, cone-shaped, flat, etc.). The sidewall  90  of the sleeve  44  includes a storage sealing section  51  comprising at least one rib  52  that is preferably generally adjacent to and/or aligned with at least a portion of the first cavity  48 . For example, as shown by at least  FIG. 3 , a single rib  52  of the storage sealing section  51  is generally adjacent to and/or aligned with the first cavity  48 . However, the number of ribs  52  of the storage sealing section  51  aligned with and/or adjacent to the first cavity  48  may vary. Further, according to certain embodiments, a rib  52  of the storage sealing section  51  may not be positioned adjacent to and/or aligned with the second cavity  50 . The sleeve  44  may be constructed from a thermoset rubber (e.g., butyl rubber) having good gas barrier properties, or a thermoplastic elastomer, among other materials. The purpose of the storage sealing section  51  is to provide CCI and optionally a barrier to one or more gases (e.g., oxygen) when the plunger  12  is in a “storage mode,” e.g., to seal the contents of a pre-filled syringe when in storage, prior to use. The gas barrier should effectively prevent ingress of gas(es) that may degrade the product contained within the syringe during the product&#39;s desired shelf life. The gas barrier should also effectively prevent egress of gas(es) that preferably remain within the product containing area  59  of the syringe. The particular gas(es) for which the storage sealing section  51  optionally provides a barrier when the plunger is in storage mode may vary depending on the product contained within the syringe. Optionally (in any embodiment), the gas barrier is an oxygen barrier. When the plunger  12  is converted from storage mode to dispensing mode, the seal initially provided by the storage sealing section  51  is either reduced or removed entirely (i.e., such that the storage sealing section  51  no longer physically contacts the sidewall  58  of the barrel  56 ). 
     The insert  42  may also be constructed from a variety of different products, including products that allow the insert to have a lower, similar, or higher rigidity than/to the sleeve  44 . Preferably, in any embodiment, the insert has a higher rigidity than the sleeve. Additionally, the insert  42  may have a variety of shapes and be generally configured to occupy at least one of the first and second cavities  48 ,  50 . According to the embodiment illustrated in  FIGS. 2-4 , the insert  42  has a generally spherical shape. Alternative insert embodiments and shapes are disclosed below. 
     The sleeve  44 , and particularly the rib  52  of the storage sealing section  51 , and the insert  42  are configured to provide a force that compresses the rib  52  against the sidewall  58  of a barrel  56 , as shown in  FIG. 4 . Such compression of the rib  52  of the storage sealing section against the sidewall  58  provides a seal, such as a compression seal in a “storage mode”, between the plunger  12  and the sidewall  58  that protects the sterility and/or integrity of injection product contained in the barrel  56 . A typical compression may be, e.g., less than 10% of the overall width or diameter of the rib  52  and/or sleeve  64  when the plunger  12 ′ is compressed to form a seal in the barrel  56 , optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. The compression is dependent on not only the geometric tolerances of the plunger and syringe barrel but also the material properties of the plunger (e.g., durometer of the rubber). Optionally, additional ribs  52  of the storage sealing section  51  may be included, which may increase the integrity of the seal and/or form separate seals between the plunger  12  and the sidewall  58  of the barrel  56 . 
     According to certain embodiments, the sleeve  44  and insert  42  are sized such that, when the plunger  12  is in the barrel  56  and the insert  42  is in the first cavity  48 , the insert  42  prevents or minimizes a reduction in the size of the first cavity  48 . Such minimizing or prevention of a reduction in size of the first cavity  48  may minimize the extent the size of the rib  52  of the storage sealing section  51 , which is generally adjacent and/or aligned to/with the first cavity  48 , may be reduced by engagement of the rib  52  with the sidewall  58  of the barrel  56 . According to such embodiment, the rib  52  may be sized such that, with the support of the insert  44  in the first cavity  48 , the rib  52  is large enough to be compressed between the sleeve  44  and the sidewall  58  to form the compression seal for storage mode of the plunger  12 . Further, according to certain embodiments, the insert  42  may be configured to limit the compression of the rib  52  and/or sleeve  44  such that the rib  52  and/or sleeve  44  is compressed less than 20% of the overall width of the sleeve  44  when the plunger  12  is being used to form a seal during storage mode in the barrel  56 . Optionally, the rib  52  and/or sleeve  44  are compressed less than 10% of the overall width or diameter of the rib  52  and/or sleeve  44  when the plunger  12  is compressed to form a seal in the barrel  56 , optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. 
     Alternatively, according to other embodiments, the insert  42  may be sized to expand the size of the first cavity  48  and rib  52  of the storage sealing section  51  so as to provide sufficient support to push or force the rib  52  against the sidewall  58  to form the compression seal during storage mode of the plunger  12 . 
     The plunger  12  may be positioned in the barrel  56  before or after the plunger  12  is connected to the exterior shaft  18 . When injection product in the syringe barrel, such as in the product containing area  59  of the barrel  56 , is to be dispensed from the barrel  56 , a user may depress the actuator  26  to displace the interior shaft  16  from the first position to the second position, as previously discussed. In the embodiment shown in  FIGS. 1-4 , as the interior shaft  16  is displaced to the second position, the proximal end  22  of the interior shaft  16  may exit the first end  28  of the exterior shaft  18  and enter into the plunger  12 . As the locking tab  24  is moved to the second recess  34 , the interior shaft  16  may push the insert  42  from the first cavity  48  to the second cavity  50 . 
     With the insert  42  in the second cavity  50 , the support and/or force that the insert  42  had been providing/exerting upon the rib  52  of the storage sealing section  51  is reduced and/or removed. Thus, under such circumstances, the force previously exerted by the rib  52  against the sidewall  58  of the barrel  56  is also at least reduced, or preferably removed (i.e., with no contact between the rib  52  of the sealing section  51  and the sidewall  58  of the barrel  56  when the plunger  12  is in a “dispensing mode.”). Additionally, according to certain embodiments, a rib  52  may not be generally adjacent to and/or aligned with the second cavity  50  of the sleeve  44  so that the presence of the insert  42  in the second cavity  50  is not supporting or pushing a different rib  52  against the sidewall  58 . Thus, with the force that had been exerted by the rib  52  against the sidewall  58  being removed or reduced by the displacement of the insert  42  to the second cavity  50 , the force needed to displace the plunger  12  along the barrel  56  is less than the force would have been had the insert  42  remained in the first cavity  48 . Thus, the force that had been exerted against the sidewall  58  by the plunger  12  is adjusted, and more specifically reduced, when the plunger  12  is to be displaced for dispensing of the injection product. Moreover, the extent of the force reduction is such that the injection product may be pushed completely forward out of the syringe against the back pressure caused by the viscosity of the injection product and/or the needle gauge. With the insert  42  in the second cavity  50  and the interior shaft  16  in the second position, the plunger assembly  10  may be displaced to reduce the size of the product containing area, and thereby dispense the injection product from the barrel  56 . 
     Additionally, according to certain embodiments, the plunger  12  may optionally be configured such that when the first cavity  48  is not occupied by the insert  42 , the rib  52  nonetheless maintains contact with the sidewall  58  of the barrel  56 . Moreover, under such conditions, the rib  52  may be configured to provide a wiper surface to assist in the removal of injection product from the barrel  56  as the plunger assembly  10  is displaced during administration/dispensing of the injection product. 
     Optionally, the outer portion  46  of the sleeve  44  may include a liquid sealing section  53 , preferably on the sidewall  90  of the sleeve  44 , optionally adjacent to, distal to or otherwise near to the nose cone  92 . The liquid sealing section  53  comprises at least one rib  55  of the liquid sealing section  53 . The purpose of the liquid sealing section  53  is to provide a liquid tight seal both when the plunger  12  is in a storage mode as explained above, and when the plunger is transitioned into a “dispensing mode,” i.e., when the storage sealing section  51  reduces or ceases compressive force against the barrel wall  58  so as to facilitate advancement of the plunger to dispense the contents of the syringe. Optionally, the liquid sealing section  53  may also provide CCI. Preferably, there is a valley  57  separating the storage sealing section  51  from the liquid sealing section  53 . 
       FIGS. 5-7  illustrate an alternative embodiment of the plunger assembly  10 , and in particular, an alternative plunger  12 ′. The plunger  12 ′ includes an insert  62 , a connector body  63 , and a sleeve  64 . As shown in  FIG. 5 , according to certain embodiments, the sleeve  64  includes a cavity  66  configured to receive placement of the proximal end  22  of the interior shaft  16 . The insert  62  may also include a relatively rigid shaft  68  that assists in the displacement of the insert  62  and/or deformation of the plunger  12 ′, as discussed below. 
     According to certain embodiments, the connector body  63  may be molded from a relatively stiff and/or rigid material, such as, for example, polyethylene or polypropylene. Additionally, the connector body  63  may have a first section  65 , a second section  67 , and a third section  69 . The first section  65  of the connector body  63  is configured for a connectable engagement with the exterior shaft  18 . For example, as shown by at least  FIG. 7 , the first section  65  may include an internal thread  40  that mates with an external thread  38  of the exterior shaft  18 . 
     According to certain embodiments, the second section  67  of the connector body  63  may provide an internal structure in the plunger  12 ′ that minimizes and/or prevents a reduction in the size, such as the width (as indicated by “W” in  FIG. 7 ) of the sleeve  64  when the plunger  12 ′ is inserted into the barrel  56 . According to such an embodiment, the sleeve  64  may be sized such that, when the plunger  12 ′ is positioned in the barrel  56 , the sleeve  64  is compressed, with the support of the second section  67 , between the sidewall  58  of the barrel  56  and the second section  67  of the connector body  63 . Such compression of the sleeve  64  may result in the formation of a seal, such as, for example, a compression seal, between the plunger  12 ′ and the barrel  56  that may be used to maintain the sterility and/or integrity of an injection product stored in the barrel  56 . In addition to the second section  67  of the connector body  63 , according to certain embodiments, the insert  62  may also be configured to provide support to the sleeve  64  and/or connector body  63  when the plunger  12 ′ is inserted into a barrel  56 . 
     Further, according to certain embodiments, one or more ribs  52  of a storage sealing section  51  may extend from the sleeve  64  and be compressed against the sidewall  58  of the barrel  56  to provide CCI during when the plunger is in a “storage mode,” e.g., to seal the contents of a pre-filled syringe when in storage, prior to use. The plunger  12 ′ may further include a liquid sealing section  53  comprising at least one rib  55  of the liquid sealing section  53 . The purpose of the liquid sealing section  53  is to provide a liquid tight seal both when the plunger  12  is in a storage mode as explained above, and when the plunger is transitioned into a “dispensing mode,” i.e., when the storage sealing section  51  reduces or ceases compressive force or radial pressure against the barrel wall  58  so as to facilitate advancement of the plunger to dispense of the contents of the syringe. Preferably, there is a valley  57  separating the storage sealing section  51  from the liquid sealing section  53 . 
     Alternatively, according to optional embodiments, each rib  52 , 55  may form a separate seal when compressed against the sidewall  58  of the barrel  56 . For example, in the embodiment illustrated in  FIGS. 5-7 , the sleeve  64  includes two ribs  52 , 55  that may be used to form a seal(s) between the sidewall  58  of the barrel  56  and the sleeve  64 . Further, according to certain embodiments, the second section  67  and/or insert  42  may be configured to limit the compression of the rib  52  and/or sleeve  64  such that the rib  52  and/or sleeve  64  are not compressed more than 20% of the overall width or diameter of the rib  52  and/or sleeve  64  when the plunger  12 ′ is compressed to form a seal in the barrel  56 . Optionally, the rib  52  and/or sleeve  64  are compressed less than 10% of the overall width or diameter of the rib  52  and/or sleeve  64  when the plunger  12 ′ is compressed to form a seal in the barrel  56 , optionally less than 9%, optionally less than 8%, optionally less than 7%, optionally less than 6%, optionally less than 5%, optionally less than 4%, optionally less than 3%, optionally less than 2%, optionally from 3% to 7%, optionally, from 3% to 6%, optionally from 4% to 6%, optionally from 4.5% to 5.5%, optionally from 4.5% to 5.5%, optionally about 4.8%. 
     The third section  69  of the connector body  63  may provide a surface upon which the insert  62  may exert a force against to elongate the length (as indicated by the “L” direction in  FIG. 7 ), and thereby reduce the width (“W”) of, the plunger  12 ′ when injection product is to be dispensed from the barrel  56 , as discussed below. 
     According to certain embodiments, the outer surface  70  of the insert  62 , the second section of the connector body  53 , and the inner surface  76  of the sleeve  64  may have a plurality of recesses  72 ,  77 ,  80  and protrusions  74 ,  78 ,  79  as shown in  FIG. 7 . Moreover, shape provided by the recesses  72  and protrusions  74  of the insert  62  may be generally be followed by the recesses  77  and protrusions  79  of the connector body  63 , which are generally followed by the recesses  80  and protrusions  78  of the sleeve  64 . Such recesses  72 ,  77 ,  80  and protrusions  74 ,  78 ,  79  may assist in maintaining the insert  62  in a sealing position in the barrel  56 . Moreover, as shown for example in  FIG. 7 , the recesses  72 ,  77 ,  80  and protrusions  74 ,  78 ,  79  may provide obstacles that prevent the premature displacement of the insert  62 . Such an accordion shaped configuration may also assist in the elongation of the plunger  12 ′, and in particular the second section  67  of the connector body  53  and the sleeve  64  when the plunger  12 ′ is to be displaced in the barrel  56  from a deactivated position, as shown in  FIG. 7 , to an activated position that elongates the length of the sleeve  64 . 
     More specifically, when the injection product is to be dispensed from the barrel  56 , the interior shaft  16  may be displaced from the first position, as shown in  FIG. 5 , to a second position, as previously discussed. As the interior shaft  16  is displaced toward the second position, the proximal end  22  of the interior shaft  16  exerts a pushing force upon an insert  62 , such as, for example, upon the shaft  68  of the insert  62 . As the interior shaft  16  exerts a force upon the insert  62 , the insert  62  is displaced within the sleeve  64  generally in the direction of the proximal end  61  of the barrel  56 , and thus at least a portion of the outer surface  70  of the insert  62  pushes against the third section  69  of the connector body  63 . As the insert  62  is displaced and presses upon the third section  69 , the second section  67  of the connector body  63  is elongated, thereby changing the prior accordion shape of the second section  67  to a generally straighter or flatter configuration. Additionally, the sleeve  64  is also elongated by this displacement of the insert  62  in the sleeve  64 , resulting in the width (as indicated by the “W” direction in  FIG. 7 ) of the sleeve  64  and thus plunger  12 ′ being reduced. The reduction in the width of the sleeve  64 /plunger  12 ′ results in a reduction in the compressive force that had been used to form the seal between the plunger  12 ′ and the sidewall  58  of the barrel  56 . In other words, slight axial stretching of the sleeve  64  (optionally achieved by displacing the insert  62  from a deactivated position to an activated position) in turn reduces the width of the sleeve  64  and plunger  12 ′, thus resulting in reduction in the compressive force that had been used to form the seal between the plunger  12 ′ and the sidewall  58  of the barrel  56 . 
     Thus, with the width of the sleeve  64 /plunger  12 ′ reduced, the force necessary to displace the plunger  12 ′ in the barrel  56  may also be reduced. Further, as previously discussed, as the interior shaft  16  may be locked in the second position by the locking tab  24 , the sleeve  64  may maintain the elongated shape while the injection product is dispensed from the barrel  56 . 
     Alternatively, two-position plunger assemblies may be desired for some applications wherein the interior shaft is displaced in a direction away from the plunger, rather than towards the plunger, from a first position to a second position relative to the exterior shaft. Such a configuration may be desired where it is preferable not to apply downward pressure on the plunger until it is time to advance the plunger into the barrel to dispense the syringe&#39;s contents. For example,  FIG. 13  shows a two-position plunger assembly  210  that functions in essentially the same way as the assembly  10  shown in  FIG. 2 , except that the assembly  210  permits a user to move from a first position to a second position by displacing the interior shaft  216  away from the plunger  212 , rather than towards the plunger  212 . The plunger  12  of the assembly  210  of  FIG. 13 , as shown, includes a first cavity and second cavity with a spherical insert disposed in the first cavity (e.g., as the plunger  12  of  FIG. 3 ). It should be understood that the plunger embodiment shown is for illustrative purposes only, and that various plunger configurations, including configurations discussed below, may optionally be used as part of the plunger assembly  210  of  FIG. 13 . 
     The plunger assembly  210  includes a plunger  212  and a plunger rod  214 . The plunger rod  214  may include an interior shaft  216  and an exterior shaft  218 . The interior shaft  216  includes a distal end  220 , a proximal end  222 , and a locking tab  224 . According to certain embodiments, the distal end  220  of the interior shaft  216  may be configured to form an actuator  226  that, during use of the plunger assembly  210 , is to be pressed upon by a user, such as, for example, by the thumb of the user. The exterior shaft  218  may include a first end  228 , a second end  230 , a first recess  232 , a second recess  234 , and an inner portion  236 . According to certain embodiments, the first end  228  may be configured for a threaded engagement with the plunger  212 . For example, as shown, the first end  228  may include an external thread  238  that is configured to mate with an internal thread  240  of the plunger  212 . 
       FIG. 13  illustrates the interior shaft  216  in a first position relative to the exterior shaft  218 , with the locking tab  224  protruding into at least a portion of the first recess  232  of the exterior shaft  218 . The orientation of the tapered surface  225  of the locking tab  232  allows, when sufficient force is exerted upon the actuator  226 , for the locking tab  232  to be at least temporarily compressed or deformed in size so that the locking tab  224  may at least temporarily enter into the inner portion  226  as the locking tab  225  is moved from the first recess  232  to the second recess  234 . However, in the absence of sufficient force, the locking tab  232  may remain in the first recess  232 , thereby maintaining the interior shaft  216  in the first position. 
     The orientation and size of the tapered surface  225  of the locking tab  224  may provide the locking tab  224  with sufficient width to prevent the locking tab  224  from being pushed into the inner portion  236  in the general direction of the first end  228  of the exterior shaft  218 . Accordingly, when the locking tab  224  is in the second recess  234 , and thus the interior shaft  216  is in the second position, the orientation and size of the tapered surface  225  of the locking tab  224  may provide the locking tab  224  with sufficient width to resist the locking tab  224  from being pushed back into the first recess  232 . As such, pressing upon the actuator  226  would cause the entire plunger assembly  210  to move together as a single unit, e.g., within a pre-filled syringe barrel to dispense contents held therein. 
     In one aspect, the invention is directed broadly to convertible plungers and assemblies incorporating the same. Convertible plungers according to the present invention are adapted to provide sufficient compressive force against the sidewall of a pre-filled syringe or cartridge barrel to effectively seal and preserve the shelf-life of the contents of the barrel during storage. When a convertible plunger provides container closure integrity (CCI) adequate to effectively seal and preserve the shelf-life of the contents of the barrel during storage, the plunger (or at least a portion of its exterior surface) may alternatively be characterized as being in an expanded state or storage mode. The expanded state or storage mode may be a product of, for example, an expanded outer diameter or profile of at least a portion of the syringe barrel-contacting surface of the plunger and/or the normal force that the plunger exerts on the inner wall of the syringe barrel in which it is disposed. The convertible plunger (or at least a portion of its exterior surface) is reducible to what may be alternatively be characterized as a constricted state or a dispensing mode, wherein the compressive force against the sidewall of the barrel is reduced, allowing a user to more easily advance the plunger in the barrel and thus dispense the contents of the syringe or cartridge. The constricted state or dispensing mode may be a product of, for example, a reduced outer diameter (relative to that of the expanded state) of at least a portion of the syringe barrel-contacting surface of the plunger and/or reduced normal force against the inner wall of the syringe barrel exerted by the plunger. Other examples of what constitutes an expanded state versus constricted state are discussed below. 
     Accordingly, in one aspect, the invention is a convertible plunger comprising an internal portion and a generally cylindrical exterior surface. As used herein, a “generally cylindrical” exterior plunger surface may include minor interruptions or variations in geometry (e.g., due to ribs, valleys, etc.) to the otherwise cylindrical shape of the plunger. For example, a generally cylindrical exterior surface of the plunger may include one or more annular ribs. At least a portion of the exterior surface is maintained in an initial expanded state by a property of the internal portion. The expanded state is reducible to a constricted state by an operation that is applied to the internal portion of the plunger to alter the property. The plunger may be reduced from the expanded state to the constricted state utilizing a variety of methods, which may include two-position configurations, e.g., as described above, or not. As used herein, “expanded state” and “constricted state” may refer to comparative dimensional measurements (e.g., expanded state being wider than constricted state) and/or comparative resistance to inward compression of the plunger (the “expanded state” being more resistant to inward compression and the “constricted state” being less resistant to inward compression) and/or comparative outward radial pressure exerted by at least a portion of the plunger&#39;s exterior surface (the plunger&#39;s exterior surface in the “expanded state” exerting more outward radial pressure and in the “constricted state” exerting less outward radial pressure). 
     For example, the property that maintains at least a portion of the exterior surface of the plunger in the expanded state may include, e.g., gas pressure, mechanically produced outward radial pressure or outward radial pressure produced by a liquid or gelatinous compression material disposed within one or more cavities within the plunger. Where the property is gas pressure, the property may be altered by releasing at least some of the pressure from the cavity or cavities. Where the property is mechanically produced outward radial pressure, such as that produced by a solid compression material, the property may be altered by, e.g., collapsing, crushing, deforming, breaking, or otherwise altering the structure of the solid compression material in whole or in part, or displacing the solid compression material, so as to reduce the outward radial pressure. Where the property is outward radial pressure produced by a liquid or gelatinous material, the property may be altered by removing at least some of the material from the cavity. 
     Optionally, the convertible plunger may be a component of a plunger assembly, for example, any of the plunger assemblies described above. The assembly comprises a plunger rod having an exterior shaft and an interior shaft. The exterior shaft has an inner portion configured for the slideable insertion of at least a portion of the interior shaft and the interior shaft is configured to be displaced from a first position to a second position relative to the exterior shaft. The assembly further comprises the convertible plunger operably connected to the plunger rod, the convertible plunger configured to receive the insertion of at least a portion of the interior shaft. Depending on the application, the interior shaft may be displaceable from a first position to a second position in a direction towards the plunger (e.g., using the assemblies shown in  FIG. 2 or 5 ), or in a direction away from the plunger (e.g., using the assembly shown in  FIG. 13 ). 
     Referring to  FIG. 14 , there is shown a substantially spherical mesh insert  300 . As shown in  FIG. 15 , the spherical mesh insert  300  may be disposed within a cavity  48   a  of a convertible plunger  12   a . The mesh insert is configured to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger  12   a  in an initial expanded state. When the plunger  12   a  is a component in a plunger assembly such as the assembly  10  shown in  FIG. 2 , displacement of the interior shaft  16  relative to the exterior shaft  18  towards the plunger  12   a  causes the interior shaft  16  to contact and press into the spherical mesh insert  300 . When sufficient pressure is applied against the spherical mesh insert  300 , its structural integrity is compromised, causing it to collapse or deform. This reduces outward radial pressure in the plunger  12   a , thereby reducing at least a portion of the exterior surface of the plunger  12   a  to a constricted state. Once the exterior surface of the plunger  12   e  is in a constricted state, the plunger rod  214 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. The spherical mesh insert  300  may be made, e.g., from metal or plastic. A skilled artisan would readily recognize that the invention may be implemented using solid materials other than mesh inserts, for example other collapsible or breakable materials and configurations. 
     For example, referring to  FIG. 16 , there is shown a substantially cylindrical insert  302 . The cylindrical insert  302  may be in the form of a collapsible mesh, for example. Alternatively, the cylindrical insert  302  may be a solid or substantially solid compression material, e.g., a polymer, which is mechanically less resistant to axially applied pressure than to inward radial pressure. While a substantially cylindrical geometry is preferred for this type of insert, it is contemplated that other geometries which are inwardly collapsible or deformable, upon application of axial pressure, may be utilized as well. The cylindrical insert  302  includes a central portion  303 . When sufficient pressure is applied to the central portion  303 , the insert  302  collapses inward (towards the central axis). Prior to the inward collapse of the insert  302 , the insert  302  has a first diameter D 1 . After the inward collapse of the insert  302 , the insert  302  is reduced to a constricted second diameter D 2 , as shown in  FIG. 16A . 
     Referring to  FIG. 17 , the cylindrical insert  302  may be disposed within a cavity  48   b  of a convertible plunger  12   b . The insert  302  is configured to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger  12   b  in an initial expanded state. When the plunger  12   b  is a component in a plunger assembly such as the assembly  10  shown in  FIG. 2 , displacement of the interior shaft  16  relative to the exterior shaft  18  towards the plunger  12   b  causes a narrow tip  16 ′ on the interior shaft  16  to contact and press into the central portion  303  of the insert  302 . When sufficient pressure is applied against the central portion  303 , the structural integrity of the insert  302  is compromised, causing it to collapse or deform inward. This reduces outward radial pressure in the plunger  12   b , causing at least a portion of the exterior surface of the plunger  12   b  to be reduced to a constricted state. Once the exterior surface of the plunger  12   b  is in a constricted state, the plunger rod  14 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring to  FIG. 18 , there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly  210  shown in  FIG. 13 . This embodiment may include a plunger  12   c  secured to the exterior shaft  218  and an interior shaft  216  axially displaceable relative to the exterior shaft  218 . The plunger  12   c  has a thin, substantially cylindrical cavity  48   c  along the central axis of the plunger  12   c , with an opening  305  at the top of the plunger  12   c . Extending axially from the proximal end  222  of the interior shaft  216  is a thin, substantially cylindrical protrusion  304  having complementary or mating geometry with the cavity  48   c  in the plunger  12   c . At least a portion of the exterior surface of the plunger  12   c  is maintained in an initial expanded state when the cavity  48   c  is mated with or occupied by the protrusion  304 . In other words, the protrusion  304  provides mechanically produced outward radial pressure to maintain the exterior surface of the plunger  12   c  in an expanded state. 
     The protrusion  304  is removable from the cavity  48   c  by displacing the interior shaft  216  in a direction away from the plunger  12   c  to retract the protrusion  304  out of the opening  305  until the protrusion  304  no longer occupies the cavity  48   c , and thus no longer provides the mechanically produced outward radial pressure within the plunger  12   c . In this position, the empty cavity  48   c  does not resist inward compression as well as it did when it was occupied by the protrusion  304  and thus the exterior surface of the plunger  12   c  is reduced to a constricted state. Optionally, the protrusion  304  and/or the cavity  48   c  are lubricated, e.g., with silicone oil or a lubricious film coating, such as those described below, to facilitate easy removal of the protrusion  304  from the cavity  48   c . Once the exterior surface of the plunger  12   c  is in a constricted state, the plunger rod  214 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring to  FIG. 19 , there is shown an anchoring device, or tapered insert  306  configured much like a plaster anchor. Plaster anchors are hollow, typically tapered tubular members that are adapted to expand upon receipt of a screw or another narrow protrusion. A plaster anchor may revert, at least in part, to its initial unexpanded state upon removal of the screw or other narrow protrusion. Likewise, the insert  306 , which may comprise one or more axially tapered wings  307  about its periphery and a narrow axial cavity  304   a , is in an expanded state when a protrusion  304   b  is inserted in the cavity  304   a . The insert  306  is reduced to a less expanded state upon removal of the protrusion  304   b  from the cavity  304   a . Although the embodiment of the insert  306  as shown is tapered, non-tapered configurations, e.g., with substantially parallel wings or sides, are within the scope of the invention. 
     Referring to  FIG. 20 , there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly  210  shown in  FIG. 13 . This embodiment may include a plunger  12   d  secured to the exterior shaft  218  and an interior shaft  216  axially displaceable relative to the exterior shaft  218 . The plunger  12   d  optionally has a substantially tapered cavity  48   d  along the central axis of the plunger  12   d , with an opening  305   a  at the top of the plunger  12   d . The insert  306  is disposed within the cavity  48   d , and may be integral with the plunger  12   d  (e.g., molded within the plunger) or a separate component inserted within the plunger cavity  48   d . Extending axially from the proximal end  222  of the interior shaft  216  is the thin, substantially cylindrical protrusion  304   b  having complementary or mating geometry with the cavity  304   a  in the insert  306 . At least a portion of the exterior surface of the plunger  12   d  is maintained in an initial expanded state when the cavity  304   a  is mated with or occupied by the protrusion  304   b . In other words, the protrusion  304   b  expands the wings  307  of the insert so as to provide mechanically produced outward radial pressure to maintain the exterior surface of the plunger  12   d  in an expanded state. The protrusion  304   b  is removable from the cavity  304   a  by displacing the interior shaft  216  in a direction away from the plunger  12   d  to retract the protrusion  304   b  out of the opening  305   a  until the protrusion  304   b  no longer occupies the cavity  304   a . Once the protrusion  304   b  has been removed from the cavity  304   a , the wings  307  slightly retract inward towards the insert&#39;s central axis, thereby reducing outward radial pressure within the plunger  12   d , thus permitting the exterior surface of the plunger  12   d  to be reduced to a constricted state. Once the exterior surface of the plunger  12   d  is in a constricted state, the plunger rod  214 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     The protrusion  304   b  may optionally be removed from the cavity  304   a  by pulling the interior shaft  216  from a first position to a second position, substantially as described above with respect to the assembly  210  shown in  FIG. 13 . Alternatively, the internal shaft  216  may be rotatable in relation to the external shaft  218 , or vice versa. With such a configuration, the protrusion  304   b  may be threaded and mated with complementary threads within the cavity  304   a . To remove the insert  304   b  from the cavity  304   a , a user may rotate the internal shaft  216  relative to the external shaft  218  (or vice versa), thereby displacing the internal shaft  216  from a first position (wherein the insert  304   b  occupies the cavity  304   a ) to a second position (wherein the insert  304   b  is removed from the cavity  304   b ). 
     Referring now to  FIG. 21 , there is shown an alternative embodiment of a plunger assembly utilizing the basic configuration of the assembly  210  shown in  FIG. 13 . This embodiment may include a plunger  12   e  secured to the exterior shaft  218  and an interior shaft  216  axially displaceable relative to the exterior shaft  218 . Part of the internal portion of the plunger  12   e  comprises a porous material  308 , such as a foam rubber. Alternatively, part of the internal portion of the plunger  12   e  comprises empty space. The plunger  12   e  further includes one or more openings  305   b  in the top thereof, providing a conduit to the porous material  308  (or empty space, as the case may be). The proximal end of the interior shaft  216  includes a stopper  309 , optionally made from a rubber or a polymer. The stopper  309  provides an air-tight seal between the one or more openings  305   b  and the inner portion  236  of the exterior shaft  218 . Accordingly, when the interior shaft  216  is displaced away from the plunger  12   e , e.g., from a first position to a second position, the stopper effectively sucks air from the porous material  308  (or empty space) creating therein at least a partial vacuum. This in turn causes the porous material  308  (or empty space) to collapse, thus reducing at least part of the exterior surface of the plunger  12   e  from an expanded state to a constricted state. Once the exterior surface of the plunger  12   e  is in a constricted state, the plunger rod  214 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring now to  FIG. 22 , there is shown a convertible plunger  12   f  having a sealed inner cavity  310  and/or a sealed insert comprising a gaseous, gelatinous or liquid compression material  310   a . The sealed inner cavity  310  and/or sealed insert comprises an inner surface or membrane  312  which effectively seals the compression material  310   a  within the insert. The compression material  310   a  is configured to provide outward radial pressure to maintain at least a portion of the exterior surface of the plunger  12   f  in an initial expanded state. When the plunger  12   f  is a component in a plunger assembly such as the assembly  10  shown in  FIG. 2 , the proximal end of the interior shaft  16  includes a substantially sharp tip  311  extending axially therefrom. Displacement of the interior shaft  16  relative to the exterior shaft  18  towards the plunger  12   f  causes the tip  311  to contact and press into the top of the plunger  12   f . When sufficient pressure is applied against the top of the plunger  12   f , the tip  311  causes the membrane  312  to be punctured, thus enabling the egress of at least some of the compression material  310   a  from the cavity  310 . This reduces outward radial pressure in the plunger  12   f , thereby reducing at least a portion of the exterior surface of the plunger  12   f  to a constricted state. Once the exterior surface of the plunger  12   f  is in a constricted state, the plunger rod  14 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring to  FIG. 23 , there is shown an alternative embodiment of a plunger assembly utilizing, e.g., the basic configuration of the assembly  210  shown in  FIG. 13 . This embodiment may include a convertible plunger  12   g  secured to the exterior shaft  218  and an interior shaft  216  axially displaceable relative to the exterior shaft  218 . The plunger  12   g  has a cavity  48   e  within the internal portion thereof. Extending from the end of the proximal end of the interior shaft  216  and into the cavity  48   e  are at least two opposing juts  314 . Optionally three to eight (or even more) juts  314  may be used. When the interior shaft  216  is in a first position, the juts  314  press into the interior surface of the cavity  48   e , thereby providing mechanically produced outward radial pressure to maintain the exterior surface of the plunger  12   g  in an expanded state. As shown in  FIG. 23A , when the interior shaft  216  is displaced in a direction away from the plunger  12   g  and into a second position relative to the exterior shaft  218 , the juts  314  retract inwardly towards the central axis of the interior shaft  216 . In so doing, the juts  314  no longer contact the interior surface of the cavity  48   e  and thus no longer provide the mechanically produced outward radial pressure within the plunger  12   c . In this position, the juts  314  do not support the cavity  408   e  in resisting inward compression and thus the exterior surface of the plunger  12   g  is reduced to a constricted state. Once the exterior surface of the plunger  12   g  is in a constricted state, the plunger rod  214 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring to  FIG. 24 , there is shown a convertible plunger  12   h  in an expanded or storage state, disposed within a syringe barrel. The plunger  12   h  includes an internal portion having a cavity  48   f  charged with gas, e.g., nitrogen, carbon dioxide, air or butane, for example. The gas pressure within the cavity  48   f  should be above atmospheric pressure, so as to maintain at least a portion of the external surface of the plunger in an initial expanded state. The cavity  48   f  may include a valve  316  which maintains the gas pressure within the cavity  48   f , but is operable to be triggered to release the pressure. The valve may be triggered, for example, by actuating the interior shaft  16  of the plunger rod, e.g., substantially as discussed above with respect to the assembly shown in  FIG. 2 . When the valve is released, the gas pressure within the cavity  48   f  is reduced, e.g., to atmospheric pressure. In this way, the plunger  12   h  effectively deflates (however insubstantially) thus reducing the profile of the exterior surface from the expanded state to a constricted state. Once the exterior surface of the plunger  12   h  is in a constricted state, the plunger rod  14 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Referring to  FIG. 25 , there is shown a convertible plunger  12   i  disposed within a syringe barrel. The plunger  12   i  includes an internal portion having an axial cavity  48   g  with annular grooves  322  axially spaced apart from one another. The plunger  12   i  is a component of an assembly having a sliding shaft  318  that is displaceable along its axis. The sliding shaft  318  includes annular rings  320  axially spaced apart from one another. The rings  320  are adapted to mate with the grooves  322 . In a first position, shown in  FIG. 25 , the rings  320  do not occupy the grooves  322 , but instead press against the interior surface of the cavity, providing outward radial pressure that maintains adjacent ribs  152  of the plunger  12   i  in an expanded state. When the sliding shaft  318  is displaced further into the plunger  12   i , the rings  320  mate with respective grooves  322  in a second position. In this second position, the outward radial pressure behind the ribs  152  is reduced, thus reducing the exterior surface of the plunger  12   g  to a constricted state. Once the exterior surface of the plunger  12   i  is in a constricted state, the plunger rod  14 , as e.g. a component of a prefilled syringe, is ready to be actuated to dispense the contents of the syringe. 
     Film Coatings and Molded Caps 
     In another aspect, the invention is directed to novel film coatings applied to plungers, e.g., any of the plungers described herein whether convertible or not. It should be understood that films and film coatings, as shown in drawing figures ( FIGS. 8-12, 26 and 26A ), are depicted as having exaggerated thicknesses, for purposes of clarity only. The films and film coatings in reality would optionally be much thinner (e.g., under 100 micrometers) than as depicted in the relevant figures. 
     For example,  FIG. 8  illustrates a cross sectional view of a film coated plunger, and more specifically, a plunger  12 ″ having at least one rib  152 , and more specifically three ribs  152 , as well as a film coating  88  on an exterior surface  86  of the plunger  12 ″. According to certain embodiments, the sidewall  90  of the plunger  12 ″ may be coated in a material that minimizes friction between the plunger  12 ″ and the sidewall  58  of the barrel  56  as the plunger  12 ″ is displaced in the barrel  56  during dispensing of the injection product. Additionally, according to certain embodiments, the nose cone  92  of the plunger  12 ″ may be coated in a material that isolates the plunger  12 ″, and more specifically the material of the plunger  12 ″ and any contaminants thereon, from the injection product contained in product containing area  59  of the barrel  56 . Additionally, according to certain embodiments, the film coating  88  may have different thicknesses at different portions of the exterior surface  86  of the plunger  12 ″, such as, for example, the nose cone  92  having a layer of the film coating  88  that is thicker than the layer of the film coating  88  along the sidewall  90 . For example, according to certain embodiments the film coating  88  about the nose cone  92  may have a thickness of approximately 50 micrometer (μm), while the thickness of the film coating  88  along the sidewall may be approximately 25-35 micrometer (μm). Such differences in coating thicknesses may limit interference the film coating  88  may provide to the ability of the plunger  12 ″ to assert a compressive force against the sidewall  58  of the barrel  56  while also providing a sufficiently thick barrier between the material of the plunger  12 ″ and the injection product stored in the product containing area  59 . Additionally, according to other embodiments, the film coating  88  may be applied to the nose cone  92  but not the sidewall  90 , or vice versa. 
     A variety of different materials may be employed for the film coating  88 , such as, for example, an inert fluoropolymer, including, fluorinated ethylene propylene (FEP), ethylene tetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE), and perfluoroalkoxy (PFA), among other coatings. Additionally, according to certain embodiments, the material used for the film coating  88  may not be an expanded fluoropolymer. Further, according to certain embodiments, additives may be added to the material for the film coating  88 , such as additives that may improve the adhesion of the film coating  88  to the plunger  12 ″ and/or decrease the friction between the plunger  12 ″ and the sidewall  58  of the barrel. Additionally, according to certain embodiments, an adhesion promoting coating or process may be employed, such as, for example, a corona treatment. 
     For some applications, it may be desirable to coextrude different materials to form the film. For example, coextruded film combinations may include a cyclic olefin copolymer (COC) with Aclar, Polyethylene (PE) with Aclar and FEP with PE, among other combinations. 
     For example, according to certain embodiments, a lubricity additive, such as a poly(tetrafluoroethylene) (PTFE) or Teflon® powder may be utilized with a thermoformed film to improve the lubricity of the film coating  88 . For example, according to certain embodiments, the additive, such as the PTFE, may be applied and/or pressed into the film that is going to be used for the film coating  88  of the plunger  12 ″. According to certain embodiments, an additive such as PTFE may only be applied to the side of the film for which the additive will have an application, such the side of the film that will be in contact with the sidewall if the additive is to reduce friction between the plunger  12 ″ and the sidewall  58  of the barrel  56 , or a side of the film that will assist in adhering the film to the plunger  12 ″. Further, according to certain embodiments, the additive may be added to the film before the film is produce in the film form that is applied to the plunger  12 ″. 
     The film coating  88  may be applied to the plunger  12 ″, or a portion of the plunger  12 ″, in a variety of different manners. For example, referencing  FIG. 9 , the film coating  88  may, prior to being applied to the plunger  12 ′,′ be in the form of a film  94  (with or without the above discussed additives), such as a film of a thermoformed FEP or other thermoformable fluoropolymer, that is placed over one or more forming dies  96 . As shown, heat may be applied to at least a portion of the film  94  to assist in molding the film  94  into the desired shape of the forming die  96 . However, in the present example, the sidewall  90  of the plunger  12 ″ may be coated with a thinner layer of film coating  88  than the layer covering the nose cone  92 . This differential thickness is obtainable in part because of the different degree of drawing of the film  94  between the sidewall  90  and the nose cone  92 . Optionally, however, this differential thickness can be increased by providing that at least the portion of the forming plug  98  that is to contact the film  94 , such as, for example a base wall  100 , may be relatively cool. According to certain embodiments, the temperature of the cooled forming plug  98  and/or base wall  100  of the forming plug  98  may depend on the material of the film  94 . For example, according to certain embodiments, the cooled portion of the forming plug  98  may have a temperature that is cooled to approximately 25-50 degrees Celsius lower than the melt temperature of the film  94 . By maintaining the forming plug  98  at a relatively lower, or cool, temperature, the stretching of the film  94  that may occur as the forming plug  98  presses a portion of the film  94  into the forming die  96  may occur to a greater extent at the portion of the film  94  that will eventually be along the sidewall  90  of the plunger  12 ″. Moreover, with respect to the forming die  96 , as shown for example in  FIG. 10 , by maintaining the forming plug  98  at a relatively low or cool temperature, the forming die and plug  96 ,  98  may be used to form a coating preform  106  of the film coating  88  in which the portion of the film  94  that was pressed into a bottom portion  102  of the forming die  96  remains thicker in relation to the portion of the film  94  that is along the sidewall  104  of the forming die  96 . 
     According to certain embodiments, multiple positions of the forming plug  98  and forming die  96  are arranged based on mold cavitation. Thus, a plurality of coating preforms  106  of the coatings  88  may be maintained on a single piece, or web, of film  94 . Thus, each coating preform  106  of the film coating  88  on the film  94  may be maintained in position on the film  94 . The coating preforms  106  the may be transported together on the film  94  through the entire process by indexing at each step. However, according to other embodiments, rather than transporting the coating preforms  106  together via the coating preforms  106  being connected to the film  94 , the coating preforms  106  may be removed from the film prior to other operations, such as, for example, prior to the coating preform  106  being placed into a mold cavity  108 , as discussed below. 
     Optionally, a fluoropolymer cap may be formed and inserted into the mold after the film material has been inserted into the mold and before the plunger material is injected into the mold. Thus, in the final product, the plunger may comprise a plunger material, a fluoropolymer cap disposed on the tip of the plunger material and a film covering the cap and the plunger material. The cap may be made from fluoropolymers such as, for example, high density polyethylene (HDPE), low density polyethylene (LDPE), or PTFE, among others. 
     Optionally, PTFE powder may be embedded on the surface of the plunger material. This may be achieved, for example, by coating the mold cavity with PTFE powder and injecting the plunger material into the mold to form the plunger. The PTFE would provide lubricity needed for inserting and operating the plunger in a cartridge or syringe barrel. 
     Alternatively, a high durometer, lubricious TPE material may be used as the plunger material and have no film disposed thereon. 
       FIG. 11  illustrates a coating preform  106  formed from the film  104  after the coating preform  106  has been loaded into a mold cavity  108  of a mold  107  and a vacuum has been applied to pull the coating preform  106  against the sidewall  110  and bottom wall  112  of the mold cavity  108 . Thus, according to certain embodiments, the shape of the film coating  88  may have a contour that matches the desired outer shape of the plunger  12 ″. With the mold  107  closed, a material for the plunger  12 ″, such as, for example, thermoset rubber (e.g., butyl rubber) or a thermoplastic elastomer (TPE) may be injected into the mold cavity  108  via an injection molding process so that plunger is molded against and/or to the coating preform  106  and a mold core  103 . The mold  107  may then be opened and the mold core  103  removed. The molded plunger  12 ″ with the film coating  88  (which may be still attached to the film  94 ) may then be removed from the mold  107 . 
       FIG. 12  illustrates the formed plunger  12 ″ and film coating  88  prior a trim tool  114  cutting or trimming the film coating  88  away from the remainder of the film  94 . While the trim tool  114  is illustrated as being a mechanical cutting device, a variety of different cutting devices may be employed, such as, for example, a laser, among other cutters. Additionally, the timing that at least the coating preform  106  and/or film coating  88  is trimmed from the film  94  may vary. For example, according to certain embodiments, the coating preform  106  and/or film coating  88  may remain connected to the film  94  so that the coating preform  106  and/or film coating  88  may be used to convey a plurality of coating preforms  106  and/or film coatings  88  during the manufacturing process (without or without the plunger  12 ″). According to such an embodiment, the coating preform(s)  106  and/or film coating(s)  88  may remain attached to the film  94  up until the time that coating preform(s)  106  and/or film coating(s)  88  are trimmed from the film  94 . 
     The material used for the film coating  88  may provide the compliance needed for the sealing function of the barrel  56 , as previously discussed. Further, by being able to use certain materials for the film coating  88 , such as, for example, a fluoropolymer film, a broader selection of materials for use in forming the plunger  12 ″ may be available, as the film coating  88  applied to the nose cone  92  will provide a barrier between the material of the plunger  12 ″ and the injection product contained in the barrel  56 . Further, according to certain embodiments, the plunger  12 ″ may be configured to limit the degree to which the rib(s)  52  and/or plunger  12 ″ are compressed when the plunger  12 ″ is inserted into the barrel  56 . For example, according to certain embodiments, the rib(s)  52  and/or plunger  12 ″ is configured to not be compressed more than 20% of the overall width of the rib  52  and/or plunger  12 ″ when the plunger  12 ″ is being used to form a seal in the barrel  56 . Alternative options for compression percentages are provided above. 
     Referring to  FIG. 26 , there is shown a film coated plunger  12  according to the present invention. The film coated plunger  12  comprises a plunger sleeve  44  (e.g., same as that of  FIG. 3 ) having a film coating  88  mounted over the nose cone  92  and a portion of the sidewall  90  of the film coated plunger  12 . Preferably, as shown, the film coating  88  covers the entire nose cone  92 . The film coating  88  also optionally covers the rib  55  of the liquid sealing section  53  and optionally a small section of the valley  57  adjacent to the rib  55 . Optionally, as shown in  FIG. 26A , the valley  57  comprises a descending slope  57   a  extending distally from the liquid sealing section  53 , the descending slope  57   a  leading to a floor  57   b , the floor  57   b  leading to an ascending slope  57   c  toward the storage sealing section  51 . Optionally, the film coating  88  terminates before the storage sealing section  51 , optionally before the ascending slope  57   c , optionally before the floor  57   b . In any event, there is preferably no film coating  88  covering the rib  52  of the storage sealing section  51 , since thermoset rubber (if that is the material of the rib  52 ) is a better oxygen barrier than contemplated film materials. The film coating  88  may be made, e.g., from any materials disclosed herein that are suitable for film coatings, e.g., an inert fluoropolymer, optionally polyethylene or polypropylene. 
     Optionally, the film coated plunger of  FIG. 26  may be part of a plunger assembly  10 ,  210  described herein and shown in  FIG. 2 or 13 . Optionally, the film coated plunger of  FIG. 26  is any one of the plunger embodiments described herein and shown in  FIG. 3, 7, 8, 15, 17, 18, 20, 21, 22, 23, 24 or 25 . Optionally, the film coated plunger of  FIG. 26  provides a first sealing force against an interior surface of a barrel wall in storage mode and a second sealing force (which is less than the first sealing force) in dispensing mode. Optionally, the first sealing force is provided by a compression material contained within the plunger  12  and aligned, at least in part, with a rib  52  of the storage sealing section  51 . The compression material is configured to provide outward radial force. The second sealing force is attainable by displacing and/or modifying the compression material, for example, in the many ways described herein. 
     The film coating  88  may be mounted to the plunger sleeve  44  in various ways. For example, a flat film piece may be placed onto a first surface of a forming block having a round passage leading to a second surface on another side of the forming block. At least an end portion of the round passage leading to the second surface of the forming block has roughly the same diameter as the plunger. A plunger holder grips a substantial portion of the plunger from the rear thereof (e.g., leaving uncovered that portion of the plunger to be covered with film). The plunger holder may be axially driven through the passage of the forming block, e.g., with a (preferably automated) pushing rod. Optionally, the pushing rod protrudes into the plunger cavity (e.g.,  48  and optionally  50  of the plunger  12  of  FIG. 26 ), slightly stretching the plunger. Optionally, prior to axially inserting the plunger and plunger holder through the passage, the plunger is heated e.g., to 100° C. to 200° C., optionally 110° C. to 190° C., optionally 120° C. to 180° C., optionally 130° C. to 170° C., optionally 135° C. to 160° C., optionally 145° C. to 155° C., optionally about 150° C. 
     After the optional heating step (if taken), the plunger and plunger holder are axially inserted through the passage thereby mounting the film piece to the plunger. Excess sections of the film piece may be trimmed from the plunger. For high volume production, for example, flat, continuous film strips may be preferred to individual film sheets for each plunger. Alternatively, continuous film strips may be perforated or otherwise weakened in circular patterns so as to provide pre-sized circular films for mounting to plungers. Preferably, such pre-sized circular films would be sized so as to leave no excess film to trim once mounted on the plunger. In this way, the plunger holder and plunger may be aligned with the circular patterns in order to punch through them when the plunger is inserted into the passage so as to mount the pre-sized circular films onto the plunger. Optionally, the film may be applied via cold forming (preferred) or thermoforming, wherein the plunger sleeve is itself used in the thermoforming process (e.g., mold rubber plunger sleeve and then thermoform film to rubber). 
     Referring to  FIG. 27 , there is shown the plunger sleeve  44  of  FIG. 3  having a cap  194  mounted over the nose cone  92  and a portion of the sidewall  90  of the plunger  12 . Preferably, as shown, the cap  194  covers the entire nose cone  92 . The cap  194  also covers the rib  55  of the liquid sealing section  53  and a small section of the valley  57  adjacent to the rib  55 . Preferably, the cap  194  does not cover the rib  52  of the storage sealing section  51 . Optionally, the cap  194  terminates in the same places in the valley  57  as described above vis-à-vis the film coating  88  as shown in  FIG. 26A . The cap  194  may be made from fluoropolymers such as, for example, high density polyethylene (HDPE), low density polyethylene (LDPE), or PTFE, among others. While it is contemplated that the cap  194  may have a thickness greater than that of the film  94  discussed above, it should be understood that the thickness of the cap  194  as shown in  FIG. 27  is not to scale, but is exaggerated for purposes of clarity. 
     The cap  194  is preferably an injection molded part that is made in a two shot injection mold process with the sleeve  44 . In other words, optionally, a cap material (e.g. polymer) is injection molded and subsequently the sleeve material (e.g. rubber) is injection molded into the same mold cavity as the cap material in a two shot process. Optionally, in molding, the cap  194  and sleeve  44  mate together through a mechanical fit such as an interference fit. Advantageously, the cap can be made from either thermoplastic or thermoset materials. In addition, a molded cap is an easier component to manage in manufacturing than a comparatively thinner film. 
     Liquid Silicone Rubber Plungers 
     The use of the fluoropolymer powders may be used in combination with non-fluoropolymer films—like polyethylene or polypropylene films that are more adhesion compatible with the thermoplastic elastomer/rubber plunger materials. The challenge with fluoropolymer films—like FEP is that they may not perfectly adhere to the plunger and can wrinkle when interested into the syringe barrel. 
     A potential solution to the problems of film adhesion and wrinkling contemplated by the inventors is to make the plunger from a liquid silicone rubber, preferably a fluoro liquid silicone rubber. Fluoro liquid silicone rubbers are injection moldable materials that possess good compression set properties, e.g., for long term storage in pre-filled cartridges or syringes, similar to butyl rubber. In addition, they adhere well to fluoropolymers. As such, according to one aspect of the invention, a fluoro liquid silicone rubber plunger (optionally incorporating features of any plunger embodiments disclosed herein) is provided, having a fluoropolymer film disposed thereon. The fluoro liquid silicone rubber plunger provides enhanced bonding with the fluoropolymer film, and thus resists wrinkling of the film. This enhanced bonding and wrinkle resistance would render the plunger more robust for handling and insertion into a syringe or cartridge. An additional potential advantage is that fluoro liquid silicone rubber may be injection molded to achieve better dimensional tolerances than traditional compression molded plungers, such as those made from butyl rubber. 
     In another embodiment, a fluoro liquid silicone rubber plunger is provided which does not include a film disposed thereon. It is contemplated that for some applications, a plunger comprising fluoro liquid silicone rubber will itself (without a film) have adequate compression set properties and would be sufficiently lubricious for insertion and handling in a cartridge or syringe barrel. 
     Examples of potentially suitable fluoro liquid silicone rubber materials for use in plungers according to an aspect of the present invention include, among others, SILASTIC® marketed by Dow Corning Corporation and ELASTOSIL® FLR marketed by Wacker Chemie AG. 
     It is contemplated that fluoro liquid silicone polymer plungers may have comparable or superior properties, in several respects (e.g., in terms of compression setting, film adhesion, plunger force, and plunger extractables), compared to standard, e.g., butyl rubber plungers. 
     It is contemplated that any of the convertible plungers described in this specification and shown in the drawing figures may optionally include film coatings or molded caps as described herein. 
     It is further contemplated that any of the plungers described herein, whether or not they include a film coating, may be made from one or more materials including, but not limited to, a thermoset rubber (e.g., butyl rubber), a thermoplastic elastomer (TPE), liquid silicone rubber and fluoro liquid silicone rubber. It is further contemplated that any plunger embodiments that are described herein without a film may include a film and that any plunger embodiments that are described herein with a film may be used without a film, depending on design requirements and/or functional needs. 
     Plunger Testing Methods and Standards 
     Testing of compression setting properties of the plunger may be conducted using methods known in the art, for example, ASTM D395. 
     Testing of adhesive properties or bonding strength between the film and the plunger may be conducted using methods known in the art, for example, according to ASTM D1995-92 (2011) or D1876-08. 
     Plunger sliding force is the force required to maintain movement of a plunger in a syringe or cartridge barrel, for example during aspiration or dispense. It can advantageously be determined using, e.g., the ISO 7886-1:1993 test known in the art, or to the currently pending published test method to be incorporated into ISO 11040-4. Plunger breakout force, which may be tested using the same method as that for testing plunger sliding force, is the force required to start a stationary plunger moving within a syringe or cartridge barrel. Machinery useful in testing plunger sliding and breakout force is, e.g., an Instron machine using a 50 N transducer. 
     Testing for extractables, i.e., amount of material that migrates from the plunger into the liquid within the syringe or cartridge, may be conducted using methods set forth in Ph. Eur. 2.9.17 Test for Extractable Volume of Parenteral Preparations, for example. 
     Testing of container closure integrity (CCI) may be done using a vacuum decay leak detection method, wherein a vacuum his maintained inside of a test volume and pressure rise is measured over time. A large enough pressure rise is an indication that there is flow into the system, which is evidence of a leak. Optionally, the vacuum decay test is implemented over two separate cycles. The first cycle is dedicated to detecting large leaks over a very short duration. A relatively weak vacuum is pulled for the first cycle because if a gross leak is detected, a large pressure differential is not necessary to detect a large pressure rise. Use of a first cycle as described helps to shorten total test time if a gross leak exists. If no leak is detected in the first cycle, a second cycle is run, which complies with ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method. The second cycle starts out with a system evaluation to lower the signal to noise ratio in the pressure rise measurements. A relatively strong vacuum is pulled for a long period of time in the second cycle to increase the chance of detecting a pressure rise in the system. 
     Syringe Embodiments and PECVD Coatings 
     In another aspect, the present invention includes use of any embodiments (or combination of embodiments) of plungers according to the invention in syringes having a PECVD coating or PECVD coating set. The syringes may be made from, e.g., glass or plastic. Optionally, the syringe barrel according to any embodiment is made from an injection moldable thermoplastic material that appears clear and glass-like in final form, e.g., a cyclic olefin polymer (COP), cyclic olefin copolymer (COC) or polycarbonate. Such materials may be manufactured, e.g., by injection molding, to very tight and precise tolerances (generally much tighter than achievable with glass). This is a benefit when trying to balance the competing considerations of seal tightness and low plunger force in plunger design. 
     This section of the disclosure focuses primarily on pre-filled syringes as a preferred implementation of optional aspects of the invention. Again, however, it should be understood that the present invention may include any parenteral container that utilizes a plunger, such as syringes, cartridges, auto-injectors, pre-filled syringes, pre-filled cartridges or vials. 
     For some applications, it may be desired to provide one or more coatings or layers to the interior wall of a parenteral container to modify the properties of that container. For example, one or more coatings or layers may be added to a parenteral container, e.g., to improve the barrier properties of the container and prevent interaction between the container wall (or an underlying coating) and drug product held within the container. 
     For example, as shown in  FIG. 4A , which is a first alternative embodiment of an enlarged sectional view of the syringe barrel  54  of  FIG. 4 , the sidewall  58  of the syringe barrel  54  may include a coating set  400  comprising one or more coatings or layers. The barrel  54  may include at least one tie coating or layer  402 , at least one barrier coating or layer  404 , and at least one organo-siloxane coating or layer  406 . The organo-siloxane coating or layer  406  preferably has pH protective properties. This embodiment of the coating set  400  is referred to herein as a “trilayer coating set” in which the barrier coating or layer  404  of SiO x  is protected against contents having a pH otherwise high enough to remove it by being sandwiched between the pH protective organo-siloxane coating or layer  406  and the tie coating or layer  402 . The contemplated thicknesses of the respective layers in nm (preferred ranges in parentheses) are given in the following Trilayer Thickness Table: 
     
       
         
           
               
            
               
                   
               
               
                 Trilayer Thickness Table 
               
            
           
           
               
               
               
            
               
                 Adhesion 
                 Barrier 
                 Protection 
               
               
                   
               
               
                 5-100 
                  20-200 
                  50-500 
               
               
                 (5-20)  
                 (20-30) 
                 (100-200) 
               
               
                   
               
            
           
         
       
     
     Properties and compositions of each of the coatings that make up the trilayer coating set are now described. 
     The tie coating or layer  402  has at least two functions. One function of the tie coating or layer  402  is to improve adhesion of a barrier coating or layer  404  to a substrate (e.g., the sidewall  58  of the barrel  54 ), in particular a thermoplastic substrate, although a tie layer can be used to improve adhesion to a glass substrate or to another coating or layer. For example, a tie coating or layer, also referred to as an adhesion layer or coating can be applied to the substrate and the barrier layer can be applied to the adhesion layer to improve adhesion of the barrier layer or coating to the substrate. 
     Another function of the tie coating or layer  402  has been discovered: a tie coating or layer  402  applied under a barrier coating or layer  404  can improve the function of a pH protective organo-siloxane coating or layer  406  applied over the barrier coating or layer  404 . 
     The tie coating or layer  402  can be composed of, comprise, or consist essentially of SiO x C y , in which x is between 0.5 and 2.4 and y is between 0.6 and 3. Alternatively, the atomic ratio can be expressed as the formula Si w O x C y . The atomic ratios of Si, O, and C in the tie coating or layer  289  are, as several options: 
     Si 100: O 50-150: C 90-200 (i.e. w=1, x=0.5 to 1.5, y=0.9 to 2); 
     Si 100: O 70-130: C 90-200 (i.e. w=1, x=0.7 to 1.3, y=0.9 to 2) 
     Si 100: O 80-120: C 90-150 (i.e. w=1, x=0.8 to 1.2, y=0.9 to 1.5) 
     Si 100: O 90-120: C 90-140 (i.e. w=1, x=0.9 to 1.2, y=0.9 to 1.4), or 
     Si 100: O 92-107: C 116-133 (i.e. w=1, x=0.92 to 1.07, y=1.16 to 1.33). 
     The atomic ratio can be determined by XPS. Taking into account the H atoms, which are not measured by XPS, the tie coating or layer  402  may thus in one aspect have the formula Si w O x C y H z  (or its equivalent S i O x C y ), for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9. Typically, a tie coating or layer  402  would hence contain 36% to 41% carbon normalized to 100% carbon plus oxygen plus silicon. 
     The barrier coating or layer for any embodiment defined in this specification (unless otherwise specified in a particular instance) is a coating or layer, optionally applied by PECVD as indicated in U.S. Pat. No. 7,985,188. The barrier coating preferably is characterized as a “SiO x ” coating, and contains silicon, oxygen, and optionally other elements, in which x, the ratio of oxygen to silicon atoms, is from about 1.5 to about 2.9. The thickness of the SiO x , or other barrier coating or layer can be measured, for example, by transmission electron microscopy (TEM), and its composition can be measured by X-ray photoelectron spectroscopy (XPS). The barrier layer is effective to prevent oxygen, carbon dioxide, or other gases from entering the container and/or to prevent leaching of the pharmaceutical material into or through the container wall. 
     Referring again to  FIG. 4A , the barrier coating or layer  404  of SiO x , in which x is between 1.5 and 2.9, is applied by plasma enhanced chemical vapor deposition (PECVD) directly or indirectly to the thermoplastic sidewall wall  58  of the barrel  54  (in this example, a tie coating or layer  402  is interposed between them) so that in the filled syringe barrel  54 , the barrier coating or layer  404  is located between the inner or interior surface of the sidewall  55  of the barrel  54  and the injectable medicine contained within the barrel  54 . 
     Certain barrier coatings or layers  404  such as SiOx as defined here have been found to have the characteristic of being subject to being measurably diminished in barrier improvement factor in less than six months as a result of attack by certain relatively high pH contents of the coated vessel as described elsewhere in this specification, particularly where the barrier coating or layer directly contacts the contents. This issue can be addressed using an organo-siloxane coating or layer as discussed in this specification. 
     Preferred methods of applying the barrier layer and tie layer to the inner surface of the barrel  54  is by plasma enhanced chemical vapor deposition (PECVD), such as described in, e.g., U.S. Pat. App. Pub. No. 20130291632, which is incorporated by reference herein in its entirety. 
     The Applicant has found that barrier layers or coatings of SiO x  are eroded or dissolved by some fluids, for example aqueous compositions having a pH above about 5. Since coatings applied by chemical vapor deposition can be very thin—tens to hundreds of nanometers thick—even a relatively slow rate of erosion can remove or reduce the effectiveness of the barrier layer in less time than the desired shelf life of a product package. This is particularly a problem for fluid pharmaceutical compositions, since many of them have a pH of roughly 7, or more broadly in the range of 5 to 9, similar to the pH of blood and other human or animal fluids. The higher the pH of the pharmaceutical preparation, the more quickly it erodes or dissolves the SiO x  coating. Optionally, this problem can be addressed by protecting the barrier coating or layer  404 , or other pH sensitive material, with a pH protective organo-siloxane coating or layer  406 . 
     Optionally, the pH protective organo-siloxane coating or layer  406  can be composed of, comprise, or consist essentially of Si w O x C y H z  (or its equivalent SiO x C y ) or Si w N x C y H z  or its equivalent SiN x C y ). The atomic ratio of Si: O: C or Si: N: C can be determined by XPS (X-ray photoelectron spectroscopy). Taking into account the H atoms, the pH protective coating or layer may thus in one aspect have the formula Si w O x C y H z , or its equivalent SiO x C y , for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9. 
     Typically, expressed as the formula Si w O x C y , the atomic ratios of Si, O, and C are, as several options:
         Si 100: O 50-150: C 90-200 (i.e. w=1, x=0.5 to 1.5, y=0.9 to 2);   Si 100: O 70-130: C 90-200 (i.e. w=1, x=0.7 to 1.3, y=0.9 to 2)   Si 100: O 80-120: C 90-150 (i.e. w=1, x=0.8 to 1.2, y=0.9 to 1.5)   Si 100: O 90-120: C 90-140 (i.e. w=1, x=0.9 to 1.2, y=0.9 to 1.4)   Si 100: O 92-107: C 116-133 (i.e. w=1, x=0.92 to 1.07, y=1.16 to 1.33), or   Si 100: O 80-130: C 90-150.       

     Alternatively, the organo-siloxane coating or layer can have atomic concentrations normalized to 100% carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS) of less than 50% carbon and more than 25% silicon. Alternatively, the atomic concentrations are from 25 to 45% carbon, 25 to 65% silicon, and 10 to 35% oxygen. Alternatively, the atomic concentrations are from 30 to 40% carbon, 32 to 52% silicon, and 20 to 27% oxygen. Alternatively, the atomic concentrations are from 33 to 37% carbon, 37 to 47% silicon, and 22 to 26% oxygen. 
     Optionally, the atomic concentration of carbon in the pH protective coating or layer  406 , normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), can be greater than the atomic concentration of carbon in the atomic formula for the organosilicon precursor. For example, embodiments are contemplated in which the atomic concentration of carbon increases by from 1 to 80 atomic percent, alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic percent, alternatively from 37 to 41 atomic percent. 
     Optionally, the atomic ratio of carbon to oxygen in the pH protective coating or layer  406  can be increased in comparison to the organosilicon precursor, and/or the atomic ratio of oxygen to silicon can be decreased in comparison to the organosilicon precursor. 
     An exemplary empirical composition for a pH protective coating according to the present invention is SiO 1.3 C 0.8 H 3.6 . 
     Optionally in any embodiment, the pH protective coating or layer  406  comprises, consists essentially of, or consists of PECVD applied silicon carbide. 
     Optionally in any embodiment, the pH protective coating or layer  406  is applied by employing a precursor comprising, consisting essentially of, or consisting of a silane. Optionally in any embodiment, the silane precursor comprises, consists essentially of, or consists of any one or more of an acyclic or cyclic silane, optionally comprising, consisting essentially of, or consisting of any one or more of silane, trimethylsilane, tetramethylsilane, Si2-Si4 silanes, triethyl silane, tetraethyl silane, tetrapropylsilane, tetrabutylsilane, or octamethylcyclotetrasilane, or tetramethylcyclotetrasilane. 
     Optionally in any embodiment, the pH protective coating or layer  406  comprises, consists essentially of, or consists of PECVD applied amorphous or diamond-like carbon. Optionally in any embodiment, the amorphous or diamond-like carbon is applied using a hydrocarbon precursor. Optionally in any embodiment, the hydrocarbon precursor comprises, consists essentially of, or consists of a linear, branched, or cyclic alkane, alkene, alkadiene, or alkyne that is saturated or unsaturated, for example acetylene, methane, ethane, ethylene, propane, propylene, n-butane, i-butane, butane, propyne, butyne, cyclopropane, cyclobutane, cyclohexane, cyclohexene, cyclopentadiene, or a combination of two or more of these. Optionally in any embodiment, the amorphous or diamond-like carbon coating has a hydrogen atomic percent of from 0.1% to 40%, alternatively from 0.5% to 10%, alternatively from 1% to 2%, alternatively from 1.1 to 1.8%. 
     Optionally in any embodiment, the pH protective coating or layer  406  comprises, consists essentially of, or consists of PECVD applied SiNb. Optionally in any embodiment, the PECVD applied SiNb is applied using a silane and a nitrogen-containing compound as precursors. Optionally in any embodiment, the silane is an acyclic or cyclic silane, optionally comprising, consisting essentially of, or consisting of silane, trimethylsilane, tetramethylsilane, Si2-Si4 silanes, triethylsilane, tetraethylsilane, tetrapropylsilane, tetrabutylsilane, octamethylcyclotetrasilane, or a combination of two or more of these. Optionally in any embodiment, the nitrogen-containing compound comprises, consists essentially of, or consists of any one or more of: nitrogen gas, nitrous oxide, ammonia or a silazane. Optionally in any embodiment, the silazane comprises, consists essentially of, or consists of a linear silazane, for example hexamethylene disilazane (HMDZ), a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or a combination of two or more of these. 
     Optionally in any embodiment, the PECVD for the pH protective coating or layer  406  is carried out in the substantial absence or complete absence of an oxidizing gas. Optionally in any embodiment, the PECVD for the pH protective coating or layer  406  is carried out in the substantial absence or complete absence of a carrier gas. 
     Optionally an FTIR absorbance spectrum of the pH protective coating or layer  406  SiOxCyHz has a ratio greater than 0.75 between the maximum amplitude of the Si—O—Si symmetrical stretch peak normally located between about 1000 and 1040 cm-1, and the maximum amplitude of the Si—O—Si asymmetric stretch peak normally located between about 1060 and about 1100 cm-1. Alternatively in any embodiment, this ratio can be at least 0.8, or at least 0.9, or at least 1.0, or at least 1.1, or at least 1.2. Alternatively in any embodiment, this ratio can be at most 1.7, or at most 1.6, or at most 1.5, or at most 1.4, or at most 1.3. Any minimum ratio stated here can be combined with any maximum ratio stated here, as an alternative embodiment. 
     Optionally, in any embodiment the pH protective coating or layer  406 , in the absence of the medicament, has a non-oily appearance. This appearance has been observed in some instances to distinguish an effective pH protective coating or layer  406  from a lubricity layer (e.g., as described in U.S. Pat. No. 7,985,188), which in some instances has been observed to have an oily (i.e. shiny) appearance. 
     The pH protective coating or layer  406  optionally can be applied by plasma enhanced chemical vapor deposition (PECVD) of a precursor feed comprising an acyclic siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, a silatrane, a silquasilatrane, a silproatrane, an azasilatrane, an azasilquasiatrane, an azasilproatrane, or a combination of any two or more of these precursors. Some particular, non-limiting precursors contemplated for such use include octamethylcyclotetrasiloxane (OMCTS). 
     Optionally, an FTIR absorbance spectrum of the pH protective coating or layer  406  of composition SiOxCyHz has a ratio greater than 0.75 between the maximum amplitude of the Si—O—Si symmetrical stretch peak between about 1000 and 1040 cm-1, and the maximum amplitude of the Si—O—Si asymmetric stretch peak between about 1060 and about 1100 cm-1. 
     Other precursors and methods can be used to apply the pH protective coating or layer  406  or passivating treatment. For example, hexamethylene disilazane (HMDZ) can be used as the precursor. HMDZ has the advantage of containing no oxygen in its molecular structure. This passivation treatment is contemplated to be a surface treatment of the SiOx barrier layer with HMDZ. To slow down and/or eliminate the decomposition of the silicon dioxide coatings at silanol bonding sites, the coating must be passivated. It is contemplated that passivation of the surface with HMDZ (and optionally application of a few mono layers of the HMDZ-derived coating) will result in a toughening of the surface against dissolution, resulting in reduced decomposition. It is contemplated that HMDZ will react with the —OH sites that are present in the silicon dioxide coating, resulting in the evolution of NH3 and bonding of S—(CH3)3 to the silicon (it is contemplated that hydrogen atoms will be evolved and bond with nitrogen from the HMDZ to produce NH3). 
     Another way of applying the pH protective coating or layer  406  is to apply as the pH protective coating or layer  406  an amorphous carbon or fluorocarbon coating, or a combination of the two. 
     Amorphous carbon coatings can be formed by PECVD using a saturated hydrocarbon, (e.g. methane or propane) or an unsaturated hydrocarbon (e.g. ethylene, acetylene) as a precursor for plasma polymerization. Fluorocarbon coatings can be derived from fluorocarbons (for example, hexafluoroethylene or tetrafluoroethylene). Either type of coating, or a combination of both, can be deposited by vacuum PECVD or atmospheric pressure PECVD. It is contemplated that that an amorphous carbon and/or fluorocarbon coating will provide better passivation of an SiOx barrier layer than a siloxane coating since an amorphous carbon and/or fluorocarbon coating will not contain silanol bonds. 
     It is further contemplated that fluorosilicon precursors can be used to provide a pH protective coating or layer  406  over a SiOx barrier layer. This can be carried out by using as a precursor a fluorinated silane precursor such as hexafluorosilane and a PECVD process. The resulting coating would also be expected to be a non-wetting coating. 
     Yet another coating modality contemplated for protecting or passivating a SiOx barrier layer is coating the barrier layer using a polyamidoamine epichlorohydrin resin. For example, the barrier coated part can be dip coated in a fluid polyamidoamine epichlorohydrin resin melt, solution or dispersion and cured by autoclaving or other heating at a temperature between 60 and 100° C. It is contemplated that a coating of polyamidoamine epichlorohydrin resin can be preferentially used in aqueous environments between pH 5-8, as such resins are known to provide high wet strength in paper in that pH range. Wet strength is the ability to maintain mechanical strength of paper subjected to complete water soaking for extended periods of time, so it is contemplated that a coating of polyamidoamine epichlorohydrin resin on a SiOx barrier layer will have similar resistance to dissolution in aqueous media. It is also contemplated that, because polyamidoamine epichlorohydrin resin imparts a lubricity improvement to paper, it will also provide lubricity in the form of a coating on a thermoplastic surface made of, for example, COC or COP. 
     Even another approach for protecting a SiOx layer is to apply as a pH protective coating or layer  406  a liquid-applied coating of a polyfluoroalkyl ether, followed by atmospheric plasma curing the pH protective coating or layer  406 . For example, it is contemplated that the process practiced under the trademark TriboGlide® can be used to provide a pH protective coating or layer  406  that is also provides lubricity. 
     Thus, a pH protective coating for a thermoplastic syringe wall according to an aspect of the invention may comprise, consist essentially of, or consist of any one of the following: plasma enhanced chemical vapor deposition (PECVD) applied silicon carbide having the formula SiOxCyHz, in which x is from 0 to 0.5, alternatively from 0 to 0.49, alternatively from 0 to 0.25 as measured by X ray photoelectron spectroscopy (XPS), y is from about 0.5 to about 1.5, alternatively from about 0.8 to about 1.2, alternatively about 1, as measured by XPS, and z is from 0 to 2 as measured by Rutherford Backscattering Spectrometry (RBS), alternatively by Hydrogen Forward Scattering Spectrometry (HFS); or PECVD applied amorphous or diamond-like carbon, CHz, in which z is from 0 to 0.7, alternatively from 0.005 to 0.1, alternatively from 0.01 to 0.02; or PECVD applied SiNb, in which b is from about 0.5 to about 2.1, alternatively from about 0.9 to about 1.6, alternatively from about 1.2 to about 1.4, as measured by XPS. 
     pH Protective Organo-Siloxane Coating—not as Part of Coating Set 
     Referring now to  FIG. 4B , there is shown a second alternative embodiment of an enlarged sectional view of the syringe barrel  54  of  FIG. 4 . As shown in  FIG. 4B , the syringe barrel  54  may include a organo-siloxane coating or layer  406  disposed directly on the wall  58  of the syringe barrel  54 , rather than, e.g., as a top layer of a coating set. Optionally, the organo-siloxane coating or layer  406  has pH protective properties. Thus an aspect of the invention involves use of a organo-siloxane coating or layer as a plunger-contacting surface, whether the organo-siloxane coating or layer is the top-most layer of a coating set or is by itself disposed directly onto the barrel wall. 
     PECVD Apparatus 
     PECVD apparatus suitable for applying any of the PECVD coatings or layers described in this specification, including the tie coating or layer  402 , the barrier coating or layer  404  or the organo-siloxane coating or layer  406 , is shown and described in U.S. Pat. No. 7,985,188 and U.S. Pat. App. Pub. No. 20130291632. This apparatus optionally includes a vessel holder, an inner electrode, an outer electrode, and a power supply. A vessel seated on the vessel holder defines a plasma reaction chamber, optionally serving as its own vacuum chamber. Optionally, a source of vacuum, a reactant gas source, a gas feed or a combination of two or more of these can be supplied. Optionally, a gas drain, not necessarily including a source of vacuum, is provided to transfer gas to or from the interior of a vessel seated on the port to define a closed chamber. 
     pH Protective Organo-Siloxane Coatings Having Lubricious Properties 
     It is contemplated that syringes having a plunger-contacting inner surface comprising an organo-siloxane coating, without a separate discrete lubricity coating or substantially without the presence of a flowable lubricant, may still provide adequate lubricity for plunger advancement. As used herein, “substantially without the presence of a flowable lubricant,” means that a flowable lubricant (e.g., PDMS) is not provided to a syringe barrel in amounts that would contribute to the lubricity of the plunger-syringe system. Since it is sometimes the practice to use a flowable lubricant when handling plungers prior to assembling them into syringes, “substantially without the presence of a flowable lubricant” in some cases may contemplate the presence of trace amounts of such lubricant as a result of such handling practices. 
     Accordingly, in one aspect, the invention is directed to an organo-siloxane coating on the inner surface of a parenteral container which provides lubricious properties conducive to acceptable plunger operation. The organo-siloxane coating may, for example, be any embodiment of the pH protective coating discussed above. The organo-siloxane coating may be applied directly to the interior wall of the container or as a top layer on a multi-layer coating set, e.g., the trilayer coating set discussed above. Preferably, this embodiment would obviate the need for a discrete lubricity coating, e.g., as described in U.S. Pat. No. 7,985,188 or a flowable lubricant, e.g., silicone oil. 
     The organo-siloxane coating can optionally provide multiple functions: (1) a pH resistant layer that protects an underlying layer or underlying polymer substrate from drug products having a pH from 4-10, optionally from 5-9; (2) a drug contact surface that minimizes aggregation, extractables and leaching; (3) in the case of a protein-based drug, reduced protein binding on the container surface; and (4) a lubricating layer, e.g., to facilitate plunger advancement when dispensing contents of a syringe. 
     Use of an organo-siloxane coating on a polymer-based container as the contact surface for a plunger provides distinct advantages. Plastic syringes and cartridges may be injection molded to tighter tolerances than their glass counterparts. It is contemplated that the dimensional precision achievable through injection molding allows optimization of the inside diameter of a syringe to provide sufficient compression to the plunger for CCI on the one hand, while not over-compressing the plunger so as to provide desired plunger force upon administration of the drug product. Optimally, this would eliminate or dramatically reduce the need for lubricating the syringe or cartridge with a flowable lubricant or a discrete lubricity coating, thus reducing manufacturing complexity and avoiding problems associated with silicone oil. 
     The invention will be illustrated in more detail with reference to the following Examples, but it should be understood that the present invention is not deemed to be limited thereto. 
     EXAMPLES 
     Example 1 
     Plunger Force 
     Three convertible plunger samples (Samples A ( 500 ), B ( 502 ) and C ( 504 )), similar to the embodiment of the film coated convertible plunger of  FIG. 26 , were subjected to plunger force testing. The samples used 3.45 mm diameter spherical inserts. The desired outcome was a glide force of under 15 N, preferably under 10 N, even more preferably at or under 5 N. The samples were tested in a syringe having a plunger contacting surface comprising a pH protective coating made from a TMDSO precursor as part of a trilayer coating set, e.g., as shown in  FIG. 4A  and as described herein. The sample plunger sleeves were made from butyl rubber and the film was made from 25 micron thick CHEMFILM® DF1100 PTFE. The syringe barrels were 6.35 mm in diameter. 
     As shown in the chart in  FIG. 28 , break loose force for the three samples was between about 3.5N-5.5N. The glide force was relatively constant and consistent for each sample and was between about 2.5N and about 5N. The test is thus regarded as a success in terms of achieving desired plunger force and consistency in the force profile of each sample (i.e., no drastic changes in glide force for a given sample). 
     Example 2 
     CCI 
     A CCI test method (vacuum decay test) is described above. Using this test, and referring to the chart in  FIG. 29 , three sets of plungers (Sets A, B and C) were used, all in a 6.35 mm diameter syringe. Set A  510  included plungers without any inserts, and consequently with no compression between the plunger storage sealing section and the syringe barrel. Set B  512  included plungers with 3.45 mm diameter spherical inserts, which caused slightly less than 3% compression of the plunger diameters on their respective storage sealing sections. Set C  514  included plungers with 3.58 mm spherical inserts, which caused about 4.8% compression of the plunger diameters on their respective storage sealing sections. For purposes of maintaining adequate CCI for prefilled syringes, a pressure drop of about 20 Pa or less is acceptable. 
     The chart in  FIG. 29  shows the pressure drop for plunger Sets A, B and C subjected to the vacuum decay test. Set A  510  showed a pressure drop of well over 20 Pa, while Set B  512  and Set C  512  had pressure drops of around 20 Pa or less, which are positive results. This test shows that the spherical inserts (similar to the insert  42  of  FIGS. 3 and 26 ) provide compression in the storage sealing section  51  of the plunger  12 , resulting in acceptable CCI. By contrast, Set A  510 , which had no inserts, did not provide adequate CCI. 
     Example 3 
     Comparative Plunger Forces Using Four Syringe Barrel Embodiments 
     This example describes plunger force testing of several convertible plunger samples, similar to the embodiment of the film coated convertible plunger of  FIG. 26 . The samples used 3.45 mm diameter spherical inserts. Results of this testing are shown in  FIG. 30 . 
     Four or five plunger samples were tested in each of the following four different syringe barrels: (a) a COP syringe barrel having an inner wall without flowable lubricant disposed between the plunger and the inner wall (the “bare COP syringe,” the force testing results of which are identified by reference numeral  516 ); (b) a COP syringe barrel with a trilayer coating set applied to the inner wall thereof without flowable lubricant disposed between the plunger and the trilayer coating set (the “trilayer syringe,” the force testing results of which are identified by reference numeral  518 ); (c) a glass syringe barrel without any flowable lubricant disposed between the plunger and the inner wall of the barrel (the “bare glass syringe,” the force testing results of which are identified by reference numeral  520 ); and (d) a glass syringe barrel with a flowable lubricant (PDMS) disposed between the plunger and the inner wall of the barrel (the “glass syringe with PDMS,” the force testing results of which are identified by reference numeral  522 ). 
     The break loose forces and maximum glide forces depicted in  FIG. 30  for a given syringe represent averages of results from testing four of five plunger samples with each syringe. The average break loose forces were as follows: (a) between 6 and 7 N for the bare COP syringe  516 ; (b) slightly above 5N for the trilayer syringe  518 ; (c) between 7 and 8 N for the bare glass syringe  520 ; and (d) between 11 and 12 N for the glass syringe with PDMS  522 . The average maximum glide forces were as follows: (a) slightly below 4N for the bare COP syringe  516 ; (b) 4N for the trilayer syringe  518 ; (c) between 6 and 7N for the bare glass syringe  520 ; and (d) between 10 and 11 N for the glass syringe with PDMS  522 . 
     Notably, the trilayer syringe  518  cumulative force results were optimal in that unlike the other syringes, both the break loose force and maximum glide force averages were about 5N or under (which is a preferred plunger force). In addition, the differential between break loose force and maximum glide force for the trilayer syringe  518  was only about 1N, which is significantly less than the approximately 2.5 N differential between break loose force and maximum glide force for the bare COP syringe  516 . Accordingly, a trilayer syringe with a plunger according to the present invention provides benefits associated with the trilayer syringe itself (e.g., pH protection, tight syringe tolerances, barrier properties) as well as a flowable lubricant free (or substantially flowable lubricant free) plunger system that provides both CCI and desired plunger forces in use. 
     While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.