Barrier coated stopper and molding method

Abstract

A method for forming a molded device such as a stopper requiring minimal post-molding processing includes providing a four-plate mold assembly 52 having a top plate 54, a sprue / vent plate 56 including a core portion 62, a main plate 58 including a recess 66 defining a mold cavity 68 having a contoured surface 70, and a bottom plate 60, and closing the mold assembly 52 so that the core portion 62 fits into the recess 66 in the main plate 58, defining a space 72 corresponding to the shape of the stopper 10, 110 to be molded. A polymeric material is introduced into the mold cavity 68 to form the stopper 10, 110. A barrier layer 14, 114 can be inserted between the main plate 58 and the bottom plate and adhered to the molded device 10, 110. The plates are opened, and the molded device is removed.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 116,533, entitled "Barrier Coated Stopper and Forming Method," filed November 20, 2020, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a method for molding devices such as stoppers for use on plunger rods in syringes and stoppers for closing vials. More particularly, the present invention relates to a method for molding stoppers using a four-plate, one-shot injection molded apparatus that requires minimal post-molding processing. [Background technology]

[0003] Syringe assemblies, particularly hypodermic syringes, are well known in the medical field for dispensing fluids such as medications. Conventional syringes typically include an elongated barrel having opposed proximal and distal ends and a chamber for receiving a fluid therebetween. A passageway extends through the distal end of the syringe barrel and communicates with the chamber. The distal end of the syringe barrel is connected to a needle cannula for delivering fluid from the chamber and the passageway. The proximal end of the syringe barrel slidably receives a plunger rod and stopper assembly, and force applied to the plunger rod urges the stopper along the barrel, driving fluid from the chamber through the needle cannula.

[0004] Some currently commercially available hypodermic syringes suffer from a problem of the amount of liquid remaining in the barrel after the stopper has advanced the entire length of the barrel during injection (i.e., "dead volume"). Therefore, there is a need to manufacture a stopper that can reduce the amount of dead space within the syringe barrel. Various stoppers have been designed to reduce or minimize the dead space within the syringe barrel and to adequately seal against the inner wall of the syringe barrel. One example of a stopper is disclosed in U.S. Pat. No. 5,795,337, which is incorporated by reference in its entirety. This design consists of a piston-like stopper body that slidably engages in a fluid-tight manner within the syringe barrel. The body includes a distal end, a proximal end, and a longitudinal axis extending therethrough. A distally oriented conical projection is disposed at the distal end of the stopper body. At least one elongated discontinuous surface is provided along the conical projection. The discontinuities serve to prevent the projections of the stopper from undesirably immediately sealing within the passageway extending from the syringe barrel to the needle cannula, allowing fluid trapped within the barrel to flow along these discontinuities into the passageway. Because the stopper is made of a resilient material, further distal pressure on the plunger rod deflects the stopper, squeezing fluid through the passageway temporarily opened by the discontinuities. Summary of the Invention [Problem to be solved by the invention]

[0005] Complex-shaped stoppers with a barrier film on their distal surface are typically formed using a two-shot molding / trimming process. This type of stopper is currently only used for low-volume production where cost is not critical. The two-shot process is roughly twice as costly as the traditional single-shot process. Some commercially available barrier-coated stoppers utilize a single-shot molding process, but these stoppers often have undesirable features. One undesirable feature is that the first rib must be a trimmed edge rather than a molded feature, which does not guarantee a fluid seal and does not ensure optimal sliding force. While the addition of two ribs to the stopper addresses the risk of container closure integrity (i.e., CCI), this design is undesirable for certain devices, such as precision syringes, where variable leakage past the first stopper rib can affect drug delivery accuracy and system hysteresis. While stoppers that overcome these limitations have been designed, they have so far only been produced using a two-step manufacturing process: molding and trimming. Not only is this production expensive, but the more steps there are, the greater the opportunity for waste and scrap. Scaling up the production of these high-precision stoppers in a single-shot molding process offers significant economic benefits. [Means for solving the problem]

[0006] According to one aspect, the present disclosure relates to a method for molding a device, such as a stopper, using a one-shot injection-molded device that requires minimal post-molding processing. The method includes providing a four-plate mold assembly having a top plate, a sprue / vent plate including a core portion, a main plate including a recess defining a mold cavity with a contoured surface, and a bottom plate; closing the mold assembly so that the core portion fits into the recess in the main plate to define a space corresponding to the shape of the molded device; and introducing a polymeric material into the mold cavity to fill the mold cavity and the space to form the molded device. The molded device has a body and a molding surface corresponding to the contoured surface of the mold cavity. The method further includes cooling the polymeric material; separating the sprue / vent plate from the main plate to remove the core portion from the molded device; then separating the sprue / vent plate from the top plate; then separating the bottom plate from the main plate; and finally removing the molded device or stopper from the main plate.

[0007] Separating the sprue / vent plate from the main plate breaks the vent and pulls the core out from within the molded device and main plate. It can be appreciated that the core can be designed to have several shapes depending on the desired interior shape of the device or stopper. For example, the core can have a threaded design, a cone-shaped section with an enlarged portion toward the intersection of the core and sprue / vent plate, straight sidewalls, etc. Once the plates of the mold are opened, the molded device can be removed from the main plate by pulling the molded device through the bottom of the main plate.

[0008] The step of introducing the polymeric material into the mold cavity comprises injecting the hot polymeric material into the cavity through an injection nozzle and runner associated with the top plate, and the step of cooling the mold assembly comprises supplying cooling material to the main plate.

[0009] The contoured surface of the main cavity is in the shape of a stopper having a main body defining an open rearward end, a closed forward end, and a cylindrical sidewall extending between the open rearward end and the closed forward end. According to one embodiment, the contoured surface shape is configured to form a plurality of ribs extending radially outwardly around and axially spaced apart along the main body. It can be appreciated that the main cavity can have other contoured surfaces to create other products and / or stoppers with different shapes.

[0010] According to one embodiment, the bottom plate can have a flat surface configured to form a stopper having a flat surface at its distal end. According to another embodiment, the bottom plate can include a contoured surface configured to form a stopper having a distal end in the form of a flat at the outer edge of the closed forward end or distal end of the stopper, extending inward from the outer edge of the stopper, the contoured surface being shaped to form a protrusion extending from the closed forward end, the protrusion intersecting the distal end of the stopper to define a base and extending from the flat at the top of the closed forward end, the protrusions configured to cooperate within the syringe barrel to reduce dead space during injection. It can be appreciated that the bottom plate can have other designs to create stoppers having various shapes at their distal ends.

[0011] The method can further include providing a film, such as a barrier film, between the bottom plate and the main plate, such that the film is sandwiched between the bottom plate and the main plate when the mold is closed and secured to the molded device when the device is removed from the mold. It can be appreciated that the barrier film can be, for example, a known film that provides a low-friction barrier between the stopper and the pharmaceutical composition (e.g., a drug, medication, or other therapeutic material) in the syringe barrel, preventing materials from leaching out of the stopper or compounds from being extracted from the pharmaceutical composition by the stopper. The method can further include trimming and removing excess film from the molded device.

[0012] According to another aspect, the present disclosure relates to a system for molding a device, such as a stopper, including a mold assembly having a top plate, a sprue / vent plate, a main plate, and a bottom plate. The sprue / vent plate includes a core extending from its surface. It can be appreciated that the core can have any shape depending on the desired interior shape of the device or stopper to be molded. For example, the core can have a threaded design, a conical section with an enlarged portion toward the intersection of the core and the sprue / vent plate, straight sidewalls, etc. The main plate of the mold includes a recess defining a mold cavity with a contoured surface. The mold cavity is configured to receive the core from the sprue / vent plate and defines a space corresponding to the shape of the molded device. An injection nozzle and runner are fitted to the top plate. The injection nozzle and runner are configured to deliver polymeric material to the mold cavity to fill the space and form a molded device having a body and molding surface corresponding to the contoured surface. At least one cooling member is provided for cooling the polymeric material within the mold cavity.

[0013] The system further includes a first mechanism for separating the sprue / vent plate from the main plate to extract the core from within the molded device, a second mechanism for separating the sprue / vent plate from the top plate, and a third mechanism for separating the bottom plate from the main plate to allow removal of the molded device from the main plate. According to one embodiment, the first, second, and third mechanisms for separating the top, sprue / vent plate, main, and bottom plates of the mold assembly comprise a series of spring mechanisms or a series of core lifters with different forces for sequentially separating the sprue / vent plate from the main plate, the sprue / vent plate from the top plate, and the bottom plate from the main plate, and the spring mechanisms include guide pins to limit the opening of each plate.

[0014] According to one embodiment, a film can be inserted between a bottom plate and a main plate, and the mold can be closed to sandwich the film between the bottom plate and the main plate, securing the film to the device being formed. The system can further include a trim die for removing excess film from the device being formed. According to one design, the trim die can be comprised of a flat punch for removing excess film, although it can be understood that other types of dies having other types of cutting surfaces, such as a razor edge, and / or other types of trimming devices, with or without an air blast, can be used to remove excess film.

[0015] According to yet another aspect, the present disclosure is directed to a stopper adapted to attach to a plunger rod for use in a syringe barrel. The stopper comprises a main body defining an open rearward end, a closed forward end, and a cylindrical sidewall extending between the open rearward end and the closed forward end. The open rearward end is adapted to receive a mounting portion of the forward end of the plunger rod. The stopper further includes at least one rib extending radially outward around the outer periphery of the main body. The at least one rib is configured to form an active seal with the syringe barrel. A flat is provided on an upper outer peripheral surface of the closed forward end of the stopper adjacent to the at least one rib. The flat extends inward from the outer edge of the stopper. The stopper further includes a protrusion extending from the closed forward end, the protrusion defining a base intersecting the distal end of the stopper and extending from the flat to the apex of the closed forward end. The base has a base diameter that is smaller than an outer diameter of the distal end of the stopper, and the protrusion has a profile configured to cooperate with an inner surface of the syringe barrel to reduce dead space during injection.

[0016] Further embodiments of the present disclosure are now described in the following numbered clauses:

[0017] Clause 1: A method of molding a device, comprising the steps of: providing a mold assembly having a top plate, a sprue / vent plate including a core portion, a main plate including a recess defining a mold cavity having a contoured surface, and a bottom plate; closing the mold assembly so that the core portion fits into the recess in the main plate to define a space corresponding to the shape of the device; introducing a polymeric material into the mold cavity to fill the mold cavity and the space and form a molded device having a body and molding surface corresponding to the contoured surface; separating the sprue / vent plate from the main plate to extract the core portion from within the molded device; then separating the sprue / vent plate from the top plate; then separating the bottom plate from the main plate; and removing the molded device from the main plate.

[0018] Clause 2: The method of clause 1, wherein the step of separating the sprue / vent plate from the main plate disengages the vent and extracts the core from within the molding apparatus and the main plate.

[0019] Clause 3: The method of clause 1 or 2, wherein the step of removing the molded device from the main plate comprises removing the molded device through the bottom of the main plate.

[0020] Clause 4: A method according to any one of clauses 1 to 3, wherein the step of introducing the polymeric material into the mold cavity comprises injecting the polymeric material into the mold cavity through an injection nozzle and runner associated with the top plate.

[0021] Clause 5: A method according to any one of claims 1 to 4, wherein after the step of introducing the polymeric material into the mold cavity, the mold assembly is heated to harden the polymeric material or the mold assembly is cooled by supplying a cooling material to the main plate.

[0022] Clause 6: The method of any one of clauses 1 to 5, wherein the contoured surface of the main cavity is in the shape of a stopper having a main body defining an open rearward end, a closed forward end, and a cylindrical sidewall extending between the open rearward end and the closed forward end.

[0023] Clause 7: The method of clause 6, wherein the contoured surface shape is configured to form a plurality of ribs extending radially outward around the outer periphery of the main body and spaced axially along the main body.

[0024] Clause 8: The method of clause 6 or clause 7, wherein the bottom plate has a flat surface configured to form a stopper having a flat surface, or the bottom plate includes a contoured surface configured to form a stopper having a flat portion at an outer edge of the closed forward end of the stopper and extending inward from the outer edge of the stopper, the contoured surface being shaped to form a protrusion extending from the closed forward end, the protrusion defining a base that intersects the distal end of the stopper and extends from the flat portion at the top of the closed forward end, the protrusions being configured to cooperate within the syringe barrel to reduce dead space during injection.

[0025] Clause 9: A method according to any one of clauses 1 to 8, comprising providing a film between the bottom plate and the main plate, wherein upon closing of the mould assembly the film is sandwiched between the bottom plate and the main plate, and upon removal of the device from the mould assembly the film is secured to the device being moulded.

[0026] Clause 10: The method of any one of clauses 1 to 9, comprising trimming excess film from the formed device.

[0027] Clause 11: A system for molding a device, comprising: a mold assembly having a top plate, a sprue / vent plate, a main plate, and a bottom plate, the sprue / vent plate including a core portion extending from a surface thereof, the main plate including a recess defining a mold cavity having a contoured surface, the mold cavity configured to receive the core portion from the sprue / vent plate to define a space corresponding to the shape of the device to be molded; and an injection nozzle and runner fitted to the mold assembly and top plate, the injection nozzle and runner providing a polymeric material to the mold cavity. a first mechanism for separating the sprue / vent plate from the main plate to extract the core from within the molded device; a second mechanism for separating the sprue / vent plate from the top plate; and a third mechanism for separating the bottom plate from the main plate to allow the molded device to be removed from the main plate.

[0028] Clause 12: The system described in Clause 11, wherein the first, second, and third mechanisms for separating the top plate, sprue / vent plate, main plate, and bottom plate of the mold assembly comprise a series of spring mechanisms or a series of core lifters with different forces for sequentially separating the sprue / vent plate from the main plate, the sprue / vent plate from the top plate, and the bottom plate from the main plate, and the spring mechanisms include guide pins for limiting the opening of each of the plates.

[0029] Clause 13: A system as described in clause 11 or clause 12, wherein a film can be inserted between the bottom plate and the main plate, and by closing the mould the film is sandwiched between the bottom plate and the main plate so that it is fixed to the device in which it is moulded.

[0030] Clause 14: A system as described in any one of clauses 11 to 13, including a trim die having a flat punch for removing excess film from the device being formed, the trim die optionally including a center portion having an opening through which a clean air blast can travel to remove trimmed parts from the trim die or die block.

[0031] Clause 15: A stopper adapted for attachment with a plunger rod for use in a syringe barrel, the stopper comprising: a main body defining an open rearward end, a closed forward end, and a cylindrical sidewall extending between the open rearward end and the closed forward end; a barrier film covering at least the closed forward end of the main body, the open rearward end being adapted to receive an attachment portion of the forward end of the plunger rod; and at least one rib extending radially outwardly around an outer periphery of the main body to facilitate active closure with the syringe barrel. and at least one rib configured to form a hole, a flat portion adjacent to the at least one rib on an upper outer peripheral surface of the closed forward end, the flat portion extending inwardly from the outer edge of the stopper, a protrusion extending from the closed forward end, the protrusion defining a base intersecting the closed forward end of the stopper and extending from the flat portion to an upper portion of the closed forward end, the base having a base diameter smaller than an outer diameter of the distal end of the stopper, the protrusion having a profile configured to cooperate with an inner surface of a syringe barrel to reduce dead space during injection.

[0032] Clause 16: The stopper of clause 15, wherein the flat portion has a width of about 0.75 to 1 mm to the start of the upwardly sloping surface forming the projection.

[0033] Clause 17: A stopper according to clause 15 or 16, wherein at least one rib comprises a first rib, a second rib, and a third rib, and the second rib has a smaller diameter than the first rib and the third rib.

[0034] Clause 18: A stopper as described in any one of clauses 15 to 17, wherein the open rear end of the stopper includes a cavity configured to receive an attachment portion of the forward end of the plunger rod, and the inner surface of the cavity includes a plunger rod cavity protrusion extending from the bottom surface of the closed forward end of the stopper.

[0035] Clause 19: A stopper as described in Clause 18, wherein the plunger rod cavity protrusion is configured to lightly engage a mounting portion at the front end of the plunger rod to increase the force transmitted to the front of the stopper, and the plunger rod cavity protrusion has sloped side walls.

[0036] Clause 20: A stopper as described in any one of clauses 15 to 19, wherein the open rear end of the stopper includes a cavity having a series of threads for screw attachment to the mounting end of the plunger rod, the threads having a slightly decreasing pitch towards the bottom of the plunger rod cavity.

[0037] Clause 21: A stopper according to any one of clauses 15 to 20, having a monotonically decreasing thickness between the roof profile spline AA-BB and the internal roof projection LL, projecting upward to a point XX.

[0038] Clause 22: A stopper according to clause 21, wherein point XX is within the range of 0.25 to 0.75 mm within the thickness of the stopper wall defined by YY. [Brief explanation of the drawings]

[0039] The above and other features and advantages of the present disclosure, and the manner in which they are achieved, will become more apparent, and the disclosure itself will be better understood, by reference to the following description of embodiments of the disclosure taken in conjunction with the accompanying drawings. [Figure 1A] FIG. 1A is a top perspective view of a stopper for use in a syringe according to one embodiment of the present invention. [Figure 1B] FIG. 1B is a side perspective view of the stopper of FIG. 1A according to an embodiment of the present invention. [Figure 2A] FIG. 2A is a top perspective view of a stopper for use in a syringe according to an embodiment of the present invention. [Figure 2B] FIG. 2B is a cross-sectional side view of the stopper of FIG. 2A in accordance with an embodiment of the present invention. [Figure 3] FIG. 3 is a cross-sectional side view of a four-plate, one-shot injection molded device that can be used to form molded devices such as the stoppers of FIGS. 1A-1B and 2A-2B according to one embodiment of the present invention. [Figure 4] FIG. 4 is a perspective view of the mold of FIG. 3 in an open state, including removal of the mold stopper, according to an embodiment of the present invention. [Figure 5A] FIG. 5A illustrates sequential steps in molding a device using the mold of FIG. 3 according to an embodiment of the present invention. [Figure 5B] FIG. 5B illustrates sequential steps in molding a device using the mold of FIG. 3 according to an embodiment of the present invention. [Figure 5C] FIG. 5C illustrates sequential steps in molding a device using the mold of FIG. 3 according to an embodiment of the present invention. [Figure 5D] FIG. 5D illustrates sequential steps in molding a device using the mold of FIG. 3 according to an embodiment of the present invention. [Figure 5E] FIG. 5E illustrates sequential steps in molding a device using the mold of FIG. 3 according to an embodiment of the present invention. [Figure 6A] FIG. 6A is a side view of a die punch for cutting excess barrier film after molding of the stopper of FIGS. 1A-1B according to an embodiment of the present invention. [Figure 6B] FIG. 6B is a side view of the die punch of FIG. 6A including air channels for removing excess film according to an embodiment of the present invention. [Figure 7A] FIG. 7A is a side view of the stopper of FIGS. 1A-1B according to an embodiment of the present invention. [Figure 7B] FIG. 7B is a cross-sectional view of the stopper of FIG. 7A taken along line BB in accordance with an embodiment of the present invention. [Figure 7C]FIG. 7C is a top view of the stopper of FIG. 7A in accordance with an embodiment of the present invention. [Figure 7D] FIG. 7D is a bottom view of the stopper of FIG. 7A in accordance with an embodiment of the present invention. [Figure 7E] 7E is a side view of the stopper of FIG. 7A with a portion of the stopper cut away to show the interaction between the plunger rod core and an interior portion of the distal end of the stopper, according to an embodiment of the present invention. [Figure 7F] 7F is a partial cross-sectional perspective view of the stopper of FIG. 7A showing the internal threads and internal portion of the distal end of the stopper in accordance with an embodiment of the present invention. [Figure 7G] FIG. 7G is a cross-sectional view of the stopper of FIG. 7A illustrating that the pitch of the internal thread of the stopper increases towards the bottom of the plunger rod cavity in accordance with an embodiment of the present invention. [Figure 8] 8 is a cross-sectional view of a stopper secured to the mounting end of a plunger rod molded with the molding apparatus of FIG. 3 according to an embodiment of the present invention. [Figure 9A] 9A shows the stopper design of FIG. 8 assembled within a syringe barrel before and after application of a distally directed force to the plunger rod and stopper in accordance with an embodiment of the present invention. [Figure 9B] 9B shows the stopper design of FIG. 8 assembled within a syringe barrel before and after application of a distally directed force to the plunger rod and stopper in accordance with an embodiment of the present invention. [Figure 10A] FIG. 10A is a representative diagram illustrating the amount of dead space created within a syringe barrel after applying a distal force to the plunger rod using the stopper design of FIGS. 1A-1B in accordance with an embodiment of the present invention. [Figure 10B] FIG. 10B is a representative diagram illustrating the amount of dead space created within a syringe barrel after applying a distal force to the plunger rod using the stopper design of FIGS. 2A-2B in accordance with an embodiment of the present invention. [Figure 11] FIG. 11 is a perspective cross-sectional view of a stopper according to an embodiment of the present invention.

[0040] Corresponding reference characters indicate corresponding parts in the several views. The illustrations set forth herein illustrate exemplary embodiments of the present disclosure, and such illustrations should not be construed as limiting the scope of the present disclosure in any way. DETAILED DESCRIPTION OF THE INVENTION

[0041] The following description is provided to enable any person skilled in the art to make and use the described embodiments contemplated for practicing the invention. However, various modifications, equivalents, variations, and alternatives will be readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the present invention.

[0042] Hereinafter, for purposes of explanation, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "transverse," "longitudinal," and their derivatives will refer to the present invention as oriented in the drawings. However, it will be understood that the present invention may assume various alternative modifications unless expressly specified to the contrary. It should also be understood that the specific devices illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the present invention. Therefore, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered limiting.

[0043] Also, in describing this invention, the term "distal end" is intended to refer to the end of the syringe from which the needle protrudes and the end of the stopper closest to the needle, and the term "proximal end" is intended to refer to the end of the syringe closest to the syringe holder and furthest from the tip of the needle and the end of the stopper furthest from the tip of the needle.

[0044] 1A-1B and 2A-2B, which illustrate two different types of stoppers 10, 110 that can be manufactured in a four-plate, one-shot injection molding system, generally designated as 50, in FIGS. 3 and 4 of the present disclosure. The stoppers can include a plurality of annular ribs 12, 112 configured to fluid-tightly engage and seal with the interior surface of the syringe barrel 16, as shown in FIGS. 9A1-9E2.

[0045] A syringe barrel typically includes an open proximal end, a distal end 38, and a cylindrical body portion therebetween that defines a chamber for holding a liquid, such as a liquid medicament, as shown in Figures 9A and 9B. The syringe barrel may be made of glass, plastic, or a combination thereof, and may include a flange at the proximal end. Examples of plastic materials that can be used to form the syringe barrel include, but are not limited to, substantially transparent thermoplastic materials such as polycarbonate, polypropylene, polyethylene terephthalate (PET), and the like.

[0046] The stopper 10, 110 can be positioned for fluid-tight engagement within the barrel by the action of the annular rib 12, 112, with the distal end 20, 120 of the stopper 10, 110 facing the distal end of the syringe barrel. The distal end 38 of the syringe barrel includes a passageway 39 in fluid communication with the chamber. Although not shown, an elongated needle cannula having a lumen extending therethrough can be provided for connection to the distal end 38 of the barrel, such that the lumen is in fluid communication with the chamber through the passageway. It can be appreciated that the needle can be permanently attached to the syringe barrel, such as with an adhesive, or can be removably attached to the syringe barrel, such as via a needle hub that is permanently attached to the needle cannula and frictionally attached to the tip at the distal end of the syringe barrel. The stopper 10, 110 can slide within the chamber for initial positioning adjacent the medicament and thereafter to urge the medicament through the lumen of the needle cannula or the passageway at the distal end of the syringe barrel 38. Alternatively, stopper 10, 110 can be slid within the syringe barrel for reconstitution purposes.

[0047] A barrier film 14,114 may be provided on the distal end 20,120 of the stopper to reduce and / or eliminate direct contact between the material of the stopper 10,110 and the contents of the syringe, reducing friction between the contents of the syringe and the stopper 10,110.

[0048] Continuing with reference to FIGS. 3 and 4, a four-plate injection molding system 50 is shown. While this molding system is directed to molding stoppers for use on syringe plunger rods, it will be understood that this molding system may also be used to mold other products, such as medical vial or test tube closures, or other known molded devices. Molding system 50 is comprised of a mold assembly 52 having a top plate 54, a sprue / vent plate 56, a main plate 58, and a bottom plate 60. Sprue / vent plate 56 includes a core portion 62 extending from its bottom surface 64. It will be appreciated that core portion 62 may have any shape depending on the desired interior shape of the molded device or stopper 10, 110. For example, core portion 62 may have a threaded design, a conical portion with an enlarged portion toward the intersection of the core portion and the sprue / vent plate, straight sidewalls, etc. The mold main plate 58 includes a recess 66 that defines a mold cavity 68 having a contoured surface 70. The mold cavity 68 is configured to receive the core 62 from the sprue / vent plate 56 and defines a space 72 corresponding to the shape of the molded device. An injection nozzle 74 and runners 76 are fitted to the top plate 54. The injection nozzle 74 and runners 76 are configured to deliver polymeric material to the mold cavity 68 to fill the space 72 and form a molded device having a body and molding surface corresponding to the contoured surface 70. At least one cooling member 78 is provided to cool the polymeric material within the mold cavity 58. The cooling member 78 may be a series of tubes containing a cooling medium flowing therethrough or other known cooling members.

[0049] The system 50 further includes a first mechanism 80 for separating the sprue / vent plate 56 from the main plate 58 to withdraw the core 62 from within the molded device 10,110, a second mechanism 81 for separating the sprue / vent plate 56 from the top plate 54, and a third mechanism 82 for separating the bottom plate 60 from the main plate 58 to allow removal of the molded device 10,110 from the main plate 58. According to one embodiment, the first, second, and third mechanisms 80, 81, 82 for separating the top, sprue / vent, main, and bottom plates of the mold assembly comprise a series of spring mechanisms with varying forces for sequentially separating the sprue / vent plate 56 from the main plate 58, the sprue / vent plate 56 from the top plate 54, and the bottom plate 60 from the main plate 58. The spring mechanisms may include guide pins that limit the opening of each plate. It can also be appreciated that the first, second, and third mechanisms 80, 81, 82 for separating the top plate, sprue / vent plate, main plate, and bottom plate of the mold assembly can be comprised of a series of core lifters.

[0050] According to one embodiment, the barrier film 14, 114 can be inserted between the bottom plate 60 and the main plate 58, and then the mold assembly 52 can be closed to sandwich the film 14, 114 between the bottom plate 60 and the main plate 58, securing the film 14, 114 to the molded body 10, 110. The use of this barrier film 14, 114 in the stopper improves the slidability of the stopper within the syringe barrel. The barrier film 14, 114 preferably does not exhibit adverse effects on the drug and does not contain silicone-based materials such as silicone oil. One example of a usable barrier film 14, 114 is a fluoropolymer resin laminate, which is known to have good biocompatibility, good mechanical integrity, is inert, and is processable. Due to the excellent strength of the expanded fluoropolymer structure, these materials can form a thin barrier that remains intact during the molding process and during attachment of the stopper to the syringe barrel. For example, the barrier film may be selected from the group consisting of polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), expanded polytetrafluoroethylene (ePTFE), etc. A trim mold 84, described in more detail below and shown in Figures 6A and 6B, may be provided to remove excess barrier film 14, 114 from the molded device.

[0051] Reference is now made to Figures 5A through 5E, which illustrate sequential steps for molding the device 10,110 using the four-plate injection molding system 50 of the present invention. Referring to Figure 5A, the method includes providing a four-plate mold assembly 52 having a top plate 54, a sprue / vent plate 56 including a core portion 62, a main plate 58 including a recess 66 defining a mold cavity 68 having a contoured surface 70, and a bottom plate 60; closing the mold assembly 52 so that the core portion 62 enters the recess 66 in the main plate 58 to define a space 72, as shown in Figure 3, corresponding to the shape of the device 10,110 to be molded; and introducing a polymeric material into the mold cavity 68 to fill the mold cavity 68 and the space to form the molded device 10,110. The mold assembly 52 may include an optional component 53 including a pin-like member (not shown) that can be manually held by an operator to push the part out of the cavity plate 58.

[0052] The molded device has a body 18, 118 and a molding surface corresponding to the contoured surface 70 of the mold cavity 68. Depending on the type of polymeric material used, such as a thermoplastic elastomer, the method may include a step of cooling the polymeric material. If the polymeric material comprises uncured rubber, the material is introduced into the mold cavity and the mold is heated to a temperature, such as about 180°C, to cure the rubber. After the polymeric material has cooled or been heated to cure the rubber, as shown in FIG. 5B, the sprue / vent plate 56 is separated from the main plate 58, and the core 62 is extracted from the mold cavity 68, recess 66, and molded device 10, 110. Next, the sprue / vent plate 56 is separated from the top plate 54, as shown in FIG. 5C. Next, the bottom plate 60 is separated from the main plate 58, as shown in FIG. 5D. The molded device or stopper 10, 110 can be removed, such as from the bottom portion 59 of the main plate 58, as shown in FIG. 5E.

[0053] Separating the sprue / vent plate 56 from the main plate 58 disengages the vents 57 and allows the core 62 to be pulled from within the molded device 10, 110 and main plate 58, as shown in FIG. 4 . It can be appreciated that the core 62 can be designed to have several shapes depending on the desired interior shape of the device or stopper 10, 110. For example, the core can have a threaded design, a cone-shaped section with an enlarged portion toward the intersection of the core and sprue / vent plate, straight sidewalls, etc. Once the plates of the mold assembly 52 are opened, the molded device 10, 110 can be removed from the main plate 58 by pulling the molded device from the bottom 59 of the main plate 58.

[0054] Returning to FIG. 3 , introducing the polymeric material into the mold cavity 68 involves injecting the polymeric material through injection nozzles 74 and runners 76 associated with the top plate 54 into the mold cavity 68. The polymeric material can be a synthetic rubber, although it is understood that other materials, such as natural rubber, elastomers, and combinations thereof, can be used. Examples of elastomers that can be used for the polymeric material include, but are not limited to, silicone rubber, natural rubber, styrene-butadiene rubber (SBR), ethylene-propylene-diene monomer (EPDM), polychloroprene, and the like. When the polymeric material comprises an elastomer, it is typically heated to approximately 225°C, depending on the material. Alternatively, when the material comprises a thermoset rubber, for example, the material is heated only to a molten state (i.e., approximately 20°C to 50°C) so that it can be poured into the mold cavity. Cooling the mold assembly, if necessary, can include supplying a cooling medium to the main plate 58, such as via cooling tubes 78.

[0055] 1A-1B and 2A-2B, the contoured surface of the main cavity may be shaped as a stopper 10,110 having a main body 18,118 defining an open rearward end 22,122 and a closed forward or distal end 20,120, and a cylindrical sidewall 24,124 extending between the open rearward end 22,122 and the closed forward or distal end 20,120. According to one embodiment, the contoured surface shape is configured to form a plurality of annular ribs 12,112 extending radially outwardly around and axially spaced apart along the main body 18,118. It can be appreciated that the main cavity may have other contoured surfaces to produce other products and / or to produce stoppers 10,110 having different shapes.

[0056] According to one embodiment, the bottom plate 60 can have a flat surface configured to form a stopper 110 having a flat surface 121 at its distal end 120, as shown in Figures 2A and 2B. According to another embodiment, the bottom plate 60 can include a contoured surface configured to form a stopper 10 having a distal end 20, as shown in Figures 1A and 1B. The overall shape of the stopper of Figures 1A and 1B is discussed below in the description of Figures 7A-7G. However, bottom plate 60 has a contoured surface configured to produce a stopper having a distal end 20 shaped at outer edge 28 of closed forward or distal end 20 of stopper 10, with flat 26 extending inward from outer edge 28 of stopper 10 and protrusion 30 extending from closed forward or distal end 20, protrusion 30 defining a base 32 that intersects with closed forward or distal end 20 of the stopper and including a sloped portion 34 extending upward from flat 26 at the top of closed forward or distal end 20 to protrusion 30. Sloped portion 34 is described in more detail below in connection with FIG. 7B . This protrusion is configured to cooperate within syringe barrel 16 to reduce dead space during injection. It can be appreciated that bottom plate 60 can have other designs to produce stoppers having various shapes at their distal ends.

[0057] The method may further include providing a film, such as barrier film 14,114, between bottom plate 60 and main plate 58, such that film 14,114 is sandwiched between bottom plate 60 and main plate 58 upon closing of mold assembly 52, and film 14,114 is secured to the molded device upon removal of the device from mold assembly 52. ​​It may be appreciated that barrier film 14,114 may be any known film that provides, for example, a low-friction barrier between stopper 10,110 and the pharmaceutical composition (e.g., a drug, medication, or other therapeutic material) within syringe barrel 16, inhibiting leaching of material from stopper 10,110 or extraction of compounds from the pharmaceutical composition by stopper 10,110.

[0058] 6A and 6B, the method further includes trimming and removing excess film 14, 114 from the molded device 10, 110. This trimming step can be performed with a trim die 84. According to one design, the trim die can consist of a flat punch 86 for removing excess film 14, 114. The trim die 84 includes a punch center with an opening 88 through which clean air can pass to remove the trimmed part from the mold block 85. The flat punch 86 has a flat surface 87 for removing excess film 14, 114. The center portion 90 of the punch 86 is deep enough to allow for repeated sharpening, making it more cost-effective than using a razor-edged die punch 86 (used when the stopper does not have a flat portion and instead has a conical slope beginning from the stopper edge and top rib). Razor edges wear quickly, requiring punches to be individually sharpened, which adds cost. However, it can be appreciated that other types of dies having other types of cutting surfaces, such as a razor edge, and / or other types of trimming devices can be used to remove excess film.

[0059] 1A and 1B, and further reference to Figures 7A-7G, one type of stopper 10 that can be manufactured using the injection molding system 50 of the present disclosure is shown. Stopper 10 is adapted for attachment to a mounting end 17 of a plunger rod for use in a syringe barrel 16, as shown in Figures 9A-9B.

[0060] As described above, stopper 10 comprises a main body 18 defining an open rearward end 22, a closed forward or distal end 20, and a cylindrical sidewall 24 extending between the open rearward end and the closed forward or distal end 20. A barrier film 14 (not shown in FIGS. 7A-7G ) may be provided adjacent at least the closed forward or distal end 20. The open rearward end 22 is adapted to receive a mounting edge 17 of the forward end of a plunger rod. Stopper 10 further includes at least one rib 12 extending radially outward around the periphery of the main body. At least one rib 12 is configured to form an active seal with a syringe barrel 16. The annular or circumferentially extending rib 12 is intended to provide a stable, fluid-tight seal between the stopper body and the syringe barrel. It can be understood that more than one rib may be provided. In the embodiment disclosed in Figures 7A-7G, the main body 18 can include first, second, and third ribs 12a, 12b, 12c extending radially outward from the outer periphery of the main body and spaced axially along the main body 18.

[0061] The ribs 12 include recesses 13 therebetween, with the ribs 12 having an outer diameter that is greater than the outer diameter of the recesses 13. The ribs 12 may have a curved shape when viewed from the distal end of the stopper body 10. It can be appreciated that other embodiments of the stopper may be formed using the molding system 50 of the present disclosure, including those having smooth cylindrical sides.

[0062] The open rearward end 22 of the stopper 10 defines a cavity 35 configured to receive the forward mounting end 17 of a plunger rod. According to the embodiment shown in FIGS. 7A-7G, the cavity 35 includes threads 36 configured to cooperate with the threads 17a of the forward mounting end 17 of the plunger rod, as shown in FIGS. 9A and 9B. It can be appreciated that there are numerous ways to couple the plunger rod to the stopper 10, 110, and the threaded arrangement is illustrative of many possibilities. For example, the cavity 35 of the stopper 10 can have a reduced diameter or neck at the proximal end of the cavity 35 and / or at the open rearward end 22 of the stopper 10. According to one arrangement, the cavity 35 can be shaped to receive the tip or protrusion 30 of the distal or forward mounting end 17 of a plunger rod having an enlarged distal end, such that the parts fit together in a snap-fit ​​arrangement. According to another embodiment, the stopper 10 is adhesively attached to or molded onto the mounting end 17 of the plunger rod.

[0063] 7A-7G, a flat 26 is provided on the upper outer peripheral surface of the closed forward or distal end 20 of the stopper 10 adjacent at least one rib 12. The flat 26 extends inward from the outer edge 28 of the stopper 10. According to one embodiment, the flat 26 may be approximately 0.75 to 1 mm wide to the beginning of an upwardly sloping surface 34 that forms a cone-shaped projection 30 with an apex at the apex of the closed forward or distal end 20 of the stopper 10. The projection 30 defines a base 32 that intersects with the closed forward or distal end 20 of the stopper 10 and extends from the flat 26 to the apex of the closed forward or distal end 20. Base 32 has a base diameter "BD" that is smaller than the outer diameter "OD" of the closed forward or distal end 20 of stopper 10, and protrusion 30 has a profile configured to cooperate with inner surface 40 of the syringe barrel, as shown in FIGS. 9A and 9B, to reduce dead space during injection.

[0064] 7B, 7E, and 7F, the stopper 10 of the present disclosure can be designed so that the second rib 12b is slightly smaller in diameter (up to 4% to 15%) than the other ribs 12a and 12c to reduce the sliding force of the stopper while maintaining a seal. The rib radius at the apex of the second rib 12b can be approximately 0.45 to 0.65 mm, depending on the barrel diameter, resulting in a low sliding force. The bottom of the cavity 35 of the stopper 10 can include a plunger rod cavity protrusion 42. This cavity protrusion 42 is designed to lightly engage the forward mounting end 17 of the plunger rod, initially pulling on the front rib 12a and quickly increasing the force transmitted to the front of the stopper (versus transmitting an axial load through the threads) for easier removal of the stopper 10 (reducing the initial removal force). The sidewall 42a of the protrusion 42 is angled steeply, such as at an angle of approximately 60°, relative to a vertical line extending through the tip of the stopper 10, to provide a light initial contact with the forward mounting end 17 of the plunger rod, but a rapid increase in force. Still referring to FIG. 7B , the thickness between the roof profile spline AA-BB and the internal roof projection LL can monotonically decrease upward to point XX, which can be located between 0.25 and 0.75 mm within the stopper wall thickness defined by YY. This special design avoids downward roof buckling and wrinkles in the barrier film 14 at locations where the stopper has a thin cross section.

[0065] As shown in FIG. 7G, the pitch of the stopper thread can be variable and non-constant, increasing toward the rearward end or proximal face 22 of the stopper and / or toward the bottom of the plunger rod cavity 35. This initially applies more pressure to the front face of the stopper 10, concentrating the applied thumb force on the plunger rod and loosening the first rib 12a of the stopper. This also results in the stopper rib being pulled, progressively disengaging from the container wall, instead of the pusher acting on the rearward end or proximal face 22 of the stopper 10. For example, as shown in FIG. 7G, the first pitch L1 can be shorter in length than the second pitch L2. According to one embodiment, the pitch can range from 2.1 mm to 1.4 mm from L2 to L1. For example, the pitch from L2 to L1 can be reduced by approximately two turns, with L2 being approximately 1.73 mm and L1 being approximately 1.57 mm.

[0066] FIG. 8 illustrates a stopper 10 secured to the mounting end 17 of a plunger rod that can be produced using the four-plate injection molding system 50 of the present invention. It can be appreciated that this stopper 10 can be formed with or without a barrier film 14, 114. FIGS. 9A and 9B illustrate the interaction of the stopper design of FIG. 8 within a syringe barrel 16 after assembly and application of 10 lbf (pound force) or 44.5 N to the plunger rod. FIG. 8 is similar in design to stopper 10 of FIGS. 7A through 7G. As shown in FIG. 9B, these stoppers minimize dead space within the syringe barrel 16 after application of 10 lbf (44.5 N) to the plunger rod.

[0067] 10A and 10B, it has been found that the stopper 10 of FIG. 10A, which has a conical head or conical projection 30 at its distal end 20, significantly reduces dead space at the end of an injection compared to the stopper 110 of FIG. 10B, which has a flat surface or flat head 121 at its distal end 120. This dead space traps the drug or medicament between the distal end 20, 120 of the stopper 10, 110 and the inner surface 40, 140 of the distal end of the syringe barrel 16, 116. This trapped drug is often referred to as dead volume, represented by 41 in FIG. 10A and 141 in FIG. 10B. This dead volume 41, 141 remains within the syringe at the end of an injection and cannot be injected, no matter how much force is applied to the plunger rod at the end of the injection. The flat-head stopper 110 shown in FIGS. 2A-2B and 10B is typically used with pre-filled syringes ranging in size from 1 ml to 3 ml. However, a finite element analysis (FEA) was performed to compare the dead volume 41 of the conical-nosed stopper 10 of Figures 1A-1B and 10A with the dead volume 141 of the flat-nosed stopper 110 of Figures 2A-2B and 10B. The results of this analysis are shown in Table 1 below. Typically, the force exerted on the stopper is between 10 and 25 N, although Table 1 also shows values ​​above (44.5 N) and below (8.9 N) this typical range.

[0068] [Table 1]

[0069] As can be seen from Table 1, the dead volume 41 of the conical stopper 10 is approximately 4.5 mm 3 The dead volume 141 is approximately 11.5 mm 3 from 18.2 mm 3 is significantly smaller than the flat head stopper 110, which is in the range of .

[0070] Reference is now made to FIG. 11 , which illustrates a stopper design including a fourth rib 12d on the base 23 of the stopper 10. This design includes a thicker front portion 46 than the designs of FIGS. 7A through 7G . This thicker front portion 46 helps to reduce buckling of the stopper 10. This particular design, like the designs of FIGS. 7A through 7G , includes a distal end 20 in the form of a flat 26 on the outer edge 28 of the closed forward or distal end 20 of the stopper 10, extending inward from the outer edge 28 of the stopper 10, and a protrusion 30 extending from the closed forward or distal end 20, the protrusion 30 defining a base 32 that intersects the closed forward or distal end 20 of the stopper, and including a sloped portion 34 extending upward from the flat 26 at the top of the closed forward or distal end 20 to the protrusion 30. As discussed above in connection with FIG. 10A , the protrusion 30 is configured to cooperate within the syringe barrel 16 to reduce dead space during injection.

[0071] While this disclosure has been described as having an exemplary design, the disclosure can be further modified within the spirit and scope of the disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the disclosure as come within known or customary practice in the art to which this disclosure pertains and fall within the scope of the appended claims.

Claims

1. A method for forming a formed product, comprising: providing a mold assembly having a top plate, a sprue / vent plate including a core portion, a main plate including a recess defining a mold cavity having a contoured surface, and a bottom plate; closing the mold assembly so that the core portion enters the recess of the main plate to define a space corresponding to the shape of the molded product to be molded; introducing a polymeric material into the mold cavity to fill the mold cavity and the space and form the molded product having a body and molding surface corresponding to the contoured surface; separating the sprue / vent plate from the main plate to extract the core from within the molded product; then separating the sprue / vent plate from the top plate; then separating the bottom plate from the main plate; removing the molded product from the main plate; A method for forming a molded product, comprising:

2. The method described in claim 1, wherein the sprue / vent plate has a vent, and the step of separating the sprue / vent plate from the main plate causes the vent to come off and the core portion to be pulled out from within the molded product and the main plate.

3. The method of claim 1 , wherein the step of removing the molded product from the main plate comprises removing the molded product through the bottom of the main plate.

4. 2. The method of claim 1, wherein the step of introducing the polymeric material into the mold cavity comprises injecting the polymeric material into the mold cavity through an injection nozzle and runner associated with the top plate.

5. 2. The method of claim 1, wherein after the step of introducing the polymeric material into the mold cavity, the mold assembly is heated to harden the polymeric material or the mold assembly is cooled by supplying a cooling material to the main plate.

6. 2. The method of claim 1, wherein the contoured surface of the mold cavity is in the shape of a stopper having a main body defining an open rearward end, a closed forward end, and a cylindrical sidewall extending between the open rearward end and the closed forward end.

7. The method of claim 6 , wherein the contoured surface is configured to define a plurality of ribs extending radially outwardly around an outer periphery of the main body and spaced axially along the main body.

8. the bottom plate has a flat surface configured to form a stopper having a flat surface; or 7. The method of claim 6, wherein the bottom plate includes a contoured surface configured to form the stopper having a flat at an outer edge of a closed forward end of the stopper and extending inwardly from the outer edge of the stopper, the contoured surface having a shape that forms a protrusion extending from the closed forward end, the protrusion defining a base that intersects the distal end of the stopper and extends from the flat at the outer edge of the closed forward end, the protrusions configured to cooperate within the syringe barrel to reduce dead space during injection.

9. 2. The method of claim 1, further comprising providing a film between the bottom plate and the main plate, wherein the film is sandwiched between the bottom plate and the main plate when the mold assembly is closed, and the film is secured to the molded product when the molded product is removed from the mold assembly.

10. 10. The method of claim 9, including the step of trimming excess film from the formed product.

11. A system for forming a formed product, comprising: a mold assembly having a top plate, a sprue / vent plate, a main plate, and a bottom plate, the sprue / vent plate including a core portion extending from a surface thereof, the main plate including a recess defining a mold cavity having a contoured surface, the mold cavity configured to receive the core portion from the sprue / vent plate to define a space corresponding to the shape of the molded product to be molded; an injection nozzle and runner fitted to the top plate, the injection nozzle and runner configured to deliver polymeric material to the mold cavity to fill the space and form the molded product having a body and molding surface corresponding to the contoured surface; at least one cooling member for cooling the polymeric material within the mold cavity; a first mechanism for separating the sprue / vent plate from the main plate to extract the core from within the molded product; a second mechanism for separating the sprue / vent plate from the top plate; a third mechanism for separating the bottom plate from the main plate to allow the molded product to be removed from the main plate; A system comprising:

12. 12. The system of claim 11, wherein the first mechanism, the second mechanism, and the third mechanism for separating the top plate, the sprue / vent plate, the main plate, and the bottom plate in the mold assembly comprise a series of spring mechanisms or a series of core lifters with different forces for sequentially separating the sprue / vent plate from the main plate, the sprue / vent plate from the top plate, and the bottom plate from the main plate, and the spring mechanisms include guide pins for limiting the opening of each of the plates.

13. 12. The system of claim 11, wherein a film can be inserted between the bottom plate and the main plate, and closing the mold assembly sandwiches the film between the bottom plate and the main plate such that the film is secured to the molded product.

14. 14. The system of claim 13, including a trim die having a flat punch for removing excess film from the formed product.

Images