Patent Application
20240286332
The present invention is directed to a method of molding a device, such as a stopper for use with a plunger rod within a syringe or a stopper for closing a vial, and more particularly, the invention is directed to a method of molding a stopper using a four-plate, one-shot injection molding device requiring minimal post-molding processing.
Syringe assemblies, in particular hypodermic syringes, are well known in the medical field for dispensing fluids, such as medications. A conventional syringe typically includes an elongate barrel having opposed proximal and distal ends and a chamber there between for receiving the fluid. 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 passageway. The proximal end of the syringe barrel slidably receives a plunger rod and stopper assembly such that force applied to the plunger rod urges the stopper along the barrel to drive liquid from the chamber through the needle cannula.
A problem with some hypodermic syringes currently on the market involves the amount of liquid which can remain in the barrel after the stopper is advanced the full length of the barrel during the injection process (i.e., the “dead volume”). Thus, there is a need to produce a stopper that is capable of reducing the amount of dead space within a syringe barrel. Various stoppers have been designed for reducing or minimizing dead space within the syringe barrel and that also adequately seal against the internal 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 comprises a piston-like stopper body for slidable fluid-tight engagement inside a syringe barrel. The body includes a distal end, a proximal end, and a longitudinal axis therethrough. A distally directed, conically-shaped projection is positioned on the distal end of the stopper body. At least one elongate discontinuity, running along the conically-shaped projection is provided. The discontinuities act to prevent unwanted immediate sealing of the projection of the stopper within a passageway extending from the syringe barrel to the needle cannula allowing any trapped fluid within the barrel to run along these discontinuities and into the passageway. Because the stopper is made of resilient material, further pressure on the plunger rod in a distal direction will distort the stopper, squeezing liquid through the passageway, which is being temporarily held open by the discontinuities.
Complex shaped stoppers having a barrier film on the distal face of the stopper are typically molded by a two-shot molding/trimming process. These types of stoppers are currently only used for low volume products where cost is not as critical. A two shot process is roughly two times as expensive as a conventional single shot process. Some commercially available barrier coated stoppers utilize a single shot molding process, however, these stoppers often have undesirable features. One of the undesirable features is that the first rib has to be a trim edge rather than a molded feature and, as such, it cannot be guaranteed to seal the fluid, nor does it ensure an optimal gliding force. Although the stopper includes two additional ribs and solves the container closure integrity (i.e., CCI) risks, such a design is not desirable for certain devices, such as precision injectors, where variable leakage past the first stopper rib affects drug dose accuracy and system hysteresis. Certain stoppers have been designed that surmount these limitations, but have so far only been produced in a manufacturing process that requires two complete molding and trimming steps. Not only is the expense of this production significant, the more steps in the process, the more chance for waste and scrap that exists. Scaling up production of these types of high-precision stoppers using a single shot molding process can result in significant economic advantages.
In accordance with one aspect, the present disclosure is directed to a method of molding a device, such as a stopper, using a one-shot injection molding device requiring minimal post-molding processing. The method comprises the steps of providing a four-plate mold assembly having 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 such that the core portion enters into the recess in the main plate to define a space corresponding to the shape of the device to be molded, and introducing a polymeric material into said mold cavity to fill said mold cavity and said space to form the molded device. The molded device will have a body and molded surface corresponding to the contoured surface of the mold cavity. The method further comprises cooling the polymeric material, separating the sprue/vent plate from the main plate to withdraw the core portion from within the molded device, followed by separating the sprue/vent plate from the top plate, which is then followed by separating the bottom plate from the main plate, and finally removing molded device or stopper from the main plate.
The step of separating the sprue/vent plate from the main plate causes the vents to break and the core portion to be withdrawn from within the molded device and the main plate. It can be appreciated that the core portion can be designed to have several shapes depending upon the desired internal shape of the device or stopper. For example, the core portion can have a threaded design, a cone-shaped portion with an enlarged portion toward the intersection of the core portion with the sprue/vent plate, a straight sidewall, and the like. Upon opening of the plates of the mold, the molded device can be removed from the main plate by pulling the molded device through the bottom of the main plate.
The step of introducing the polymeric material into the mold cavity comprises injecting a 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 includes supplying a cooling material to the main plate.
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 front end, and a cylindrical sidewall extending between the open rearward and the closed front end. According to one embodiment, the shape of the contoured surface is configured to create a plurality of ribs extending radially outward around a perimeter of the main body and axially spaced apart along this main body. It can be appreciated that the main cavity can have other contoured surfaces to make other products and/or to create stoppers having different shapes.
According to one embodiment, the bottom plate can have a flat face configured to create a stopper having a flat face at its distal end. According to another embodiment, the bottom plate can include a contoured surface configured to create a stopper having distal end in the shape of a flat portion on an outer edge of the closed front end or distal end of the stopper and extending inward from the outer edge of the stopper and wherein the contoured surface is shaped to create a projection extending from the closed front end, wherein the projection defines a base as it intersects with the distal end of the stopper and extends from the flat portion of the top of the closed front end, said projection being configured to cooperate within a syringe barrel to reduce dead space during injection. It can be appreciated that the bottom plate can have other designs to create stoppers having a variety of shapes at their distal end.
The method can further include the step of providing a film, such as a barrier film, between the bottom plate and the main plate and wherein upon closing of the mold, the film is sandwiched between the bottom plate and the main plate and upon removal of the device from the mold, the film is secured to the molded device. It can be appreciated that the barrier film can be a known film that provides a low friction barrier between, for example, the stopper and a pharmaceutical composition (e.g., a drug, medicine, or other therapeutic material) in the syringe barrel and may inhibit materials from leaching from the stopper or from extraction of compounds from the pharmaceutical composition by the stopper. The method further includes the step of trimming and removing excess film from the molded device.
In accordance with another aspect, the present disclosure is directed to a system for molding a device, such as a stopper, comprising a mold assembly having top plate, a sprue/vent plate, a main plate, and a bottom plate. The sprue/vent plate includes a core portion extending from a surface thereof. It can be appreciated that the core portion can have any shape, depending upon the desired internal shape of the device or stopper being molded. For example, the core portion can have a threaded design, a cone-shaped portion with an enlarged portion toward the intersection of the core portion with the sprue/vent plate, a straight sidewall, and the like. The main plate of the mold includes a recess defining a mold cavity having a contoured surface. This mold cavity is configured for receiving the core portion from the sprue/vent plate to define a space corresponding to the shape of the device to be molded. An injection nozzle and runner are mated to the top plate. The injection nozzle and runner are configured to supply a polymeric material into the mold cavity to fill the space to form the molded device having a body and molded surface corresponding to this contoured surface. At least one cooling member is provided for cooling the polymeric material within the mold cavity.
The system further includes a first mechanism for separating the sprue/vent plate from the main plate to withdraw the core portion 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 enable removal of the molded device from the main plate. According to one embodiment, the first, second, and third mechanisms for separating the top plate, sprue/vent plate, main plate, and bottom plate of the mold assembly comprises a series of spring mechanisms of varying force or a series of core lifters to 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 wherein the spring mechanisms include leader pins to limit the opening of each of the plates.
According to one embodiment, a film can be inserted between the bottom plate and the main plate such that closing of the mold causes the film to be sandwiched between the bottom plate and the main plate to secure the film to the molded device. The system can further include a trim die for removing excess film from the molded device. According to one design, the trim die can comprise a flat faced punch for removing the excess film, 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, with or without an air blast, can be used for removing the excess film.
In accordance with yet another aspect, the present disclosure is directed to a stopper adapted for attachment with a plunger rod for use within a syringe barrel. The stopper comprises a main body defining an open rearward end, a closed front end, and a cylindrical sidewall extending between the open rearward end and the closed front end. The open rearward end is adapted to receive a front forward end attachment portion of the plunger rod. The stopper further includes at least one rib extending radially outward around a perimeter of the main body. The at least one rib is configured for forming an active seal with the syringe barrel. A flat portion is provided on a top outer edge surface of the closed front end of the stopper adjacent the at least one rib. The flat portion extends inward from the outer edge of the stopper. The stopper further includes a projection extending from the closed front end, wherein the projection defines a base as it intersects with the distal end of the stopper and extends from the flat portion to the top of the closed front end. The base has a base diameter less than an outside diameter of the distal end of the stopper and the projection has a profile configured to cooperate with an internal surface of the syringe barrel to reduce dead space during injection.
Further examples of the present disclosure will now be described in the following numbered clauses.
Clause 1: A method of molding a device comprising the steps of: providing a mold assembly having 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 such that the core portion enters into the recess in the main plate to define a space corresponding to the shape of the device; introducing a polymeric material into said mold cavity to fill said mold cavity and said space to form said molded device having a body and molded surface corresponding to said contoured surface; separating the sprue/vent plate from the main plate to withdraw the core portion from within the molded device; followed by separating the sprue/vent plate from the top plate; followed by separating the bottom plate from the main plate; and removing said molded device from the main plate.
Clause 2: The method according to clause 1, wherein the step of separating the sprue/vent plate from the main plate causes the vents to break and the core portion to be withdrawn from within the molded device and the main plate.
Clause 3: The method according to clauses 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.
Clause 4: The method according to any one of clauses 1-3, wherein the step of introducing the polymeric material into the mold cavity comprises injecting a polymeric material into the mold cavity through an injection nozzle and runner associated with the top plate.
Clause 5: The method according to any one of claims 1-4, wherein after the step of introducing polymeric material into the mold cavity, the mold assembly is heated to cure the polymeric material or the mold assembly is cooled by supplying a cooling material to the main plate
Clause 6: The method according to any one of clauses 1-5, 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 front end, and a cylindrical sidewall extending between the open rearward and the closed front end.
Clause 7: The method according to clause 6, wherein the shape of the contoured surface is configured to create a plurality of ribs extending radially outward around a perimeter of the main body and axially spaced apart along this main body.
Clause 8: The method according to clauses 6 or 7, wherein the bottom plate has a flat face configured to create a stopper having a flat face or the bottom plate includes a contoured surface configured to create a stopper having a flat portion on an outer edge of a closed front end of the stopper and extending inward from the outer edge of the stopper and wherein the contoured surface is shaped to create a projection extending from the closed front end, wherein the projection defines a base as it intersects with the distal end of the stopper and extends from the flat portion of the top of the closed front end, said projection being configured to cooperate within a syringe barrel to reduce dead space during injection.
Clause 9: The method according to any one of clauses 1-8, including the step of providing a film between the bottom plate and the main plate and wherein upon closing of the mold assembly, the film is sandwiched between the bottom plate and the main plate and upon removal of the device from the mold assembly, the film is secured to the molded device.
Clause 10: The method according to any one of clauses 1-9, including the step of trimming excess film from the molded device.
Clause 11: A system for molding a device comprising: a mold assembly having 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, said mold cavity configured for receiving the core portion from the sprue/vent plate to define a space corresponding to the shape of the device to be molded; an injection nozzle and runner mated to the top plate, said injection nozzle and runner configured for supplying a polymeric material into the mold cavity to fill said space to form said molded device having a body and molded surface corresponding to said 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 withdraw the core portion 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 enable removal of the molded device from the main plate.
Clause 12: The system according to 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 comprises a series of spring mechanisms of varying force or a series of core lifters to sequentially separate 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 wherein the spring mechanisms include leader pins to limit the opening of each of the plates.
Clause 13: The system according to clauses 11 or 12, wherein a film can be inserted between the bottom plate and the main plate and wherein closing of the mold causes the film to be sandwiched between the bottom plate and the main plate such that the film is secured to the molded device.
Clause 14: The system according to any one of clauses 11-13, including a trim die with a flat faced punch for removing excess film from the molded device and wherein the trim die optionally includes a center having an opening through which a clean air blast can move therethrough to clear trimmed parts from the trim die or a die block.
Clause 15: A stopper adapted for attachment with a plunger rod for use within a syringe barrel, said stopper comprising: a main body defining an open rearward end, a closed front end, and a cylindrical sidewall extending between the open rearward end and the closed front end, a barrier film covering at least the closed front end of the main body; said open rearward end adapted to receive a front forward end attachment portion of the plunger rod; at least one rib extending radially outward around a perimeter of said main body, said at least one rib configured for forming an active seal with the syringe barrel; a flat portion on a top outer edge surface of the closed front end and adjacent the at least one rib, the flat portion extending inward from the outer edge of the stopper; and a projection extending from the closed front end, wherein the projection defines a base as it intersects with the closed front end of the stopper and extends from the flat portion to the top of the closed front end, said base having a base diameter less than an outside diameter of the distal end of the stopper and said projection having a profile configured to cooperate with an internal surface of the syringe barrel to reduce dead space during injection.
Clause 16: The stopper according to clause 15, wherein the flat portion is approximately 0.75-1 mm wide until a start of an upward slope forming the projection.
Clause 17: The stopper according to clauses 15 or 16, wherein the at least one rib comprises a first rib, a second rib, and a third rib, and wherein the second rib has a smaller diameter than the first and third rib.
Clause 18: The stopper according to any one of clauses 15-17, wherein the open rearward end of the stopper includes a cavity configured for receiving a front attachment end of the plunger rod and wherein an inner surface of the cavity includes a plunger rod cavity protrusion extending from a bottom surface of the closed front end of the stopper.
Clause 19: The stopper according to clause 18, wherein the plunger rod cavity protrusion is configured to lightly engage the front attachment end of the plunger rod to increase the force transmitted to the front of the stopper and wherein the plunger rod cavity protrusion has an angled sidewall.
Clause 20: The stopper according to any one of clauses 15-19, wherein the open rearward end of the stopper includes a cavity having a series of threads for threaded attachment with an attachment end of the plunger rod and wherein the threads have a pitch that is slightly decreasing toward a bottom of the plunger rod cavity.
Clause 21: The stopper according to any one of clauses 15-20, wherein a thickness between a roof profile spline AA-BB and an internal roof projection LL is monotonically decreasing and projects upward to point XX.
Clause 22: The stopper according to clause 21, wherein point XX is within the range of 0.25-0.75 mm within a thickness of a stopper wall defined by YY.
The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and the disclosure itself will be better understood by reference to the following descriptions of embodiments of the disclosure taken in conjunction with the accompanying drawings, wherein:
Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner.
The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention.
For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the concept as it is oriented in the drawing figures. However, it is to be understood that the concept may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the concept. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting.
Also, for purposes of the description of the present invention, the term “distal end” is intended to refer to the end of the syringe from which the needle projects and the end of the stopper which is closer to the syringe needle, whereas the term “proximal end” is intended to refer to the end of the syringe closer to the holder of the syringe and furthest from the needle tip and the end of the stopper furthest from the needle tip.
Reference is now made to
A syringe barrel typically includes an open proximal end, distal end 38, as shown in
The stopper 10, 110 can be positioned in fluid-tight engagement inside the barrel through the action of annular ribs 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 which is in fluid communication with the chamber. An elongated needle cannula having a lumen extending therethrough, not shown, can be provided for connection to the distal end 38 of the barrel so that the lumen is in fluid communication with the chamber through passageway. It can be appreciated that the needle can be permanently attached to the syringe barrel, such as through the use of adhesives, or it can be removably attached to the syringe barrel, such as through a needle hub, which 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 will be able to slide in the chamber for initial positioning adjacent a drug and for subsequently urging a drug through the lumen of the needle cannula or through the passageway of the distal end of the syringe barrel 38. Alternatively, the stopper 10, 110 can slide within the syringe barrel for reconstitution purposes.
A barrier film 14, 114 can be provided on a distal end 20, 120 of the stopper to reduce and/or eliminate direct contact of the material of the stopper 10, 110 and the syringe contents and to reduce friction between the syringe contents and the stopper 10, 110.
With continuing reference to
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 portion 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 enable 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 plate, sprue/vent plate, main plate, and bottom plate of the mold assembly comprises a series of spring mechanisms of varying force to sequentially separate 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 can include leader pins to limit the opening of each of the plates. 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 comprise a series of core lifters.
According to one embodiment, a barrier film 14, 114 can be inserted between the bottom plate 60 and the main plate 58 such that closing of the mold assembly 52 causes the film 14, 114 to be sandwiched between the bottom plate 60 and the main plate 58 to secure the film 14, 114 to the molded 10, 110. The use of this barrier film 14, 114 on a stopper improves the sliding action of the stopper within the syringe barrel. The barrier film 14, 114 should not exhibit detrimental effects to the drug and should be free of silicone-based materials, such as silicone oil. One example of barrier films 14, 114 that can be used are fluoropolymer laminates, which are known to have good biocompatibility, good mechanical integrity, are inert, and are processable. The superior strength of the expanded fluoropolymer structure allows these materials to form thin barriers, which remain intact during the forming process and installation of the stopper into the syringe barrel. For example, the barrier film may be selected from the group consisting of polytetrafluoroethylene resin (PTFE), an ethylenetetrafluoroethylene resin (ETFE), expanded polytetrafluoroethylene (ePTFE) and the like. A trim die 84, discussed in further detail below, and shown in
Reference is now made to
The molded device will have a body 18, 118 and molded outer surface corresponding to the contoured surface 70 of the mold cavity 68. Depending upon the type of polymeric material being used, such as with the use of a thermoplastic elastomer, the method can includes the step of cooling the polymeric material. If the polymeric material comprises an uncured rubber, after the material is introduced into the mold cavity, the mold is heated, such as to approximately 180° C. to cure the rubber. After the polymeric material is cooled or after the rubber is heated to cure, the sprue/vent plate 56 is separated from the main plate 58, as shown in
The step of separating the sprue/vent plate 56 from the main plate 58 causes the vents 57, as shown in
Referring back to
Referring back to
According to one embodiment, the bottom plate 60 can have a flat face configured to create a stopper 110 having a flat face 121 at its distal end 120, as shown in
The method can further include the step of providing a film, such as a barrier film 14, 114, between the bottom plate 60 and the main plate 58 and wherein upon closing of the mold assembly 52, the film 14, 114 is sandwiched between the bottom plate 60 and the main plate 58 upon removal of the device from the mold assembly 52, the film 14, 114 is secured to the molded device. It can be appreciated that the barrier film 14, 114 can be a known film that provides a low friction barrier between, for example, a stopper 10, 110 and a pharmaceutical composition (e.g., a drug, medicine, or other therapeutic material) in the syringe barrel 16 and may inhibit materials from leaching from the stopper 10, 110 or from extraction of compounds from the pharmaceutical composition by the stopper 10, 110.
With reference to
With continuing reference to
As discussed above, the stopper 10 comprises a main body 18 defining an open rearward end 22, a closed front or distal end 20, and a cylindrical sidewall 24 extending between the open rearward end and the closed front or distal end 20. A barrier film 14 (not shown in
The ribs 12 include recesses 13 therebetween wherein the ribs 12 have an outside diameter that is greater than an outside diameter of the recesses 13. The ribs 12 can be curvilinearly shaped when viewed from a distal end of the stopper body 10. It can be appreciated that other embodiments of the stopper can be formed using the molding system 50 of the present disclosure, including those having a smooth cylindrical side surface.
The open rearward end 22 of the stopper 10 comprises a cavity 35 that is configured for receiving the front attachment end 17 of the plunger rod. According to the embodiment shown in
With continuing reference to
With particular reference to
As illustrated in
With reference to
As can be seen in Table 1, the conical head stopper 10 has a dead volume 41 of approximately 4.5 mm3, which is significantly less than the flat head stopper 110, where the dead volume 141 ranges from approximately 11.5 mm3 to 18.2 mm3.
Reference is now made to
While the disclosure has been described as having exemplary designs, the present disclosure can be further modified within the spirit and scope of this disclosure. This application is, therefore, 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 present disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the limits of the appended claims.
The present application claims priority to U.S. Provisional Application Ser. No. 63/116,533, entitled “Barrier Coated Stopper and Method of Forming Same”, filed Nov. 20, 2020, the entire disclosure of which is hereby incorporated by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US21/60005 | 11/19/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63116533 | Nov 2020 | US |
