WO2022051470A1

WO2022051470A1 - Tamper-evident cap

Info

Publication number: WO2022051470A1
Application number: PCT/US2021/048831
Authority: WO
Inventors: Lou KENNEDY; Lance ROGERS; William YTTRE
Original assignee: Nephron Pharmaceuticals Corporation
Priority date: 2020-09-02
Filing date: 2021-09-02
Publication date: 2022-03-10

Abstract

A tamper-evident cap comprises a housing having an inner receiving space, a first end, and a second end positioned opposite the first end, the second end having a syringe receiving opening in communication with the inner receiving space; an end plug connected to the second end of the housing; and an inner plug positioned in the inner receiving space.

Description

TAMPER-EVIDENT CAP

RELATED APPLICATIONS

[0001] The presently disclosed subject matter claims priority and is related to U.S. Provisional Patent Application No. 63/073,664 entitled “Tamper-Evident Cap” and filed on September 2, 2020; the entire disclosure of which is incorporated herein by reference.

FIELD

[0002] The invention is generally related to syringe caps, and, more specifically, to tamper- evident caps for syringes (such as, for example, a Luer Lock IV syringe by Medicina Ltd.).

BACKGROUND

[0003] Tamper-evident caps for syringes are commonly used to close and seal prefilled syringes, and to provide visual indications as to whether the prefilled syringe has been tampered with. Typically these conventional tamper-evident caps use various configurations of two or three piece assemblies having a luer lock engaging component and a breakaway component connected to the luer lock engaging component through a frangible connection. The tamper- evident cap can be screwed onto a female or male luer lock on a dispensing end of a syringe. Unscrewing the tamper-evident cap from the syringe results in the frangible connection breaking, separating the breakaway component from the luer lock engaging component.

[0004] While these conventional tamper-evident caps often provide the desired visual indications, one of the drawbacks is that the designs are often problematic when large scale automated manufacturing processes are employed. For instance, a common issue observed with the conventional tamper-evident caps is that the luer lock engaging component is mis-threaded on the syringe luer lock during installation, causing the cap to fall off or not seal the syringe. The cause of this is often associated with a common design characteristic and the automated process used to install the conventional of the tamper-evident caps. For example, the luer lock engaging component typically can freely spin in relation to the other components in the cap, which is needed in order for the cap to be screwed onto the syringe luer lock. When a tamper evident cap is being connected to the syringe luer lock, the automated equipment use torque measurements to gauge whether a cap has been fully seated on the syringe luer lock. The luer lock engaging component has been observed to engage the syringe luer lock threads prematurely and essentially thread lock before the luer lock engaging component is fully aligned with the syringe luer lock. However, since the automated equipment is only using torque as a measurement threshold, when thread lock occurs, the torque force is met, which is incorrectly interpreted by the automated equipment as the tamper-evident cap being fully seated on the syringe luer lock.

[0005] Therefore, there is a need for tamper-evident caps that have one or more improvements over conventional caps.

SUMMARY

[0006] In an aspect, a tamper-evident cap comprises a housing having: an inner receiving space, a first end, and a second end positioned opposite the first end, the second end having a syringe receiving opening in communication with the inner receiving space; an end plug connected to the second end of the housing; and an inner plug positioned in the inner receiving space. In some embodiments, the inner receiving space comprises a first region having a first inner diameter proximate to the first end, and a second region having a second inner diameter proximate to the second end, the first inner diameter being less than the second inner diameter. [0007] In some instances, an outer housing surface forming the first region comprises at least one rib positioned along a longitudinal axis extending along the first end to the second end of the housing. The outer housing surface can comprise 2, 3, 4, 5, 6, 7, 8, or more ribs in some cases. [0008] The inner receiving space can have an approximate t-shape cross-sectional view along the longitudinal axis. In some embodiments, an inner housing surface forming the second region of the inner receiving space comprises a circumferentially extending groove proximate the second end of the housing.

[0009] In some embodiments, an end plug comprises an outer securing ring having an inner circumferential surface, and an outer circumferential surface with an outer diameter approximately equal to the second inner diameter of the inner receiving space; and an inner breakaway ring connected to the inner circumferential surface of the outer securing ring through two or more frangible linkers. The outer circumferential surface of the outer securing ring can in some instances comprise a circumferentially extending protrusion having a shape complementary to the circumferentially extending groove. The end plug can be snap fit into the syringe receiving opening of the housing with the circumferentially extending protrusion being positioned in the circumferentially extending groove. In some instances, the outer circumferential surface of the end plug contacts at least a portion of the inner surface of the second region of the inner receiving space.

[0010] In some cases, the housing can comprise two or more ramps protruding from an inner surface of the first end of the housing into the inner receiving space. Each ramp comprises an inclined surface and an opposite vertical surface extending perpendicular from the inner surface of the first end along the longitudinal axis. The inner plug can in some instances comprise a ratcheting end, and a syringe engaging end positioned opposite the ratcheting end. The inner plug comprises two or more ramps protruding from the ratcheting end of the inner plug. Each ramp of the inner plug comprises an inclined surface and an opposite vertical surface extending perpendicular from the ratcheting end. The inclined surfaces of the housing ramps engage the inclined surfaces of the inner plug ramps upon rotation of the inner plug in a first direction, allowing the inner plug to spin freely in the first direction; and the vertical surfaces of the housing ramps engage the vertical surfaces of the inner plug ramps upon rotation of the inner plug in an opposite second direction, preventing rotation of the inner plug in the second direction.

[0011] In some embodiments, the syringe engaging end of the inner plug comprises a female portion of a luer locking or luer slip mechanism. In some cases, the inner plug further comprises a breakaway flange positioned proximate to the syringe engaging end, the flange protrudes radially outward from the inner plug perpendicular to a longitudinal axis extending from ratcheting end to the syringe engaging end. The flange can have a flange diameter greater than the inner diameter of the first region and less than the inner diameter of the second region of the inner receiving space of the housing. In some cases, the flange has a diameter greater than or equal to a diameter of the inner breakaway ring, and less than a diameter of the outer securing ring .

[0012] In some embodiments, removal of the inner plug from the cap contacts a surface of the flange facing the syringe receiving end with the inner breakaway ring of the end plug, the frangible linkers of the inner breakaway ring being broken upon application of a force from the flange on the inner breakaway ring. [0013] In another aspect, method of assembling a tamper- evident cap described herein comprises inserting the ratcheting end of the inner plug into the inner receiving space of the housing to contact the ratcheting end with the inner surface of the first end of the housing; and inserting the outer securing ring of the end plug into the syringe receiving opening of the housing; and snap fitting the end plug into the syringe receiving opening by engaging the circumferentially extending protrusion on the end plug into the circumferentially extending groove of the housing.

[0014] In yet another aspect, a method of connecting and removing a syringe from the taper- evident cap described herein comprises inserting a male luer lock hub of a syringe through a hub receiving aperture of the inner breakaway ring to contact the female luer lock portion of the inner plug; rotating the syringe in the second direction to engage the female luer lock portion of the inner plug with the male luer lock hub of the syringe to form a friction fit between the inner plug and the syringe, the rotation in the second direction engaging the vertical surfaces of the housing ramps with the vertical surfaces of the inner plug ramps. In some instances, the housing turns freely in the first direction and not in the second direction when the syringe is attached to the tamper-evident cap. The method can in some instances further comprise breaking the frangible linkers and separating the inner breakaway ring by pulling the attached syringe out of the inner receiving space. In some cases, the surface of the inner plug flange facing the syringe receiving end contacts the inner breakaway ring and breaks the frangible linkers through applying a force from the flange to the inner breakaway ring. The removed syringe comprises the syringe hub attached to the inner plug and the inner breakaway ring surrounding the syringe hub, the inner plug and inner breakaway rings serving as a visual and physical indicator that the cap has been tampered with.

BRIEF DESCRIPTION OF THE FIGURES

[0015] FIG. 1 is a perspective view of an assembled exemplary tamper-evident cap.

[0016] FIG. 2A is a side view of a conventional luer lock syringe and the exemplary tamper- evident cap of FIG. 1 prior to the cap being installed on the syringe.

[0017] FIG. 2B is a side view of a conventional luer lock syringe with the exemplary tamper- evident cap of FIG. 1 installed on the syringe luer lock.

[0018] FIG. 3 is a side view of an exemplary tamper-evident cap housing. [0019] FIG. 4 is a plan view of a first end of the housing shown in FIG. 3.

[0020] FIG. 5 is a perspective view of a second end of the housing shown in FIG. 4.

[0021] FIG. 6 is a side view of an exemplary tamper-evident cap end plug.

[0022] FIG. 7 is a perspective view of an exemplary tamper-evident cap end plug.

[0023] FIG. 8 is a top view of an exemplary tamper-evident cap end plug.

[0024] FIG. 9 is a cross-sectional view of an exemplary tamper-evident cap inner plug.

[0025] FIG. 10 is an exploded view of the exemplary tamper-evident cap in FIG. 1.

[0026] FIG. 11 is a cross-sectional view of an exemplary tamper-evident cap of FIG. 1 installed on a conventional luer lock syringe.

[0027] FIG. 12 is a perspective view of a syringe with a breakaway ring and inner plug attached.

DETAILED DESCRIPTION

[0028] Embodiments described herein can be understood more readily by reference to the following detailed description and examples. Elements, apparatus and methods described herein, however, are not limited to the specific embodiments presented in the detailed description and examples. It should be recognized that these embodiments are merely illustrative of the principles of this disclosure. Numerous modifications and adaptations will be readily apparent to those of skill in the art without departing from the spirit and scope of this disclosure.

[0029] In addition, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of “1.0 to 10.0” should be considered to include any and all subranges beginning with a minimum value of 1.0 or more and ending with a maximum value of 10.0 or less, e.g., 1.0 to 5.3, or 4.7 to 10.0, or 3.6 to 7.9.

[0030] All ranges disclosed herein are also to be considered to include the end points of the range, unless expressly stated otherwise. For example, a range of “between 5 and 10,” “from 5 to 10,” or “5-10” should generally be considered to include the end points 5 and 10.

[0031] The terms “tamper-evident cap” and “cap are used interchangeably for purposes of brevity, and have the same meaning unless stated otherwise.

I. Tamper-Evident Cap [0032] In an aspect, a tamper-evident cap is described and disclosed herein. FIGS. 1-11 show an exemplary tamper-evident cap 1 comprising a housing 10, an end plug 30, and an inner plug 20. Referring to FIGS. 3-5 and 11, housing 10 comprises an inner receiving space 15, a first end 10a, and a second end 10b positioned opposite the first end 10a, the second end 10b having a syringe receiving opening 17 in communication with the inner receiving space 15. Housing 10 is generally cylindrical in a preferred embodiment, but is not limited to this shape. In some embodiments, housing 10 can have any shape not inconsistent with the objectives of this disclosure.

[0033] For reference purposes herein, a longitudinal axis L extends from the first end 10a to the second end 10b.

[0034] In some embodiments, inner receiving space 15 comprises a first region 11 and a second region 12. The first region 11 has a first inner diameter DI proximate to the first end 10a, and second region 12 has a second inner diameter D2 proximate to the second end 10b. In some cases, the first inner diameter DI is less than the second inner diameter D2. The changes in diameter between DI and D2 result in a shelf 13 being formed. As shown in FIG. 11, shelf 13 extends approximately perpendicular to longitudinal axis L, although in other embodiments, shelf 13 can extend orthogonally to longitudinal axis L.

[0035] In some embodiments, housing 10 comprises an outer housing surface forming first region 11. One or more ribs 14 are positioned longitudinally on the outer housing surface, extending approximately from first end 10a of the first region 11 to the beginning of the second region 12 of housing 10 approximately where shelf 13 is formed. In some instances, the outer housing surface comprises a plurality of ribs 14, such as 2, 3, 4, 5, 6, 7, 8, or more ribs. Ribs 14 have several notable functions that provide one or more advantages over conventional tamper- evident caps. For example, as previously discussed, automated equipment typically uses torque measurements to gauge whether a tamper-evident cap has been fully seated on the syringe luer lock. By only using torque as a measurement threshold, when a conventional cap is mis-threaded onto a syringe, thread lock can occur, prematurely meeting the predetermined torque force threshold. The automated equipment incorrectly interprets this event as the conventional tamper- evident cap being fully seated on the syringe luer lock, when, in fact, the conventional cap is not. This results in the production of a statistically relevant number of syringes with conventional caps that leak or fall off. [0036] The use of ribs 14 on a tamper evident cap 1 described herein provides a visual index for automated equipment to rapidly measure an angle of rotation when installing tamper-evident cap. By combining an angle of rotation measurement with a torque measurement, multiple verification methods are employed to verify that the tamper-evident cap 1 has been correctly installed on a syringe.

[0037] An additional advantage is that the ribs provide a contoured surface optimized for gripping the tamper-evident cap 1 with automated equipment during installation, allowing precise torque and angle of rotation measurements.

[0038] Ribs 14 can have any shape not inconsistent with the objectives of this disclosure, such as having a general quadrilateral shape. Ribs 14 can have a uniform thickness or width in some embodiments, or can vary in thickness and/or width along the longitudinal axis. In the exemplary embodiments shown in FIGS. 3 and 4, ribs 14 are tapered along longitudinal axis L. [0039] Inner receiving space 15 has an approximate t-shaped cross-sectional view along longitudinal axis L, formed from first region 11 and first inner diameter DI, and second region 12 and second inner diameter D2, as shown for example in FIG. 11. In some embodiments, inner housing surface forming second region 12 comprises a circumferentially extending groove 16 proximate the second end 10b of housing 10, such as is shown in FIGS. 5 and 11. In other embodiments, the inner housing surface comprises a circumferentially extending protrusion 16 instead of a groove. As described in more detail below, end cap 30 comprises a complimentarily shaped protrusion or groove that engages with the groove/protrusion 16 of housing 10.

[0040] In some embodiments, housing 10 comprises two or more ramps 18 protruding from an inner surface of first end 10a into inner receiving space 15. Each ramp comprises an inclined surface and an opposite vertical surface extending perpendicular from the inner surface of the first end 10a along the longitudinal axis.

[0041] As shown for example in FIGS. 6-8, end plug 30 is connected to the second end 10b of housing 10. End plug 30 comprises an outer securing ring 31 and an inner breakaway ring 34. Outer securing ring 31 has a stepped profile, such as is shown in FIG 6, with a flange 33a and a securing insert 33b extending from one end of flange 33a. Securing insert 33b has an inner circumferential surface and an outer circumferential surface with an outer diameter OD approximately equal to the second inner diameter D2 of the inner receiving space 15. [0042] The outer circumferential surface of securing insert 33b comprises a circumferentially extending protrusion or groove 32 having a shape complementary to the circumferentially extending groove or protrusion 16 of housing 15. In practice, end plug 30 is snap fit into the syringe receiving opening 17 of housing 10 with the circumferentially extending protrusion 16 being positioned in the circumferentially extending groove 32 in some cases, such as is shown in FIG. 11. In other cases, circumferentially extending protrusion 32 of end cap 30 is positioned in the circumferentially extending groove 16 of housing 10 to snap fit end cap 30 to housing 10. When end cap 30 is connected to housing 10, the outer circumferential surface of the end plug 30 contacts at least a portion of the inner surface of the second region 12 of the inner receiving space 15 of housing 10.

[0043] Inner breakaway ring 34 is connected to the inner circumferential surface of outer securing ring 31 through two or more frangible linkers 35, shown for example, in FIG. 8. Inner breakaway ring 34 further comprises a syringe receiving aperture 36, through which a dispensing end of a syringe can be inserted to engage inner plug 20, as illustrated in FIGS. 2A and 2B. As described in more detail below and shown in FIG. 12, when the syringe is pulled out of the syringe receiving aperture 36 along the longitudinal axis L, inner plug 20 is displaced from the inner receiving space 15 of housing 10 to contact inner breakaway ring 34. When a user pulls the syringe with a force greater than a force needed to break the frangible linkers 35, the frangible linkers 35 will break, separating the inner breakaway ring 34 from the end plug 30 and housing

10, as shown in FIG. 12. The inner breakaway ring 34 will remain on the end of the syringe until inner plug 20 is detached from the syringe. The separated inner breakaway ring 34 therefore serves as a visual indicator that the syringe has been tampered with.

[0044] FIGS. 9-11 illustrate different views of inner plug 20. As shown specifically in FIG.

11, inner plug 20 is positioned in the inner receiving space 15 of housing 10, and is secured therein by end cap 30. Inner plug 20 comprises a ratcheting end 22a, and a syringe engaging end 22b positioned opposite the ratcheting end 22a along longitudinal axis L.

[0045] The inner plug 20 comprises two or more ramps 24 protruding from the ratcheting end22a. Each ramp 24 comprises an inclined surface and an opposite vertical surface extending perpendicular (outward along longitudinal axis L) from the ratcheting end 22a. The inclined surfaces of the housing ramps 18 engage the inclined surfaces of the inner plug ramps 24 upon rotation of the inner plug 20 in a first direction, allowing the inner plug 20 to spin freely in the first direction; and the vertical surfaces of the housing ramps 18 engage the vertical surfaces of the inner plug ramps 24 upon rotation of the inner plug in an opposite second direction, preventing rotation of the inner plug 20 in the second direction. For example, when the inner plug 20 is turned in a counter-clockwise manner with respect to housing 10, the inner plug 20 will freely spin since the includes surfaces of both ramps 18,24 will rotationally slide across one another. However, turning the inner plug 20 in a clockwise manner will contact the vertical surfaces of ramps 18,24, preventing movement of the inner plug 20 in the clockwise direction. As described in more detail herein, when a syringe is being screwed onto the syringe engaging end 22b of the inner plug 20, the inner plug 20 does not rotate in the second direction (e.g. clockwise), allowing the syringe to be screwed into the syringe engaging end 22b. However, rotation in the first direction after syringe engagement will offer low resistance, allowing the inner plug 20 to freely spin in the second direction (e.g. counterclockwise) without offering enough resistance to allow the syringe to unscrew from the inner plug 20.

[0046] In some embodiments, a syringe engaging end 22b comprises a female portion of a luer locking or luer slip mechanism. In the embodiments shown for example in FIG. 9, a luer locking mechanism 21 is shown on the syringe engaging end, comprising a threaded outer surface 22 for engaging complimentary threads on a syringe. In embodiments where a luer slip mechanism is used, the threads 22 can optionally be omitted. The dimensions of the luer locking or luer slip mechanism 21 can be any standardized dimensions known in the art. FIG. 11 illustrates a cross-sectional view of a luer lock syringe 100 engaged

[0047] Referring again to FIG. 9, the inner plug 20 can further comprise a breakaway flange 23 positioned proximate to the syringe engaging end 22b, the flange 23 protrudes radially outward from the inner plug perpendicular to longitudinal axis L extending from ratcheting end 22a to the syringe engaging end 22b. Flange 23 has a flange diameter greater than the inner diameter of the first region 11 and less than the inner diameter of the second region 12 of the inner receiving space 15 of the housing 10. Flange 23 also has a flange diameter greater than or equal to a diameter of the inner breakaway ring 34, and less than a diameter of the outer securing ring 31 of end plug 30. When the inner plug 20 is removed from the cap 1, a surface of inner plug flange 23 facing the syringe receiving end 22b of inner plug 20 contacts the inner breakaway ring 34 of the end plug 30, the frangible linkers 35 of the inner breakaway ring 34 are broken upon application of a force from the flange 23 on the inner breakaway ring 34. Stated differently, when an attached syringe 100 is pulled outward from cap 1 along longitudinal axis 1, flange 23 off the inner plug 20 contacts the inner breakaway ring 34, severing the frangible linkers 35, allowing the syringe 100 to be removed from the cap 1. As shown in FIG. 12, the inner breakaway ring 34 and inner plug 20 remain connected to the removed syringe 100, providing a visual indicator that cap 1 has been removed.

II. Method of Assembling Tamper-Evident Cap

[0048] In another aspect shown in FIG. 10, a method of assembling a tamper-evident cap described in Section I herein comprises inserting the ratcheting end of the inner plug into the inner receiving space of the housing to contact the ratcheting end with the inner surface of the first end of the housing; and inserting the outer securing ring of the end plug into the syringe receiving opening of the housing; and snap fitting the end plug into the syringe receiving opening by engaging the circumferentially extending protrusion on the end plug into the circumferentially extending groove of the housing.

III. Method of Installing and Using Tamper-Evident Cap

[0049] In another aspect as shown for instance in FIGS. 2 A and 2B, a method of connecting a syringe from the taper-evident cap of Section I herein comprises inserting a male luer lock hub of a syringe through a hub receiving aperture of the inner breakaway ring to contact the female luer lock portion of the inner plug; and rotating the syringe in the second direction to engage the female luer lock portion of the inner plug with the male luer lock hub of the syringe to form a friction fit between the inner plug and the syringe, the rotation in the second direction engaging the vertical surfaces of the housing ramps with the vertical surfaces of the inner plug ramps. The cap housing can turn freely in the first direction and not in the second direction when the syringe is attached to the tamper-evident cap.

[0050] To remove the connected syringe, the method can further comprise breaking the frangible linkers and separating the inner breakaway ring by pulling the attached syringe out of the inner receiving space. In some embodiments, a surface of the inner plug flange facing the syringe receiving end contacts the inner breakaway ring and breaks the frangible linkers through applying a force from the flange to the inner breakaway ring. As shown for instance in FIG. 12, the removed syringe comprises the syringe hub (luer locking mechanism port) attached to the inner plug and the inner breakaway ring surrounding the syringe hub. The broken inner breakaway ring serves as a tamper-evidence indicator that the cap has been removed from the syringe.

Claims

1. A tamper-evident cap comprising: a housing having: an inner receiving space, a first end, and a second end positioned opposite the first end, the second end having a syringe receiving opening in communication with the inner receiving space; an end plug connected to the second end of the housing; and an inner plug positioned in the inner receiving space.

2. The cap of claim 1, wherein the inner receiving space comprises: a first region having a first inner diameter proximate to the first end, and a second region having a second inner diameter proximate to the second end, the first inner diameter being less than the second inner diameter.

3. The cap of claim 2, wherein an outer housing surface forming the first region comprises at least one rib positioned along a longitudinal axis extending along the first end to the second end of the housing.

4. The cap of claim 3, wherein the outer housing surface comprises 2, 3, 4, 5, 6, 7, 8, or more of the ribs.

5. The cap of any of claims 1-4, wherein the inner receiving space has an approximate t- shape cross-sectional view along the longitudinal axis.

6. The cap of any of claims 1-5, wherein an inner housing surface forming the second region of the inner receiving space comprises a circumferentially extending groove proximate the second end of the housing.

7. The cap of claim 6, wherein the end plug comprises: an outer securing ring having: an inner circumferential surface, and an outer circumferential surface with an outer diameter approximately equal to the second inner diameter of the inner receiving space; and an inner breakaway ring connected to the inner circumferential surface of the outer securing ring through two or more frangible linkers.

8. The cap of claim 7, wherein the outer circumferential surface of the outer securing ring comprises a circumferentially extending protrusion having a shape complementary to the circumferentially extending groove.

9. The cap of claim 8, wherein the end plug is snap fit into the syringe receiving opening of the housing with the circumferentially extending protrusion being positioned in the circumferentially extending groove.

10. The cap of claim 9, wherein the outer circumferential surface of the end plug contacts at least a portion of the inner surface of the second region of the inner receiving space.

11. The cap of any of claims 1-10, wherein the housing comprises two or more ramps protruding from an inner surface of the first end of the housing into the inner receiving space.

12. The cap of claim 11, wherein each ramp comprises an inclined surface and an opposite vertical surface extending perpendicular from the inner surface of the first end along the longitudinal axis.

13. The cap of claim 11 or 12, wherein the inner plug comprises: a ratcheting end, and a syringe engaging end positioned opposite the ratcheting end.

14. The cap of claim 13, wherein the inner plug comprises two or more ramps protruding from the ratcheting end of the inner plug.

15. The cap of claim 14, wherein each ramp of the inner plug comprises an inclined surface and an opposite vertical surface extending perpendicular from the ratcheting end.

16. The cap of claim 14 or 15, wherein the inclined surfaces of the housing ramps engage the inclined surfaces of the inner plug ramps upon rotation of the inner plug in a first direction, allowing the inner plug to spin freely in the first direction; and the vertical surfaces of the housing ramps engage the vertical surfaces of the inner plug ramps upon rotation of the inner plug in an opposite second direction, preventing rotation of the inner plug in the second direction.

17. The cap of any of claims 13-16, wherein the syringe engaging end comprises a female portion of a luer locking or luer slip mechanism.

18. The cap of claim 17, wherein the inner plug further comprises a breakaway flange positioned proximate to the syringe engaging end, the flange protrudes radially outward from the inner plug perpendicular to a longitudinal axis extending from ratcheting end to the syringe engaging end.

19. The cap of claim 18, wherein the flange has a flange diameter greater than the inner diameter of the first region and less than the inner diameter of the second region of the inner receiving space of the housing.

20. The cap of claim 18, wherein the flange has a diameter greater than or equal to a diameter of the inner breakaway ring, and less than a diameter of the outer securing ring .

21. The cap of claim 18, wherein removal of the inner plug from the cap contacts a surface of the flange facing the syringe receiving end with the inner breakaway ring of the end plug, the frangible linkers of the inner breakaway ring being broken upon application of a force from the flange on the inner breakaway ring.

22. A method of assembling the tamper-evident cap of any of claims 1-21, comprising:

14 inserting the ratcheting end of the inner plug into the inner receiving space of the housing to contact the ratcheting end with the inner surface of the first end of the housing; and inserting the outer securing ring of the end plug into the syringe receiving opening of the housing; and snap fitting the end plug into the syringe receiving opening by engaging the circumferentially extending protrusion on the end plug into the circumferentially extending groove of the housing.

23. A method of connecting and removing a syringe from the tamper-evident cap of any of claims 1-21 comprising: inserting a male luer lock hub of a syringe through a hub receiving aperture of the inner breakaway ring to contact the female luer lock portion of the inner plug; rotating the syringe in the second direction to engage the female luer lock portion of the inner plug with the male luer lock hub of the syringe to form a friction fit between the inner plug and the syringe, the rotation in the second direction engaging the vertical surfaces of the housing ramps with the vertical surfaces of the inner plug ramps.

24. The method of claim 23, wherein the housing turns freely in the first direction and not in the second direction when the syringe is attached to the tamper-evident cap, and in the second direction when there is no downward force.

25. The method of claims 23 or 24, further comprising breaking the frangible linkers and separating the inner breakaway ring by pulling the attached syringe out of the inner receiving space.

26. The method of claim 25, wherein the surface of the inner plug flange facing the syringe receiving end contacts the inner breakaway ring and breaks the frangible linkers through applying a force from the flange to the inner breakaway ring.

27. The method of claims 25 or 26, wherein the removed syringe comprises the syringe hub attached to the inner plug and the inner breakaway ring surrounding the syringe hub.

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