U.S. patent application number 10/951039 was filed with the patent office on 2005-05-26 for system for filling and assembling pharmaceutical delivery devices.
This patent application is currently assigned to Duoject Medical Systems. Invention is credited to Reynolds, David L..
Application Number | 20050113763 10/951039 |
Document ID | / |
Family ID | 25539361 |
Filed Date | 2005-05-26 |
United States Patent
Application |
20050113763 |
Kind Code |
A1 |
Reynolds, David L. |
May 26, 2005 |
System for filling and assembling pharmaceutical delivery
devices
Abstract
The present invention provides for an assembly for filling and
capping a barrel of a pre-filled syringe. The assembly includes a
syringe body having a neck end, a rimmed end, and a side wall
extending between the neck end and rimmed end. The body has an
outer surface and an inner surface. The assembly includes a piston
having an upper surface, a lower surface, and a side surface
extending between the upper and lower surfaces. The inner surface
of the body and the side surface of the piston is in contact to
form a liquid impermeable seal. The assembly further includes a
stabilization member that at least partially surrounds and contacts
the outer surface of the body. The stabilization member is
positioned proximate the rimmed end of the body to provide
additional mass thereto in an amount sufficient to permit the
assembly to be conveyed freestanding in a longitudinally upright
position on the stabilization member through an apparatus for
filling and capping pharmaceutical vials. Methods for producing a
pre-filled syringe barrel are also provided.
Inventors: |
Reynolds, David L.;
(Bromont, CA) |
Correspondence
Address: |
KENNETH L. MITCHELL
WOODLING, KROST AND RUST
9213 CHILLICOTHE ROAD
KIRTLAND
OH
44094
US
|
Assignee: |
Duoject Medical Systems
Bromont
CA
|
Family ID: |
25539361 |
Appl. No.: |
10/951039 |
Filed: |
September 25, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10951039 |
Sep 25, 2004 |
|
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09993299 |
Nov 23, 2001 |
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6802828 |
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Current U.S.
Class: |
604/187 ; 222/1;
29/777 |
Current CPC
Class: |
B65B 3/003 20130101;
Y10T 29/53339 20150115; A61M 2005/31506 20130101; A61L 2/07
20130101; A61L 2/206 20130101; A61J 1/2013 20150501; A61J 1/062
20130101; A61M 2207/00 20130101; A61M 2209/045 20130101; A61L 2/20
20130101; A61J 1/2089 20130101; B65B 7/2821 20130101; A61J 1/201
20150501; Y10T 29/49826 20150115 |
Class at
Publication: |
604/187 ;
029/777; 222/001 |
International
Class: |
A61M 005/00 |
Claims
1. An assembly for filling and capping a barrel of a pre-filled
syringe, the assembly comprising: a) a syringe body having a neck
end, a rimmed end, and a side wall extending between the neck end
and rimmed end, the body having an outer surface and an inner
surface; b) a piston having an upper surface, a lower surface, and
a side surface extending between the upper and lower surfaces, the
inner surface of the body and the side surface of the piston in
contact to form a liquid impermeable seal; and c) a stabilization
member that at least partially surrounds and contacts the outer
surface of the body, the stabilization member is positioned
proximate the rimmed end of the body to provide additional mass
thereto in an amount sufficient to permit the assembly to be
conveyed freestanding in a longitudinally upright position on the
stabilization member through an apparatus for filling and capping
pharmaceutical vials.
2. An assembly according to claim 1, wherein the stabilization
member comprises a sleeve, the sleeve has a top end and a base end,
and the rimmed end of the body is positioned within the sleeve
proximate the base end of the sleeve.
3. An assembly according to claim 2, wherein the base end of the
sleeve has a radially projecting flange.
4. An assembly according to claim 3, wherein the flange has a
substantially flat outwardly facing wall that is substantially
vertical when the assembly is standing longitudinally upright.
5. An assembly according to claim 2, wherein the stabilization
member further comprises a stabilization cap having a hollow
portion with an upper end and a lower end, the lower end having a
finger flange that extends radially outwardly therefrom, the hollow
portion is sized to closely fit within the body, and the finger
flange is sized to fit within the base end of the sleeve.
6. An assembly according to claim 1, wherein the piston comprises a
material that is impermeable to liquid and sufficiently permeable
to a sterilizing gas to permit sterilization of the seal between
the inner surface of the body and the side surface of the piston
upon exposure to a sterilizing gas.
7. An assembly according to claim 1, wherein the piston comprises
neoprene.
8. An assembly according to claim 1, wherein the piston comprises a
material that is substantially resistant to the effects of at least
one standard cycle of gamma radiation.
9. An assembly according to claim 1, wherein the piston comprises
bromo-butyl rubber.
10. An assembly according to claim 9, wherein the syringe body
comprises cerium oxide in an amount sufficient to prevent
discoloration of the body upon exposure to at least one standard
cycle of gamma radiation.
11. An assembly according to claim 9, wherein the syringe body
comprises about 1 wt % cerium oxide based on the total weight of
the syringe body.
12. A method for producing a barrel for a pre-filled syringe,
comprising: a) providing a syringe body having a neck end, a rimmed
end, and a side wall extending between the neck end and rimmed end,
the body having an outer surface and an inner surface; b) providing
a piston having an upper surface, a lower surface, and a side
surface extending between the upper and lower surfaces; c)
providing a stabilization member; and d) forming an assembly
comprising the syringe body, the piston, and the stabilization
member such that: (i) the inner surface of the body contacts at
least a portion of the side surface of the piston to form a liquid
impermeable seal; (ii) the stabilization member at least partially
surrounds and contacts the outer surface of the body; and (iii) the
stabilization member is positioned proximate the rimmed end of the
body to provide additional mass thereto in an amount sufficient to
permit the assembly to be conveyed freestanding in a longitudinally
upright position on the stabilization member through an apparatus
for filling and capping pharmaceutical vials.
13. A method according to claim 12, wherein the syringe body
provided in step (a) is pre-sterilized, the piston provided in step
(b) is pre-sterilized, and the stabilization member provided in
step (c) is pre-sterilized and steps (a)-(d) are performed in an
aseptic environment.
14. A method according to claim 13, further comprising, subsequent
to step (d), the step of (e) overwrapping the assembly with an
overwrap material in an aseptic environment to maintain
sterility.
15. A method according to claim 14, further comprising, subsequent
to step (e), the steps of: f) removing the overwrap; g) filling the
body with at least one pharmaceutical component through the neck
end using the apparatus for filling and capping pharmaceutical
vials; and h) capping the neck end of the body using the apparatus
for filling and capping pharmaceutical vials.
16. A method according to claim 15, wherein the at least one
pharmaceutical component is in the form of a solid when filled into
the body.
17. A method according to claim 15, wherein the at least one
pharmaceutical component is in the form of a liquid when filled
into the body.
18. A method according to claim 17, further comprising, subsequent
to step (g) and prior to step (h), the step of lyophilizing the at
least one pharmaceutical.
19. A method according to claim 12, further comprising, prior to
step (b), the step of selecting a material for the piston that is
impermeable to liquid but sufficiently permeable to a sterilizing
gas to permit sterilization of the seal between the inner surface
and the body and the side surface of the piston upon exposure to a
sterilizing gas.
20. A method according to claim 19, further comprising, subsequent
to step (d), the step of (e) overwrapping the assembly with an
overwrap material.
21. A method according to claim 20, further comprising, subsequent
to step (e), the step of (f) sterilizing the barrel with a
sterilizing gas.
22. A method according to claim 21, further comprising, subsequent
to step (f), the steps of: g) removing the overwrap; h) filling the
body with at least one pharmaceutical component through the neck
end using the apparatus for filling and capping pharmaceutical
vials; and i) capping the neck end of the body using the apparatus
for filling and capping pharmaceutical vials.
23. A method according to claim 22, wherein the at least one
pharmaceutical component is in the form of a solid when filled into
the body.
24. A method according to claim 22, wherein the at least one
pharmaceutical component is in the form of a liquid when filled
into the body.
25. A method according to claim 24, further comprising, subsequent
to step (h) and prior to step (i), the step of lyophilizing the at
least one pharmaceutical.
26. A method according to claim 12, further comprising, prior to
step (b), the step of selecting a material for the piston that is
sufficiently resistant to at least one cycle of gamma
radiation.
27. A method according to claim 26, further comprising, prior to
step (a), the step of selecting a material for the syringe body
material that comprises cerium oxide in an amount sufficient to
prevent discoloration of the body upon exposure to at least one
cycle of gamma radiation.
28. A method according to claim 27, further comprising, subsequent
to step (d), the step of (e) overwrapping the assembly with an
overwrap material.
29. A method according to claim 28, further comprising, subsequent
to step (e), the step of (f) sterilizing the barrel with at least
one cycle of gamma radiation.
30. A method according to claim 29, further comprising, subsequent
to both steps (f) the steps of: g) removing the overwrap; h)
filling the body with at least one pharmaceutical component through
the neck end using the apparatus for filling and capping
pharmaceutical vials; and i) capping the neck end of the body using
the apparatus for filling and capping pharmaceutical vials.
31. A method according to claim 30, wherein the at least one
pharmaceutical component is in the form of a solid when filled into
the body.
32. A method according to claim 30, wherein the at least one
pharmaceutical component is in the form of a liquid when filled
into the body.
33. A method according to claim 32, further comprising, subsequent
to step (h) and prior to step (i), the step of lyophilizing the at
least one pharmaceutical.
34. A method for producing a pre-filled syringe barrel, comprising:
a) providing a sterile assembly comprising a syringe body having a
neck end, a rimmed end, a side wall extending between the neck end
and the rimmed end, an outer surface and an inner surface, a piston
having an upper surface, a lower surface, and a side surface
extending between the upper and lower surfaces and a stabilization
member, the sterile assembly formed such that: (i) the inner
surface of the body contacts at least a portion of the side surface
of the piston to form a liquid impermeable seal; (ii) the
stabilization member is at least partially surrounds and contacts
the outer surface of the body; and (iii) the stabilization member
is positioned proximate the rimmed end of the body to provide
additional mass thereto in an amount sufficient to permit the
assembly to be conveyed freestanding in a longitudinally upright
position on the stabilization member through an apparatus for
filling and capping pharmaceutical vials; b) filling the body with
at least one pharmaceutical component through the neck end using
the apparatus for filling and capping pharmaceutical vials; and c)
capping the neck end of the body using the apparatus for filling
and capping pharmaceutical vials.
35. A method according to claim 34, further comprising, prior to
step (b), the step of maintaining the assembly in an aseptic
environment until it is ready to be filled through the neck end of
the body with the at least one pharmaceutical component.
36. A method according to claim 35, wherein steps (b) and (c) are
performed in an aseptic environment.
37. A method according to claim 36, wherein the at least one
pharmaceutical component is in the form of a solid when filled into
the body.
38. A method according to claim 36, wherein the at least one
pharmaceutical component is in the form of a liquid when filled
into the body.
39. A method according to claim 38, further comprising, subsequent
to step (b) and prior to step (c), the step of lyophilizing the at
least one pharmaceutical.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of co-pending
patent application Ser. No. 09/993,299, filed on Nov. 23, 2001.
FIELD OF THE INVENTION
[0002] This invention relates to the production of prefilled
syringes for use in medical or veterinary treatment.
BACKGROUND OF THE INVENTION
[0003] Prefilled disposable syringes have gained wide acceptance as
a preferred dosage form for administration of medicaments,
primarily for reasons of safety and convenience. Most importantly,
prefilled syringes minimize handling of a medicament prior to
administration, thereby reducing the chance of dosage errors or
contamination of the medicament.
[0004] Many different types of prefilled disposable syringes have
been developed. Most known prefilled syringes include an elongate
syringe "cartridge" or "barrel" comprising a cylindrical glass or
plastic container into which the medicament or a component thereof
is prefilled. In some types of prefilled syringes, the barrel forms
the body of a syringe, having a mouth which permits attachment to
an injection needle, and a movable bottom comprising an elastomeric
piston which is acted upon by a plunger to administer the
medicament.
[0005] One common problem with prefilled disposable syringes is
that a dedicated filling and capping line is usually required to
fill the medicament into the syringe barrel. This problem has
previously been addressed by the invention described in European
Patent No. 298,585, which describes a system for producing
prefilled syringe barrels on ordinary equipment for filling and
capping pharmaceutical vials. That patent describes a system
whereby the syringe barrel is made shorter and wider than a
conventional barrel, so that it has the shape of a standard
pharmaceutical vial, and is then filled and capped on standard
machinery for filling and capping vials, through which the barrels
are conveyed while standing on their bases. Since the
pharmaceutical vial is a standardized container which is widely
used in the pharmaceutical industry, most pharmaceutical companies
have existing vial filling equipment. The equipment need only be
modified by the addition of a station for insertion of the rubber
piston into the body of the barrel. Therefore, the invention
described in that prior patent eliminates the need for specialized
filling equipment, thereby reducing cost.
[0006] Despite the improvements described in the applicant's
above-mentioned European patent, the further disadvantage exists
that the relatively squat vial-shaped barrels cannot be used in all
types of delivery systems. Some delivery systems, such as syringe
pumps and two component systems, may require the use of
conventional, elongate barrels which cannot be filled on standard
vial-filling equipment. Therefore, it would be advantageous to
provide a system which allows the preparation of conventional,
elongate prefilled syringe barrels on standard equipment for
filling and capping pharmaceutical vials.
SUMMARY OF THE INVENTION
[0007] The one aspect, the present invention provides for an
assembly for filling and capping a barrel of a pre-filled syringe
comprising:
[0008] a) a syringe body having a neck end, a rimmed end, and a
side wall extending between the neck end and rimmed end, the body
having an outer surface and an inner surface;
[0009] b) a piston having an upper surface, a lower surface, and a
side surface extending between the upper and lower surfaces, the
inner surface of the body and the side surface of the piston in
contact to form a liquid impermeable seal; and
[0010] c) a stabilization member that at least partially surrounds
and contacts the outer surface of the body, the stabilization
member is positioned proximate the rimmed end of the body to
provide additional mass thereto in an amount sufficient to permit
the assembly to be conveyed freestanding in a longitudinally
upright position on the stabilization member through an apparatus
for filling and capping pharmaceutical vials.
[0011] In a further aspect, the stabilization member comprises a
sleeve, the sleeve has a top end and a base end, and the rimmed end
of the body is positioned within the sleeve proximate the base end
of the sleeve.
[0012] In still a further aspect, the base end of the sleeve has a
radially projecting flange.
[0013] In yet a further aspect, the flange has a substantially flat
outwardly facing wall that is substantially vertical when the
assembly is standing longitudinally upright.
[0014] In still a further aspect, the stabilization member further
comprises a stabilization cap having a hollow portion with an upper
end and a lower end, the lower end having a finger flange that
extends radially outwardly therefrom, the hollow portion is sized
to closely fit within the body, and the finger flange is sized to
fit within the base end of the sleeve.
[0015] In yet a further aspect, the piston comprises a material
that is impermeable to liquid and sufficiently permeable to a
sterilizing gas to permit sterilization of the seal between the
inner surface of the body and the side surface of the piston upon
exposure to a sterilizing gas.
[0016] In still a further aspect, the piston comprises
neoprene.
[0017] In yet a further aspect, the piston comprises a material
that is substantially resistant to the effects of at least one
standard cycle of gamma radiation.
[0018] In still a further aspect, the piston comprises bromo-butyl
rubber.
[0019] In yet a further aspect, the syringe body comprises cerium
oxide in an amount sufficient to prevent discoloration of the body
upon exposure to at least one standard cycle of gamma
radiation.
[0020] In still a further aspect, the syringe body comprises about
1 wt % cerium oxide based on the total weight of the syringe
body.
[0021] In a second aspect, the present invention provides a method
for producing a barrel for a pre-filled syringe, comprising:
[0022] a) providing a syringe body having a neck end, a rimmed end,
and a side wall extending between the neck end and rimmed end, the
body having an outer surface and an inner surface;
[0023] b) providing a piston having an upper surface, a lower
surface, and a side surface extending between the upper and lower
surfaces;
[0024] c) providing a stabilization member; and
[0025] d) forming an assembly comprising the syringe body, the
piston, and the stabilization member such that: (i) the inner
surface of the body contacts at least a portion of the side surface
of the piston to form a liquid impermeable seal; (ii) the
stabilization member at least partially surrounds and contacts the
outer surface of the body; and (iii) the stabilization member is
positioned proximate the rimmed end of the body to provide
additional mass thereto in an amount sufficient to permit the
assembly to be conveyed freestanding in a longitudinally upright
position on the stabilization member through an apparatus for
filling and capping pharmaceutical vials.
[0026] In a further aspect, the syringe body provided in step (a)
is pre-sterilized, the piston provided in step (b) is
pre-sterilized, and the stabilization member provided in step (c)
is pre-sterilized and steps (a)-(d) are performed in an aseptic
environment.
[0027] In still a further aspect, the method further comprises,
subsequent to step (d), the step of (e) overwrapping the assembly
with an overwrap material in an aseptic environment to maintain
sterility.
[0028] In yet a further aspect, the method further comprises,
subsequent to step (e), the steps of:
[0029] f) removing the overwrap;
[0030] g) filling the body with at least one pharmaceutical
component through the neck end using the apparatus for filling and
capping pharmaceutical vials; and
[0031] h) capping the neck end of the body using the apparatus for
filling and capping pharmaceutical vials.
[0032] In still a further aspect, the at least one pharmaceutical
component is in the form of a solid when filled into the body.
[0033] In yet a further aspect, the at least one pharmaceutical
component is in the form of a liquid when filled into the body.
[0034] In still a further aspect, the method further comprises,
subsequent to step (g) and prior to step (h), the step of
lyophilizing the at least one pharmaceutical.
[0035] In yet a further aspect, the method further comprises, prior
to step (b), the step of selecting a material for the piston that
is impermeable to liquid but sufficiently permeable to a
sterilizing gas to permit sterilization of the seal between the
inner surface and the body and the side surface of the piston upon
exposure to a sterilizing gas.
[0036] In still a further aspect, the method further comprises,
subsequent to step (d), the step of (e) overwrapping the assembly
with an overwrap material.
[0037] In yet a further aspect, the method further comprises,
subsequent to step (e), the step of (f) sterilizing the barrel with
a sterilizing gas.
[0038] In still a further aspect, the method further comprises,
prior to step (b), the step of selecting a material for the piston
that is sufficiently resistant to at least one cycle of gamma
radiation.
[0039] In yet a further aspect, the method further comprises, prior
to step (a), the step of selecting a material for the syringe body
material that comprises cerium oxide in an amount sufficient to
prevent discoloration of the body upon exposure to at least one
cycle of gamma radiation.
[0040] In still a further aspect, the method further comprises,
subsequent to step (d), the step of (e) overwrapping the assembly
with an overwrap material.
[0041] In yet a further aspect, the method further comprises,
subsequent to step (e), the step of (f) sterilizing the barrel with
at least one cycle of gamma radiation.
[0042] In a third aspect, the present invention provides a method
for producing a pre-filled syringe barrel, comprising:
[0043] a) providing a sterile assembly comprising a syringe body
having a neck end, a rimmed end, a side wall extending between the
neck end and the rimmed end, an outer surface and an inner surface,
a piston having an upper surface, a lower surface, and a side
surface extending between the upper and lower surfaces and a
stabilization member, the sterile assembly formed such that: (i)
the inner surface of the body contacts at least a portion of the
side surface of the piston to form a liquid impermeable seal; (ii)
the stabilization member is at least partially surrounds and
contacts the outer surface of the body; and (iii) the stabilization
member is positioned proximate the rimmed end of the body to
provide additional mass thereto in an amount sufficient to permit
the assembly to be conveyed freestanding in a longitudinally
upright position on the stabilization member through an apparatus
for filling and capping pharmaceutical vials;
[0044] b) filling the body with at least one pharmaceutical
component through the neck end using the apparatus for filling and
capping pharmaceutical vials; and
[0045] c) capping the neck end of the body using the apparatus for
filling and capping pharmaceutical vials.
[0046] In a further aspect, the method further comprises, prior to
step (b), the step of maintaining the assembly in an aseptic
environment until it is ready to be filled through the neck end of
the body with the at least one pharmaceutical component.
[0047] In still a further aspect, steps (b) and (c) are performed
in an aseptic environment.
BRIEF DESCRIPTION OF THE DRAWINGS
[0048] The invention will now be described, by way of example only,
by reference to the accompanying drawings in which:
[0049] FIG. 1 schematically illustrates a method for preparing a
prefilled syringe barrel according to a first preferred embodiment
of the present invention;
[0050] FIG. 2 illustrates the lower portion of the syringe barrel
of FIG. 1 prior to insertion of the piston into the body;
[0051] FIG. 3 illustrates the lower portion of the syringe barrel
of FIG. 1 after insertion of the piston into the body;
[0052] FIG. 4 schematically illustrates a variant of the method
shown in FIG. 1 in which the syringe barrels are packaged in trays
for sterilization;
[0053] FIG. 5 schematically illustrates a variant of the method
shown in FIG. 1 in which the body is filled with a powder;
[0054] FIG. 6 schematically illustrates a variant of the method
shown in FIG. 1 in which the body is filled with a freeze-dried
medicament;
[0055] FIG. 7 illustrates combination of the syringe barrel of the
first preferred embodiment with other components to form a delivery
device for a two component medicament;
[0056] FIG. 8 schematically illustrates a method for preparing a
prefilled syringe barrel according to a second preferred embodiment
of the present invention;
[0057] FIG. 9 schematically illustrates a variant of the second
preferred embodiment in which a plurality of piston supports and
sleeves are secured to a handling tray;
[0058] FIG. 10 schematically illustrates another variant of the
second preferred embodiment in which a plurality of piston supports
are secured to a handling tray;
[0059] FIG. 11 illustrates a variant of the syringe barrel
according to the second preferred embodiment of the present
invention;
[0060] FIG. 12 illustrates a further variant of the syringe barrel
according to the second preferred embodiment of the present
invention;
[0061] FIG. 13 illustrates a further variant of the syringe barrel
according to the second preferred embodiment of the present
invention;
[0062] FIG. 14 illustrates a variant of the syringe barrel
according to the first preferred embodiment of the present
invention; and
[0063] FIG. 15 illustrates a variant of the syringe barrel
according to the first or second preferred embodiment of the
present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0064] A first preferred embodiment of the invention will now be
discussed below in the context of a syringe barrel which is
intended for use in a delivery device for a two component
medicament. Such a delivery device is described in U.S. Pat. No.
6,149,623, issued on Nov. 21, 2000 which is incorporated herein by
reference in its entirety.
[0065] FIG. 1 illustrates a preferred sequence of steps to be
followed during preparation of a prefilled syringe barrel 10 for
use in a two component delivery device. The illustrations of the
syringe barrel shown in FIG. 1 are somewhat schematic. Details of
the lower portions of the syringe barrel 10 are more clearly shown
in FIGS. 2 and 3.
[0066] The barrel 10 comprises a body 12 preferably made of glass
and having a generally cylindrical side wall 14 with an inner
surface 16 and an outer surface 18. At one end, the body 12 has a
relatively narrow neck 20 with a neck flange 21 surrounding an open
mouth 22, and at the other end the body 12 has an open rimmed end
24. Although the lower end of the body 12 is referred to herein as
the "rimmed end", it is to be appreciated that the body 12 may or
may not have a perceptible inwardly or outwardly extending rim or
flange at its lower edge.
[0067] The body 12 illustrated in FIG. 1 has a height to base ratio
of approximately 4.5:1. It will be appreciated that the present
invention can be utilized with barrels of various dimensions,
including barrels having greater height to base ratios than that
shown in FIG. 1, and barrels having lower height to base ratios,
such as the vial-shaped barrels previously described which
generally have height to base ratios not exceeding 2.5:1.
[0068] Barrel 10 further comprises a generally cylindrical
elastomeric piston 26 having an upper surface 28 which forms the
bottom wall of the barrel 10 in its assembled state, and an opposed
lower surface 30 with an internally threaded bore (not shown).
Piston 26 also has a side surface 32 connecting the upper and lower
surfaces 28 and 30, the side surface 32 being adapted to form a
hermetic seal with the inner surface 16 of body 12, and preferably
being provided with one or more ribs 34 to improve the seal with
the body 12. Piston 26 is preferably made from an elastomeric
material such as rubber.
[0069] The open mouth 22 of body 12 is sealed in a conventional
manner by an elastomeric closure 36 with an overlying metal cap 38
crimped over the neck flange 21.
[0070] Barrel 10 is also provided with an activation cap 40 at its
rimmed end 24, the cap 40 performing a number of functions which
are described below. As best seen in FIGS. 2 and 3, activation cap
40 comprises a generally cylindrical sleeve 42 having a base end 44
and a top end 46, the rimmed end 24 of body 12 being received
inside the top end 46 of sleeve 42 in a close fit with the rimmed
end 24 being located intermediate the top end 46 and the base end
44 of the sleeve 42 (best seen in FIG. 2).
[0071] Preferably, the sleeve 42 has an inwardly projecting portion
48 extending radially inwardly from the inner wall of the sleeve
42. The inwardly projecting portion 48 shown in FIG. 1 comprises a
detent of sufficient shape and size to retain the rimmed end 24 of
the syringe body 12 intermediate the top end 46 and the base end 44
of the sleeve 42 in the absence of a force which pushes the rimmed
end 24 of the body 12 and the base end 44 of the sleeve 42 toward
one another, but which permits the rimmed end 24 to be pushed
toward the base end 44 in response to a predetermined force, such
as a downward force applied to the body 12 when the barrel 10 is
standing upright on the base end 44 of the sleeve 42. As defined
herein, a detent includes any inward projection of the sleeve 42
which is effective to retain the rimmed ends 24 of the body 12,
including a continuous circumferential lip or one or more
protrusions, as shown in FIGS. 1 to 3, on the inner surface of the
sleeve 42.
[0072] The activation cap 40 further comprises piston support means
50 including a piston support surface 52 on which the piston 26 is
supported such that its upper surface 28 is spaced from the rimmed
end 24 of the body 12 (shown in FIG. 2), thereby providing a gap 54
between the piston 26 and the body 12 which permits exposure of
substantially the entire piston 26 and body 12 to a sterilizing gas
as discussed below in greater detail. Furthermore, the piston 26 is
supported such that it is substantially concentric with the rimmed
end 24 of the body 12, ready for insertion into the rimmed end 24
of the body 12.
[0073] In the preferred embodiment of FIG. 1, the piston support
means 50 is in contact with the sleeve 42 and is integrally formed
therewith, both being components of the activation cap 40. As best
seen in FIGS. 1 and 2, the piston support surface 52 is positioned
radially inwardly of the inner surface of the sleeve 42.
Preferably, the piston support surface 52 is spaced inwardly from
the inner surface of the sleeve 42 by a distance which is
substantially equal to the thickness of the body side wall, thereby
forming an annular recess 56 between the piston support surface 52
and the inner surface of the sleeve 42. The annular recess 56 has a
bottom wall 58 connecting the piston support means 50 and the
sleeve 42 and located intermediate the piston support surface 52
and the lower surface of the base end 44 of the sleeve 42, such
that when a predetermined force is applied to push the rimmed end
24 of the body 12 into the annular recess 56 until the rimmed end
24 engages the bottom wall 58, the piston 26 becomes fully inserted
in the body 24 with its side surface 32 forming a hermetic seal
with the inner surface 16 of the body 12.
[0074] In order to permit engagement of piston 26 by a plunger, the
piston support surface 52 is annular with a central aperture 64,
and engages an outer edge of the lower surface 30 of the piston 26.
In the embodiment illustrated in FIGS. 1 to 3, the piston is
preferably provided with a threaded bore (not shown) open to its
lower surface 30 which is adapted for connection to the threaded
end of a plunger.
[0075] As discussed above, the system of the invention is adapted
to improve the stability of conventional, elongate syringe barrels,
thereby permitting them to be conveyed standing upright through
standard equipment for filling and capping pharmaceutical vials.
This object is partly attained by provision of the sleeve 42, which
may lower the centre of gravity of the barrel 10 somewhat, thereby
improving its stability. Stability can be further enhanced by
increasing the thickness of the sleeve 42 throughout part or all of
its height. For example, as shown in FIG. 1, the sleeve 42 may
preferably be provided with an outwardly projecting flange 66 at
its base end 44. The flange 66 has a diameter and a height so as to
prevent interference such as would cause tipping when the barrel 10
is conveyed standing upright on the base end 44 through standard
equipment for filling and capping pharmaceutical vials. Such
interference typically comprises a phenomenon known as "shingling",
in which the flange or one barrel rides up over the flange of
another barrel, resulting in tipping.
[0076] Shingling can be prevented as shown in the preferred
embodiment of FIG. 1, in which the flange 66 has a substantially
flat radially outwardly facing wall 68 and is of sufficient height
that the flanges 66 of adjacent barrels 10 will not ride up over
one another.
[0077] FIG. 1 illustrates the steps involved in assembling and
filling a barrel 10 with a liquid component of a medicament, which
may comprise an active ingredient or a diluent to be combined with
an active ingredient prior to administration.
[0078] The first step of the method, illustrated in FIG. 1a,
comprises the formation of a first assembly 70 by inserting the
piston 26 inside the sleeve 42 of activation cap 40 such that the
lower surface 30 of piston 26 is supported by the piston support
surface 52.
[0079] In the second step illustrated in FIG. 1b, a second assembly
72 (shown in FIG. 1c) is formed by inserting the rimmed end 24 of
body 12 into the top end 46 of sleeve 42 to a sufficient depth that
the body 12 is stably supported in the sleeve 42, and so that the
rimmed end 24 is located intermediate the top end 46 and the base
end 44 of the sleeve and gap 54 being formed between the upper
surface 28 of piston 26 and the rimmed end 24 of the body 12,
thereby permitting sterilization of the body 12, piston 26 and
activation cap 40 by a sterilizing gas. A close-up cross-sectional
view of the lower portion of second assembly 72 is shown in FIG.
2.
[0080] The next step in the method, schematically illustrated in
FIG. 1d comprises sterilization of the second assembly 72 by a
sterilizing gas such as steam or ethylene oxide. FIG. 4
schematically illustrates a variant of the method in which the
sterilization is performed while a plurality of assemblies 72 are
packaged in trays 73 and covered with a plastic overwrap 75 so as
to maintain sterility and keep them in place. A preferred plastic
overwrap is sold under the trade-mark TYVEK.TM., which maintains
sterility while allowing penetration of sterilizing gases such as
ethylene oxide.
[0081] After sterilization, a force is applied to the second
assembly 72 to cause relative movement of the body 12 toward the
base end 44 of the sleeve 42, thereby causing insertion of the
piston 26 into the body 12 such that the side surface 32 of the
piston 26 forms a hermetic seal with the inner surface 16 of the
body 12 and seals the rimmed end 24. Preferably, the body 12 is
pushed downward into sleeve 42 in the direction shown by the arrow
in FIG. 1e. This step may be performed while the assemblies 72 are
packaged in trays 73 and covered with the overwrap 75.
Alternatively, the overwrap 75 may preferably be removed from the
sterile assemblies 72 (preferably in a sterile environment) prior
to pushing the body 12 into sleeve 42, and the assemblies 72 may
preferably also be removed from the tray 73 prior to performing
this step. The sterile tray of assemblies may be shipped to a
location for filling, stored for future filling, or immediately
filled with a pharmaceutical component. In the first two
situations, preferably the tray 73 and assemblies 72 are maintained
in the overwrap 75 until they are to be filled, thus maintaining
them in a sterile environment.
[0082] With the piston 26 fully inserted in the body 12 as shown in
FIG. 1e, and shown in greater detail in FIG. 3, the body 12 is now
ready to be filled with a medicament, or a component thereof. In
this embodiment, the medicament is a liquid which is filled into
the open mouth 22 of the body 12. As discussed above, the body 12
is filled on standard equipment for filling and capping
pharmaceutical vials, and is conveyed through at least part of said
equipment freestanding on the base end 44 of sleeve 42. The filled
body 12 is illustrated in FIG. 1f.
[0083] The mouth 22 of the body 12 is then sealed in a conventional
manner by application of an elastomeric closure 36 as shown in FIG.
1g, followed by application of a metal cap 38 over the closure 36
as shown in FIG. 1h, the cap 38 preferably being crimped over the
neck flange 21 of the body 12. This is also the most common method
for sealing standard pharmaceutical vials and is therefore easily
performed on standard equipment for filling and capping
pharmaceutical vials.
[0084] The next step in the method is illustrated in FIG. 1i and
comprises an optional terminal sterilization step, in which the
sealed barrel 10 is subjected to sterilization, for example by
exposure to high temperatures in an autoclave. This step is also
part of the normal vial filling process and is performed on
standard equipment for filling and capping pharmaceutical
vials.
[0085] As mentioned above, the barrel 10 of the first preferred
embodiment comprises an activation cap 40 and is therefore
specifically directed to delivery devices for two component
pharmaceuticals. In the example described above, a liquid
medicament, or a liquid component of a medicament, is contained in
the barrel 10. However, the first preferred embodiment is also
adaptable to the situation where the barrel 10 contains a solid
medicament or a solid component of a medicament, which is to be
combined with a liquid, such as a diluent, prior to
administration.
[0086] A first preferred method for filling barrel 10 with a solid
medicament is illustrated in FIG. 5. The steps followed in FIG. 5
are preferably the same as those described above with reference to
FIG. 1, with the exception of step 5f, in which a powdered
substance is filled into body 12 through the mouth 22. Powder
filling is also performed on standard equipment for filling and
capping pharmaceutical vials.
[0087] A second preferred method for filling barrel 10 with a solid
medicament is illustrated in FIG. 6. FIGS. 6a to 6e show
preparation of the second assembly 72, followed by sterilization
and seating of the piston 26 in the barrel body 10. These steps are
identical to the steps followed in FIGS. 1a to 1e, discussed above.
Next, the body 12 is filled in FIG. 6f with a liquid composition
containing a medicament or a component thereof. This step is
identical to that shown in FIG. 1f. Next, a lyophilization stopper
74, comprising a vented elastomeric closure, is partially inserted
into the neck 20 of body 12 such that a vent space 76 is formed.
The liquid contents of the body 12 are then lyophilized as shown in
FIG. 6g such that only a solid remains in the body 12. The stopper
74 is then completely inserted into neck 20 to close vent space 76
and seal the body, and a metal cap 38 is applied as in FIG. 1h.
Although not shown in FIG. 6, the sealed barrel may be subjected to
terminal sterilization. The steps shown in FIGS. 6f to 6i are
performed on standard equipment for filling, lyophilizing and
capping pharmaceutical vials.
[0088] As mentioned above, the barrel 10 according to the first
preferred embodiment is capable of use in a two component delivery
device, such as preferred delivery device 78 shown in FIG. 7b. In
order to assemble delivery device 78, the barrel 10 is combined
with a pre-assembly 80 of the type illustrated in FIG. 7a,
comprising a standard pharmaceutical vial 82 having a sealed neck
84, a vial coupling 86 with a vial socket 88 into which the neck 84
of vial 82 is received, and a syringe socket 90 with a finger
flange 91 into which the barrel 10 is received.
[0089] The pre-assembly further comprises a rear needle 93 and a
forward needle 94 housed in a luer lock assembly 96 which is
secured to both the vial coupling 86 and the syringe socket 90.
When the delivery device 78 is assembled as in FIG. 7b with the
finger flange 92 engaging the top end 46 of activation cap 40, the
ends of needles 93 and 94 do not penetrate the elastomeric closures
of either the vial 82 or the barrel 10. The device 78 is activated
by pushing the syringe socket 90 and the activation cap 40 together
such that the sleeve 42 of cap 40 is received inside syringe socket
90. The socket 90 and cap 40 are pushed together until the finger
flange 92 engages the flange 66 of activation cap 40, at which
point the ends of needles 93 and 94 penetrate the closures of the
barrel 10 and the vial 82 respectively, allowing mixing of the
respective contents of the vial 82 and barrel 10, in this example
by attaching plunger 98 to the piston 26 and aspirating the liquid
contents of the vial 82 into the barrel 10. The vial coupling 86 is
then unthreaded from the luer 96, also removing the forward needle
94. An injection needle (not shown) is then threaded onto the
exposed luer 96 to provide a complete prefilled disposable syringe
(not shown). The components of pre-assembly 80, and the method for
combining barrel 10 and pre-assembly 80 are described in greater
detail in above-mentioned U.S. Pat. No. 6,149,623, which is
incorporated herein by reference in its entirety. It will be
appreciated that the activation cap 40 described herein functions
in a manner similar to the driver described in the above-mentioned
U.S. patent and identified by reference numeral 21 in FIGS. 17 and
18 thereof.
[0090] Where the barrel 10 contains a liquid medicament or a
component thereof, the vial 82 of pre-assembly 80 may comprise
either a solid or liquid. Where the vial 82 contains a solid, the
medicament is formed by pushing the liquid contents of barrel 10
into the vial 82, mixing the solid and liquid ingredients, followed
by aspirating the medicament suspension or solution into the barrel
10 prior to removal of the vial coupling 86.
[0091] A second preferred embodiment of the present invention is
now described below with reference to FIG. 8, comprising
preparation of a barrel 110 for use in the preparation of a
prefilled disposable syringe for administration of a single
component medicament. A barrel similar to barrel 110 is shown in
FIG. 13 of U.S. Pat. No. 5,137,511, issued on Aug. 11, 1992, and is
incorporated herein by reference in its entirety.
[0092] Barrel 110 comprises a body 112 preferably made of glass and
having a generally cylindrical side wall 114 with an inner surface
116 and an outer surface 118. At one end, the body 112 has a
relatively narrow neck 120 with a neck flange 121 surrounding an
open mouth 122, and at the other end the body 112 has an open
rimmed end 124. Preferably, the rimmed end 124 is provided with an
inwardly extending projection 125 which has a function to be
described below. The dimensions of body 112 are similar to those of
body 12 described above, although it will be appreciated that the
dimensions of body 112 can be varied as discussed above in the
context of the first preferred embodiment.
[0093] Barrel 110 further comprises a generally cylindrical
elastomeric piston 126 having an upper surface 128 which forms the
bottom wall of barrel 110 in its assembled state, and an opposed
lower surface 130. Piston 126 also has a side surface 132
connecting the upper and lower surfaces 128 and 130, the side
surface 132 being adapted to form a hermetic seal with the inner
surface 116 of body 112, and preferably being provided with one or
more ribs 134 to improve the seal with the body 112. Piston 126 is
preferably made from an elastomeric material such as rubber. The
lower surface of piston 126 comprises an extension 139 for
attachment to a plunger as described in greater detail in
above-mentioned European Patent No. 298,585.
[0094] The open mouth 122 of body 112 is sealed in a conventional
manner by an elastomeric closure 136 with an overlying metal cap
138 crimped over the neck flange 121.
[0095] The barrel 110 further comprises a stabilization cap 140
which has a number of functions. Firstly, stabilization cap 140
functions as a piston support means, having a cylindrical portion
142 with an upper end 144 and a lower end 146, the upper end having
a piston support surface 148. The outer diameter of the cylindrical
portion 142 is such that the cylindrical portion 142 can be
received inside the body 112. The stabilization cap 140 also has a
radially projecting flange 150 at its lower end which functions as
a finger flange during use of the syringe. Furthermore, the
cylindrical portion 142 of cap 140 has a radially inwardly recessed
band 152 which is adapted to form a snap fit with the inwardly
projecting portion 125 of the body side wall 114, thereby
preventing removal of piston 126 from the body.
[0096] FIG. 8 illustrates the steps involved in assembling and
filling a barrel 110 with a liquid component of a medicament. The
first step, illustrated in FIG. 8a, comprises placement of the
piston 126 on top of the piston support surface 148 of the
stabilization cap 140, such that the extension 139 of piston 126 is
received inside the cylindrical portion 142, which is of sufficient
height that the extension 139 does not contact the surface on which
the stabilization cap 140 is supported.
[0097] The next step comprises placement of a cylindrical sleeve
154 over the piston 126 and cap 140 as illustrated in FIG. 8b. The
cylindrical sleeve 154 performs a function similar to that of
sleeve 42 of activation cap 40 described above, namely to add
stability to the barrel 110 and to support the body 112 in spaced
relation to the piston 126 during initial assembly of the barrel
110. In contrast to sleeve 42 of cap 40, the cylindrical sleeve 154
does not form part of the barrel 110, but rather is removed after
filling and capping of the barrel 110 on standard equipment for
filling and capping pharmaceutical vials. As with sleeve 42, the
cylindrical sleeve 154 can further enhance stability of the barrel
110 by being increased in thickness, by providing a flange similar
to flange 66 of cap 40 and/or by forming the sleeve 154 from a
relatively dense material, such as stainless steel. Since the
sleeve 154 is removed from the barrel, preferably for re-use,
forming the sleeve from a relatively thick and/or dense material
does not add to the weight or cost of the barrel.
[0098] As shown in FIG. 8, it may be preferred to form the sleeve
with a partial recess 156 in its lower surface 158 to fit over the
flange of the stabilization cap 140, thereby substantially
centering the piston 126 within the sleeve 154 and preventing
relative movement between the sleeve 154 and the cap 140.
[0099] After combining the piston 126, stabilization cap 140 and
sleeve 154 to form a first assembly 160 as shown in FIG. 8c, the
body 112 is inserted into the top end of the sleeve 154 to form a
second assembly 162, with the body 112 being inserted into the
sleeve 154 to a sufficient depth that the body 112 is stably
supported therein and so that the rimmed end 124 of the body 112 is
supported intermediate the top end of sleeve 154 and the flange 150
of the stabilization cap 140.
[0100] Preferably, the inner surface of the sleeve 154 is provided
with a detent 164 which prevents premature insertion of the piston
126 into the body 112, as discussed in detail with reference to the
first preferred embodiment.
[0101] The next step of the method, illustrated in FIG. 8d,
comprises sterilization of the second assembly 162 by a sterilizing
gas. As in the first preferred embodiment, a plurality of
assemblies 162 may preferably be packaged in trays with a plastic
overwrap prior to sterilization. After sterilization, the piston
126 is inserted into the body 112 by pushing the body 112 downward
relative to sleeve 154 in the direction of the arrow shown in FIG.
8e until the inward projection 125 of body 112 snaps into the
recess 152 of the stabilization cap.
[0102] The steps followed for filling, capping and terminal
sterilization of the sealed body 112 are shown in FIGS. 8e to 8i
and are identical to the corresponding steps followed in FIGS. 1e
to 1i. As with the first preferred embodiment, these steps are
performed on standard equipment for filling and capping
pharmaceutical vials, with the sealed body 112 and the associated
sleeve 154 being conveyed through at least a portion of this
equipment while freestanding upright on the finger flange 150.
[0103] After removal of the sleeve 154, the barrel 110 can be
combined with a needle (not shown) and a plunger (not shown) to
form a prefilled disposable syringe, as described in
above-mentioned U.S. Pat. No. 5,137,511.
[0104] FIGS. 9 and 10 illustrate variants of the second preferred
embodiment of the invention in which components of the system are
attached to trays. In the variant shown in FIG. 9, prefilled
syringe barrels 168 are produced by combining a body 12 or 112 with
a piston 126 having an extension 139. The barrels 168 include
neither an activation cap 40 or a stabilization cap 140 and are
therefore similar to pharmaceutical vials, although they may
preferably have a greater height to base ratio than standard
pharmaceutical vials.
[0105] In the variant shown in FIG. 9, a handling tray 170 is
provided on which are arranged a plurality of support assemblies
172, each of which comprises a generally cylindrical sleeve 174
having a base end 175 and a top end 177, and piston support means
176 integrally formed with the sleeve 174 and having an annular
piston support surface 178 adapted to support piston 126 by
engaging the lower surface 130 thereof. A plan view of tray 170
with support assemblies 172 is shown in FIG. 9d. As in the first
embodiment shown in FIGS. 1 to 3, piston support surface 178 is
spaced from the inner surface of sleeve by a distance substantially
equal to a thickness of the wall of the body 12 or 112 to form an
annular gap 180 into which the rimmed end of the body 12 or 112 is
received during insertion of the piston 126 into the body 12 or
112.
[0106] In order to assemble syringe barrels 168, the pistons 126
are first inserted into the support assemblies 172 as shown in FIG.
9a and supported on the piston support means 176. Next, the bodies
12 or 112 are inserted into the sleeves 174 as shown in FIG. 9b and
supported therein with their rimmed ends spaced above the upper
surfaces 128 of the pistons 126. In order to support the bodies 12
or 112 in the position shown in FIG. 9c, the inner surface of each
sleeve 174 is preferably provided with a detent (not shown) as
described above in the context of sleeve 42 and 154. After
sterilization, the pistons 126 are then inserted into the bodies 12
or 112 by pushing the bodies 12 or 112 downward such that the
rimmed ends thereof are pushed down into the gaps 180 (FIGS. 9c and
9e), as described above in connection with the first preferred
embodiment illustrated in FIG. 1.
[0107] After insertion of the pistons 126, the trays 170 and the
barrels 168 are conveyed through equipment adapted for filling
syringe barrels packaged in trays. After filling, the barrels 168
are sealed and capped as described above, preferably while standing
on the trays 170. The filled and capped barrels 168 may then be
removed from trays 170 prior to shipment, with the trays being
reused. Alternatively, the tray 170 and barrels 168 may be shipped
as a unit to their final destination.
[0108] FIG. 10 illustrates a variant of the method of FIG. 9, in
which trays 182 are provided with piston support means 184 attached
thereto. A plan view of the tray is shown in FIG. 10a. As shown in
FIGS. 10b and 10c, pistons 139 are placed on the support means. The
bodies 12 or 112 are inserted into an assembly 186 comprising a
plurality of sleeves 188 joined together, the inner surface of each
sleeve 188 having a detent (not shown) to support the rimmed end of
the body 12 or 112 as shown in FIG. 10d. After insertion of bodies
12 or 112 into sleeves 188 as shown in FIG. 10d, the assembly 186
is placed over the tray 182 so that a piston support means 184 and
an associated piston is inserted into each sleeve 188 as shown in
FIG. 10e. After sterilization, the pistons 126 are inserted into
bodies 12 or 112 as shown in FIG. 10e, thereby providing a tray of
sterilized barrels shown in FIG. 10f, ready for filling and capping
as described above with reference to FIG. 9.
[0109] FIG. 11 illustrates a variant of the second preferred
embodiment in which a syringe barrel 192 is produced by combining a
body 12 or 112 with a piston 26 having an internally threaded bore.
As in the variant shown in FIGS. 9 and 10, the variant of FIG. 11
does not include an activation cap 40 or a stabilization cap 140.
In the variant of FIG. 11, the barrel 192 is stabilized on standard
equipment for filling and capping vials by a stabilization means
194 comprising a sleeve 196 and an integrally formed piston support
means 198 comprising an annular piston support surface 200 and
having a raised central portion 201 to be received in the bore of
the piston 26, thereby centering the piston inside the sleeve 196.
The sleeve 196 is provided with a plurality of axially extending,
circumferentially spaced support ribs 195, best seen in FIG. 11d,
which is a cross-sectional plan view showing the stabilization
means 194 in isolation, the cross-section being taken in a plane
perpendicular to the axis of sleeve 196 and between the detents 202
and the piston support means 198. As shown in FIG. 11a, each rib
195 is provided with a detent 202 on its inner surface for
supporting the body 12 or 112 above the upper surface 28 of the
piston.
[0110] To produce a prefilled syringe barrel 192, the piston 26 is
first inserted into the stabilization means as shown in FIG. 11a.
Next, the body 12 or 112 is inserted into the sleeve 196 as shown
in FIG. 11b until the rimmed end engages the detents 202 on ribs
195 as shown in FIG. 11c. It is to be noted that only stabilization
means 194 is shown in cross-section in FIGS. 11a to 11c, with the
other components being shown in elevation. The remaining steps are
analogous to those shown in FIG. 8, with the exception that, after
the barrel 192 is filled and capped, it is pulled out of engagement
with the stabilization means 194.
[0111] FIG. 12 also illustrates a variant of the second preferred
embodiment, and is similar to the variant of FIG. 11, with the
exception that it is adapted for forming a syringe barrel
comprising a body 12 or 112 and a piston 126 having an extension
139. As in FIG. 11, the embodiment of FIG. 12 utilizes a
stabilization means 190 comprising a sleeve 191 and a piston
support means 193, the sleeve 191 having a plurality of axially
extending ribs 197, each of which is provided with a detent 199.
FIG. 12a illustrates the subassembly of the piston 126 and the
stabilization means 190 prior to insertion of body 12 or 112. FIG.
12b illustrates body 12 or 112 having been inserted into sleeve 191
and being supported by detent 189, such that a gap exists between
the rimmed end of the body 12 and the upper surface of piston 126.
In FIGS. 12a and 12b, only the stabilization means 190 is shown in
cross section, with the other components being shown in elevation.
FIG. 12c is a cross-sectional plan view showing the stabilization
means in isolation, in a plane which is perpendicular to the axis
of sleeve 191, and which is between the detents 199 and piston
support means 193.
[0112] FIG. 13 illustrates yet another variant of the second
preferred embodiment, which is similar to that illustrated in FIG.
8 except that piston 126 is replaced by piston 26 having an
internal bore, and sleeve 154 is replaced by sleeve 203, having
axially extending ribs 205, each of which is provided with a detent
207. As shown in FIG. 13b, ribs 205 terminate immediately below
detent 207. FIG. 13a illustrates piston 26 being placed on
stabilization cap 204, comprising a cylindrical portion 206 with a
flange 208 at the base end thereof, the flange 208 serving as a
finger flange. Stabilization cap 204 also comprises a recessed band
210 adapted to snap into engagement with the inwardly projecting
portion 125 at the rimmed end 124 of body 112. FIG. 13b illustrates
the placement of the cylindrical sleeve 203 over the piston 26 and
the stabilization means 204 to form the assembly 212 shown in FIG.
13c. FIG. 13c also shows insertion of the insertion of body 112
into sleeve 203 to form the assembly 213 shown in FIG. 13d, which
is ready for sterilization and further processing according to the
method described in connection with FIG. 8. FIGS. 13a to 13d
illustrate the sleeve 203 in cross section and the other components
in elevation. FIG. 13a is a cross-sectional plan view showing the
sleeve 203 in isolation, taken in a plane extending through ribs
205 and perpendicular to the axis of sleeve 203.
[0113] FIG. 14 illustrates a variant of the first preferred
embodiment of the present invention, identical to that shown in
FIGS. 1 to 3 except that body 214 replaces syringe body 12. Body
214 has a rimmed edge 216 with slight outward projection 218 and a
slight inward projection 220. FIG. 14a is analogous to FIG. 2 and
illustrates an assembly comprising the body 214, piston 26 and
activation cap 40 prior to insertion of piston 26 into body 214.
FIG. 14b is analogous to FIG. 3 and illustrates the assembly of
FIG. 14a after the body 214 has been pushed down into activation
cap 40, and piston 26 is inserted into body 214.
[0114] FIG. 15 illustrates a variant that may be implemented with
either the first or second preferred embodiments of the invention,
but for convenience will be described having reference to the first
preferred embodiment shown in FIG. 1. In addition to the body,
piston, sleeve, and other components previously described in
reference to FIG. 1, the variant shown in FIG. 15 includes an upper
cylindrical sleeve 250. The upper cylindrical sleeve 250 has an
upper end 252, a lower end 254, and inner surface 256 and an outer
surface 258. The interior diameter of the upper sleeve 250 is such
as to closely, but not tightly, surround the body of the syringe
barrel. Preferably, the outer diameter of the upper sleeve 250 is
approximately the same as the outer diameter of the sleeve 42. The
upper sleeve may have an outer collar 260, having an inner surface
262 and an outer surface 264, the collar 260 surrounding at least a
portion of the upper sleeve 250. The inner surface 262 of the
collar 260 preferably has a greater diameter than the outer surface
258 of the upper sleeve 250 thereby creating an annular gap 266
between the upper sleeve 250 and the collar 260. Preferably the
collar 260 has an open bottom end 268 towards the lower end 254 of
the sleeve 250, and a closed end 270 towards the upper end 252
where the collar 260 has the same outer diameter as the flange 66
of the base end 44 of the sleeve 42. After the barrel is filled
with a pharmaceutical component, the upper sleeve 250 may be
removed before packaging and shipment, and reused. For example, the
upper sleeve 250 may be removed by blasting air into the annular
gap 266, causing the upper sleeve to blow off the top of the
barrel.
[0115] The inclusion of the upper sleeve may increase the stability
of the barrels as they travel through a filling line, since the
upper collar 260 and the flange 66 are preferably of the same
diameter. Thus, if adjacent barrels traveling through the filling
line contact one another, they will do so at the flange 66 near the
base of the barrel, and also at the collars 260. This will increase
the stability of the barrels as they travel through the filling
line.
[0116] It will be appreciated that the activation caps,
stabilization caps, sleeves and handling trays described above will
preferably be made from materials which are substantially
unaffected by the conditions employed during sterilization. As
sterilization is usually performed at elevated temperature, it is
preferred that these components be made of heat-resistant
materials. It is preferred that these components be formed from
plastics, more preferably heat-resistant plastics.
[0117] Furthermore, it may be preferred in some embodiments of the
present invention to utilize syringe bodies and pistons which are
siliconized. Siliconization is preferably performed during
manufacture of the syringe body and the piston.
[0118] In one aspect, the present invention provides an assembly
for filling and capping a barrel 10 of a pre-filled syringe. The
assembly generally has a syringe body 12, a piston 26, and a
stabilization member. The stabilization member is positioned
proximate the rimmed end of the body to provide additional mass
thereto in an amount sufficient to permit the barrel 10 to be
conveyed freestanding in a longitudinally upright position on the
stabilization member through an apparatus for filling and capping
pharmaceutical vials. In essence, the stabilization member acts to
lower the center of gravity of the barrel 10 while the barrel 10 is
in a longitudinally upright position (see FIGS. 1e, 4f, 5e 6e, 8e,
and 9e). This permits the stable conveyance of the assembly through
an apparatus for filling and capping pharmaceutical vials. In the
embodiment illustrated in FIGS. 1-7, the stabilization member is
sleeve 42. In the embodiment illustrated in FIG. 8, the
stabilization member includes sleeve 154 and stabilization cap 140.
In the embodiment illustrated in FIG. 9, the stabilization member
is sleeve 174. In the embodiment illustrated in FIG. 11, the
stabilization member is sleeve 196. In the embodiment illustrated
in FIG. 12, the stabilization member is sleeve 191. In the
embodiment illustrated in FIG. 13, the stabilization member
includes sleeve 203 and stabilization cap 204.
[0119] The following description is a variant on the method steps
for assembling and filling a barrel with at least one
pharmaceutical component in accordance with either the first or the
second preferred embodiments of the invention. For convenience, the
method variant will be described having reference to FIG. 1.
[0120] The syringe body 12, piston 26, and sleeve 42 can be
pre-sterilized in any method known in the art. The pre-sterilized
syringe body 12, the pre-sterilized piston 26, and the
pre-sterilized sleeve 42 can be assembled in an aseptic environment
to form the assembly shown in FIG. 1e. While in this position, the
piston 26 is located within the body 12 so that a liquid
impermeable seal is formed between the inner surface 16 of the body
12 and the side surface 34 of the piston 26. Preferably, the
assembly shown in FIG. 1e is packaged in a plastic overwrap sold
under the trade-mark TYVEK.TM. while still in the aseptic
environment. Preferably, the assembly is maintained in the sterile
packaging until it is ready to be filled. It is understood that the
subsequent steps for filling and capping can be identical to the
corresponding steps previously described depending on the state of
the at least one pharmaceutical component to be filled (e.g., FIGS.
1f to 1i or FIGS. 8f to 8j for filling an assembly with at least
one liquid pharmaceutical component, FIGS. 5f to 5i for filling an
assembly with at least one solid pharmaceutical, FIGS. 6f to 6j for
filling an assembly with at least one liquid pharmaceutical
followed by lyophilization such that only a solid remains).
[0121] The following description is a variant on the method steps
for assembling and filling a barrel with at least one
pharmaceutical component in accordance with either the first or the
second preferred embodiments of the invention. For convenience, the
method variant will be described having reference to FIG. 1.
[0122] The syringe body 12, piston 26, and sleeve 42 can be
assembled in a relatively clean room to form the assembly shown in
FIG. 1e. While in this position, the piston is located within the
body 12 so that a liquid impermeable seal is formed between the
inner surface 16 of the body 12 and the side surface 34 of the
piston 26. The material for the piston 26 is selected to be liquid
impermeable and sufficiently permeable to a sterilizing gas to
permit sterilization of the seal between the inner surface 16 of
the body 12 and the side surface 34 of the piston 26 upon exposure
to a sterilizing gas. The material for the piston 26 can be
selected from any material that is known in the art to be liquid
impermeable and permeable to a sterilizing gas. Examples of such
materials include, but are not limited to, elastomer formulations
comprising neoprene (e.g., elastomer formulation FM-27 which is
commercially available from Helvoet Pharma). Preferably, the
assembly shown in FIG. 1e is packaged in a plastic overwrap sold
under the trade-mark TYVEK.TM.. The wrapped assembly can then be
sterilized by exposure to a sterilizing gas such as ethylene oxide.
Preferably, the assembly is maintained in the sterile packaging
until it is ready to be filled. It is understood that the
subsequent steps for filling and capping can be identical to the
corresponding steps previously described depending on the state of
the at least one pharmaceutical component to be filled.
[0123] The following description is a variant on the method steps
for assembling and filling a barrel with at least one
pharmaceutical component in accordance with either the first or the
second preferred embodiments of the invention. For convenience, the
method variant will be described having reference to FIG. 1.
[0124] The syringe body 12, piston 26, and sleeve 42 can be
assembled in a relatively clean room to form the assembly shown in
FIG. 1e. While in this position, the piston is located within the
body 12 so that a liquid impermeable seal is formed between the
inner surface 16 of the body 12 and the side surface 34 of the
piston 24. Preferably, the syringe body 12 is selected from a
material that comprises cerium oxide in an amount sufficient to
prevent discoloration of the body upon exposure to at least one
standard cycle of gamma radiation (e.g., 25 kilogray). Preferably,
the syringe body 12 comprises about 1 wt % cerium oxide based on
the total weight of the syringe body 12. The material for the
piston 26 is selected to be substantially resistant to the effects
of at least one standard cycle of gamma radiation (e.g., 25
kilogray) to the extent that the function of the piston 26 is not
impaired. The material for the piston 26 can be selected from any
material that is known in the art to be resistant to the effects of
at least one standard cycle of gamma radiation. Examples of such
materials include, but are not limited to, elastic formulations
comprising bromobutyl rubber (e.g., elastomer fomulation FM-457
which is commercially available from Helvoet Pharma). Preferably,
the assembly shown in FIG. 1e is packaged in a plastic overwrap
sold under the trade-mark TYVEK.TM.. The wrapped assembly can then
be sterilized by exposure to at least one standard cycle of gamma
radiation (e.g., 25 kilogray). Preferably, the assembly is
maintained in the sterile packaging until it is ready to be filled.
It is understood that the subsequent steps for filling and capping
can be identical to the corresponding steps previously described
depending on the state of the at least one pharmaceutical component
to be filled.
[0125] Although the invention has been described with reference to
certain preferred embodiments, it is not limited thereto. Rather,
the invention includes all embodiments which may fall within the
scope of the following claims.
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