U.S. patent application number 10/554126 was filed with the patent office on 2006-11-30 for device for introducing a liquid into a pharmaceutical container.
This patent application is currently assigned to GlaxoSmithKline Biologicals. Invention is credited to Jacques Thilly, Christian Vandecasserie.
Application Number | 20060266431 10/554126 |
Document ID | / |
Family ID | 9957284 |
Filed Date | 2006-11-30 |
United States Patent
Application |
20060266431 |
Kind Code |
A1 |
Thilly; Jacques ; et
al. |
November 30, 2006 |
Device for introducing a liquid into a pharmaceutical container
Abstract
An apparatus for introducing a liquid into a pharmaceutical
container such as a vial, having a puncturable closure, comprising
a hollow needle with at least one orifice through the needle side
wall being oriented to direct liquid flowing along the bore in a
direction having a component parallel to the flow direction, with a
vent groove in its outer surface. A preferred construction of
needle and a process for making it are disclosed.
Inventors: |
Thilly; Jacques; (Rixensart,
BE) ; Vandecasserie; Christian; (Rixensart,
BE) |
Correspondence
Address: |
SMITHKLINE BEECHAM CORPORATION;CORPORATE INTELLECTUAL PROPERTY-US, UW2220
P. O. BOX 1539
KING OF PRUSSIA
PA
19406-0939
US
|
Assignee: |
GlaxoSmithKline Biologicals
rue de l'Institut 89
Rixensart
BE
B-1330
|
Family ID: |
9957284 |
Appl. No.: |
10/554126 |
Filed: |
April 26, 2004 |
PCT Filed: |
April 26, 2004 |
PCT NO: |
PCT/EP04/04501 |
371 Date: |
June 21, 2006 |
Current U.S.
Class: |
141/329 ;
604/416 |
Current CPC
Class: |
A61M 5/162 20130101;
B65B 3/003 20130101; A61J 1/2096 20130101; A61M 2207/00 20130101;
A61J 1/201 20150501; A61M 5/3291 20130101 |
Class at
Publication: |
141/329 ;
604/416 |
International
Class: |
B65B 1/04 20060101
B65B001/04 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 28, 2003 |
GB |
0309705.2 |
Claims
1. Apparatus for introducing a liquid into a pharmaceutical
container having a puncturable closure, comprising; a hollow needle
suitable for passing through the closure, the needle comprising a
tubular conduit defined by a side wall and having an internal bore
for the flow of a fluid along the bore in an flow direction, the
conduit terminating externally at a pointed end, the bore
terminating internally at a closed end, at least one orifice
through the side wall for the exit of fluid flowing along the bore,
the at least one orifice being oriented to direct liquid flowing
along the bore in a direction having a component parallel to the
flow direction, the conduit having at least one vent groove in its
outer surface; means to cause the needle to puncture the closure to
the extent that the at least one orifice is within the container;
means to cause the liquid to flow along the bore; means to withdraw
the needle from the container and closure.flow
2. Apparatus according to claim 1 comprising means to hold the
needle and support the container, and to cause them to move
relatively together along the longitudinal axis of the needle.
3. Apparatus according to claim 3 wherein the container is a vial
supported with its closure uppermost, and the needle is held above
the container and moved downwardly toward the closure.
4. Apparatus according to claim 2 wherein the container is
supported on a conveyor below the needle holder.
5. Apparatus according to claim 2 wherein the means to withdraw the
needle from the container and closure comprises the means to hold
the needle and support the container, operating in a reverse
reciprocal movement.
6. Apparatus according to claim 2 wherein the means to support the
container incorporates means to restrain the container against the
withdrawing force of the needle.
7. A hollow needle comprising a tubular conduit defined by a side
wall and having an internal bore for the flow of a fluid along the
bore in an flow direction, the conduit terminating externally at a
pointed end, the bore terminating internally at a closed end, at
least one orifice through the side wall for the exit of fluid
flowing along the bore, the at least one orifice being oriented to
direct liquid flowing along the bore in a direction having a
component parallel to the flow direction, the conduit having at
least one vent groove in its outer surface and wherein the pointed
end of the conduit is provided as a separate plug part which can be
plugged into the downstream open end of the conduit.
8. A needle according to claim 3 which comprises: a cylindrical
tubular conduit defined by a side wall and having an internal bore
for the flow of a fluid along the bore in an flow direction, the
conduit terminating externally at a pointed end, the bore
terminating internally at a closed end, at least one orifice
through the side wall for the exit of fluid flowing along the bore,
wherein at least one orifice has upstream and downstream perimeter
surfaces through the side wall converging toward the upstream
direction at an angle between 10-60.degree. relative to the
upstream direction, the total cross sectional area of the one or
more orifice is +/-20% of the cross sectional area of the bore of
the conduit, and the internal closed end of the bore comprises
surfaces that converge toward the upstream direction.
9. A process for making a hollow needle according to claim 2
comprising the steps of: (1) providing a tubular conduit defined by
a side wall and having an internal bore for the flow of a fluid
along the bore in an flow direction, the bore having an open end;
(2) providing a plug part for the open end, the plug part having a
longitudinal axis and being adapted to longitudinally mate with the
open end of the bore and having an end surface and an opposite end,
(3) mating the plug part longitudinally with the bore, (4) cutting
at least one orifice through the side wall in a direction
converging toward the upstream direction, and forming the end
surface of the plug part into side surfaces that converge toward
the upstream direction, (5) before or after any of steps (1) to (4)
forming the opposite end of the plug part into a point.
10. A process according to claim 9 wherein prior to step (3) the
end surface of the plug part is formed into the shape of a valley
with its bottom extending across the end surface perpendicular to
the longitudinal direction.
11. A process according to claim 9 wherein in step (4) the orifice
is cut by drilling from a direction parallel to the line of the
bottom of the valley.
12. A process for introducing a fluid into a puncturable container
comprising the use of an apparatus according to claim 1 to perform
the steps of; (1) inserting the point of the needle into the
interior of the container by puncturing the container, (2) flowing
a fluid along the bore of the needle in the flow direction, (3)
causing the fluid to exit the needle through the one or more
orifice and thereby enter the container, then (4) withdrawing the
needle from the container.
13. A process for introducing a fluid into a puncturable container
comprising the steps of; (1) inserting the point of a needle as
claimed in claim 7 into the interior of the container by puncturing
the container, (2) flowing a fluid along the bore of the needle in
the flow direction, (3) causing the fluid to exit the needle
through the one or more orifice and thereby enter the container,
then (4) withdrawing the needle from the container.
14. A process according to claim 13 wherein the container is a
pharmaceutical vial having a puncturable closure.
15. A process for introducing a fluid into a puncturable container
comprising the steps of; (1) inserting the point of a needle as
claimed in claim 8 into the interior of the container by puncturing
the container, (2) flowing a fluid along the bore of the needle in
the flow direction, (3) causing the fluid to exit the needle
through the one or more orifice and thereby enter the container,
then (4) withdrawing the needle from the container.
16. A process according to claim 15 wherein the container is a
pharmaceutical vial having a puncturable closure.
Description
[0001] This invention relates to an apparatus for use in filling
pharmaceutical vials which have an elastomeric closure which can be
punctured by a needle point and fluid medicament content thereby
introduced into the vial.
[0002] Such a process is known from US-A-2002/0023409 in which the
residual puncture site left by the needle is heat sealed using a
laser beam.
[0003] Needles for this purpose are known, but a problem with such
needles is that of achieving an optimised flow pattern of the fluid
as it exits the needle when within the vial. A further problem is
that the point and side orifices of known needles can cut through
the vial closure during puncture in a way which forms particles of
the closure material which can contaminate the medicament
introduced into the vial or block or obstruct flow through the
needle.
[0004] There are numerous disclosures of hollow, pointed ended
needles having side orifices for the exit of fluid. For example
U.S. Pat. No. 5,478,328 and U.S. Pat. No. 6,221,056 disclose
needles in which the side orifices are profiled to direct a fluid
flowing along the bore of the needle and out through the orifices
forwards, i.e. in the direction in which the needle is pointing.
The needles disclosed therein are not disclosed or suggested for
use in a vial filling operation.
[0005] It is an object of this invention to provide an improved
vial filling apparatus based on improved needles, addressing these
problems among others. Other objects and advantages of this
invention will become apparent from the following description.
[0006] According to this invention an apparatus for introducing a
liquid into a pharmaceutical container having a puncturable closure
is provided, comprising;
[0007] a hollow needle suitable for passing through the closure,
the needle comprising a tubular conduit defined by a side wall and
having an internal bore for the flow of a fluid along the bore in a
flow direction, the conduit terminating externally at a pointed
end, the bore terminating internally at a closed end, at least one
orifice through the side wall for the exit of fluid flowing along
the bore, the at least one orifice being oriented to direct liquid
flowing along the bore in a direction having a component parallel
to the flow, the conduit having at least one vent groove in its
outer surface;
[0008] means to cause the needle to puncture the closure to the
extent that the at least one orifice is within the container;
[0009] means to cause the liquid to flow along the bore;
[0010] means to withdraw the needle from the container and
closure.
[0011] The orientation of the orifice to direct liquid flowing
along the bore in a direction having a component parallel to the
flow direction may be achieved by an orifice which has a perimeter
surface through the side wall converging toward the upstream
direction so as to direct a flow of fluid passing through the
orifice from the bore toward the outside of the needle in a
direction which has a component in the downstream direction.
[0012] Herein the term "downstream" refers to the general direction
between the end of the needle into which fluid is introduced and
the pointed end, and "upstream" refers to the opposite
direction.
[0013] The benefit of such an alignment of the perimeter surfaces
of the bore is that fluid exiting through the orifice is thereby
directed in the downstream direction, rather than exiting
substantially perpendicularly to the downstream direction.
[0014] Preferably the conduit is cylindrical and there are two
orifices with their centres 180.degree. apart i.e. on opposite
sides of a diameter of the conduit.
[0015] Preferably the orifice(s) is(are) elongate in the
longitudinal direction of the conduit, for example being oval.
[0016] Preferably the total cross sectional area of the one or more
orifice is substantially the same +/-20% as the cross sectional
area of the bore of the conduit so that flow of fluid out through
the orifice(s) from the bore is not restricted.
[0017] Preferably the orifice has an upstream perimeter surface
through the side wall inclined to converge toward the upstream
direction. Preferably the orifice has a downstream perimeter
surface through the side wall inclined to converge toward the
upstream direction. If both upstream and downstream perimeter
surfaces are inclined to converge with the upstream direction they
may incline parallel to each other. Preferably the angle of
convergence toward the upstream direction of the upstream and if
present downstream perimeter surface of the orifice is at an angle
of 10-60.degree., more preferably ca. 30.degree., with the upstream
direction.
[0018] Preferably the perimeter of the orifice is rounded rather
than sharp to reduce the possibility of cutting of the closure by
sharp edges of the orifices as they pass through an elastomer vial
closure, and the consequent formation of particles of the closure
material.
[0019] Preferably the internal closed end of the bore comprises
surfaces that converge toward the upstream direction.
[0020] Preferably these surfaces converge toward the upstream
direction in the form of an edge with its ridge pointing in the
upstream direction, being more preferably a sharp knife edge
between the surfaces of the closed end. Preferably the angle of
convergence is the same as that of one or more of the converging
perimeter surfaces of the orifice.
[0021] Preferably if there are two orifices the edge formed by
these converging surfaces of the internal closed end of the bore is
aligned with the line of its ridge perpendicular to the axis
between the two orifices. The sloping alignment of these surfaces
of the edge is preferably the same as that of the upstream
perimeter surface of the orifice, i.e. at the angles disclosed
above, and preferably merges smoothly with the perimeter of the
orifice.
[0022] Preferably the converging surfaces of the internal closed
end of the bore, e.g. the ridge of a so-formed edge, extend in the
upstream direction at least as far as the upstream perimeter of the
orifice. The edge is preferably part of a so called "saddle" shaped
surface.
[0023] The advantage of such converging internal surfaces,
particularly this edge, is that flow of fluid exiting from the
orifice is guided thereby in the downstream direction, and such an
edge, e.g. in the form of a saddle shaped surface provides no flat
surface for particles or other contamination to rest upon.
[0024] The pointed end may be a pyramid with three faces. The apex
of such a pyramid may enclose an angle of 30-60.degree.. Preferably
the pointed end is a conical shape, suitably having a cone angle of
15-30.degree., preferably 20-25.degree., at the pointed tip. The
benefit of a cone shape over a pyramidal shape is that the conical
shape damages less of the elastomer material as it punctures the
closure, whereas a pyramid can leave a larger "star" shaped
puncture hole with cuts radiating from the apexes of the polygonal
e.g. triangular, section of the pyramid. Such a cone shape can
generate no particles of the closure material is it punctures the
closure.
[0025] Therefore a specific preferred form of the needle for the
apparatus of this invention comprises:
[0026] a cylindrical tubular conduit defined by a side wall and
having an internal bore for the flow of a fluid along the bore in
an flow direction, the conduit terminating externally at a
conically pointed end, the bore terminating internally at a closed
end, at least one orifice through the side wall for the exit of
fluid flowing along the bore,
[0027] wherein at least one orifice has upstream and downstream
perimeter surfaces through the side wall converging toward the
upstream direction at an angle between 10-60.degree. relative to
the upstream direction,
[0028] the total cross sectional area of the one or more orifice is
+/-20% of the cross sectional area of the bore of the conduit,
[0029] and the internal closed end of the bore comprises surfaces
that converge toward the upstream direction.
[0030] Preferably the pointed end of the conduit is provided as a
separate plug part which can be plugged into the downstream open
end of the conduit. Such a plug part may consequently comprise a
male plug end which can be inserted into the open downstream end of
the bore of a tubular conduit, the plug part having a pointed end
longitudinally opposite this male plug end, the plug end being
shaped into the above-described edge. Such a plug end may be welded
into the bore of the conduit.
[0031] The conduit is also provided on its external surface with
one or more vent groove to allow the atmosphere within a container
such as a vial to escape as fluid is introduced into the container.
Suitably such a groove may extend in a direction parallel to the
longitudinal axis of the conduit, e.g. parallel to the
upstream-downstream direction. The length of such a groove need be
sufficient that when the needle has punctured the closure to its
fully intended extent one end of the groove is within the container
and the other end is exposed outside of the container. There may be
one or more such vent groove, preferably two or more vent grooves.
It is found that the venting efficiency can influence the vial
filling speed, and four grooves can be better for filling larger
volume vials. It is found that when the needle is used to puncture
an elastomer closure, e.g. of a vial, the elastomer tends to fill
the vent groove(s). It is found that this can be avoided by a
groove which is of a profile, cut across the axis of the needle,
which has sharp corners, which are not easily completely filled by
the elastomer. For example the groove may have a rectangular
profile. Plural grooves may be regularly spaced around the
circumference of the conduit. An alternative arrangement is four
grooves arranged in two pairs, each pair disposed on opposite sides
of a diameter of the conduit, grooves in each pair, with a
20-50.degree., e.g. 40 .+-.5.degree. angular spacing between the
grooves of the pair. The groove may for example have a depth of ca.
50% of the thickness of the conduit wall, e.g. 0.2 mm deep, and a
width 0.2-0.4 mm. It is preferred that at the ends of the groove(s)
the groove accomodates gradually to the outer profile of the
conduit, rather than at a sharp step, to avoid cutting particles of
the elastomer of the closure on insertion or removal of the needle
through the closure. Needles having these dispositions of vent
grooves are believed to be novel.
[0032] The above-mentioned guiding of the flow of fluid exiting
from the bore into the downstream direction has a further advantage
in reducing the possibility of the fluid being sprayed in the
upstream direction and entering the vent groove.
[0033] The conduit and plug part as described above may be made of
metals such as stainless steel as commonly used in the art.
Typically the conduit may have an outside diameter ca. 2-3 mm, and
the bore may have an internal diameter 1-2 mm, with a side wall
thickness typically 0.3-0.5 mm.
[0034] The container may suitably be a pharmaceutical vial having a
puncturable elastomeric closure. Suitable vials are disclosed for
example in WO 04/018317. Such a vial for example has an
upwardly-facing mouth opening bounded by a rim in the form of a
flange having upper and lower surfaces extending transverse to its
upper-lower axis, and has an elastomer closure part shaped to
sealingly engage with the mouth opening, having a lower surface to
face the interior of the vial and an opposite upper surface to face
away from the vial, and capable of being punctured by a needle is
inserted into the mouth opening of the vial, and has a clamp part
engaged with the flange around the rim of the mouth opening of the
vial by a resilient snap-fit engagement of a snap fit part of the
clamp part underneath a downwardly facing surface of such a flange
part, and bearing upon the upper surface of the closure part to
hold the closure part in a closing relationship with the mouth
opening.
[0035] The means to cause the needle to puncture the closure may
comprise means to hold the needle and support the container, e.g. a
vial, and cause them to move relatively together along the
longitudinal axis of the needle. For example the container may be a
vial supported with its closure uppermost, and the needle may be
held above the container and moved downwardly toward the closure.
Suitably the container such as a vial may be supported on a
conveyor below the needle holder. The means to withdraw the needle
from the container and closure may comprise the same means but
operating in a reverse reciprocal movement. The means to support
the container, particularly a vial, should incorporate means to
restrain the container against the withdrawing force of the needle.
A suitable means is for example disclosed in WO-A-04/026735. For
example the vial may have a bottom opposite its mouth opening which
fits into a vial stand, and this means may bear upon the stand to
hold the combination of vial and stand down against the withdrawing
force.
[0036] The means to cause the liquid to flow along the bore may
comprise a conventional metering pump connected to a supply of the
liquid. Such a pump may be operated to deliver a metered amount of
the liquid into the container, and may be controlled to that the
liquid is only delivered whilst the orifice is within the
container. In another aspect the invention provides a process for
making a hollow needle as described above comprising the steps
of:
[0037] (1) providing a tubular conduit defined by a side wall and
having an internal bore for the flow of a fluid along the bore in
an flow direction, the bore having an open end;
[0038] (2) providing a plug part for the open end, the plug part
having a longitudinal axis and being adapted to longitudinally mate
with the open end of the bore and having an end surface and an
opposite end,
[0039] (3) mating the plug part longitudinally with the bore,
[0040] (4) cutting at least one orifice through the side wall in a
direction converging toward the upstream direction and forming the
end surface of the plug part into side surfaces that converge
toward the upstream direction,
[0041] (5) before or after any of steps (1) to (4) forming the
opposite end of the plug part into a point.
[0042] Preferably prior to step (3) the end surface of the plug
part is formed e.g. cut into the shape of a valley with its bottom
extending across the end surface perpendicular to the longitudinal
direction, preferably a "V" or "U" sectioned valley.
[0043] In step (4) the orifice is cut e.g. by drilling from a
direction parallel to the line of the bottom of the valley. Cutting
in this preferred way can form the above mentioned saddle shaped
closed end surface of the bore.
[0044] Preferred features of the so-made needle are as disclosed
above.
[0045] For example in step (3) the plug part may be welded e.g.
laser welded to the conduit side wall when in place in the bore.
Preferably after being made as described above the outer surface of
the needle is polished, e.g. electropolished, to remove burrs but
not to produce a surface that is so smooth that there is high
friction between the needle and a vial closure which it
punctures.
[0046] The vent groove(s) may be made in the outer surface of the
conduit at any stage in the above needle-making process. The vent
groove(s) may be made using a milling tool which penetrates the
outer surface of the conduit progressively.
[0047] In another aspect the invention provides a process for
introducing a fluid into a puncturable container comprising the
steps of;
[0048] (1) inserting the point of a needle as described above into
the interior of the container by puncturing the container,
[0049] (2) flowing a fluid along the bore of the needle in the flow
direction,
[0050] (3) causing the fluid to exit the needle through the one or
more orifice and thereby enter the container, then
[0051] (4) withdrawing the needle from the container.
[0052] For example the container may be a pharmaceutical vial
having a puncturable closure and the fluid may be a liquid
medicament.
[0053] The invention will now be described by way of example only
with reference to the accompanying drawings.
[0054] FIG. 1 shows a longitudinal and cross section through the
pointed end of a needle of this invention.
[0055] FIG. 2 shows sequentially a process for making the needle of
FIG. 1.
[0056] Referring to FIG. 1 the end of a needle 10 (overall)
adjacent to the point 11 is shown. Needle 10 comprises a
cylindrical tubular conduit 12 made of stainless steel of circular
section of outside diameter 2.4 mm defined by a side wall 13 and
having an internal circular sectioned bore 14 of inside diameter
1.65 mm, the thickness of the side wall 13 being 0.38 mm. The
conduit 12 is suitable for the flow of a fluid (not shown) along
the bore 14 in an flow direction indicated by the arrow.
[0057] Externally the conduit terminates externally at pointed end
11, which is in shape a cone with a cone angle at its apex of ca.
20-45.degree.. Such a conical profile avoids sharp cutting edges
which could form particles of elastomer material as the point
punctures an elastomer closure.
[0058] There are two orifices 15 through the side wall 13 for the
exit of fluid flowing along the bore 14. These orifices are located
180.degree. apart, i.e. diametrically opposite each other on
opposite sides of the bore 14. Each orifice 15 is of an oval shape
elongated parallel to the upstream-downstream direction. Each of
the orifices 15 has an upstream perimeter surface 15A and also a
downstream perimeter surface 15B through the side wall 13
converging toward the upstream direction at an angle (A) of ca.
30.degree. with the upstream direction, i.e. parallel to the
upstream surface 15A.
[0059] The edge 15C of the upstream perimeter surface 15A is
rounded to reduce any possibility of the edge 15C cutting material
of a closure through which the needle is passed. The total cross
sectional area of the two orifices 15, i.e. at the extrapolated
inner surface of the bore 14 is substantially the same as the cross
sectional area of the bore 14.
[0060] The bore 14 terminates at a closed end 16 which is profiled.
This closed end 16 of the bore comprises surfaces 17 that converge
toward the upstream direction, and which meet at a sharp knife edge
ridge 18. The orientation of the line of the edge 18 is
perpendicular to the axis between the two orifices 15, i.e. aligned
with a diameter at 90.degree. to the diameter on which are located
the orifices 15. The sloping surfaces 17 consequently are
intersected by the same diameter that passes through the orifices
15. As is seen in FIG. 1 the sloping alignment of the side surfaces
17 of the edge 18 is the same as that of the downstream perimeter
surfaces 15B of the orifices 15 so that the surfaces 17 merge
smoothly with the perimeter surface 15B of the orifice 15. The edge
18 extends in the upstream direction beyond the upstream perimeter
15A of the orifice.
[0061] The pointed end 11 is provided as a separate plug part 20
which can be plugged into the downstream open end 21 of the bore.
Plug part 20 comprises a male plug end 22 which can be inserted
into the open downstream end 21 of the bore 14 of the tubular
conduit 12 and has an opposite pointed end part 23 comprising the
point 11, the plug end 22 being shaped into the above-described
edge 18 with its sloping side surfaces 17.
[0062] The conduit 12 is also provided externally with two
diametrically opposite vent grooves 24, each ca. 0.2 mm deep,
visible in FIG. 2. The longitudinal ends 24A of each groove 24
accomodates gradually to the outer profile of the conduit 12,
rather than with a sharp step.
[0063] It will be apparent that fluid flowing along bore 14 will be
directed into a direction having a component in the downstream
direction upon exiting through the orifices 15, because of the
directing effect of the fluid guide surfaces 15A, 15B, 17.
[0064] FIG. 1A shows a cross section through the conduit 12 of the
needle 10 of FIG. 1 at the line A-A of FIG. 1. The two vent grooves
24 more clearly seen in FIG. 2 can be seen situated 180.degree.
apart around the outer circumference of the conduit 12. FIG. 1B
shows an alternative cross section through the conduit 12 of the
needle 10 of FIG. 1 at the line A-A of FIG. 1. The two vent grooves
24 more clearly seen in FIG. 2 can be seen situated 180.degree.
apart around the outer circumference of the conduit 12. The
thickness of the steel wall of the conduit 12 is ca. 0.38 mm. The
two vent grooves 24 each have a width of ca. 0.4 mm and a depth of
ca. 0.2 mm. FIG. 1C shows another alternative cross section through
the conduit 12 of the needle 10 of FIG. 1 at the line A-A of FIG.
1. Four vent grooves 24 are seen, disposed in two pairs situated
1800 apart across a diameter of conduit 12. The grooves 24 of each
pair are spaced ca. 40.degree. apart around the outer circumference
of the conduit 12. The thickness of the steel wall of the conduit
12 is ca. 0.40 mm, the conduit diameter being 2.4 mm. The four vent
grooves 24 each have a width of ca. 0.2 mm and a depth of ca. 0.2
mm. In FIGS. 1B and 1C the edge between the sides of the groove 24
and the outer surface of conduit 12 is radiused at ca. 0.05 mm to
avoid cutting particles of a closure as the needle punctures the
closure.
[0065] Referring to FIG. 2 a process for making the needle of FIG.
1 is shown sequentially.
[0066] Referring to FIG. 2A step (2) of the above-described process
is shown. A plug part 30 for the open end of the bore 14 of a
conduit is shown. The plug part 30 is elongated along the vertical
longitudinal axis. One end 31 is formed into a male plug adapted to
longitudinally mate with the open end 21 of the bore of a conduit,
i.e. being of an outside diameter corresponding to the internal
diameter of the open end 21 of the bore 14 so that end 31 is a
tight fit in open end 21. The opposite end 32 is formed into a
pyramidal point. The end surface 31 of the plug part 30 has been
cut into the shape of a "V" sectioned valley 33 with its bottom
extending across the end surface 31 in the direction B-B
perpendicular to the longitudinal direction. There is an abutment
ledge 34 around the part of the plug part 31 closest to the point
32 to limit the extent to which the part 31 can enter the bore
14.
[0067] As seen in FIG. 2B the plug part 30 has been mated with the
open end of the tubular conduit 12, i.e. step (3).
[0068] FIG. 2C shows step (4). Two orifices 15 have been drilled at
diametrically opposite positions through the side wall 13 of
conduit 12 in a direction converging toward the upstream direction.
The line B-B of the bottom of the valley 33 is aligned parallel to
the diameter of the conduit joining the two orifices 15. The
downstream perimeter surface 15B of orifice 15 is visible.
[0069] FIG. 2D shows the rounding of the upstream perimeter
surfaces 15A of the orifices 15 using a tool 35, to form the
rounded edge 15C.
[0070] FIG. 2E shows in an exploded view how the drilling of the
orifices 15 through the side wall 13 has formed the end surface 16
of the plug end 22 of plug part 20 into side surfaces 17 that
converge toward the upstream direction to form the edge 18, and
which form part of an overall "saddle" shaped surface, i.e. with
surfaces 19 inclined relative to the upstream-downstream direction
and generally in planes perpendicular to the planes of the side
surfaces 17.
[0071] FIG. 3 shows how the needle of FIG. 1 is used in an
apparatus of the invention. As seen in FIG. 3A a pharmaceutical
vial 31 is provided having a puncturable elastomer closure 32, held
in place in a closing relationship with the mouth of the vial 31 by
a clap part 33 which has a central aperture 34 through which the
closure 32 is exposed. The interior of vial 31 and the part of
closure 32 exposed within aperture 34 have been pre-sterilised.
[0072] A hollow needle 35 of the type shown and described with
reference to FIGS. 1 and 2 is supported above vial 32, with its
point downwards and aimed at closure 32 through aperture 34. Needle
35 is supported by holder 36 which can be moved reciprocally
upwardly and downwardly relative to vial 31 by suitable means (not
shown). Holder 36 also connects needle 35 to a source (not shown)
of a liquid via line 37.
[0073] Vial 31 has its bottom held by a base 38 which enable vial
31 to be held down onto a conveyor (not shown) by which vial 31 may
be moved underneath needle 35 into the relationship shown.
[0074] As seen in FIG. 3B, the needle 35 has been moved downwardly
by means of a corresponding downward movement of holder 36, so that
needle 35 punctures and passes through the closure 32 with orifices
shown 15 in FIGS. 1 and 2 within vial 31.
[0075] As seen in FIG. 3C, a liquid 39 is caused to flow along line
37 through conduit 12 (as seen in FIGS. 1 and 2) of the needle 35,
to exit via the orifices 15 into vial 31. The orientation of the
orifices 15 directs the liquid 39 to flow out of the needle 35 in a
direction having a component parallel to the flow direction, i.e.
having a downward component as seen in FIG. 3C. The flow of liquid
39 is seen to be in a direction at a non-zero, non-perpendicular
direction to the longitudinal axis of the needle 35. Flowing in
this direction the liquid 39 is directed away from the underside of
closure 32 and the upper regions of the interior of vial 31 toward
the bottom of vial 31. The vent groove shown 24 in FIG. 2 in the
outer surface of needle 35 has a length sufficient that when the
needle 35 has punctured the closure 32 to its fully intended extent
as seen in FIG. 3C one end of the groove 24 is within the vial 31
and the other end is exposed outside of the vial, so that air
within the vial 31 can escape via the groove 24 as shown 310.
[0076] As seen in FIG. 3D a reciprocal upward movement of the
holder 36 and needle 35 has caused the needle 35 to be withdrawn
from the vial 31 and closure 32. The vial 31 may be held down by a
holding means (not shown) applied to the base 38. The residual
puncture hole 311 may be heat sealed.
[0077] The entire operation shown in FIGS. 3A-3D is preferably
performed under a downward laminar flow of sterilised air (not
shown).
* * * * *