U.S. patent application number 13/058348 was filed with the patent office on 2011-08-04 for prefilled container insert for mixing two or more ingredients for use in a pharmaceutical container system.
This patent application is currently assigned to ASTRAZENECA AB. Invention is credited to Pontus Dersjo, Anders Lofgren.
Application Number | 20110186451 13/058348 |
Document ID | / |
Family ID | 41669083 |
Filed Date | 2011-08-04 |
United States Patent
Application |
20110186451 |
Kind Code |
A1 |
Dersjo; Pontus ; et
al. |
August 4, 2011 |
PREFILLED CONTAINER INSERT FOR MIXING TWO OR MORE INGREDIENTS FOR
USE IN A PHARMACEUTICAL CONTAINER SYSTEM
Abstract
The present invention relates to pharmaceutical container
systems, and to prefilled container inserts for use therein, for
mixing two or more ingredients of a pharmaceutical product. The
prefilled container insert of one embodiment comprises a molded
container casing having walls, a bottom and an open top for
receiving a solid component, a resilient stopper for sealing the
open top of the molded container casing, and a bottom disc formed
by a weakening rim in the bottom periphery of the molded container
casing. The bottom disc is openable to allow mixing of the
prefilled solid component with a diluents fluid of the
pharmaceutical container system by introducing a spike through the
resilient stopper applying a pushing force on the bottom disc, by
which force the weakening rim is broken and the container is
opened. The prefilled container insert of a further embodiment
comprises a molded container casing having walls, a bottom and an
open top for receiving an inner open cylinder and a solid
component, a resilient stopper for sealing the open top of the
molded container casing, and a bottom disc formed by a weakening
rim in the bottom periphery of the molded container casing. The
bottom disc is openable to allow mixing of the prefilled solid
component with a diluents fluid of the pharmaceutical container
system by applying a pushing force onto the top of the molded
container compressing the casing and forcing the inner cylinder to
push on the bottom disc, by which force the weakening rim is broken
and the container insert is opened.
Inventors: |
Dersjo; Pontus; (Sodertalje,
SE) ; Lofgren; Anders; (Sodertalje, SE) |
Assignee: |
ASTRAZENECA AB
Sodertalje
SE
|
Family ID: |
41669083 |
Appl. No.: |
13/058348 |
Filed: |
August 10, 2009 |
PCT Filed: |
August 10, 2009 |
PCT NO: |
PCT/SE2009/050922 |
371 Date: |
April 20, 2011 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
61087784 |
Aug 11, 2008 |
|
|
|
61087789 |
Aug 11, 2008 |
|
|
|
Current U.S.
Class: |
206/219 |
Current CPC
Class: |
B65B 29/10 20130101;
B65D 51/285 20130101; A61J 1/2027 20150501; B65D 51/002 20130101;
A61J 1/2093 20130101; A61J 1/1406 20130101 |
Class at
Publication: |
206/219 |
International
Class: |
B65D 25/08 20060101
B65D025/08 |
Claims
1. A prefilled container insert for use in a pharmaceutical
container system for mixing two or more ingredients of a
pharmaceutical product, the pre-filled container insert comprising:
a molded container casing having walls, a bottom and an open top
for receiving a solid component; a resilient stopper for sealing
the open top of the molded container casing; and a bottom disc
formed by a weakening rim in the bottom periphery of the molded
container casing, wherein the bottom disc is openable to allow
mixing of the pre-filled solid component with a diluents fluid of
the pharmaceutical container system by introducing a spike through
the resilient stopper applying a pushing force on the bottom disc,
by which force the weakening rim is broken and the container insert
is opened.
2. A prefilled container insert for use in a pharmaceutical
container system for mixing two or more ingredients of a
pharmaceutical product, the pre-filled container insert comprising:
a molded container casing having walls, a bottom and an open top
for receiving an inner open cylinder and a solid component; a
resilient stopper for sealing the open top of the molded container
casing; and a bottom disc formed by a weakening rim in the bottom
periphery of the molded container casing, wherein the bottom disc
is openable to allow mixing of the pre-filled solid component with
a diluents fluid of the pharmaceutical container system by applying
a pushing force onto the top of the molded container, thereby
compressing the casing and forcing the inner cylinder towards the
bottom disc, by which force the weakening rim is broken and the
container insert is opened.
3. A prefilled container insert according to claim 2, wherein the
molded container casing has pleated sidewalls forming a bellows
container insert.
4. A prefilled container insert according to claim 1, wherein the
weakening rim in the bottom disc is arranged around the periphery
of the bottom of the container casing forming a hinged disc such
that the bottom disc remains connected to the container casing when
the weakening rim is broken and the container is opened.
5. A prefilled container insert according to claim 1, wherein the
resilient stopper is secured in place by a clamp ring to
hermetically seal the top opening.
6. A pre-filled prefilled container insert according to claim 1,
wherein the bottom disc is covered by a moisture barrier foil.
7. A prefilled container insert according to claim 1, wherein the
resilient stopper is covered by a moisture barrier foil.
8. A prefilled container insert according to claim 1, wherein the
prefilled container insert is aseptically mounted into the top of a
Blow-Fill-Seal (BFS) container forming a multi-chamber
pharmaceutical container system.
9. A prefilled container insert according to claim 1, wherein the
prefilled container insert is aseptically mounted into a container,
the container having a delivery mechanism capable of attachment
thereto, such that there is provided a multi-chamber pharmaceutical
delivery system.
10. A prefilled container insert according to claim 9, wherein the
delivery mechanism comprises a nasal delivery component, preferably
a spray, dropper or the like.
11. A pharmaceutical container system for mixing two or more
ingredients of a pharmaceutical product, comprising: a first
container comprising a diluents liquid; and a second container
insert aseptically mounted into the top of the first container, the
second container including: a molded container casing for receiving
a solid component; a resilient stopper for sealing the open top of
the molded container casing; and a bottom disc formed by a
weakening rim in the bottom periphery of the molded container
casing, wherein the bottom disc is openable to allow mixing of the
prefilled solid component with a diluents fluid of the
pharmaceutical container system by introducing a spike through the
resilient stopper applying a pushing force on the bottom disc, by
which force the weakening rim is broken and the container is
opened.
12. A pharmaceutical container system for mixing two or more
ingredients of a pharmaceutical product, comprising: a first
container comprising a diluents liquid; and a second container
insert aseptically mounted into the top of the first container, the
second container including: a molded container casing having walls,
a bottom and an open top for receiving an inner open cylinder and a
solid component; a resilient stopper for sealing the open top of
the molded container casing; and a bottom disc formed by a
weakening rim in the bottom periphery of the molded container
casing, wherein the bottom disc is openable to allow mixing of the
prefilled solid component with a diluents fluid of the
pharmaceutical container system by applying a pushing force onto
the top of the molded container, thereby compressing the casing and
forcing the inner cylinder towards the bottom disc, by which force
the weakening rim is broken and the container insert is opened.
Description
TECHNICAL FIELD
[0001] The present invention relates to a pharmaceutical
multi-chamber container system for mixing two or more ingredients
of a pharmaceutical product, and more particularly to a pre-filled
container insert to be used with such a system.
BACKGROUND OF THE INVENTION
[0002] Solid active pharmaceutical ingredients (API) or formulated
products generally have better shelf-life, i.e. degrade at a slower
rate than solutions (or dispersions/emulsions) of the same
compound. Therefore, it is commonplace to use dry powder, for
example to freeze-dry or spray-dry pharmaceutical products to
extend shelf-life of a pharmaceutical product to practical length,
typically at least 18-24 months. At time of use, such a solid
product must be dissolved in a suitable solvent before it can be
administered to the patient, usually via is oral or parenteral
routes or by nasal delivery. The dissolution of the solid in a
solvent is typically made via transfer of the solvent from a vial
or bag using a syringe. Although such a process is a standard
procedure amongst hospital staff, it does take training and skill
to do it in a safe and efficient manner without risk of
needle-stick injury or compromising product sterility and thereby
patient safety.
[0003] Patent abstract of Japan, JP2000037441A relates to an
infusion container system having a solid drug storing part
connected to a liquid solution container. A fluid communication
channel is established between the two containers by pressing the
solid medicine storing part to the solution container side and a
partitioning member is opened and moved from a seal part. After
making the solid drug storage container and the solution container
open for free passage the solid drug dissolves in the liquid
solution by shaking the whole transfusion container. The solution
is now ready to be administered to a patient and a puncture needle
is introduced into an infusion solution take off connection
provided in the top of the solid drug storage container. A drawback
with this device is that it requires a complicated construction of
the solid drug storing part comprising several parts and which will
involve a number of production steps. A further drawback is that
two steps need to be carried out before the solution can be
administered to a patient, namely first allow for mixing of the two
ingredients and then introducing a needle to connect for example an
infusion set.
THE OBJECT OF THE INVENTION
[0004] It is an object of the present invention, in preferred
embodiments at least, to provide a container system in which mixing
of two or more ingredients of a pharmaceutical product, e.g. a
solid and solvent or two different liquids, is made using a simple,
effective and intuitive procedure with minimum risks for hospital
staff and patients.
[0005] It is a further object of the present invention, in
preferred embodiments at least, to provide a robust concept to be
used in connection with blow-fill-seal (BFS) equipment having a
construction involving few parts as well as few production
steps.
SUMMARY OF THE INVENTION
[0006] In accordance with the present invention, from a first broad
aspect at least, there is provided a pre-filled container insert
for use in a pharmaceutical container system for mixing two or more
ingredients of a pharmaceutical product. The pre-filled container
insert comprises;
[0007] a moulded container casing having walls, bottom and an open
top for receiving a solid component,
[0008] a resilient stopper for sealing the open top of the moulded
container casing,
[0009] a bottom disc formed by a weakening rim in the bottom
periphery of the moulded container casing, wherein the bottom disc
is openable to allow mixing of the pre-filled solid component with
a diluents fluid of the pharmaceutical container system by
introducing a spike through the resilient stopper applying a
pushing force on the bottom disc, by which force the weakening rim
is broken and the container insert is opened.
[0010] In accordance with the present invention, from a further
broad aspect at least, there is provided a pre-filled container
insert for use in a pharmaceutical container system for mixing two
or more ingredients of a pharmaceutical product. The pre-filled
container insert comprises;
[0011] a moulded container casing having walls, bottom and an open
top for receiving an inner open cylinder and a solid component,
[0012] a resilient stopper for sealing the open top of the moulded
container casing,
[0013] a bottom disc formed by a weakening rim in the bottom
periphery of the moulded container casing, wherein the bottom disc
is openable to allow mixing of the pre-filled solid component with
a diluents fluid of the pharmaceutical container system by applying
a pushing force onto the top of the moulded container, thereby
compressing the casing and forcing the inner cylinder towards the
bottom disc, by which force the weakening rim is broken and the
container insert is opened.
[0014] An advantage of preferred embodiments of the present
invention is that there is provided a pre-filled container insert
that is constructed from a minimum of parts and at the same time
has efficient and robust construction. A further advantage of
preferred embodiments of the present invention is that there is
provided a pre-filled container insert that easily can be opened to
provide mixing of contents in the insert and the liquids container.
A still further advantage is that the pre-filled container insert
is manufactured as a separate device and can be incorporated into
different types of blow-fill-seal containers forming a
pharmaceutical multi-chamber container system. Yet another
advantage is that the separate device can be aseptically filled,
sealed and processed (e.g. terminally sterilised) under controlled
conditions before the next unit operation of actually mounting the
device into the diluents container.
[0015] According to preferred embodiments of the invention, the
weakening rim in the bottom disc is arranged around the periphery
of the bottom of the container casing forming a hinged disc such
that the bottom disc remains connected to the container casing when
the weakening rim is broken and the container is opened.
[0016] In this way the bottom disc is prevented from falling out
into the diluents container after opening of the pre-filled
container insert.
[0017] According to preferred embodiments of the invention, the
resilient stopper is secured in place by a clamp ring to
hermetically seal the top opening.
[0018] The clamp ring locks and fixes the resilient stopper in the
open top of the container casing and the moulded casing is
hermetically sealed.
[0019] According to preferred embodiments of the invention, the
bottom disc is covered by a moisture barrier foil.
[0020] According to preferred embodiments of the invention, the
resilient stopper is covered by a moisture barrier foil.
[0021] By covering the container insert with a moisture barrier
foil, both on the bottom side or on the resilient top side, the
pre-filled content has a maximum of protection from the outside
environment, i.e. light, moisture and/or oxygen.
[0022] According to preferred embodiments of the invention, the
pre-filled container insert is aseptically mounted into the top of
a BFS-container forming a multi-chamber pharmaceutical container
system.
[0023] According to preferred embodiments of the invention, the
moulded container casing has pleated sidewalls forming a bellows
container insert.
[0024] By forming the container casing as a bellows container an
easily deformable casing is formed in one single piece.
[0025] According to preferred embodiments of the invention, the
pre-filled container insert is capable of use with one or more
delivery systems, such as a nasal delivery system. Preferably the
pre-filled container insert is connectable to or within, or
otherwise can be incorporated with, for example, a standard nasal
delivery mechanism such as a nasal spray.
[0026] According to preferred embodiments of the invention, there
is provided a pharmaceutical container system for mixing two or
more ingredients of a pharmaceutical product, comprising
[0027] a first container comprising a diluents liquid,
[0028] a second container insert aseptically mounted into the top
of the first container, the second container comprising
[0029] a moulded container casing for receiving a solid
component,
[0030] a resilient stopper for sealing the open top of the moulded
container casing,
[0031] a bottom disc formed by a weakening rim in the bottom
periphery of the moulded container casing, wherein the bottom disc
is openable to allow mixing of the pre-filled solid component with
a diluents fluid of the pharmaceutical container system by
introducing a spike through the resilient stopper applying a
pushing force on the bottom disc, by which force the weakening rim
is broken and the container insert is opened.
[0032] According to preferred embodiments of the invention, there
is provided a pharmaceutical container system for mixing two or
more ingredients of a pharmaceutical product comprising
[0033] a first container comprising a diluents liquid,
[0034] a second container insert aseptically mounted into the top
of the first container, the second container comprising
[0035] a moulded container casing having walls, bottom and an open
top for receiving an inner open cylinder and a solid component,
[0036] a resilient stopper for sealing the open top of the moulded
container casing,
[0037] a bottom disc formed by a weakening rim in the bottom
periphery of the moulded container casing, wherein the bottom disc
is openable to allow mixing of the pre-filled solid component with
a diluents fluid of the pharmaceutical container system by applying
a pushing force onto the top of the moulded container, thereby
compressing the casing and forcing the inner cylinder towards the
bottom disc, by which force the weakening rim is broken and the
container insert is opened.
[0038] A standard procedure for a nurse preparing an intra-venous
(IV)-container is to visually inspect, and in some procedures to
spike, the IV-container before starting infusion. Therefore, using
a pharmaceutical container system according to embodiments of the
present invention, the standard working procedure is not changed.
In preferred embodiments, by simply pushing the container top to
allow mixing and then ensure the complete mixing operation by
visual inspection, a simple an intuitive procedure is obtained. In
addition, no separate mixing step using hypodermic needles are
necessary, eliminating the risk of needle-stick injuries. Mixing is
made without risk of microbial contamination since the solid and
liquid chambers are both parts of the same hermetically sealed
container. In other embodiments, similar steps are carried out but
for preparing a nasal delivery device such as a nasal spray, which
typically comprises a container, and a spray or other nasal
delivery mechanism attached thereto.
[0039] Medicaments suitable for administration via a pharmaceutical
multi-chamber container system for mixing two or more ingredients
of a pharmaceutical product, and more particularly to be pre-filled
with the container insert of the present invention include for
example proton pump inhibitors, for example omeprazol, anticancer
medicaments, antibiotics, immunotherapies, vaccines, antiviral
medicaments, polypeptides and peptides, for example, peptide
hormones and growth factors, polypeptide vaccines, enzymes
endorphines, lipoproteins and polypeptides involved in the blood
coagulation cascade.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] The present invention will now be described, for exemplary
purposes, in more detail by way of embodiments and with reference
to the enclosed drawings, in which: FIGS. 1a-1g illustrate
schematically the manufacturing steps of a pre-filled container
insert in accordance with a preferred embodiment of the present
invention, and,
[0041] FIGS. 2a and 2b schematically illustrate the opening
procedure of the pre-filled container insert, and,
[0042] FIGS. 3a-3d show a pharmaceutical container system for
mixing two or more ingredients s of a pharmaceutical product, which
system consists of a BFS-container filled with a diluents liquid
and a pre-filled insert sealed to the container, and,
[0043] FIGS. 4a-4h illustrate schematically the manufacturing steps
of a further pre-filled container insert in accordance with a
preferred embodiment of the present invention, and,
[0044] FIGS. 5a-5c schematically illustrate the opening procedure
of the pre-filled container insert of FIGS. 4a-4h, and;
[0045] FIGS. 6a-6d show a pharmaceutical container system for
mixing two or more ingredients of a pharmaceutical product, which
system consists of a BFS-container filled with a diluents liquid
and a pre-filled insert sealed to the container.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0046] FIGS. 1a to 1g and 4a to 4h schematically illustrate how
pre-filled container inserts can be manufactured. The container
inserts, being manufactured separately e.g. by injection moulding
can use any type thermoplastic material, e.g. high-barrier
engineering plastics if necessary to impart high-barrier
properties, e.g. with light, moisture or oxygen sensitive
compounds.
[0047] FIG. 1a shows the moulded container casing 1 having walls 2,
bottom 3 and an open top 4 for receiving a medicament component.
The container casing 1 which is made using e.g. injection moulding
preferably has a cylindrical geometry and the bottom 3 has a
suitable weakening rim 5 in the bottom periphery. The weakening rim
5 will make it possible to push open the bottom disc 3 to allow
material transfer between the pre-filled insert and a liquid
container. Preferably, a small portion of the weakening rim is kept
thicker, functioning as a hinge 6 so as to prevent the bottom disc
3 to completely disengage from the solids container on opening.
[0048] To further augment the moisture or gas barrier of the
container insert and thus to protect the content, a barrier foil 7,
e.g. an aluminium foil can be used to cover the bottom disc 3,
which can be seen in FIG. 1b.
[0049] In FIG. 1c the moulded container casing is pre-filled with a
content 8, a powder or other suitable solid (or semi-solid) in a
well-defined, clean environment (e.g. aseptic filling in isolator
or other suitable uni directional air flow hood (UDF)). According
to another aspect of this invention not shown in the drawings, the
moulded container casing is pre-filled with a semi-solid content or
a liquid, which is to be mixed with the diluents prior to
infusion.
[0050] FIGS. 1d, 1e and 1f show how the container insert is
hermetically closed using a resilient stopper 9, e.g. a standard
rubber stopper or thermoplastic elastomer (TPE) part, which is
mounted through the open top and secured by a clamp ring 10 to
ensure a safe and tight fastening of the stopper 9. As shown in
FIG. 1g, a barrier foil 15, i.e. an aluminium foil, can be used to
cover the resilient stopper 9 and clamp ring 10 to further augment
the moisture or gas barrier of the pre-filled container insert 17.
The open centre of the clamp ring 10 reveals a circular area of the
resilient stopper where the spike (or a puncture needle) can be
entered through the stopper. The pre-filled container insert 17 can
be sterilised either in-line or in a separate step after
filling/closing using standard methods such as e-beam or gamma
irradiation. Such a sterile pre-filled container insert can then be
transported to a suitable standard filling line for liquids to be
mounted to a blow-fill-seal container or other suitable liquids
plastic container. The container may comprise a component of a
nasal delivery device, which preferably contains the appropriate
liquid.
[0051] FIG. 2a schematically illustrate how a spike 20 is pushed
through the resilient stopper 9 of the pre-filled container insert
and in 2b how the pushing force from the spike 20 breaks the
weakened rim 5 in bottom periphery (as well as the barrier foil 7)
and the content 8 of the pre-filled container insert is free to
leave the container.
[0052] FIG. 3a illustrates an embodiment of a pharmaceutical
container system 21 wherein a pre-filled container insert 17
according to the present invention is mounted into the top of a
blow-fill-seal container 22. In the embodiment of FIGS. 3a to 3d,
the system 21 comprises means suitable for intravenous delivery of
a medicament, but the system may comprise any other, suitable
pharmaceutical system, such as a container (e.g. a bottle, vial or
tube) for use with a nasal delivery mechanism, e.g. a spray or
dropper that connects to the container. The pre-filled container
insert 17 of the FIG. 3a embodiment filled with a content 8 will be
enclosed into the liquid blow-fill-seal container and the top
portion of the pre-filled container is revealed to the user by
opening a twist-off top 23 of the blow-fill-seal container 22,
which is shown in FIG. 3b. In a preferred embodiment, also shown in
FIG. 3b, a moisture barrier seal 15 covers the top, i.e. a
resilient stopper 9 of the pre-filled container under the twist-off
top 23. After the moisture barrier seal 15 has been removed the
content 8 of the pre-filled container insert 17 is ready to be
mixed with the diluents fluid in the blow-fill-seal container 22.
FIG. 3c shows how a spike 20 punctures the resilient stopper 9 and
enters into the pre-filled container 17. The pushing force from the
spike 20 acts on the bottom disc 3 and the weakened rim 5 in the
periphery of the disc breaks up. The disc 3 is prevented from
falling out into the blow-fill-seal container 22 by a hinge 6
connecting the bottom disc to the wall 2 of the container insert.
The content of the pre-filled container can now be mixed with the
diluents fluid of the blow-fill-seal container by gentle shaking
the container. In FIG. 3d a bottom flap 25 is pulled up to allow
hanging of the container system near a patient while administering
the substance to the patient. According to another aspect of the
present invention not shown in the drawings, the pre-filled
container insert is welded into a flexible bag wall being filled
with the diluents liquid.
[0053] FIG. 4a shows another embodiment of the present invention.
Like reference numerals are used to indicate components similar to
those of the embodiment of FIGS. 1 to 3. The moulded container
casing 1 has walls 2, bottom 3 and an open top 4 for receiving a
medicament component. The container casing 1 which is made using
e.g. injection moulding preferably has a cylindrical geometry and
differs from the previous embodiment in that the walls 2 are
pleated such that the container casing has the form of a bellows.
The bottom 3 has a suitable weakening rim 5 in the bottom
periphery. Preferably, a small portion of the weakening rim is kept
thicker, functioning as a hinge 6 so as to prevent the bottom disc
3 to completely disengage from the solids container on opening. To
further augment the moisture or gas barrier of the container insert
and thus to protect the content, a barrier foil 7, e.g. an
aluminium foil can be used to cover the bottom disc 3, which can be
seen in FIG. 4b.
[0054] In FIG. 4c an inner cylinder 30 is placed inside the moulded
container casing and, as shown in FIG. 4d, the inner cylinder
placed within the container walls is then pre-filled with a content
8, a powder or other suitable solid (or semi-solid) in a
well-defined, clean environment (e.g. aseptic filling in isolator
or other suitable uni directional air flow hood (UDF)). According
to another aspect of this invention not shown in the drawings, the
inner cylinder with container is pre-filled with a semi-solid
content or a liquid which is to is be mixed with the diluents prior
to infusion. The weakening rim 5 will make it possible to push open
the bottom disc 3 using the inner cylinder 30 to allow material
transfer between the pre-filled insert and a liquid container. The
inner cylinder 30 is tapered and oriented in relation to the
weakening rim so that the tapered end push first at the position
directly opposite the hinge part of the weakening rim along the
periphery.
[0055] FIGS. 4e and 4f show how the container insert is
hermetically closed using a resilient stopper 9, e.g. a standard
rubber stopper or thermoplastic elastomer (TPE) part, which is
mounted through the open top and secured by a clamp ring 10 to
ensure a safe and tight fastening of the stopper 9. As shown in
FIG. 4h, a barrier foil 15, i.e. an aluminium foil, can be used to
cover the resilient stopper 9 and clamp ring 10 to further augment
the moisture or gas barrier of the pre-filled container insert 17.
Alternatively, the aluminium foil is replaced with a standard
tamper-evident protective seal. The open centre of the clamp ring
10 reveals a circular area of the resilient stopper where the spike
(or a puncture needle) can be entered through the stopper. The
pre-filled container insert 17 can be sterilised either in-line (at
filling) or in a separate step after filling/closing using standard
methods such as e-beam or gamma irradiation. Such a sterile
pre-filled container insert can then be transported to a suitable
standard filling line for liquids to be mounted to a blow-fill-seal
container or other suitable liquids plastic container.
[0056] FIG. 5a schematically illustrates how a pressing force is
applied to the top of the bellows container insert 17 and how the
pushing force compresses the walls 2 of the container insert. In
FIG. 5b the inner cylinder 30 presses on the bottom 3 and breaks
the weakened rim 5 in bottom periphery (as well as the barrier foil
7) and the content 8 of the pre-filled container insert is free to
leave the container and be mixed with a diluent fluid (not shown).
In FIG. 5c a spike 20 is introduced through the rubber stopper 9 to
make the container ready for administration to a patient.
[0057] FIG. 6a illustrates an embodiment of a pharmaceutical
container system 21 wherein a pre-filled container insert 17
according to the present invention is mounted into the top of a is
blow-fill-seal container 22. As discussed above, the system may
comprise any other, suitable pharmaceutical system, such as a
container for use with a nasal delivery mechanism. The pre-filled
container insert 17 filled with a content 8 will be enclosed into
the liquid blow-fill-seal container and the top portion of the
pre-filled container is revealed to the user by opening a twist-off
top 23 of the blow-fill-seal container 22, which is shown in FIG.
6b. In a preferred embodiment, also shown in FIG. 6b, a moisture
barrier seal 15 covers the top, i.e. a resilient stopper 9 of the
pre-filled container under the twist-off top 23. After removal of
the twist-off top the content 8 of the pre-filled container insert
17 is ready to be mixed with the diluents fluid in the
blow-fill-seal container 22. FIG. 6c shows how the walls 2 of the
bellows insert are compressed. The pushing force makes the inner
cylinder 30 to break the weakened rim 5 in the periphery of the
bottom disc 3 and the rim breaks up. The disc 3 is prevented from
falling out into the blow-fill-seal container 22 by a hinge 6
connecting the bottom disc to the wall 2 of the container insert.
The content of the pre-filled container can now be mixed with the
diluents fluid of the blow-fill-seal container by gentle shaking of
the container. After visual inspection to ensure complete mixing of
the contents and confirmation of the absence of particulates, the
moisture barrier seal (or tamper-evident seal) can be removed. A
spike 20 (or puncture needle) may be introduced through the stopper
9 to make the container ready to be administered to a patient.
According to another aspect of the present invention not shown in
the drawings, the pre-filled container insert is welded into a
flexible bag wall being filled with the diluents liquid.
[0058] To mix the content of the solid and liquid containers in the
above intravenous examples, the user (typically a nurse) adopts a
normal working procedure with intravenous, i.e. IV-infusions. A
preferred use of a system in accordance with an embodiment of the
present invention as illustrated in FIGS. 1 to 3 is described below
in chronological order.
[0059] 1) The nurse twists off the blow-fill seal container top and
peels off the moisture barrier seal if there is one (and disinfects
the rubber stopper top if that is standard procedure).
[0060] 2) A sterile IV-administration set bag is opened.
[0061] 3) The IV-spike of the administration set is inserted into
the rubber stopper top, thereby piercing the rubber stopper. As the
spike is fully inserted, the bottom disc of the solids chamber is
pushed open by the spike, and the solids and liquids chambers are
now communicating to enable mixing.
[0062] 4) The contents of the solids and liquids chambers are mixed
by gently rocking the container.
[0063] 5) The nurse visually inspects the contents of the container
to ensure full dissolution and absence of particulate matter.
[0064] 6) The needle is attached to the patient after purging, and
IV-infusion is ready to start.
[0065] A preferred use of a system in accordance with another
embodiment of the present invention as illustrated in FIGS. 4 to 6
is described below in chronological order.
[0066] 1) The nurse twists off the blow-fill seal container
top.
[0067] 2) The nurse compresses the bellows insert to make the
pre-filled content fall into the diluents container and the solids
and liquids chambers are now communicating to enable mixing.
[0068] 3) The contents of the solids and liquids chambers are mixed
by gently rocking the container.
[0069] 4) The nurse peels off the moisture barrier (or protective)
seal and disinfects the rubber stopper top if that is standard
procedure
[0070] 4) A sterile IV-administration set bag is opened. The
IV-spike of the administration set is inserted into the rubber
stopper top, thereby piercing the rubber stopper.
[0071] 5) The nurse visually inspects the contents of the container
to ensure full dissolution and absence of particulate matter.
[0072] 6) The needle is attached to the patient after purging, and
IV-infusion is ready to start.
[0073] In other embodiments, for example where the pre-filled
insert is for use with, e.g., a nasal is delivery device, some of
the above steps may be carried out, but with the insert contained
within, or otherwise associated with, a suitable container such as
a nasal spray bottle or the like.
[0074] Further, it will be understood that the present invention is
not limited to the described embodiments but can be modified in
many different ways without departing from the scope of the
appended claims.
* * * * *