CN113573752A

CN113573752A - System comprising a prefillable syringe and a package for a prefillable syringe

Info

Publication number: CN113573752A
Application number: CN202080020984.3A
Authority: CN
Inventors: J·普夫朗; A·戈什奥费尔; M·隆巴迪尼
Original assignee: Chiesi Farmaceutici SpA
Current assignee: Chiesi Farmaceutici SpA
Priority date: 2019-03-15
Filing date: 2020-03-11
Publication date: 2021-10-29
Also published as: MA55294A; WO2020187660A1; CA3130030A1; JP2022523408A; EP3938010A1; MX2021010362A; BR112021015970A2; AU2020244071A1; KR20210141501A

Abstract

The invention discloses a system, comprising: a prefillable syringe having a syringe barrel and a syringe tip; and a package adapted and adapted for receiving a prefillable syringe, wherein the syringe tip is provided with a tip cap, wherein the system comprises a replacement cap for the prefillable syringe, wherein the package is adapted and adapted for receiving the replacement cap.

Description

System comprising a prefillable syringe and a package for a prefillable syringe

Technical Field

The present invention relates to a package suitable and intended for receiving a prefillable syringe comprising a syringe barrel and a syringe tip, wherein the syringe tip is provided with a tip cap. The invention also relates to a system comprising a prefillable syringe having a syringe barrel and a syringe tip, wherein the syringe tip is provided with a tip cap, and a package adapted and adapted for containing the prefillable syringe, and a method of using the system. Furthermore, the present invention relates to a replacement cap for a prefillable syringe.

Background

The prefillable syringe may be used as a kit with a medium to be administered or delivered to a user, wherein the prefillable syringe of the kit is filled with the medium.

In particular, prefilled syringes have become one of the fastest growing options for unit dose drugs today. Such a syringe is easy to handle as there is no need to transfer the medium to be administered to the syringe before use. The use of pre-filled syringes minimizes medication waste and extends product life.

Due to the development of new drugs, it is becoming increasingly popular to administer drugs to patients, rather than by injection. Possible modes of administration are in particular oral, intranasal, topical, cutaneous and more external administration. For such administration, pre-filled syringes may be the best way to store, transport and administer the drug.

In addition, for in vivo injection of media or drugs, pre-filled syringes are a convenient option. In particular, modern vaccines are very sensitive to external influences and are therefore safely stored in pre-filled syringes.

The prefillable syringe body comprises a syringe barrel, a syringe tip and optionally a finger flange. In some cases, the syringe tip is already provided with a piercing device. The puncture device may be a needle, a cannula or the like.

The syringe bodies are produced by the primary packaging manufacturer under clean room conditions. After sterilization, the syringe body is provided with a tip cap and placed in a so-called syringe nest. A tip cap is typically placed over the syringe tip and may also enclose a needle disposed in the syringe tip.

The prefillable syringe is then delivered to a pharmaceutical company that provides the kit along with the medium to administer the medium or preferably to fill the syringe with the medium.

In the latter case, after the filling process, a plunger or piston is introduced into the syringe barrel, thereby closing the barrel on its proximal side. The filled syringe is then placed into a secondary package.

The tip cap may seal the tip and optional needle. Typically, the tip cap is made at least partially of an elastic material. Because of the limited space for the syringes in the syringe nest, the tip cap is typically designed to be as small as possible. However, such a small size tip cap may be inconvenient for a user to operate.

In some cases, the user needs to set the dose before actually administering the medium, which may be done later. For this reason, the tip cap may need to be temporarily removed. Reclosing of the syringe with the tip cap may result in an undesirable introduction of a portion of air in the syringe barrel. This air can cause irritation to the patient. In case the medium in the syringe barrel is a relatively high viscosity medium, the enclosed air part may be difficult to remove.

WO 2018/038078 a1 discloses a medical device package having a plurality of syringe package bodies including a pre-filled syringe system and a package body, and an outer box containing the plurality of syringe package bodies. The needle unit of the pre-filled syringe system is supported relative to the needle unit housing with the largest outer diameter portion being provided at the tip of the needle hub which engages with the inner surface of the needle unit housing. In the casing, the plurality of syringe package bodies are arranged such that the axial direction of the needle body is in the up-down direction of the casing. The prefilled syringe is sealed with a sealing cap, but no replacement cap is provided.

Disclosure of Invention

It is therefore an object of the present invention to provide a prefillable syringe, a package for containing a prefillable syringe and a system comprising a prefillable syringe and a package overcoming the above mentioned disadvantages.

The invention also relates to a system according to the invention, wherein the syringe is pre-filled with a ready-to-use pharmaceutical preparation.

Furthermore, the invention relates to a kit comprising the system of the invention and a pharmaceutical formulation in the form of a ready-to-use aqueous solution or powder for reconstitution in a suitable carrier, together with instructions for administration of said pharmaceutical formulation.

Drawings

Fig. 1 shows a prefillable syringe without a tip cap;

figure 2a shows a prefillable syringe with a tip cap;

FIG. 2b shows a replacement cap;

FIG. 3 shows a prefillable syringe with a replacement cap;

FIG. 4 shows a prefillable syringe with a replacement cap on a support surface;

FIG. 5a shows the prefillable syringe with the tip cap as shown in FIG. 2 a;

FIG. 5b shows an alternative cap as in FIG. 2b with different feet;

FIG. 6 illustrates a package body without a prefillable syringe according to one embodiment;

FIG. 7 illustrates a package body having a prefillable syringe and a replacement cap according to one embodiment;

FIG. 8 illustrates a package body having a prefillable syringe disposed in a replacement cap, according to one embodiment;

FIG. 9 illustrates a bottom perspective view of a plunger in accordance with one or more embodiments;

FIG. 10 shows a top perspective view of the plunger;

FIG. 11 is a bottom view of the plunger;

FIG. 12 is a top view of the plunger; and

fig. 13 shows a side view of the plunger.

List of reference numerals

1, packaging;

2a first containing member;

3a package body;

4 a first cavity of the packaging main body;

5 packaging the side wall of the object body;

6 the bottom wall of the package body;

7a second containing element;

7a first one of the second containing elements;

7b a second one of the second containing elements;

8a third containing element;

8a, 8b third containment element wall;

12 a first containment element side wall;

13 sidewall height;

15 a closure element;

26 a semi-circular top of the second receiving member;

27 a second containment element base;

30 a clamp element;

31 a flange;

100 prefillable syringe;

101a syringe barrel;

101a syringe barrel distal end

101b Syringe barrel proximal end

102a syringe tip;

102a syringe tip outer diameter;

103a tip cap;

103a tip cap outer diameter;

103b tip cap distal end face;

104 a rod;

105 a finger flange;

106 pre-filled syringe length;

107 finger flange width;

108 syringe barrel width;

109 finger-like supports;

110 area of syringe barrel to syringe tip junction;

111 prefillable syringe central axis;

112 syringe barrel radius;

200 systems;

300 replacing the cap;

301 an inner cap;

302 an outer collar;

303 a foot section;

304 opening of the inner cap;

305 a ring;

306 a strut;

307 replacement cap central axis;

308, margin distance;

309 replacing the opening of the cap;

309a replacement of the opening area of the cap;

310 height;

311 a support region;

312 distal foot surface;

313 support zone edges;

314 a cut-out portion;

400 a support surface;

500 plunger piston;

501 plunger ridge;

502 plunger bottom;

x package body longitudinal axis;

a Y wrapper body horizontal axis;

z wrapper body vertical axis;

x' longitudinal axis of prefillable syringe;

y' prefillable syringe horizontal axis;

z' prefillable syringe vertical axis;

x "replacement cap longitudinal axis;

y "replacement cap horizontal axis;

z "replacement cap vertical axis;

x'1 distal direction

X'2 proximal direction;

height of the L2 syringe central axis above the bottom wall; and

l4 package body side wall height.

Detailed Description

This problem is solved by a system comprising: a prefillable syringe having a syringe barrel and a syringe tip; and a package adapted and adapted for receiving a prefillable syringe, wherein the syringe tip is provided with a tip cap, wherein the system comprises a replacement cap for the prefillable syringe, and wherein said package is adapted and adapted for receiving the replacement cap.

An advantage of this system is that the package presented to the user comprises the prefillable syringe to be used and a suitable replacement cap. The user may remove the prefillable syringe from the package, remove the tip cap and optionally set a dose of the prefillable syringe. The replacement cap is already available to the user without additional access. Furthermore, there is no need to remove the replacement cap from the extra packaging. To remove the replacement cap from the additional packaging, the user needs to put down the syringe, which may have been opened. Setting down the prefillable syringe may contaminate the syringe tip and imply unnecessarily complicated operations.

In contrast, the system according to the present invention provides the user with a prefillable syringe and a replacement cap in one package. Thus, the replacement cap is always provided with the prefillable syringe and does not need to be obtained when the tip cap may have been removed. The mounting of the replacement cap can thus be carried out in an uncomplicated manner.

The further use of the replacement cap also has the following advantages: because it may be difficult to grasp and remove the relatively small tip cap, it is easier for the user to handle the syringe.

In the following, the expressions "distal" and "proximal" are understood to mean that the distal end of the syringe is closer to the administration site than the proximal end. The expressions "distal direction" and "proximal direction" may be understood similarly.

In the following, the longitudinal (X), horizontal (Y) and vertical (Z) axes are used with respect to the wrapper body. The longitudinal axis (X '), the horizontal axis (Y ') and the vertical axis (Z ') are used with respect to the prefillable syringe. The longitudinal axis (X "), the horizontal axis (Y") and the vertical axis (Z ") are used with respect to the replacement cap.

According to a preferred embodiment, the package comprises a package body forming a first cavity defined by a side wall and a bottom wall. Preferably, a prefillable syringe may be disposed in the first cavity. Preferably, the wrapper body extends along a longitudinal axis (X), a horizontal axis (Y) and a vertical axis (Z) which are mutually perpendicular.

According to a preferred embodiment, at least one second receiving element is provided in the first cavity of the pack body, in which the syringe barrel can be received. Preferably, two second receiving elements are provided in the first cavity of the package body. Preferably, at least one second receiving element is arranged on the bottom wall. It is further advantageous if the at least one second receiving element comprises a semicircular top portion arranged on the base portion. The semicircular top preferably extends along a horizontal axis (Y) and a longitudinal axis (X) and is open on a vertical axis (Z). In addition, the semi-circular top portion is adapted and configured to receive a syringe barrel. The semi-circular top portion includes two arms that at least partially enclose the syringe barrel.

According to another preferred embodiment, the distal end of the syringe barrel is supported by a first one of the second containment elements and the proximal end of the syringe barrel is supported by a second one of the second containment elements. Preferably, the first of the second receiving members is located adjacent to or on the region where the syringe barrel is joined to the syringe tip. Furthermore, it is preferred that the second one of the second receiving elements is located in the vicinity of a finger flange of a syringe arranged in the package body. Preferably, the first and second of the second containing elements are separated along the longitudinal axis (X') of the prefillable syringe. Thus, in a state in which the pre-filled syringe is arranged in the package body and the syringe barrel is accommodated by the preferably two second accommodation elements, the central axis of the pre-filled syringe preferably extends parallel to the bottom wall of the package body. Preferably, the central axis extends above the bottom wall at a height L2. The height L2 is sized so that the prefillable syringe can be easily handled.

According to another preferred embodiment, at least one third receiving element is provided in the first cavity of the pack body, in which the stem of the prefillable syringe can be received. Preferably, the third containing element comprises two walls extending along a vertical axis (Z), forming a cavity containing the rod. Preferably, said wall extends along a longitudinal axis (X). Preferably, at least one third containing element has a bottom wall which is formed in a semi-circle and connects said walls to each other.

It is further advantageous if a gap is provided between the second of the second receiving elements and the third receiving element. Preferably, the finger flange of the prefillable syringe protrudes through the gap such that the finger flange is clamped between the second one of the second receiving elements and the third receiving element. Through this gap, the finger flange of the prefillable syringe may preferably protrude when the syringe is placed inside the package body. Since the finger flange is preferably clamped between the second one of the second receiving elements and the third receiving element, the prefillable syringe is secured in the package body due to the engagement of the finger flange with the second one of the second receiving elements and the third receiving element. The length of said wall is substantially determined by the length of a section of the stem projecting from the syringe barrel, rather than the length of the stem in said gap between the second of the second containing elements and the third containing element.

According to a preferred embodiment, the prefillable syringe further comprises a plunger or piston connected to a rod extending from the syringe barrel. Preferably, the prefillable syringe also includes a finger flange. The finger flange may be formed on the syringe barrel. It is also conceivable that a separate finger flange element is connected to the syringe barrel, which provides a larger gripping surface. The syringe tip is preferably formed in a conical shape. Preferably, the syringe tip has a Luer taper. Currently, ISO 80369 manages the Luer standard. The syringe tip may also preferably be provided with a puncture device, which may be a needle, a cannula or similar device.

However, because it is intended for sublingual administration to newborns, it is preferable to use a syringe without a piercing device on the tip to avoid accidental injury to its mouth.

The prefillable syringe is preferably provided with a tip cap arranged on the syringe tip. The tip cap may be at least partially constructed of an elastomeric material. Preferably, the prefillable syringe may be constructed of glass or plastic.

According to a preferred embodiment, the replacement cap is arranged at the package such that the opening of the replacement cap or the replacement cap is oriented along the package body vertical axis (Z). Preferably, the open area of the replacement cap is oriented parallel to the bottom wall of the package body. This arrangement allows for easy mounting of a replacement cap on the prefillable syringe. The replacement cap need not be removed from the package during installation. The prefillable syringe may be inserted into the replacement cap while the replacement cap remains in the package. Once the replacement cap is installed on the prefillable syringe, the replacement cap is removed from the package along with the prefillable syringe. This allows the syringe to be operated with only one hand. Obtaining a separate replacement cap may require two-handed operation because the replacement cap needs to be removed from a separate package and oriented with respect to the prefillable syringe to enable installation.

According to a preferred embodiment, the replacement cap comprises an inner cap for engagement with the syringe tip. Preferably, the replacement cap includes an outer collar that engages the syringe barrel for mounting the replacement cap on the syringe barrel. Furthermore, it is advantageous for the replacement cap to include a foot.

The inner cap is preferably arranged on the foot of the replacement cap. Preferably, the inner cap may be at least partly made of an elastic material, such that a sealing connection with the syringe tip is possible. The syringe tip may preferably be introduced into the inner cap through an opening of the inner cap.

The outer collar is preferably formed as a ring arranged along the longitudinal axis (X ") above the opening of the inner cap. The ring is preferably supported by struts arranged on the foot and radially surrounding the inner cap. Preferably, the three struts are placed at equal distances from each other along the circumference of the ring. When the replacement cap is placed on the prefillable syringe, the posts project radially inward from the ring and abut the syringe barrel.

Preferably, the opening area of the replacement cap is defined by the ring and the opening of the inner cap, the inner cap being placed along the longitudinal axis (X ") below the ring opening. The ring opening and the opening are preferably parallel to each other and share the same central axis. Preferably, the open area of the replacement cap is defined by a ring. The open area of the replacement cap and the open area of the inner cap, which are preferably defined by the ring, are preferably oriented parallel to the bottom wall of the wrapper body.

According to a preferred embodiment, the first receiving element is arranged in the first cavity of the package body. Preferably, the replacement cap is accommodated in the first accommodation element. Preferably, the foot of the replacement cap is received in the first receiving member. Thus, the replacement cap is placed vertically in the package. Thus, the open area of the replacement cap is defined by the ring and the open area of the inner cap is preferably oriented parallel to the bottom wall of the wrapper body.

According to a preferred embodiment, the foot is adapted to provide a stable upright positioning of the prefillable syringe with the replacement cap on a support surface. Preferably, the foot includes a bearing area that contacts the support surface. Preferably, the support area comprises an edge that surrounds the central axis of the replacement cap at a margin.

Standing upright is a very convenient and practical way for a user to place a prefillable syringe after it has been removed from the package. In the upright position, the positioning of the distal end of the prefillable syringe on the support surface is understood. The advantage of this positioning is that the proximal end is provided with a finger flange, and the rod is easy to grip. Prefillable syringes generally have a much greater extension along the longitudinal axis (X ') than along the horizontal axis (Y').

As long as the center of gravity is within the area defined by the inclined edges of the support area, a stable positioning is possible. The support region may extend over a portion of the distal face of the replacement cap that constitutes the distal end of the foot. It is also conceivable that the support area extends over the entire distal end face. Further, it is conceivable that the support area extends along the edge of the distal end face.

The displacement of the center of gravity in the radial direction does not affect the stability of standing as long as the center of gravity is not placed more radially outward than the inclined edge. Due to the provision of the finger flange at the proximal end of the prefillable syringe, the center of gravity is closer to the proximal end of the syringe. This means that a slight displacement of the centre of gravity will cause the upright syringe to tip over.

Preferably, the edge distance between the edge of the support area and the central axis is at least two times the radius of the syringe barrel, more preferably, the edge distance is at least three times the radius of the syringe barrel. Preferably, the margin is at least four times the radius of the syringe barrel. Preferably, the margin is at least five times the radius of the syringe barrel. Due to such an embodiment, the slanted edge is further away from the central axis. Thus, a greater displacement of the center of gravity is possible before the upright syringe topples over. Thus, standing stability is enhanced.

Preferably, the distal face of the foot includes an edge at a distance about the central axis of the replacement cap. The edge may preferably be parallel to the edge of the support area, which is considered to be a slanted edge. The edges of the distal face define the shape of the foot, which may be arbitrary. Preferably, the foot has a disc-like shape. Preferably, the foot is substantially circular. Alternatively, the foot may be rectangular.

After the described outfitting of the syringe with the replacement cap can be accomplished with only one hand, the syringe can be placed upright due to the preferred position and orientation of the replacement cap in the package and easily accessed by the user when desired.

According to a preferred embodiment, the support area and/or the edges around the support surface are at least partially coated with a rubber material. Such an embodiment has the following advantages: sliding of the foot on the support surface is inhibited or minimized.

According to a preferred embodiment, the foot is designed as a suction cup. A suction cup is a device or object that uses the negative fluid pressure of air to adhere to a non-porous surface to create a partial vacuum. The working surface of the foot is preferably made of a resilient, flexible material and has a curved surface. When the center of the foot is pressed against the flat support surface, the volume of the space between the foot and the flat surface decreases. Thus, air or water between the foot and the surface will be expelled past the edge of the disc. Thereby creating an under pressure between the foot and the support surface. The pressure differential between the atmosphere outside the foot and the low pressure between the foot and the support surface maintains the foot adhered to the surface.

Preferably, the replacement cap is manufactured by injection moulding, preferably by multicomponent injection moulding.

According to another preferred embodiment, the side walls of the wrapper body extend substantially along a vertical axis (Z). By substantially extended, it is meant that the side wall may have a relatively small angle (a) relative to the vertical axis (Z). Such an angle may be in the range between 0 ° and 25 °, preferably in the range between 0 ° and 10 °, more preferably in the range between 0 ° and 5 °.

Preferably, the side walls of the package body are provided with a flange at their upper end, wherein the flange extends substantially outwardly in the longitudinal (X) or horizontal (Y) axial direction. Preferably, the flange surrounds the package body.

According to another preferred embodiment, the package comprises a closure element, which at least partially covers the package body. Preferably, the closure element completely covers the package body. According to another preferred embodiment, the closing element is arranged on the flange, provided on the side wall. The closure element may be a foil or a dimensionally stable element. The closure element may preferably be connected to the flange by a clamping connection, a snap connection, a welded connection or an adhesive connection or the like. Preferably, prior to use, this connection is torn off to expose the prefillable syringe in the package body.

According to a further preferred embodiment, the closure element is slidably arranged on the package body. Preferably, the closing element is slidable along a sliding direction, preferably oriented along the longitudinal direction (X). Preferably, the closing element is provided with a guide element extending in the sliding direction, in particular in the longitudinal direction (X) on each edge, in the direction of the closing element. Preferably, each flange of the two side walls extending in the sliding direction, in particular in the longitudinal direction, is accommodated in the guide element.

According to another preferred embodiment, the package may be constructed of plastic. Preferably, the package is manufactured in an injection moulding process, preferably in a multi-component injection moulding process.

The object is also achieved by a package adapted and adapted for receiving a prefillable syringe comprising a syringe barrel and a syringe tip, wherein the syringe tip is provided with a tip cap, wherein the package is adapted and adapted for receiving a replacement cap for the prefillable syringe.

The package may comprise a single feature or a combination of features as described above for the system. Further, the system may comprise a single feature or a combination of features as described above for the wrapper. Furthermore, those advantages described above for the system may be applicable to packages.

According to a preferred embodiment, the package comprises a package body forming a first cavity defined by a side wall and a bottom wall. Preferably, a prefillable syringe is disposed in the first cavity. Preferably, at least one second receiving element is provided in the first cavity of the pack body, in which the syringe barrel is received.

According to another preferred embodiment, the distal end of the syringe barrel may be supported by a first one of the second containment elements and the proximal end of the syringe barrel may be supported by a second one of the second containment elements. Preferably, the first of the second receiving members may be located adjacent to or on the region where the syringe barrel is joined to the syringe tip. Furthermore, preferably, the second one of the second receiving elements may be located in the vicinity of a finger flange of a syringe arranged in the package body. Preferably, the first and second of the second containing elements are separated along the longitudinal axis (X') of the prefillable syringe. Thus, in a state in which the prefillable syringe is arranged in the package body and the syringe barrel is accommodated by the preferably two second accommodation elements, the central axis of the prefillable syringe preferably extends parallel to the bottom wall of the package body. Preferably, the central axis extends at a height L2 above the bottom wall of the package body.

According to a preferred embodiment, the first receiving element is arranged in the first cavity of the package body. Preferably, the replacement cap is accommodated in the first accommodation element such that the replacement cap is oriented along the vertical axis (Z) of the packaging body and the opening area of the replacement cap is oriented parallel to the bottom wall of the packaging body. Preferably, the foot of the replacement cap is received in the first receiving member. Preferably, the support area of the replacement cap contacts the bottom wall of the package body.

The object is also achieved by a replacement cap for a prefillable syringe, wherein the replacement cap comprises an inner cap for engaging with a syringe tip, an outer collar for engaging with a syringe barrel for mounting the replacement cap on the syringe barrel, and a foot replacement cap comprising a foot adapted to provide a stable upright positioning of the syringe with the replacement cap.

The replacement cap may include a single feature or a combination of features described above for the system. Further, the system may include a single feature or a combination of features described for the replacement cap. Furthermore, those advantages described above for the system may be applicable to replacement caps.

The outer collar is preferably formed as a ring arranged along the vertical axis (Z') above the opening of the inner cap. The ring is preferably supported by struts arranged on the foot and radially surrounding the inner cap. Preferably, the three struts are placed at equal distances from each other along the circumference of the ring. When the replacement cap is placed on the prefillable syringe, the posts project radially inward from the ring and abut the syringe barrel.

Preferably, the opening area of the replacement cap is defined by the ring and the opening of the inner cap, which is placed below the ring opening along the vertical axis (Z). The opening of the ring and the opening are preferably parallel to each other and share the same central axis. Preferably, the open area of the replacement cap is defined by a ring. The open area of the replacement cap and the open area of the inner cap defined by the ring are preferably oriented parallel to the bottom wall of the wrapper body.

According to a preferred embodiment, the foot is adapted to provide a stable upright positioning of the prefillable syringe with the replacement cap on a surface. Upright placement is a very convenient and practical way for a user to place a syringe. Upright positioning may refer to positioning the distal end on a support surface such that the proximal end provided with the finger flange and stem is easy to grasp.

Preferably, the foot includes an edge about a central axis of the replacement cap. This edge may be considered as the above-mentioned inclined edge. The edges define the shape of the foot, which may be arbitrary. Preferably, the foot has a disc-like shape. Preferably, the foot has a disc-like shape. Preferably, the foot has a substantially circular base region. Preferably, the foot has a substantially rectangular base region. Preferably, the distance between the edge and the central axis is at least two times the radius of the syringe barrel, more preferably, the distance between the edge and the central axis is at least three times the radius of the syringe barrel. Preferably, the distance between the edge and the central axis is at least four times the radius of the syringe barrel. Preferably, the distance between the rim and the central axis is at least five times the radius of the syringe barrel. Due to such an embodiment, the slanted edge is further away from the central axis. Thus, a greater displacement of the center of gravity is possible before the upright syringe topples over. Thus, standing stability is enhanced.

After the preparation of the syringe with the replacement cap can be accomplished with only one hand, the syringe can be placed upright and easily accessed by the user when desired due to the preferred location and orientation of the replacement cap in the package.

According to a preferred embodiment, the support area and/or the edges around the support surface are at least partially coated with a rubber material. Such an embodiment has the advantage of inhibiting sliding of the foot on the support surface.

According to a preferred embodiment, the foot is designed as a suction cup. A suction cup is a device or object that uses the negative fluid pressure of air to adhere to a non-porous surface to create a partial vacuum. The working surface of the foot is preferably made of a resilient, flexible material and has a curved surface. When the center of the foot is pressed against a flat support surface, the volume of the space between the foot and the flat surface decreases. Thus, air or water between the foot and the surface will be expelled through the rim of the cup. Thereby creating an under pressure between the foot and the support surface. The pressure differential between the atmosphere outside the foot and the low pressure between the foot and the support surface maintains the foot adhered to the surface.

Preferably, the replacement cap may be constructed of a plastic material. Preferably, the replacement cap is manufactured by injection moulding, preferably by multicomponent injection moulding.

The object is also achieved by a method of use of a system according to any of the above embodiments, comprising the steps of:

a) removing the prefillable syringe from the package;

b) removing the tip cap from the syringe tip;

c) placing the syringe tip into a replacement cap disposed within the package; and

d) the prefillable syringe with the replacement cap is removed from the package.

The method of use of the system may comprise a single feature or a combination of features described above in relation to the system or package. Further, the system or package may include a single feature or a combination of features described above with respect to the method of use. Furthermore, those advantages described above for the system or package may be adapted to the method of use of the system.

According to a preferred embodiment, the method of use comprises the step of setting a dose of the prefillable syringe.

According to a preferred embodiment, the method of use may further comprise the step of removing the closure element.

According to a preferred embodiment, after removal of the syringe provided with the replacement cap in the package, the syringe can be placed in an upright position on a support surface. Preferably, the foot of the replacement cap is adapted to provide a stable upright positioning of the prefillable syringe with the replacement cap on a support surface. Preferably, the bearing area of the foot of the replacement cap contacts the support surface.

In the following, the longitudinal (X), horizontal (Y) and vertical (Z) axes are used with respect to the wrapper body (3). The longitudinal axis (X '), the horizontal axis (Y ') and the vertical axis (Z ') are used with respect to the prefillable syringe (100). The longitudinal axis (X "), the horizontal axis (Y") and the vertical axis (Z ") are used with respect to the replacement cap (300).

A prefillable syringe is shown in figures 1, 2a, 3, 4 and 5 a. A prefillable syringe (100) includes a syringe barrel (101) and a syringe tip (102). The syringe barrel (101) is cylindrical and open at its proximal end. At its distal end, the syringe barrel (101) is incorporated into the syringe tip (102) in the distal direction (X' 1). The syringe tip (102) may have a tapered form. Preferably, the syringe tip (102) is a luer taper. Although not necessarily preferred, it is also conceivable to arrange a puncture device, in particular a needle, cannula or the like, in the syringe tip (102). In the syringe barrel (101), the medium to be administered is stored. At its proximal end, the syringe barrel (101) is closed by a plunger or piston 500 (shown in fig. 9-13) that is movable within the syringe barrel (101).

In a preferred embodiment, the plunger 500 (shown in fig. 9-13) may have a flat surface on its bottom 502 rather than a conical section as in a standard plunger. The bottom flat surface 502 of the plunger 500 allows for better dose adjustment. The side wall of the plunger has an annular ridge 501 to facilitate sealing sliding movement within the syringe barrel 101.

More preferably, the plunger may be completely coated with silicone, teflon or the like, even more preferably with a Polytetrafluoroethylene (PTFE) membrane.

Using a standard plunger stopper and siliconized syringe barrel, the Break-Loose Force (BLF) of the plunger stopper increases, as well as the duration of storage of the filled syringe. Such an increase in Glide-Force (GF) may not be seen on storage. Thus, the difference (Δ F) between the two (2) forces increases with the duration of storage. This results in the following user experience after storage: the user increases the pushing force on the plunger rod until the plunger stopper moves. As the difference between the breaking release force and the glide force becomes relatively large, the user may not be able to stop the force fast enough to be able to set a small dose difference.

Furthermore, according to the present invention, the coating facilitates the easiest start-up and lowest level of secondary visible particles of the inventive device.

A plunger or piston (e.g., as shown in fig. 9-13) may be attached to a rod (104) that protrudes in the proximal direction (X'2) from the syringe barrel (101). A finger support (109) is arranged on the proximal end of the rod (104). Further, the syringe barrel (101) is provided with a finger flange (105). In the case presented, the finger flange (105) is a finger grip flange that can be clipped onto a finger flange on the syringe barrel (101). Such finger grip flanges have the advantage of a larger area available for gripping by a user.

The prefillable syringe (100) is provided with a tip cap (103), the tip cap (103) being arranged on the syringe tip (102). The tip cap (103) may be at least partially constructed of an elastomeric material.

A replacement cap (300) is depicted in fig. 2b and 5 b. In fig. 3, 4 and 8a prefillable syringe (100) is depicted, provided with a replacement cap (300). In fig. 7, 8 and 10, a package (1) is shown in which a replacement cap (300) is arranged.

The replacement cap (300) comprises an inner cap (301) for engagement with the syringe tip (102). The inner cap (301) is arranged on the foot (303) of the replacement cap. Preferably, the inner cap (301) may be at least partially constructed of an elastic material such that a sealing connection may be made to the syringe tip (102). The syringe tip (102) may be introduced into the inner cap (301) through the opening (304) of the inner cap (301).

Further, the replacement cap (300) includes an outer collar (302) and feet (303) for mounting the replacement cap (300) in engagement with the syringe barrel (101).

The outer collar (300) comprises a ring (305) arranged along the longitudinal axis (X ") above the opening (304) of the inner cap (301). The ring (305) is supported by struts (306). Preferably, the three struts (306) are placed at equal radial distances from each other along the circumference of the ring (305). The struts (306) are arranged at the foot (303) and radially surround the inner cap (301). Furthermore, when the replacement cap (300) is placed on the prefillable syringe (100), the struts (306) protrude radially inward from the ring (305) and abut the syringe barrel (101).

The replacement cap (300) includes an opening (309) and an open area (309a) defined by the ring (305). The opening (304) of the inner cap (301) is placed along the longitudinal axis (X') below the ring opening (309). Thus, the opening region (309a) is oriented parallel to the opening region of the opening (304) of the inner cap (301). The prefillable syringe (100) is first introduced through the opening (309) and then into the opening (304) of the inner cap (301). The opening (309) and the opening (304) share the same central axis (307). In fig. 7 and 8, a package (1) is shown in which a replacement cap (300) is arranged. The opening area (309a) is then oriented parallel to the bottom wall (6) of the package body (3).

The foot (303) is adapted to provide a stable upright positioning of the prefillable syringe (100) on a support surface (400). This is depicted in fig. 4. The positioning of the distal end of the prefillable syringe (100) on the support surface (400) in the upright position is understood to be such that the proximal end of the prefillable syringe (100) provided with the finger flange (105) and the stem (104) is easy to grip. The foot (303) includes a bearing area (311) that contacts the support surface (400). The support region (311) may extend over a portion of the distal face (312) of the replacement cap (300) that constitutes the distal end of the foot. It is also contemplated that the bearing region (311) may extend over the entire distal end face (312). Further, it is contemplated that the bearing region (311) extends along an edge of the distal end face (312).

The prefillable syringe (100) has an extension along the longitudinal axis (X ') that is much greater than along the horizontal axis (Y'). As long as the center of gravity is within the area defined by the edges of the support area (311), a stable positioning is possible. As long as the center of gravity is not placed radially outward of the beveled edge, displacement of the center of gravity in the radial direction (along the horizontal axis (Y ') or the vertical axis (Z')) may not affect standing stability. Due to the provision of the finger flange (105) at the proximal end of the prefillable syringe (100), the center of gravity is closer to the proximal end of the prefillable syringe (100). This means that a slight displacement of the centre of gravity will cause the upright syringe to tip over.

The support region (311) comprises an edge (313) that surrounds the central axis (307) of the replacement cap (300) with a margin (308). The margin (308) is at least twice the radius (112) of the syringe barrel (101), more preferably the margin (308) is at least three times the radius (112) of the syringe barrel (101). Preferably, the margin (308) is at least four times the radius (112) of the syringe barrel (101). Preferably, the margin (308) is at least five times the radius (112) of the syringe barrel (101). Due to such an embodiment, the slanted edge is further away from the central axis. Thus requiring more displacement to tip the prefillable syringe (100).

The distal face (312) of the foot (303) includes an edge. The edge of the distal end face (312) and the edge (313) of the bearing region (311) are parallel and adjacent to each other.

In fig. 2b, 3, 4, 7 and 8, the replacement cap (300) has a substantially circular disc-like shape except for the cut-out portion (314). Thus, the margin (308) is substantially the radius of the disc-shaped foot (313). The cut portion (314) extends along a secant (referring to a line intersecting the circular replacement cap at two points of the diameter) that does not pass through the center of the circular replacement cap. The cutout portion (314) is adjacent to the side wall (5) extending along the longitudinal axis (X).

The foot (303) according to the embodiment of fig. 5b is rectangular. Thus, the margin (308) will be the distance from the edge closest to the central axis (307).

Due to its size, the foot (303) is also a suitable grip for the user to grip the replacement cap (300). The foot (303) may also be designed as a suction cup, which is a device or object that adheres to a non-porous surface using the negative fluid pressure of air to create a partial vacuum.

The package (1) and/or the system (200) is depicted in fig. 6 to 8.

The system (200) comprises a prefillable syringe (100) having a syringe barrel (101) and a syringe tip (102) and a package (1) adapted and intended for accommodating the prefillable syringe (100), wherein the syringe tip (102) is provided with a tip cap (103), wherein the system (200) comprises a replacement cap (300) for the prefillable syringe (100), and wherein the package (1) is adapted and intended for accommodating the replacement cap (300).

A pack (1) adapted and adapted for receiving a prefillable syringe (100) comprises a syringe barrel (101) and a syringe tip (102), wherein the syringe tip (102) is provided with a tip cap (103), wherein the pack (1) is adapted and adapted for receiving a replacement cap (300) for the prefillable syringe (100).

The package (1) comprises a package body (3) forming a first cavity (4) defined by a side wall (5) and a bottom wall (6), wherein a prefillable syringe (100) is arrangeable or arranged in said first cavity (4). The packaging body (3) extends along a longitudinal axis (X), a horizontal axis (Y) and a vertical axis (Z) which are perpendicular to each other. Further, the package body (3) has a rectangular shape.

At least one second receiving element (7, 7a, 7b) is arranged in the first cavity (4) of the packaging body (3), in which the syringe barrel (101) can be received. The embodiment shown in the figures has two second containing elements (7, 7a, 7b) arranged at the bottom wall (6) of the pack body (3).

A first one (7a) of the second containing elements (7) comprises a semicircular top portion (26) arranged on a base portion (27). The semi-circular top portion (26) is sized to receive a syringe barrel (101). According to the embodiment in fig. 6 to 8, the second one (7b) of the second containing elements (7) also comprises a semicircular top portion (26) arranged on the base portion (27).

The distal end (101a) of the syringe barrel (101) is supported by a first one (7a) of the second containing elements (7), while the proximal end (101b) of the syringe barrel (101) is supported by a second one (7b) of the second containing elements (7).

In the case of a prefillable syringe (100) arranged in a pack (1), the first one (7a) of the second containing elements (7) is located close to the area (110) or at the area (110), wherein the syringe barrel (101)) is bonded to the syringe tip (102). Furthermore, a second one (7b) of the second containing elements (7) is close to the finger flange (105) of the prefillable syringe (100) arranged in the package body (3).

The first cavity (4) of the pack body (3) is provided with a third receiving element (8), in which the stem (104) of the prefillable syringe (100) can be received or accommodated. The third containing element (8) comprises two walls (8a, 8b) which, along a vertical axis (Z), form a cavity in which the rod (105) can be housed or accommodated. Furthermore, the third containing element (8) has a bottom wall formed in a semicircular shape and connecting the walls (8a, 8 b). The third receiving element (8) terminates at its proximal end in a fixing element (30), the finger supports (109) of the lever (104) being received in the fixing element (30).

A gap (29) is formed between the second one of the second receiving elements (7, 7b) and the third receiving element (8). The finger flange (105) of the prefillable syringe (100) may protrude through the gap (29) when the prefillable syringe (100) is placed within the package body (3). The finger flange (105) is thus clamped between the second (7b) of the second containing elements (7) and the third containing element (8), so that the prefillable syringe (100) is fastened in the pack body (3).

The third containing element (8) extends after the gap (29) substantially along the length of the portion of the stem (104) protruding from the syringe barrel (101).

When the prefillable syringe (100) is placed in the pack body (3), it is supported by a first one (7a) of the second containing elements (7), preferably by a second one (7b) of the second containing elements (7), and more preferably by a third containing element (8), in particular by a fixing element (30). Thus, in a state in which the prefillable syringe (100) is located in the package body (3), the central axis (111) of the prefillable syringe (100) extends parallel to the bottom wall (6) of the package body (3). The central axis (111) extends at a height L2 above the bottom wall (6) of the package body (3). Height L2 allows for easy handling of prefillable syringe (100).

The replacement cap (300) is arranged in the package (1) such that the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the package body (3). The opening area (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the pack body (3). Preferably, the central axis (307) of the replacement cap (300) extends parallel to the height of the side wall (5) of the pack body (3).

The side walls (5) of the packaging body (3) surround the packaging body (3) along a longitudinal axis (X) and a horizontal axis (Y). The side wall (5) extends along a vertical axis (Z) with a height L4. Height L4 is at least height L2 plus the radius (112) of the syringe barrel (101). The upper end of the side wall (5) (along the vertical axis (Z)) is provided with a flange (31). The flange (31) extends outwardly along the longitudinal axis (X) and the horizontal axis (Y) and around the package body (3), preferably without any gaps.

On the flange (31), a closure element (15) can be arranged. Preferably, the closure element is connected to the flange (31) by means of a suitable connection. The closure element (15) is only partially shown in fig. 6 and may be a foil or a slidable stabilizing element.

According to the embodiment of fig. 6 to 8, the first cavity (4) of the packaging body (3) is provided with a first containing element (2) in which the replacement cap (300) is contained. In particular, the foot (303) of the replacement cap (300) is accommodated in the first accommodation element (2). The first receiving element (2) is therefore substantially in the shape of the outer perimeter of the foot (303). In the case of fig. 6 to 8, the shape is substantially circular, with a cut portion extending along the secant.

The first containing element (2) comprises a side wall (12), which side wall (12) is arranged on the bottom wall (6) of the pack body (3). The side wall (12) and the side wall (5) of the pack body (3) define a cavity which conforms to the shape of the foot (303) of the replacement cap (300). In the case presented in fig. 6 to 8, the cavity and the foot (303) of the replacement cap (300) are substantially shaped as a circle. Thus, the support surface (311) of the replacement cap (300) is located on the bottom wall (6) of the wrapper body (3) such that the replacement cap (300) is arranged in the wrapper (1) such that the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the wrapper body (3). The opening area (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the pack body (3).

The height (13) of the side wall (12) along the vertical axis (Z) is substantially the height (310) of the replacement cap (300) at its outer edge.

In fig. 1 to 8, a method of use of the system (200) is also shown. The method of use comprises preferably removing the closure element from the package body (3). The prefillable syringe (100) is then removed from the package (1). The tip cap (103) is then removed. Optionally, a dose of the prefillable syringe is set. A replacement cap (300) is then installed on the prefillable syringe (100). To this end, the syringe tip (102) is placed in a replacement cap (300) arranged in the package (1). The syringe tip (102) is passed through the opening (309) of the replacement cap (300) and the opening (304) of the inner cap (301). Finally, an inner cap (301) is attached to the syringe tip (102) and a ring (305) or post (306) is abutted on the syringe barrel (101). During installation, the replacement cap (300) remains within the package (1). Since the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the pack body (3), the syringe tip (102) can be easily introduced into the replacement cap (300). The syringe (100) can be operated using only one hand. There is no need to put down the prefillable syringe (100) to obtain or align the replacement cap (300) with respect to the prefillable syringe (100). The prefillable syringe (100) with the replacement cap (300) attached thereto may then be removed from the package (1).

The prefillable syringe (100) may preferably be placed in an upright position on a support surface (400). Preferably, the foot (303) of the replacement cap (300) is adapted to provide a stable upright positioning of the prefillable syringe (100) with the replacement cap (300) on a support surface (400), wherein the bearing area (311) of the foot (303) of the replacement cap (300) contacts the support surface (400).

An advantage of such a system (200) is that it provides the user with a package (1) comprising a prefillable syringe (100) to be used and a suitable replacement cap (300). The replacement cap (300) is already available to the user and does not need to be otherwise available. Furthermore, the replacement cap (300) need not be removed from the additional packaging.

The present invention also relates to the system disclosed herein, wherein the syringe is pre-filled with a ready-to-use pharmaceutical formulation.

Preferably, the pharmaceutical formulation is in the form of a solution or emulsion and comprises one or more active ingredients suitable for oral, intramuscular or intravenous administration.

More advantageously, the formulation is an aqueous or hydroalcoholic solution.

Preferably, the pharmaceutical formulation is an aqueous or hydroalcoholic solution comprising buprenorphine, which is suitable for use in the effective treatment of patients affected by Opioid Withdrawal Syndrome (OWS), more preferably neonates affected by neonate OWS, by sublingual and/or buccal administration.

More preferably, the buprenorphine formulation in aqueous solution comprises:

i) from 0.005 to 0.02% w/v buprenorphine or a pharmaceutically acceptable salt thereof as the only active ingredient;

ii) 0.5% to 10% w/v of a thickening agent; and

iii) an amount of buffer to provide a pH of 5.0-7.0.

Buprenorphine should be used as a base or in the form of a pharmaceutically acceptable salt with an inorganic or organic acid (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, mandelic acid, tartaric acid, citric acid, ascorbic acid, palmitic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, salicylic acid, methanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid).

Preferably, buprenorphine is present as the hydrochloride salt.

Preferably, the buprenorphine concentration expressed as the free base should be between 0.005 and 0.02% w/v, preferably between 0.006 and 0.01% w/v.

In a particular embodiment, the buprenorphine hydrochloride is present at a concentration of 0.0075% w/v expressed as the free base.

The concentration of the thickener should be between 0.5% and 10% w/v, preferably between 0.6% and 8.0% w/v. The type and amount of thickening agent should be chosen correctly to achieve sufficient viscosity to keep the formulation as sublingual as possible in the patient, thereby minimising absorption through the gastrointestinal tract.

At the same time, the viscosity should not be too high so as to prevent the release of the active ingredient from the matrix and thus its local absorption.

More preferably, the concentration of the thickener may be between 1.0 and 6.0% w/v.

In particular embodiments, the concentration is 1.0% w/v, or 1.5% w/v, or 2.0% w/v, or 6.0% w/v.

Preferably, the thickening agent may be selected from water-soluble polysaccharides, such as alginates, carrageenans, pectins, water-soluble derivatives of cellulose: alkylcelluloses, hydroxyalkylcelluloses and hydroxyalkylalkylcelluloses, for example methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, esters and hydroxyalkylcelluloses, such as Cellulose Acetate Phthalate (CAP), Hydroxypropylmethylcellulose (HPMC); carboxyalkyl celluloses, carboxyalkylalkyl celluloses, carboxyalkylcellulose esters such as carboxymethyl cellulose and alkali metal salts thereof; water-soluble synthetic polymers, such as polyacrylic acids and polyacrylates, polymethacrylic acids and polymethacrylates, polyvinyl acetate, polyvinyl alcohol, polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone (PVP) and crotonic acid; also suitable are phthalated gelatin, succinic gelatin, crosslinked gelatin, shellac, water-soluble chemical derivatives of starch, cationically modified acrylates and methacrylates, for example having a tertiary or quaternary amino group, such as diethylaminoethyl, which may be quaternized if desired.

Preferably, the thickener is a water-soluble cellulose derivative selected from Hydroxyethylcellulose (HEC) or an alkali metal salt of carboxymethylcellulose (CMC) (e.g. sodium salt).

In fact, thickeners belonging to the above-mentioned classes can provide suitable viscosities, while other agents of this type (e.g. xanthan gum) are used, which results show that the viscosity of the formulation is too high.

Preferably, the viscosity of the formulation at 25 ± 2 ℃ should be between 500 and 2300mPas (1mPas corresponding to 1 centipoise), preferably between 700 and 2100 mPas. The viscosity can be determined by any known method (e.g., using a rheometer).

Advantageously, the pH of the formulation of the invention may be between 5.0 and 7.0, more advantageously between 5.2 and 6.8, preferably between 5.5 and 6.5.

When water-soluble cellulose derivatives are used, preferred formulations have a pH value between 5.5 and 6.5 and a thickener amount between 1.0% and 2.0% w/v, even more preferably between 1.5% w/v. Such a preferred thickener may be hydroxyethyl cellulose. The excipient is commercially available as Natrosol 250 HXTM.

Any buffer capable of providing a pH may be used, for example a phosphate or citrate buffer such as a sodium or potassium salt. One skilled in the art will determine the appropriate amount.

In a preferred embodiment, anhydrous citric acid and anhydrous sodium citrate are used as buffering agents.

The formulation may also include other excipients, such as flavoring and/or sweetening agents.

The flavoring agent can be selected from natural and synthetic flavoring liquids. An exemplary list of such agents includes volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins, or extracts derived from plants, leaves, flowers, fruits, stems, and combinations thereof. A representative example list includes peppermint, cocoa, and citrus oils such as lemon, orange, grape, lime, and grapefruit, as well as fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, or other fruit flavors.

Other useful flavoring agents include aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alpha-citral (lemon, lime), neral, i.e., beta-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruit), aldehyde C-9 (citrus fruit), aldehyde C-12 (citrus fruit), tolualdehyde (cherry, almond), 2, 6-dimethyl octanol (green fruit), and 2-dodecenal (citrus fruit, mandarin), combinations thereof, and the like.

The sweetener may be selected from the following non-limiting list: glucose (corn syrup), dextrose, invert sugar, fructose, and combinations thereof; saccharin and its sodium salts; dipeptide sweeteners, such as aspartame; dihydrochalcone compounds, glycyrrhizin; stevia rebaudiana (steviol glycosides); chloro derivatives of sucrose, such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol, and the like. Also contemplated are hydrogenated starch hydrolysates and synthetic sweeteners 3, 6-dihydro-6-methyl-1-1-1, 2, 3-oxathian-4-one-2, 2-dioxide, especially the potassium salt (acesulfame potassium) and sodium and its calcium salts. Other sweeteners may also be used.

Generally, the skilled person will select sweeteners and/or flavouring agents from those preparations which are considered safe for neonatal administration.

The formulation may also include penetration enhancers such as propylene glycol and polyoxyl hydrogenated castor oil derivatives, for example polyoxyl 40 hydrogenated castor oil (commercially available as Kolliphor RH 40 TM).

In a preferred embodiment, the formulation has the following composition: 0.05-0.01% w/v buprenorphine hydrochloride, 1.5% w/v hydroxyethylcellulose, 0.12% w/v anhydrous citric acid, 1.13% w/v anhydrous sodium citrate, water for injection, expressed as a base, and having a pH of 6.0. + -. 0.3.

In an alternative embodiment, the formulation may have the following composition: 0.05-0.01% w/v buprenorphine hydrochloride, 6.0% w/v sodium carboxymethylcellulose, 0.12% w/v anhydrous citric acid, 1.13% w/v sodium citrate anhydrous, water for injection, expressed as a base, and having a pH of 6.0 ± 0.3.

Further details are reported in International PCT patent application PCT/EP2018/078447 and U.S. application No. 16/164,282, the entire contents of each of which are incorporated herein by reference.

The pharmaceutical preparation can be prepared according to known methods.

In a preferred embodiment, the pharmaceutical formulation is sterile and prefilled under sterile conditions according to methods known in the art.

Even less preferred, the pharmaceutical formulation may have a dry powder form that dissolves immediately prior to use.

Thus, the invention also relates to a kit comprising the system disclosed herein and a pharmaceutical formulation in the form of a ready-to-use aqueous solution or powder to be reconstituted in a suitable carrier, together with instructions for administration of said pharmaceutical formulation.

Claims

1. A system (200), comprising: a prefillable syringe (100) having a syringe barrel (101) and a syringe tip (102); and a package (1) adapted to accommodate a prefillable syringe (100), wherein said syringe tip (102) is provided with a tip cap (103), characterized in that said system (200) comprises a replacement cap (300) for a prefillable syringe (100), wherein said package (1) is adapted to accommodate said replacement cap (300).

2. System (200) according to claim 1, wherein the pack (1) comprises a pack body (3) forming a first cavity (4) defined by a side wall (5) and a bottom wall (6), wherein the prefillable syringe (100) is arranged in the first cavity (4), wherein at least one second accommodation element (7, 7a, 7b) is provided in the first cavity (4) of the pack body (3) in which the syringe barrel (101) is accommodated, wherein the distal end (101a) of the syringe barrel (101) is supported by a first one (7a) of the second accommodation elements (7) and the proximal end (101b) of the syringe barrel (101) is supported by a second one (7a) of the second accommodation elements (7).

3. The system (200) according to any one of claims 1 or 2, wherein the replacement cap (300) is arranged in the package (1) such that the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the package body (3), wherein the opening area (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the package body (3).

4. System (200) according to any one of claims 1-3, characterized in that at least one third receiving element (8) is provided inside the first cavity (4) of the pack body (3), in which the stem (104) of the prefillable syringe (100) is received, wherein a gap (29) is provided between the second receiving element (7b) and the third receiving element in the second receiving element (7), wherein the finger flange (105) of the prefillable syringe (100) protrudes through the gap (29) such that it is clamped between the second receiving element (7b) and the third receiving element (8) in the second receiving element (7).

5. The system (200) of any of claims 1-4, wherein the replacement cap (300) comprises: an inner cap (301) for engaging with the syringe tip (102); an outer collar (302) engaged with the syringe barrel (101) for mounting the replacement cap (300) on the syringe barrel (101); and a foot (303).

6. System (200) according to any one of claims 2 to 4, characterized in that a first housing element (2) is provided inside the first cavity (4) of the pack body (3), wherein the replacement cap (300) is housed in the first housing element (2), wherein the foot (303) of the replacement cap (300) is housed in the first housing element (2).

7. System (200) according to claim 4, wherein the foot (303) is adapted to provide a stable upright positioning of the prefillable syringe (100) with the replacement cap (300) on a support surface (400), wherein the foot (303) comprises a resting area (311) contacting the support surface (400), wherein the resting area (311) comprises an edge (313) surrounding a central axis (307) of the replacement cap (300) with an edge distance (308), wherein the edge distance (308) is at least twice a radius (112) of the syringe barrel (101), wherein the foot (303) has a disc-like shape.

8. The system (200) according to any one of the preceding claims, wherein the side wall (5) of the packaging body (3) is provided with a flange (31) on its upper end, wherein the packaging body (1) comprises a closure element at least partially covering the packaging body (3), wherein the closure element is arranged on the flange (31).

9. A package (1) adapted and adapted for receiving a prefillable syringe (100), the prefillable syringe (100) comprising a syringe barrel (101) and a syringe tip (102), wherein said syringe tip (102) is provided with a tip cap (103), characterized in that said package (1) is adapted and adapted for receiving a replacement cap (300) for said prefillable syringe (100).

10. Package (1) according to claim 9, characterized in that the package (1) comprises a package body (3) forming a first cavity (4) delimited by a side wall (5) and a bottom wall (6), wherein the prefillable syringe (100) is arranged in the first cavity (4), wherein at least one second housing element (7, 7a, 7b) is provided in the first cavity (4) of the package body (3), wherein the syringe barrel (101) is housed.

11. Package (1) as claimed in claim 10, characterized in that a first containing element (2) is provided inside the first cavity (4) of the package body (3), the replacement cap (300) being housed inside the first containing element (2) such that the replacement cap (300) is oriented along the vertical axis (Z) of the package body (3) and the opening area (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the package body (3), wherein the foot (303) of the replacement cap (300) is housed in the first containing element (2).

12. Pack (1) according to any one of claims 10 or 11, wherein at least one third containing element (8) is provided inside the first cavity (4) of the pack body (3), in which the stem (104) of the prefillable syringe (100) can be accommodated, wherein a gap (29) is provided between the second containing element (7b) of the second containing element (7) and the third containing element (8), wherein the finger flange (105) of the prefillable syringe (100) can protrude through the gap (29) such that the finger flange (105) is clamped between the second containing element (7b) of the second containing element (7) and the third containing element (8).

13. A replacement cap (300) for a prefillable syringe, said replacement cap (300) comprising: an inner cap (301) for engaging with the syringe tip (102); an outer collar (302) engaged with the syringe barrel (101) for mounting the replacement cap (300) on the syringe barrel (101); and a foot (30) adapted to provide a stable upright positioning of the prefillable syringe (100) with the replacement cap (300) on a support surface (400).

14. The replacement cap (300) according to claim 13, wherein the foot (303) comprises a bearing area (311) contacting the support surface (400), wherein the bearing area (311) comprises an edge (313) surrounding a central axis (307) of the replacement cap (300) with an edge distance (308), wherein the edge distance (308) is at least twice a radius (112) of the syringe barrel (101), wherein the foot (303) has a disc-like shape.

15. Method of use of a system (200) according to any of claims 1 to 8, comprising the steps of:

a) -removing the prefillable syringe (100) from the package (1);

b) removing a tip cap (103) from the syringe tip (102);

c) -placing the syringe tip (102) in the replacement cap (300) arranged in the package (1); and

d) removing the prefillable syringe (100) with the replacement cap (300) from the package (1).

16. The system (200) according to any one of the preceding claims 1 to 8, wherein the syringe is pre-filled with a ready-to-use pharmaceutical formulation.

17. The system (200) according to claim 16, wherein the pharmaceutical formulation is in the form of a solution or emulsion and comprises one or more active ingredients suitable for oral, intramuscular or intravenous administration.

18. The system (200) according to claim 16 or 17, wherein the formulation is an aqueous or hydroalcoholic solution.

19. The system (200) according to any one of claims 16 to 18, wherein the pharmaceutical formulation is an aqueous or hydroalcoholic solution for sublingual and/or buccal administration comprising buprenorphine as active ingredient.

20. A kit comprising the system according to any one of claims 1 to 8 and 16 to 19, a pharmaceutical formulation in the form of a ready-to-use aqueous solution or powder to be reconstituted in a suitable carrier and instructions for administration of the pharmaceutical formulation.