System comprising a prefilled syringe and a packaging for a prefilled syringe

Abstract

A system comprising a prefillable syringe having a syringe barrel and a syringe tip, and a package adapted and used for containing the 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 used for containing the replacement cap.

Description

Technical Field

[0001] This invention relates to a package suitable for and used to accommodate a pre-fillable 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 and a method of using the system, the system comprising a pre-fillable syringe having a syringe barrel and a syringe tip, and a package suitable for and used to accommodate the pre-fillable syringe, wherein the syringe tip is provided with a tip cap. Furthermore, this invention relates to a replacement cap for a pre-fillable syringe. Background Technology

[0002] Prefillable syringes can be used as kits with media to be applied or delivered to a user, wherein the prefillable syringes in the kit are filled with the media.

[0003] In particular, pre-filled syringes have become one of the fastest-growing options for unit-dose medications. Because the medium to be administered does not need to be transferred into the syringe before use, these syringes are easy to handle. Using pre-filled syringes minimizes medication waste and extends product lifespan.

[0004] As new drugs are developed, administering medications to patients, rather than through injection, is becoming increasingly popular. Possible routes of administration include oral, intranasal, topical, transdermal, and more external delivery methods. For such administrations, pre-filled syringes may be the optimal method for storing, transporting, and delivering the medication.

[0005] Furthermore, pre-filled syringes are a convenient option for media or drugs injected into the body. In particular, modern vaccines are highly sensitive to external influencing factors and are therefore safely stored in pre-filled syringes.

[0006] The pre-fillable syringe body includes a syringe barrel, a syringe tip, and optional finger-shaped flanges. In some cases, the syringe tip already has a puncture device. The puncture device can be a needle, a cannula, or a similar element.

[0007] The syringe body is manufactured by the primary packaging manufacturer under cleanroom conditions. After sterilization, the syringe body is fitted with a tip cap and placed within a so-called syringe nest. The tip cap is typically placed on the syringe tip and may also surround the needle disposed within the syringe tip.

[0008] The pre-fillable syringe is then delivered to a pharmaceutical company, which provides a kit along with the medium to administer the medium or, preferably, to fill the syringe with the medium.

[0009] In the latter case, after the filling process, a plunger or piston is introduced into the syringe barrel, thereby sealing the barrel proximally. The filled syringe is then placed in a secondary packaging.

[0010] The tip cap seals the tip and, optionally, the needle. Typically, the tip cap is at least partially made of a flexible material. Because of the limited space within the syringe nest for the syringe, the tip cap is usually designed to be as small as possible. However, such a small tip cap can be inconvenient for the user to handle.

[0011] In some cases, users need to set the dosage before actually administering the medium, which can be done later. For this, it may be necessary to temporarily remove the tip cap. Resealing the syringe with the tip cap may unintentionally introduce some air into the syringe barrel. This air may irritate the patient. If the medium in the syringe barrel is a high-viscosity medium, the trapped air portion may be difficult to remove.

[0012] WO 2018 / 038078 A1 discloses a medical device packaging having multiple syringe packaging bodies, including a pre-filled syringe system and a packaging body, and an outer box housing the multiple syringe packaging bodies. The needle unit of the pre-filled syringe system is supported relative to a needle unit housing, with the largest outer diameter portion located at the tip of a needle hub that engages with the inner surface of the needle unit housing. Within the outer box, the multiple syringe packaging bodies are arranged such that the axial direction of the needle body is aligned vertically with the outer box. The pre-filled syringes are sealed with sealing caps, but replacement caps are not provided. Summary of the Invention

[0013] Therefore, one object of the present invention is to provide a prefillable syringe, a package for containing the prefillable syringe, and a system comprising the prefillable syringe and the package that overcomes the above-mentioned disadvantages.

[0014] The present invention also relates to a system of the present invention, wherein the syringe is pre-filled with a ready-to-use pharmaceutical preparation.

[0015] Furthermore, the present invention relates to a kit comprising the system of the present invention, a pharmaceutical formulation in the form of a ready-to-use aqueous solution or a powder to be reconstituted in a suitable carrier, and instructions for administering the pharmaceutical formulation. Attached Figure Description

[0016] Figure 1 A pre-fillable syringe without a tip cap is shown;

[0017] Figure 2a shows a prefillable syringe with a pointed cap;

[0018] Figure 2b shows the replacement cap;

[0019] Figure 3 A pre-fillable syringe with a replaceable cap is shown;

[0020] Figure 4 A prefillable syringe with a replaceable cap on a support surface is shown;

[0021] Figure 5a shows a prefillable syringe with a pointed cap, as shown in Figure 2a;

[0022] Figure 5b shows a replacement cap with different feet, as shown in Figure 2b;

[0023] Figure 6 A package body without a prefillable syringe is shown according to one embodiment;

[0024] Figure 7 A package body having a pre-fillable syringe and a replaceable cap is shown according to one embodiment;

[0025] Figure 8 A package body having a prefillable syringe placed in a replacement cap is shown according to one embodiment;

[0026] Figure 9 A bottom perspective view of a plunger according to one or more embodiments is shown;

[0027] Figure 10 A top perspective view of the plunger is shown;

[0028] Figure 11 This is a bottom view of the plunger;

[0029] Figure 12 This is a top view of the plunger; and

[0030] Figure 13 A side view of the plunger is shown.

[0031] List of reference numerals

[0032] 1. Packaging materials;

[0033] 2. First receiving element;

[0034] 3. Main body of the packaging;

[0035] 4. The first cavity of the main body of the packaging;

[0036] 5. Side walls of the main body of the packaging;

[0037] 6. The bottom wall of the main body of the packaging;

[0038] 7. Second housing element;

[0039] 7a The first of the second receiving elements;

[0040] 7b The second of the second receiving elements;

[0041] 8. Third housing element;

[0042] 8a, 8b Third receiving element wall;

[0043] 12. First receiving element sidewall;

[0044] 13. Sidewall height;

[0045] 15. Enclosing elements;

[0046] 26. The semi-circular top of the second receiving element;

[0047] 27. Second receiving element base;

[0048] 30. Fixture components;

[0049] 31. Flange;

[0050] 100 Prefillable Injectors;

[0051] 101 Syringe cartridge;

[0052] 101a syringe barrel distal end

[0053] 101b Syringe barrel proximal end

[0054] 102 Syringe tip;

[0055] 102a Outer diameter of syringe tip;

[0056] 103 Pointed Cap;

[0057] 103a Tip Cap Outer Diameter;

[0058] 103b Tip cap distal end face;

[0059] 104 rods;

[0060] 105 finger-shaped flanges;

[0061] 106 pre-filled syringe length;

[0062] 107 finger-shaped flange width;

[0063] 108 syringe barrel width;

[0064] 109 finger support;

[0065] 110 The area where the syringe barrel and syringe tip meet;

[0066] 111 Prefillable syringe center axis;

[0067] 112 syringe barrel radius;

[0068] 200 system;

[0069] 300 replacement caps;

[0070] 301 inner cap;

[0071] 302 outer ring;

[0072] 303 Foot;

[0073] The opening of the 304 inner cap;

[0074] 305 rings;

[0075] 306 pillars;

[0076] 307 Replacement Cap Center Axis;

[0077] 308 margin;

[0078] 309 Replacement cap opening;

[0079] The opening area of ​​the 309a replacement cap;

[0080] 310 meters high;

[0081] 311 Support area;

[0082] 312 Distal surface of the foot;

[0083] 313 Edge of the support area;

[0084] 314. Incision area;

[0085] 400 Support surface;

[0086] 500 plunger;

[0087] 501 plunger ridge;

[0088] 502 Piston bottom;

[0089] X is the longitudinal axis of the main body of the packaging;

[0090] Y represents the horizontal axis of the main body of the packaging;

[0091] Z is the vertical axis of the main body of the packaging;

[0092] X' is the longitudinal axis of a pre-fillable syringe;

[0093] Y' is the horizontal axis of a prefillable syringe;

[0094] Z' is the vertical axis of a prefillable syringe;

[0095] X" replaces the vertical axis of the cap;

[0096] Y" replaces the horizontal axis of the cap;

[0097] Z" replaces the vertical axis of the cap;

[0098] X'1 Distal direction

[0099] X'2 proximal direction;

[0100] L2 The height of the syringe's central axis above the bottom wall; and

[0101] L4 Height of the main body sidewall of the packaging. Detailed Implementation

[0102] The problem is solved by a system comprising: a prefillable syringe having a syringe barrel and a syringe tip; and a package adapted to and for containing the prefillable syringe, wherein the syringe tip is provided with a tip cap, wherein the system includes a replacement cap for the prefillable syringe, and wherein the package is adapted to and for containing the replacement cap.

[0103] The advantage of this system is that the package presented to the user includes a pre-filled syringe and a suitable replacement cap. The user can remove the pre-filled syringe from the package, remove the tip cap, and selectively set the dosage. The replacement cap is already provided and does not need to be obtained separately. Furthermore, there is no need to remove the replacement cap from an additional package. To remove the replacement cap from an additional package, the user would need to put down the syringe, which may have been opened. Putting down the pre-filled syringe could contaminate the syringe tip and imply unnecessary complexity.

[0104] In contrast, the system according to the invention provides the user with a pre-fillable syringe and a replacement cap in a single package. Therefore, the replacement cap is always provided with the pre-fillable syringe and does not need to be obtained when the tip cap may have been removed. Thus, the installation of the replacement cap can be performed in a straightforward manner.

[0105] Further use of the replacement cap has the following advantages: it makes it easier for the user to operate the syringe because the relatively small tip cap can be difficult to grasp and remove.

[0106] In the following text, the terms "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 terms "distal direction" and "proximal direction" can be understood similarly.

[0107] In the following text, the longitudinal axis (X), horizontal axis (Y), and vertical axis (Z) are used relative to the main body of the packaging. The longitudinal axis (X'), horizontal axis (Y'), and vertical axis (Z') are used relative to a pre-fillable syringe. The longitudinal axis (X"), horizontal axis (Y"), and vertical axis (Z") are used relative to a replacement cap.

[0108] According to a preferred embodiment, the packaging includes a packaging body forming a first cavity defined by sidewalls and a bottom wall. Preferably, a prefillable syringe can be disposed in the first cavity. Preferably, the packaging body extends along mutually perpendicular longitudinal (X), horizontal (Y), and vertical (Z) axes.

[0109] According to a preferred embodiment, at least one second receiving element is provided in a first cavity of the packaging body, wherein a syringe barrel can be accommodated. Preferably, two second receiving elements are provided in the first cavity of the packaging body. Preferably, at least one second receiving element is arranged on the bottom wall. Further advantageously, at least one second receiving element includes a semi-circular top arranged on the base. The semi-circular top preferably extends along a horizontal axis (Y) and a longitudinal axis (X) and opens on a vertical axis (Z). Furthermore, the semi-circular top is adapted to and used to accommodate a syringe barrel. The semi-circular top includes two arms that at least partially surround the syringe barrel.

[0110] According to another preferred embodiment, the distal end of the syringe barrel is supported by the first of the second receiving elements, while the proximal end of the syringe barrel is supported by the second receiving element. Preferably, the first of the second receiving elements is located near or on the region where the syringe barrel is attached to the syringe tip. Furthermore, preferably, the second of the second receiving elements is located near the finger-like flange of the syringe disposed within the packaging body. Preferably, the first and second receiving elements are separated along the longitudinal axis (X') of the prefillable syringe. Therefore, with the prefilled syringe disposed within the packaging body and the syringe barrel received by the preferred two second receiving elements, the central axis of the prefilled syringe preferably extends parallel to the bottom wall of the packaging body. Preferably, the central axis extends at a height L2 above the bottom wall. The height L2 is such that the prefillable syringe can be easily gripped.

[0111] According to another preferred embodiment, at least one third receiving element is provided in a first cavity of the packaging body, wherein the rod of a prefillable syringe can be received. Preferably, the third receiving element includes two walls extending along a vertical axis (Z) to form a cavity for receiving the rod. Preferably, the walls extend along a longitudinal axis (X). Preferably, at least one third receiving element has a bottom wall formed in a semi-circular shape and connecting the walls to each other.

[0112] A further advantage is that a gap is provided between the second and third receiving elements in the second receiving element. Preferably, the finger-shaped flange of the prefillable syringe protrudes through the gap, such that the finger-shaped flange is clamped between the second and third receiving elements in the second receiving element. Through this gap, the finger-shaped flange of the prefillable syringe can preferably protrude when the syringe is placed inside the packaging body. Since the finger-shaped flange is preferably clamped between the second and third receiving elements in the second receiving element, the prefillable syringe is secured in the packaging body due to the engagement of the finger-shaped flange with the second and third receiving elements in the second receiving element. The length of the wall is determined substantially by the length of a section of the rod protruding from the syringe barrel, rather than the length of the rod in the gap between the second and third receiving elements in the second receiving element.

[0113] According to a preferred embodiment, the prefillable syringe further includes a plunger or piston connected to a rod extending from the syringe barrel. Preferably, the prefillable syringe also includes a finger-like flange. The finger-like flange may be formed on the syringe barrel. It is also conceivable that a separate finger-like flange element is connected to the syringe barrel, providing a larger gripping surface. The syringe tip is preferably formed as a cone. Preferably, the syringe tip has a Luer cone. Currently, ISO 80369 governs the Luer standard. The syringe tip may also preferably be provided with a puncture device, which may be a needle, cannula, or similar device.

[0114] However, since it is intended for sublingual administration to newborns, it is preferable to use a syringe without a puncture device at the tip to avoid accidental injury to their mouth.

[0115] Prefillable syringes preferably have a tip cap disposed at the tip of the syringe. The tip cap may be at least partially made of an elastic material. Preferably, the prefillable syringe may be made of glass or plastic.

[0116] According to a preferred embodiment, a replacement cap is arranged in the packaging such that the replacement cap, or its opening, is oriented along the vertical axis (Z) of the packaging body. Preferably, the opening area of ​​the replacement cap is oriented parallel to the bottom wall of the packaging body. This arrangement allows the replacement cap to be easily installed onto the pre-fillable syringe. The replacement cap does not need to be removed from the packaging during installation. The pre-fillable syringe can be inserted into the replacement cap while the replacement cap remains in the packaging. Once the replacement cap is installed onto the pre-fillable syringe, it is removed from the packaging along with the pre-fillable syringe. This allows the syringe to be operated with only one hand. Because the replacement cap needs to be removed from a separate package and needs to be oriented relative to the pre-fillable syringe for installation to be possible, obtaining a separate replacement cap may require two hands.

[0117] According to a preferred embodiment, the replacement cap includes an inner cap for engaging with the syringe tip. Preferably, the replacement cap includes an outer ring for engaging with the syringe barrel for mounting the replacement cap onto the syringe barrel. Furthermore, it is advantageous for the replacement cap to include a foot.

[0118] The inner cap is preferably positioned on the foot of the replacement cap. Preferably, the inner cap can be at least partially made of an elastic material, allowing for a sealing connection with the syringe tip. The syringe tip can preferably be introduced into the inner cap through an opening in the inner cap.

[0119] The outer ring is preferably formed as a ring arranged along the longitudinal axis (X") above the opening of the inner cap. This ring is preferably supported by supports arranged at the foot and radially surrounding the inner cap. Preferably, three supports are placed at equal intervals along the circumference of the ring. When the replacement cap is placed on the prefillable syringe, the supports project radially inward from the ring and abut against the syringe barrel.

[0120] Preferably, the opening area of ​​the replacement cap is defined by a ring and an opening of an inner cap, the inner cap being positioned below the ring opening along the longitudinal axis (X"). The ring opening and the inner cap are preferably parallel to each other and share the same central axis. Preferably, the opening area of ​​the replacement cap is defined by a ring. Preferably, the opening areas of the replacement cap and the inner cap, both defined by the ring, are preferably oriented parallel to the bottom wall of the package body.

[0121] According to a preferred embodiment, a first receiving element is disposed within a first cavity of the packaging body. Preferably, a replacement cap is received within the first receiving element. Preferably, the foot of the replacement cap is received within the first receiving element. Thus, the replacement cap is placed vertically within the packaging. Consequently, the opening area of ​​the replacement cap is defined by a ring, and the opening area of ​​the inner cap is preferably oriented parallel to the bottom wall of the packaging body.

[0122] According to a preferred embodiment, the foot is adapted to provide stable upright positioning of a prefillable syringe with a replaceable cap on a support surface. Preferably, the foot includes a support region that contacts the support surface. Preferably, the support region includes an edge that surrounds the central axis of the replaceable cap with a side distance.

[0123] For users, upright placement is a very convenient and practical way to store a pre-filled syringe after removing it from its packaging. In upright positioning, understand the positioning of the distal end of the pre-filled syringe on the supporting surface. The advantage of this positioning is the presence of a finger-like flange at the proximal end, making the rod easy to grip. Pre-filled syringes typically have an extension along the longitudinal axis (X') that is much larger than that along the horizontal axis (Y').

[0124] Stable positioning is feasible as long as the center of gravity is within the area defined by the inclined edge of the support region. The support region can extend on a portion of the distal face of the replacement cap, which constitutes the distal end of the foot. It is also conceivable that the support region extends across the entire distal face. Furthermore, it is conceivable that the support region extends along the edge of the distal face.

[0125] Radial displacement of the center of gravity does not affect the stability of the standing syringe, as long as the center of gravity is not positioned radially outward beyond the tilted edge. Because of the finger-like flange provided proximally in the pre-fillable syringe, the center of gravity is closer to the proximal end of the syringe. This means that even a small displacement of the center of gravity can cause the upright syringe to tip over.

[0126] Preferably, the distance between the edge of the support area and the central axis is at least twice the radius of the syringe barrel; more preferably, the distance is at least three times the radius of the syringe barrel. Preferably, the distance is at least four times the radius of the syringe barrel. Preferably, the distance is at least five times the radius of the syringe barrel. Due to this embodiment, the inclined edge is further away from the central axis. Therefore, a larger displacement of the center of gravity is possible before the upright syringe tipps over. Thus, standing stability is enhanced.

[0127] Preferably, the distal facet of the foot includes an edge that surrounds the central axis of the replacement cap at a distance. This edge may preferably be parallel to the edge of the support area, and is considered to be a sloping edge. The edge of the distal facet defines the shape of the foot, which can be arbitrary. Preferably, the foot has a disc-shaped shape. Preferably, the foot is substantially circular. Alternatively, the foot may be rectangular.

[0128] After the described assembly of the syringe with the replacement cap can be completed with just one hand, the syringe can be placed upright due to the preferred position and orientation of the replacement cap in the packaging, and can be easily accessed by the user when needed.

[0129] According to a preferred embodiment, the support area and / or the edges surrounding the support surface are at least partially coated with a rubber material. This embodiment has the advantage that foot slippage on the support surface is suppressed or minimized.

[0130] According to a preferred embodiment, the foot is designed as a suction cup. A suction cup is a device or object that uses negative fluid pressure of air to adhere to a non-porous surface, thereby creating a partial vacuum. The working surface of the foot is preferably made of an elastic, flexible material and has a curved surface. When the center of the foot presses against a flat supporting surface, the volume of the space between the foot and the flat surface decreases. Therefore, air or water between the foot and the surface is expelled through the edge of the cup. This creates a pressure deficit between the foot and the supporting surface. The pressure difference between the atmosphere outside the foot and the low pressure between the foot and the supporting surface keeps the foot adhered to the surface.

[0131] Preferably, the replacement cap is manufactured by injection molding, and more preferably by multi-component injection molding.

[0132] According to another preferred embodiment, the sidewalls of the main body of the packaging extend substantially along a vertical axis (Z). By substantially extending, it means that the sidewalls can have a relatively small angle (α) relative to the vertical axis (Z). Such an angle can be in the range of 0° to 25°, preferably in the range of 0° to 10°, and more preferably in the range of 0° to 5°.

[0133] Preferably, the sidewall of the main body of the packaging has a flange at its upper end, wherein the flange extends outward substantially in a longitudinal (X) or horizontal (Y) axial direction. Preferably, the flange surrounds the main body of the packaging.

[0134] According to another preferred embodiment, the packaging includes a closure element that at least partially covers the packaging body. Preferably, the closure element completely covers the packaging body. According to another preferred embodiment, the closure element is disposed on a flange and provided on a sidewall. The closure element may be a foil or a dimensionally stable element. The closure element may preferably be attached to the flange by a clamping connection, snap-fit ​​connection, welded connection, adhesive connection, or similar connection. Preferably, this connection is torn off before use to expose the pre-fillable syringe within the packaging body.

[0135] According to a further preferred embodiment, the closure element is slidably arranged on the body of the packaging. Preferably, the closure element is slidable along a sliding direction, which is preferably oriented along a longitudinal direction (X). Most preferably, the closure element is provided with a guide element that extends along the sliding direction, particularly longitudinally (X) at each edge, in the direction of the closure element. Preferably, each flange of the two sidewalls extending in the sliding direction, particularly the longitudinal direction, is received in the guide element.

[0136] According to another preferred embodiment, the packaging may be made of plastic. Preferably, the packaging is manufactured using an injection molding process, and more preferably using a multi-component injection molding process.

[0137] This objective is also achieved by a package suitable for and intended to contain a prefillable syringe, the package comprising a syringe barrel and a syringe tip, wherein the syringe tip is provided with a tip cap, and wherein the package is suitable for and intended to contain a replacement cap for the prefillable syringe.

[0138] The packaging may include the single feature or combination of features described above for the system. Furthermore, the system may include the single feature or combination of features described above for the packaging. Moreover, the advantages described above for the system are applicable to the packaging.

[0139] According to a preferred embodiment, the packaging includes a packaging body forming a first cavity defined by side walls 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 packaging body, wherein the syringe barrel is received.

[0140] According to another preferred embodiment, the distal end of the syringe barrel may be supported by a first of the second receiving elements, and the proximal end of the syringe barrel may be supported by a second of the second receiving elements. Preferably, the first of the second receiving elements may be located near or on the region where the syringe barrel is attached to the syringe tip. Furthermore, preferably, the second of the second receiving elements may be located near the finger-like flange of the syringe disposed in the packaging body. Preferably, the first and second receiving elements are separated along the longitudinal axis (X') of the prefillable syringe. Therefore, with the prefillable syringe disposed in the packaging body and the syringe barrel received by the preferred two second receiving elements, the central axis of the prefillable syringe preferably extends parallel to the bottom wall of the packaging body. Preferably, the central axis extends at a height L2 above the bottom wall of the packaging body.

[0141] According to a preferred embodiment, a first receiving element is disposed within a first cavity of the packaging body. Preferably, a replacement cap is received in the first receiving element such that the replacement cap is oriented along the vertical axis (Z) of the packaging body and the opening region 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 element. Preferably, the support region of the replacement cap contacts the bottom wall of the packaging body.

[0142] This objective is also achieved by a replacement cap for a prefillable syringe, wherein the replacement cap includes an inner cap for engaging with the syringe tip, an outer ring for engaging with the syringe barrel to mount the replacement cap onto the syringe barrel, and a foot-type replacement cap including a foot adapted to provide stable upright positioning of the syringe with the replacement cap.

[0143] The replacement cap may include the single feature or combination of features described above for the system. Furthermore, the system may include the single feature or combination of features described for the replacement cap. Moreover, the advantages described above for the system are applicable to the replacement cap.

[0144] The inner cap is preferably positioned on the foot of the replacement cap. Preferably, the inner cap can be at least partially made of an elastic material, allowing for a sealing connection with the syringe tip. The syringe tip can preferably be introduced into the inner cap through an opening in the inner cap.

[0145] The outer ring is preferably formed as a ring arranged along a vertical axis (Z') above the opening of the inner cap. This ring is preferably supported by supports arranged at the foot and radially surrounding the inner cap. Preferably, three supports are placed at equal intervals along the circumference of the ring. When the replacement cap is placed on the pre-fillable syringe, the supports project radially inward from the ring and abut against the syringe barrel.

[0146] Preferably, the opening area of ​​the replacement cap is defined by a ring and an opening of an inner cap, the inner cap being positioned below the opening of the ring along a vertical axis (Z). The opening of the ring and the inner cap are preferably parallel to each other and share the same central axis. Preferably, the opening area of ​​the replacement cap is defined by a ring. The opening areas of the replacement cap and the inner cap, defined by the ring, are preferably oriented parallel to the bottom wall of the package body.

[0147] According to a preferred embodiment, the foot is adapted to provide stable upright positioning of a pre-fillable syringe with a replaceable cap on a surface. Upright positioning is a very convenient and practical way for the user to place the syringe. Upright positioning can refer to positioning the distal end on a supporting surface, making the proximal end, which has finger-like flanges and a shaft, easy to grip.

[0148] Preferably, the foot includes an edge surrounding the central axis of the replacement cap. This edge can be considered as the aforementioned sloping edge. The edge defines the shape of the foot, which can be arbitrary. Preferably, the foot has a disc-shaped shape. Most preferably, the foot has a disc-shaped 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 twice the radius of the syringe barrel, more preferably, 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 edge and the central axis is at least five times the radius of the syringe barrel. Due to this embodiment, the sloping edge is further away from the central axis. Therefore, a larger displacement of the center of gravity is possible before the upright syringe tipps over. Thus, standing stability is enhanced.

[0149] After the syringe with the replacement cap can be equipped with only one hand, the syringe can be placed upright and easily accessible to the user when needed due to the preferred position and orientation of the replacement cap in the packaging.

[0150] According to a preferred embodiment, the support area and / or the edges surrounding the support surface are at least partially coated with a rubber material. This embodiment has the advantage of inhibiting foot slippage on the support surface.

[0151] According to a preferred embodiment, the foot is designed as a suction cup. A suction cup is a device or object that uses negative fluid pressure of air to adhere to a non-porous surface, thereby creating a partial vacuum. The working surface of the foot is preferably made of an elastic, flexible material and has a curved surface. When the center of the foot presses against the flat supporting surface, the volume of the space between the foot and the flat surface decreases. Therefore, air or water between the foot and the surface will be expelled through the edge of the cup. This creates a pressure deficit between the foot and the supporting surface. The pressure difference between the atmosphere outside the foot and the low pressure between the foot and the supporting surface keeps the foot adhered to the surface.

[0152] Preferably, the replacement cap may be made of plastic material. Preferably, the replacement cap is manufactured by injection molding, and more preferably by multi-component injection molding.

[0153] This objective is also achieved by a method of using the system according to any of the above embodiments, comprising the following steps:

[0154] a) Remove the pre-fillable syringe from the packaging;

[0155] b) Remove the tip cap from the syringe tip;

[0156] c) Insert the syringe tip into the replacement cap provided within the packaging; and

[0157] d) Remove the pre-fillable syringe with a replacement cap from the packaging.

[0158] The system's usage methods may include the single features or combinations of features described above for the system or packaging. Furthermore, the system or packaging may include the single features or combinations of features described above for the usage methods. Additionally, the advantages described above for the system or packaging may be suitable for the system's usage methods.

[0159] According to a preferred embodiment, the method of use includes the step of setting the dosage of the prefillable syringe.

[0160] According to a preferred embodiment, the method of use may further include the step of removing the closure element.

[0161] According to a preferred embodiment, after removing the syringe with a replacement cap from the packaging, the syringe can be placed in an upright position on a support surface. Preferably, the foot of the replacement cap is adapted to provide stable upright positioning of the pre-fillable syringe with the replacement cap on the support surface. Preferably, the support area of ​​the foot of the replacement cap contacts the support surface.

[0162] In the following text, the longitudinal axis (X), horizontal axis (Y), and vertical axis (Z) are used relative to the main body of the package (3). The longitudinal axis (X'), horizontal axis (Y'), and vertical axis (Z') are used relative to the pre-fillable syringe (100). The longitudinal axis (X"), horizontal axis (Y"), and vertical axis (Z") are used relative to the replacement cap (300).

[0163] exist Figure 1 Prefillable syringes are shown in 2a, 3, 4, and 5a. A prefillable syringe (100) includes a syringe barrel (101) and a syringe tip (102). The syringe barrel (101) is cylindrical and opens at its proximal end. At its distal end, the syringe barrel (101) is coupled into the syringe tip (102) in a distal direction (X'1). The syringe tip (102) may be tapered. Preferably, the syringe tip (102) is a Luer cone. Although not necessarily preferred, it is also conceivable to arrange a puncture device, particularly a needle, cannula, or similar device, in the syringe tip (102). The medium to be administered is stored in the syringe barrel (101). At its proximal end, the syringe barrel (101) is closed by a plunger or piston 500 movable within the syringe barrel (101). Figure 9-13 (As shown).

[0164] In a preferred embodiment, the plunger 500 (e.g.) Figures 9 to 13 (As shown) The plunger 500 may have a flat surface 502 on its bottom instead of a conical cross-section as in a standard plunger. The flat surface 502 on the bottom of the plunger 500 allows for better dose adjustment. The sidewalls of the plunger have annular ridges 501 to facilitate sealing and sliding within the syringe barrel 101.

[0165] More preferably, the plunger may be completely coated with silicone resin, Teflon, etc., or even more preferably with a polytetrafluoroethylene (PTFE) membrane.

[0166] When using a standard plunger stopper and a siliconized syringe barrel, the break-loose-force (BLF) of the plunger stopper increases, as does the storage duration of the filled syringe. This increase in glide-force (GF) may not be visible during storage. Therefore, the difference (ΔF) between the two (2) forces increases over time. This results in the following user experience after storage: the user increases the thrust on the plunger rod until the plunger stopper moves. As the difference between the break-loose-force and glide-force becomes relatively large, the user may not be able to stop the force quickly enough to set a small dose difference.

[0167] Furthermore, according to the present invention, the coating facilitates the easiest start-up of the device and minimizes sub-visible particles.

[0168] A plunger or piston (as shown, for example, in Figures 9-13) can be attached to a rod (104) that protrudes proximally (X'2) from the syringe barrel (101). A finger-like support (109) is arranged on the proximal end of the rod (104). Furthermore, the syringe barrel (101) is provided with a finger-like flange (105). In the presented case, the finger-like flange (105) is a finger-clamping flange that can be gripped onto the finger-like flange on the syringe barrel (101). This finger-clamping flange has the advantage of providing a larger area for the user to grasp.

[0169] The prefillable syringe (100) is provided with a tip cap (103) disposed on the tip (102) of the syringe. The tip cap (103) may be at least partially made of an elastic material.

[0170] The replacement cap (300) is depicted in Figures 2b and 5b. Figure 3 , 4 Figure 8 depicts a pre-fillable syringe (100) equipped with a replacement cap (300). Figure 7 , 8 Packaging (1) is shown in Figure 10, in which a replacement cap (300) is arranged.

[0171] The replacement cap (300) includes an inner cap (301) for engaging with the syringe tip (102). The inner cap (301) is disposed on the foot (303) of the replacement cap. Preferably, the inner cap (301) may be at least partially made of an elastic material, so as to allow for a sealing connection with the syringe tip (102). The syringe tip (102) may be introduced into the inner cap (301) through an opening (304).

[0172] In addition, the replacement cap (300) includes an outer ring (302) and a foot (303) that engage with the syringe barrel (101) for attaching the replacement cap (300).

[0173] The outer ring (300) includes a ring (305) arranged along the longitudinal axis (X") above the opening (304) of the inner cap (301). The ring (305) is supported by supports (306). Preferably, three supports (306) are placed at equal radial distances from each other along the circumference of the ring (305). The supports (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 supports (306) protrude radially inward from the ring (305) and abut against the syringe barrel (101).

[0174] The replacement cap (300) includes an opening (309) and an opening region (309a) defined by a ring (305). The opening (304) of the inner cap (301) is positioned below the ring opening (309) along the longitudinal axis (X''). Therefore, the opening region (309a) is oriented parallel to the opening region of the opening (304) of the inner cap (301). A pre-fillable syringe (100) is first introduced through the opening (309) and then into the opening (304) of the inner cap (301). The openings (309) and (304) share the same central axis (307). Figure 7 and 8 The packaging (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 main body of the packaging (3).

[0175] The foot (303) is adapted to provide a stable, upright position of the prefillable syringe (100) on a support surface (400). This is described in Figure 4. In the upright position, the positioning of the distal end of the prefillable syringe (100) on the support surface (400) is understood to facilitate gripping of the proximal end of the prefillable syringe (100) having finger-like flanges (105) and a rod (104). The foot (303) includes a support region (311) that contacts the support surface (400). The support region (311) may extend over a portion of the distal facet (312) of the replacement cap (300), which constitutes the distal end of the foot. It is also conceivable that the support region (311) may extend over the entire distal facet (312). Furthermore, it is envisioned that the support region (311) extends along the edge of the distal facet (312).

[0176] The prefillable syringe (100) has an extension along the longitudinal axis (X') much greater than that along the horizontal axis (Y'). Stable positioning is feasible as long as the center of gravity is within the area defined by the edge of the support region (311). Displacement of the center of gravity radially (along the horizontal axis (Y') or vertical axis (Z')) is unlikely to affect the stability of the standing syringe, provided that the center of gravity is not placed radially outward beyond the inclined edge. Due to the finger-shaped flange (105) provided 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 small displacement of the center of gravity will cause the upright syringe to tip over.

[0177] The support area (311) includes 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 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 this embodiment, the inclined edge is further away from the central axis. Therefore, a larger displacement is required to tip the prefillable syringe (100).

[0178] The distal surface (312) of the foot (303) includes an edge. The edge of the distal surface (312) is parallel to and adjacent to the edge (313) of the support region (311).

[0179] In Figures 2b, 3, 4, 7, and 8, the replacement cap (300) has a substantially circular disc shape except for the cut-out portion (314). Therefore, the margin (308) is essentially the radius of the disc-shaped foot (313). The cut-out portion (314) extends along a secant line (a line intersecting the circular replacement cap at two points on the diameter), wherein the secant line does not pass through the center of the circular replacement cap. The cut-out portion (314) is adjacent to a sidewall (5) extending along the longitudinal axis (X).

[0180] According to the embodiment of FIG5b, the foot (303) is rectangular. Therefore, the side distance (308) will be the distance from the edge closest to the central axis (307).

[0181] Due to its size, the foot (303) is also a suitable grip for the user to hold the replacement cap (300). The foot (303) can also be designed as a suction cup, which is a device or object that uses the negative fluid pressure of air to adhere to a non-porous surface to create a local vacuum.

[0182] exist Figures 6 to 8 The packaging (1) and / or system (200) are depicted.

[0183] The system (200) includes a prefillable syringe (100) having a syringe barrel (101) and a syringe tip (102) and a package (1) adapted for and intended to contain the prefillable syringe (100), wherein the syringe tip (102) is provided with a tip cap (103), wherein the system (200) includes a replacement cap (300) for the prefillable syringe (100), and wherein the package (1) is adapted for and intended to contain the replacement cap (300).

[0184] The package (1) suitable for and intended to contain a prefillable syringe (100) includes a syringe barrel (101) and a syringe tip (102), wherein the syringe tip (102) is provided with a tip cap (103), and wherein the package (1) is suitable for and intended to contain a replacement cap (300) for the prefillable syringe (100).

[0185] The packaging (1) includes a packaging body (3) forming a first cavity (4) defined by sidewalls (5) and a bottom wall (6), wherein a prefillable syringe (100) may be disposed or arranged in the first cavity (4). The packaging body (3) extends along mutually perpendicular longitudinal axes (X), horizontal axes (Y), and vertical axes (Z). Further, the packaging body (3) has a rectangular shape.

[0186] At least one second receiving element (7, 7a, 7b) is provided in the first cavity (4) of the packaging body (3), in which the syringe barrel (101) can be accommodated. The embodiment shown in the figure has two second receiving elements (7, 7a, 7b) arranged at the bottom wall (6) of the packaging body (3).

[0187] The first (7a) of the second receiving element (7) includes a semi-circular top (26) arranged on the base (27). The semi-circular top (26) is sized to receive the syringe barrel (101). Figures 6 to 8 In the embodiment, the second (7b) of the second receiving element (7) also includes a semi-circular top (26) arranged on the base (27).

[0188] The distal end (101a) of the syringe barrel (101) is supported by the first (7a) of the second receiving elements (7), while the proximal end (101b) of the syringe barrel (101) is supported by the second (7b) of the second receiving elements (7).

[0189] When the prefillable syringe (100) is arranged in the package (1), the first (7a) of the second receiving element (7) is located near or at region (110), where the syringe barrel (101) is attached to the syringe tip (102). Furthermore, the second (7b) of the second receiving element (7) is located near the finger flange (105) of the prefillable syringe (100) arranged in the package body (3).

[0190] The first cavity (4) of the main body of the packaging (3) is provided with a third receiving element (8), in which the rod (104) of the prefillable syringe (100) can be received or accommodated. The third receiving element (8) includes two walls (8a, 8b) that form a cavity along a vertical axis (Z), in which the rod (105) can be received or accommodated. In addition, the third receiving element (8) has a bottom wall formed in a semi-circular shape and connecting the walls (8a, 8b). The third receiving element (8) terminates at its proximal end in a fixing element (30), in which the finger support (109) of the rod (104) is accommodated.

[0191] A gap (29) is formed between the second (7, 7b) and the third receiving element (8) in the second receiving element. When the prefillable syringe (100) is placed inside the packaging body (3), the finger-shaped flange (105) of the prefillable syringe (100) can protrude through this gap (29). Thus, the finger-shaped flange (105) is clamped between the second (7b) and the third receiving element (8) in the second receiving element (7), so that the prefillable syringe (100) is secured in the packaging body (3).

[0192] The third receiving element (8) extends substantially along the length of the portion of the rod (104) that protrudes from the syringe barrel (101) after the gap (29).

[0193] When the prefillable syringe (100) is placed in the packaging body (3), it is supported by the first (7a) of the second receiving elements (7), preferably by the second (7b) of the second receiving elements (7), and more preferably by the third receiving element (8), particularly by the fixing element (30). Thus, with the prefillable syringe (100) in the packaging body (3), the central axis (111) of the prefillable syringe (100) extends parallel to the bottom wall (6) of the packaging body (3). The central axis (111) extends at a height L2 above the bottom wall (6) of the packaging body (3). Height L2 allows for easy gripping of the prefillable syringe (100).

[0194] A 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 package body (3). Preferably, the central axis (307) of the replacement cap (300) extends parallel to the height of the side wall (5) of the package body (3).

[0195] The sidewall (5) of the packaging body (3) surrounds the packaging body (3) along the longitudinal axis (X) and the horizontal axis (Y). The sidewall (5) extends along the vertical axis (Z) at a height L4. The height L4 is at least the height L2 plus the radius (112) of the syringe barrel (101). The upper end of the sidewall (5) is provided with a flange (31) along the vertical axis (Z). The flange (31) extends outward along the longitudinal axis (X) and the horizontal axis (Y) and surrounds the packaging body (3) preferably without any gaps.

[0196] A closure element (15) may be arranged on the flange (31). Preferably, the closure element is connected to the flange (31) by a suitable connector. The closure element (15) is located on... Figure 6 Only a portion is shown in the diagram, and it can be a foil or a sliding stabilizing element.

[0197] according to Figures 6 to 8 In one embodiment, the first cavity (4) of the packaging body (3) is provided with a first receiving element (2) for receiving a replacement cap (300). Specifically, the foot (303) of the replacement cap (300) is received within the first receiving element (2). Therefore, the first receiving element (2) is essentially the shape of the outer periphery of the foot (303). Figures 6 to 8 In the case of [the shape], the shape is basically circular with cutouts extending along the secant line.

[0198] The first receiving element (2) includes a sidewall (12) disposed on the bottom wall (6) of the packaging body (3). The sidewall (12) and the sidewall (5) of the packaging body (3) define a cavity that conforms to the shape of the foot (303) of the replacement cap (300). Figures 6 to 8 In the presented configuration, the cavity and the foot (303) of the replacement cap (300) are substantially circular. Therefore, the supporting surface (311) of the replacement cap (300) is located on the bottom wall (6) of the package body (3), such that the replacement cap (300) is arranged in the package (1), and the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the package body (3). The opening region (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the package body (3).

[0199] The height (13) of the sidewall (12) along the vertical axis (Z) is essentially the height (310) of the replacement cap (300) at its outer edge.

[0200] exist Figures 1 to 8The diagram also illustrates a method of using the system (200). This method of use includes, preferably, removing the closure element from the main body of the packaging (3). The pre-fillable syringe (100) is then removed from the packaging (1). The tip cap (103) is then removed. Optionally, the dosage of the pre-fillable syringe is set. A replacement cap (300) is then installed on the pre-fillable syringe (100). For this purpose, the syringe tip (102) is placed in the replacement cap (300) arranged in the packaging (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, the inner cap (301) is attached to the syringe tip (102), and a ring (305) or post (306) is abutted against the syringe barrel (101). During installation, the replacement cap (300) remains inside the packaging (1). Because the opening (309) of the replacement cap (300) is oriented along the vertical axis (Z) of the package body (3), the syringe tip (102) can be easily inserted into the replacement cap (300). Therefore, the syringe (100) can be operated with only one hand. It is not necessary to lower the pre-filled syringe (100) to obtain or align the replacement cap (300) relative to the pre-filled syringe (100). The pre-filled syringe (100) with the replacement cap (300) attached can then be removed from the package (1).

[0201] The prefillable syringe (100) can preferably be placed in an upright position on the support surface (400). Preferably, the foot (303) of the replacement cap (300) is adapted to provide a stable upright position of the prefillable syringe (100) with the replacement cap (300) on the support surface (400), wherein the support area (311) of the foot (303) of the replacement cap (300) contacts the support surface (400).

[0202] The advantage of this system (200) is that it provides the user with a package (1) that includes a pre-fillable syringe (100) for use and a suitable replacement cap (300). The replacement cap (300) is already available to the user and does not need to be obtained separately. Furthermore, the replacement cap (300) does not need to be removed from the additional package.

[0203] The present invention also relates to the systems disclosed herein, wherein the syringe is pre-filled with a ready-to-use pharmaceutical formulation.

[0204] Preferably, the pharmaceutical preparation is in the form of a solution or emulsion and includes one or more active ingredients suitable for oral, intramuscular or intravenous administration.

[0205] More advantageously, the formulation is an aqueous solution or a water-alcohol solution.

[0206] Preferably, the pharmaceutical preparation is an aqueous or hydroalcoholic solution comprising buprenorphine, which is suitable for the effective treatment of patients affected by opioid withdrawal syndrome (OWS) by sublingual and / oral administration, more preferably newborns affected by neonatal OWS.

[0207] More preferably, the aqueous solution form of buprenorphine includes:

[0208] i) 0.005 to 0.02% w / v buprenorphine or a pharmaceutically acceptable salt thereof as the sole active ingredient;

[0209] ii) 0.5% to 10% w / v thickener; and

[0210] iii) A certain amount of buffer to provide a pH of 5.0-7.0.

[0211] Buprenorphine should be used as a base or in the form of a pharmaceutically acceptable salt that forms 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).

[0212] Preferably, buprenorphine is present as a hydrochloride salt.

[0213] Ideally, the concentration of buprenorphine expressed as a free base should be between 0.005 and 0.02% w / v, preferably between 0.006 and 0.01% w / v.

[0214] In one specific embodiment, buprenorphine hydrochloride is expressed as a free base at a concentration of 0.0075% w / v.

[0215] 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 thickener should be correctly selected to achieve sufficient viscosity to keep the formulation as far under the patient's tongue as possible, thereby minimizing absorption through the gastrointestinal tract.

[0216] At the same time, the viscosity should not be too high, so as not to hinder the release of active ingredients from the matrix, thereby hindering their local absorption.

[0217] More preferably, the concentration of the thickener can be between 1.0% and 6.0% w / v.

[0218] In a particular embodiment, the concentration is 1.0% w / v, or 1.5% w / v, or 2.0% w / v, or 6.0% w / v.

[0219] Ideally, the thickener can be selected from water-soluble polysaccharides, such as alginate, carrageenan, pectin, and water-soluble derivatives of cellulose: alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkylalkyl cellulose, such as methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, esters, and hydroxyalkyl cellulose esters, such as cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose (HPMC); carboxyl cellulose, carboxylalkyl cellulose, and carboxyl cellulose esters, such as... Carboxymethyl cellulose and its alkali metal salts; water-soluble synthetic polymers, such as polyacrylic acid and polyacrylate, polymethacrylic acid and polymethacrylate, polyvinyl acetate, polyvinyl alcohol, polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone (PVP) and polycrotonic acid; also suitable are phthalated gelatin, succinic gelatin, cross-linked gelatin, shellac, water-soluble chemical derivatives of starch, cationic modified acrylates and methacrylates, for example having tertiary or quaternary amino groups, such as diethylaminoethyl, which may be quaternized if desired.

[0220] Preferably, the thickener is a water-soluble cellulose derivative selected from hydroxyethyl cellulose (HEC) or carboxymethyl cellulose alkali metal salts (CMCs) (such as sodium salts).

[0221] In fact, thickeners belonging to the above categories can provide suitable viscosity, while other reagents using this type of adhesive (such as xanthan gum) show that the viscosity of the formulation is too high.

[0222] Ideally, the viscosity of the formulation at 25±2°C should be between 500 and 2300 mPas (1 mPas corresponds to 1 centipoise), preferably between 700 and 2100 mPas. Viscosity can be determined by any known method (e.g., using a rheometer).

[0223] Preferably, the pH value of the formulation of the present invention can be between 5.0 and 7.0, more advantageously between 5.2 and 6.8, and most preferably between 5.5 and 6.5.

[0224] When using water-soluble cellulose derivatives, preferred formulations have a pH value between 5.5 and 6.5 and a thickening dosage between 1.0% and 2.0% w / v, or even more preferably between 1.5% w / v. Such preferred thickeners may be hydroxyethyl cellulose. The excipient is commercially available as Natrosol 250 HX™.

[0225] Any buffer capable of providing pH can be used, such as phosphate or citrate buffers like sodium or potassium salts. Those skilled in the art should determine the appropriate amount.

[0226] In a preferred embodiment, anhydrous citric acid and anhydrous sodium citrate are used as buffers.

[0227] The formulation may also include other excipients, such as flavoring agents and / or sweeteners.

[0228] Flavoring agents can be selected from natural and synthetic flavoring liquids. An exemplary list of such agents includes volatile oils, synthetic flavor oils, flavorings, oils, liquids, oleoresins, or extracts derived from plants, leaves, flowers, fruits, stems, and combinations thereof. Representative examples include peppermint oil, cocoa and citrus oils such as lemon, orange, grape, lime, and grapefruit, and fruit flavorings including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, or other fruit flavors.

[0229] Other useful flavorings include aldehydes and esters, such as benzaldehyde (cherries, almonds), citral (α-citral, lemons, limes), neraldehyde (β-citral, lemons, limes), decanal (oranges, lemons), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolualdehyde (cherries, almonds), 2,6-dimethyloctanol (green fruits), and 2-dodecenal (citrus fruits, Mandarin), as well as combinations thereof.

[0230] Sweeteners may be selected from the following non-restricted list: glucose (corn syrup), dextrose, invert sugar, fructose, and combinations thereof; saccharin and its sodium salt and various salts thereof; dipeptide sweeteners, such as aspartame; dihydrochalcone compounds, glycyrrhizin; stevia (steviosides); chlorinated derivatives of sucrose, such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol, etc. Also desirable are hydrogenated starch hydrolysates and synthetic sweeteners 3,6-dihydro-6-methyl-1-1-1,2,3-oxothiaza-4-one-2,2-dioxide, particularly its potassium salt (acesulfame potassium) and its sodium and calcium salts. Other sweeteners may also be used.

[0231] Generally, those skilled in the art should select sweeteners and / or flavorings from those formulations that are considered safe for use on newborns.

[0232] The formulation may also include penetration enhancers, such as propylene glycol and polyoxygenated castor oil derivatives, such as polyoxygenated 40 hydrogenated castor oil (commercially available as Kolliphor RH 40™).

[0233] In a preferred embodiment, the formulation has the following composition: 0.05-0.01% w / v buprenorphine hydrochloride (indicated by alkali), 1.5% w / v hydroxyethyl cellulose, 0.12% w / v anhydrous citric acid, 1.13% w / v anhydrous sodium citrate, water for injection, and a pH of 6.0 ± 0.3.

[0234] In an alternative embodiment, the formulation may have the following composition: 0.05-0.01% w / v buprenorphine hydrochloride (in base form), 6.0% w / v sodium carboxymethyl cellulose, 0.12% w / v anhydrous citric acid, 1.13% w / v sodium anhydrous citrate, water for injection, and a pH of 6.0 ± 0.3.

[0235] 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.

[0236] Pharmaceutical formulations can be prepared using known methods.

[0237] In a preferred embodiment, the pharmaceutical preparation is sterile and prefilled under sterile conditions according to methods known in the art.

[0238] Even if not the most preferred, pharmaceutical preparations can be in the form of a dry powder that dissolves immediately before use.

[0239] Therefore, the present invention also relates to a kit comprising the system disclosed herein, a pharmaceutical formulation in the form of a ready-to-use aqueous solution or a powder to be reconstituted in a suitable carrier, and instructions for administering said pharmaceutical formulation.

Claims

1. A system (200) comprising a prefillable syringe (100) and a package (1) adapted to contain the prefillable syringe (100), wherein the prefillable syringe (100) comprises a syringe barrel (101), a syringe tip (102), a plunger or piston (500) connected to a rod (104) extending from the syringe barrel (101), and a finger flange (105), wherein the syringe tip (102) is provided with a tip cap (103). Its features are, The prefillable syringe (100) is used for sublingual administration to newborns and has no puncture device at the syringe tip (102), and the system (200) includes a replacement cap (300) for the prefillable syringe (100), wherein the package (1) is adapted to accommodate the replacement cap (300). The packaging (1) includes a packaging body (3) forming a first cavity (4) defined by a side wall (5) and a bottom wall (6), wherein a prefillable syringe (100) is disposed in the first cavity (4), wherein at least one second receiving element (7) is provided in the first cavity (4) of the packaging body (3), and the syringe barrel (101) is received in the at least one second receiving element, wherein the distal end (101a) of the syringe barrel (101) is supported by a first second receiving element (7a) of the second receiving element (7), and the proximal end (101b) of the syringe barrel (101) is supported by a second second receiving element (7b) of the second receiving element (7); 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), and the opening area (309a) of the replacement cap (300) is oriented parallel to the bottom wall (6) of the package body (3). The replacement cap (300) includes an inner cap (301) for engaging with the syringe tip (102); An outer ring (302) engages with the syringe barrel (101) for mounting the replacement cap (300) onto the syringe barrel (101); and a foot (303), wherein a first receiving element (2) is provided within the first cavity (4) of the package body (3), wherein the replacement cap (300) is received in the first receiving element (2), and wherein the foot (303) of the replacement cap (300) is received in the first receiving element (2); The foot (303) is adapted to provide stable upright positioning of the prefillable syringe (100) with the replacement cap (300) on a support surface (400), wherein the foot (303) includes a support region (311) that contacts the support surface (400), wherein the support region (311) includes an edge (313) that surrounds the central axis (307) of the replacement cap (300) with a side distance (308), wherein the side distance (308) is at least twice the radius (112) of the syringe barrel (101), wherein the foot (303) has a disc-shaped shape.

2. The system (200) according to claim 1, wherein at least one third receiving element (8) is provided in the first cavity (4) of the packaging body (3), the rod (104) of the prefillable syringe (100) is received in the at least one third receiving element, wherein a gap (29) is provided between the second second receiving element (7b) in the second receiving element (7) and the third receiving element (8), wherein the finger-shaped flange (105) of the prefillable syringe (100) protrudes through the gap (29) such that the finger-shaped flange is clamped between the second second receiving element (7b) in the second receiving element (7) and the third receiving element (8).

3. The system (200) according to claim 1 or 2, wherein the sidewall (5) of the packaging body (3) is provided with a flange (31) at its upper end, wherein the packaging (1) includes a closure element that at least partially covers the packaging body (3), wherein the closure element is arranged on the flange (31) of the sidewall.

4. The system (200) according to claim 1 or 2, wherein the foot (303) is designed as a suction cup.

5. The system (200) according to claim 1 or 2, wherein the prefillable syringe is prefilled with a ready-to-use pharmaceutical preparation.

6. The system (200) according to claim 5, wherein the pharmaceutical preparation is in solution or emulsion form and comprises one or more active ingredients suitable for oral administration.

7. The system (200) according to claim 5, wherein the pharmaceutical preparation is an aqueous solution or an aqueous alcohol solution.

8. The system (200) according to claim 5, wherein the pharmaceutical preparation is an aqueous or hydroalcoholic solution for sublingual and / oral administration, comprising buprenorphine as an active ingredient.

9. A kit comprising a system according to any one of claims 1 to 8, a pharmaceutical preparation in the form of an aqueous solution ready for use or a powder to be reconstituted in a suitable carrier, and instructions for administering the pharmaceutical preparation.

10. A method of using the system (200) according to any one of claims 1 to 4, comprising the following steps: a) Remove the prefillable syringe (100) from the package (1). b) Remove the tip cap (103) from the syringe tip (102); c) Insert the syringe tip (102) into the replacement cap (300) arranged in the package (1); as well as d) Remove the prefillable syringe (100) with the replacement cap (300) attached thereto from the package (1).

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