GB2563867A

GB2563867A - Drug delivery apparatus

Info

Publication number: GB2563867A
Application number: GB1710280.7A
Authority: GB
Inventors: Fazlul Hoque Chowdhury Dewan
Original assignee: NDM Technologies Ltd
Current assignee: NDM Technologies Ltd
Priority date: 2017-06-28
Filing date: 2017-06-28
Publication date: 2019-01-02
Anticipated expiration: 2037-06-28
Also published as: GB201710280D0; GB2563867B

Abstract

A container 1 has a pierceable septum 4 disposed across its opening and a displaceable sealing barrier 3 which isolates the septum 4 from a drug reservoir 2, to prevent contact of the drug with the septum 4 and to store separately another drug prior to mixing in the reservoir. The drug can be delivered from the reservoir 2 by inserting a displacement needle 6, such as in a needle hub, into the opening, first to pierce the septum 4 and then to displace the barrier 3. The displacement needle 6 may be a hollow needle through which the drug is delivered or alternatively it may be a longer, solid needle, offset from the central axis to facilitate displacement of the barrier 3, with a secondary, shorter, hollow needle 5 in the hub for drug delivery.

Description

TITLE

Drug delivery apparatus

DESCRIPTION

Technical field

The invention relates to the various types of containers in which drugs may be stored in a reservoir prior to being administered to a patient. Examples include glass vials, pre-filled syringes and cartridges having a plunger and septum for use in pen injectors and auto-injectors. The invention relates in particular to such containers comprising a septum that is pierced by a hollow needle to extract the drug.

Background

Pre-filled cartridges are used to load into auto-injectors and pen injectors. Common features of such systems are a main reservoir body with openings at its proximal and distal ends, the proximal end having a sealing septum which is pierced using a needle to provide a fluid communication pathway to allow the drug to be administered to a patient, and the distal end having a sealing plunger which is forced into the reservoir using a plunger rod to expel the contents out from the proximal end.

The plunger and the septum material are composed of a number of materials well established in the art, such as butyl rubbers, polypropylene, polyisobutylene, silicone, and other natural and synthetic rubbers and polymers. The primary function of the plunger is twofold: to provide a seal and to allow movement inside the cartridge to force the contents out without breaking the seal integrity. The plunger must have sufficient rigidity to ensure it does not flex, thus avoiding variations in dosing, which is critical when the container is intended to deliver multiple doses.

The main reservoir is usually composed of an inert material such as glass or a polymer such as PTFE or a polyester material. The reservoir body is generally sufficiently inert that it does not interact with drugs. However, the septum and plunger suffer from the impediment that they must have an element of flexibility, and in the case of the septum must also allow a needle to penetrate the septum and be removed or withdrawn from the septum, allowing self-sealing of the septum so that the sterile integrity of the container is preserved. As a result, inert materials may be unsuitable and the materials generally used pose issues with respect to seepage of constituents from the body of the septum or plunger into the drug, leading often to either unacceptable levels of these components, which can be toxic, or to breakdown and degradation of the drug.

The invention may also be used in reservoir having a septum but no plunger, e.g. a vial that is used to store a drug until it is extracted by inserting the needle of a syringe through the septum.

Patent US 5607400 discloses a pre-fillable hypodermic syringe, in which two stoppers are provided to slide with the barrel of the syringe. One stopper forms a microbiological seal, for which purpose it is treated with a lubricant such as silicone oil. The other stopper is positioned adjacent a drug in the syringe barrel and functions to isolate the drug from the lubricant. A similar arrangement could not be used to isolate the drug from a septum because the stopper would prevent access to the drug by a needle that pierces the septum.

Summary of the invention

The invention provides a drug delivery apparatus as defined in claim 1.

The invention further provides a method of unsealing a drug container as defined in claim 10.

The invention further provides a drug container as defined in claim 16.

Features of the invention that are preferred but not essential are defined in the dependent claims.

This invention provides a releasable barrier between the septum and the liquid drug, preventing the drug from damage during storage, but allowing the septum to be pierced by a needle to provide a fluid communication pathway for the drug to be removed from the reservoir. The same mechanism can also be used to isolate one or more components of the drug formulation from the liquid contents of the reservoir and release them only when the septum is pierced, at which point the liquid contents mix with the component(s) protected behind the releasable barrier. A releasable inert barrier is described which is capable of being secured to or against the surface of the septum to prevent components leaching into the drug from the septum. This barrier may be composed of an inert material such as glass, ceramic, PTFE, metal, or a solid polymer, polyester etc., which may be selected according to its reactivity with the drug in question, so as to either completely eliminate any interaction with the drug or minimise it sufficiently to prevent degradation of the drug as a result of components leaching into the drug from the barrier itself. The barrier material is preferably inert and non-reactive with the drug and non-leaching and will not allow any constituent to be extracted from it by the drug formulation. The barrier may be only coated with the inert material, its bulk being formed from a different material having different physical properties.

The thickness of the barrier will depend on the material of construction and preferably the thickness will be sufficient to ensure the barrier remains rigid throughout its life, since any flexing or expansion or contraction could lead to the drug reaching the septum in quantities that allow interaction between the drug and the septum; the primary objective of the invention being to avoid any such gross interaction. The thickness of the barrier need not be uniform, for example it could be lens-shaped or its proximal surface could include features to guide the needle.

The barrier may be secured to the septum mechanically using techniques established in literature, such as male to female connection points, tolerance fit, utilising anchoring members on either the septum or the barrier. The barrier may also be reieasabiy secured to the septum using a chemical adhesive such as silicone adhesive, which is relatively inert and widely used in transdermal drug patches for example. The adhesive may be applied only to the periphery of the barrier to enable ease of release at the point of use. The barrier may be reieasabiy secured using other techniques and methods known to those skilled in the art. The barrier may be secured to the reservoir walls instead of or in addition to being secured directly to the septum.

The barrier is released by being pushed aside as the needle tip penetrates the septum. In order to facilitate this, it may be preferable to offset the needle from its usual position in the centre of the septum, so that the needle naturally displaces the barrier to one side at the same time as lifting it off the septum, thus freeing the needle tip to come into full fluid communication with the drug formulation. Alternatively, the barrier may be secured to the septum or the reservoir walls asymmetrically so that a needle inserted centrally will displace it to one side. In a further embodiment of the invention, a separate, solid needle may be used to release the barrier prior to the hollow cannula needle being fully inserted. This is of particular importance when the hollow needle may be of a very narrow diameter thus potentially not having the mechanical strength to be able to push the barrier away from the septum or potentially leading to damage of the tip of the needle and obstruction of fluid flow through the needle. In such instance, the solid needle could be an integral part of the needle hub or it could be an ancillary part of the drug cartridge, whereby the solid needle is pushed into the septum as the hollow needle from the drug delivering needle hub locates onto the proximal end of the drug reservoir and the needle starts to pierce the septum.

In a further embodiment of the invention, the barrier may be used to segregate a component of the drug formulation, which may be a drug or an ingredient that is required in the formulation, but which when in liquid form leads to some incompatibility or degradation over long periods of storage. Many drugs are reconstituted prior to being injected in to a patient. This embodiment of the invention would allow the drug to be kept within the same container as the liquid vehicle that is used to reconstitute the drug. Once the needle has pierced the septum, the barrier is released and exposes the drug to the formulation vehicle, where it will mix and can be injected directly without further intervention. This may be ideal for vaccines and other biologies, where the drugs are very often freeze-dried and the powder stored in one container and mixed with water, the vehicle for injection, immediately prior to use.

This component of the formulation could be in a solid or semi-solid form adhered to the inner wall of the barrier, in contact with the septum. Preferably it is in a solid form as that would avoid the possibility of interaction of the component with the septum material, since diffusion and chemical reaction generally requires thermodynamic movement of molecules, and in a solid state the molecules are generally constrained physically at least to a degree that prevents high rates of chemical reaction. In the case where a semi-solid or liquid component of the drug formulation needs to be kept segregated from the main drug vehicle, it may be contained within a pouch adhered to or separate from the barrier, placed between the barrier and the septum. The pouch could be formed of a suitable polymer that would disrupt rather than forming a selfsealing puncture, such as the methacrylic acid polymers, which without plasticisers form strong yet brittle barriers. Having pierced the septum, the needle would disrupt the pouch before displacing the barrier. This would release the contents of the pouch and as the barrier is also then released the contents of the drug cartridge can then be mixed prior to administration.

Drawings

Figure lisa schematic cross section of the proximal end of a drug cartridge according to the invention.

Figures 2A and 2B are schematic cross sections of the proximal end of a drug cartridge according to a second embodiment of the invention, at successive stages in the application of a needle hub.

Figures 3 A and 3B are schematic cross sections of the proximal end of a drug cartridge according to a third embodiment of the invention, at successive stages in the application of a needle hub.

Figure 4 is a schematic cross section of the proximal end of a drug cartridge according to a third embodiment of the invention.

Figure 1 shows the proximal end of a drug cartridge 1 according to the invention. The drug cartridge 1 defines a reservoir 2 for holding a liquid drug. A septum 4 is disposed across an opening of the drug cartridge 1. A septum barrier 3 is reieasabiy secured in the opening to seal the opening between the septum 4 and the reservoir 2. The septum barrier 3 is composed of an inert material and separates the contents of the reservoir (i.e., the liquid drug) from the septum 4

Figures 2A and 2B show a needle hub 7 being applied to the drug cartridge of Figure 1. The needle hub 7 is configured to engage the opening of the drug container 1 and includes a hollow needle 5 and a solid needle 6. In Figure 2A the needle hub 7 is shown positioned adjacent the proximal end of the drug cartridge 1 such that the solid needle 6 has fully pieced the septum 4 and is in contact with the barrier 3. The hollow needle 5 has not yet pierced the septum 4. The solid needle 6 is mounted in the needle hub 7 so as to be offset from the central axis of the opening when the needle hub is in engagement with the opening.

In Figure 2B the needle hub 7 and the drug cartridge 1 have been moved closer together. The hollow needle 5 has started to pierce the septum 4 and the solid needle 6 has displaced or released the barrier 3 from the opening and pushed it into the reservoir 2. Once the hollow needle 5 has fully pierced the septum 4 a fluid communication pathway is provided between the needle and the contents of the drug cartridge 1. The hollow needle 5 can be used for delivery of the liquid drug from the reservoir 2. Although not shown, the barrier 3 can be displaced or released from the opening by a hollow needle that is used for drug delivery.

Figure 3A shows how a drug formulation compartment 8 containing a different drug or different drug component can be provided between the septum 4 and the barrier 3. The drug or drug component in the drug formulation compartment 8 can be in a solid or semi-solid form. Figure 3B shows how the contents of the drug formulation compartment 8 are released into the reservoir 2 of the drug cartridge 1 when the barrier 3 is displaced or released by the solid needle 6 so that it can mix with the liquid drug or other bulk formulation medium.

Figure 4 shows the proximal end of a drug cartridge 1 according the invention where a different drug or different drug component is contained within a pouch 9 placed between the barrier 3 and the septum 4.

Although a drug cartridge is shown in the Figures, it will be readily understood that the invention can be utilised in other containers for storing drugs prior to being administered to a patient, including vials, pre-filled syringes and cartridges having a plunger and septum for use in pen injectors and auto-injectors, for example.

Claims

1. Drug delivery apparatus comprising: a container that defines a reservoir and an opening through which a drug is to be delivered from the reservoir; a septum disposed across the opening; a barrier releasably secured in the opening to seal the opening between the septum and the reservoir; and a displacement needle having a length and stiffness such that the needle can be inserted through the opening to pierce the septum and then to displace the barrier.

2. Drug delivery apparatus according to claim 1, further comprising a needle hub configured to engage the opening of the container, the displacement needle being mounted in the needle hub.

3. Drug delivery apparatus according to claim 2, wherein the opening has a central axis and wherein the displacement needle is mounted in the needle hub so as to be offset from the central axis when the needle hub is in engagement with the opening.

4. Drug delivery apparatus according to any of claims 1 to 3, wherein the displacement needle is a hollow needle for delivery of the drug from the reservoir.

5. Drug delivery apparatus according to claim 2 or claim 3, further comprising a second, hollow delivery needle mounted in the hub for delivery of the drug from the reservoir.

6. Drug delivery apparatus according to claim 5, wherein the displacement needle extends further into the opening than the delivery needle.

7. Drug delivery apparatus according to any preceding claim, further comprising a drug component stored between the septum and the barrier.

8. Drug delivery apparatus according to claim 7, wherein the drug component is coated on a surface of the barrier.

9. Drug delivery apparatus according to claim 7, wherein the drug component is stored in a pouch.

10. A method of unsealing a container that defines a reservoir and an opening through which a drug is to be delivered from the reservoir, the method comprising the steps of: inserting a displacement needle into the opening of the container to pierce a septum that is disposed across the opening; and continuing to insert the displacement needle into the opening to displace a barrier that is releasably secured in the opening to seal the opening between the septum and the reservoir.

11. A method according to claim 10, wherein the displacement needle is inserted into the opening so as to be offset from a central axis of the opening.

12. A method according to claim 10 or claim 11, wherein the displacement needle is hollow, further comprising the step of delivering the drug from the reservoir through the displacement needle.

13. A method according to claim 10 or claim 11, further comprising the steps of: inserting a second, hollow delivery needle into the opening of the container to pierce the septum; and delivering the drug from the reservoir through the delivery needle.

14. A method according to any of claims 10 to 13, wherein the step of displacing the barrier permits a drug component stored between the septum and the barrier to enter the reservoir.

15. A method according to claim 14, further comprising the step of, between the steps of piercing the septum and displacing the barrier, using the displacement needle to disrupt a pouch in which the drug component is stored.

16. A container that defines a reservoir and an opening through which a drug is to be delivered from the reservoir, the container comprising: a septum disposed across the opening; and a barrier reieasabiy secured in the opening to seal the opening between the septum and the reservoir.

17. A container according to claim 16, wherein the barrier is adapted to be displaced by a displacement needle.

18. A container according to claim 16 or claim 17, further comprising a drug component stored between the septum and the barrier.

19. A container according to claim 18, wherein the drug component is coated on a surface of the barrier.

20. A container according to claim 18, wherein the drug component is stored in a pouch.