DRUG DELIVERY DEVICE

Abstract

A novel device and method for intradermal delivery of an active agent is provided. The device comprises a housing which contains a reservoir chamber. A flexible reservoir containing the active agent is placed in the chamber. Upon pressure on an actuator the active agents is delivered via a hollow needle to the skin.

Claims

1. A device for administering to an animal a fluid drug comprising: a housing having a housing open upper end and a housing bottom base defining an interior chamber; the housing bottom base having an aperture therein; the interior chamber adapted to slideably receive therein a reservoir chamber in an initial reservoir chamber position at a first predetermined distance from the interior surface of the base of the housing, the reservoir chamber being confined to travel along a reservoir chamber travel path relative the housing; the reservoir chamber defined by a reservoir chamber bottom base and surrounding reservoir chamber wall extending from the reservoir bottom base so as provide a reservoir open top; the reservoir bottom base including a single hollow needle having a lower end and an upper non-skin contacting end wherein the single hollow needle is mounted in and transverses the reservoir bottom base such that the upper non-skin contacting end is disposed within the interior of the reservoir chamber and just below the reservoir and the lower skin-contacting end can extend beyond the aperture to a second position at a predetermined distance defined by the reservoir chamber travel path of the reservoir chamber bottom base to the housing base relative the housing; a flexible filled reservoir body containing therein the fluid drug being located in the reservoir chamber near the reservoir open top and separated from the upper end of the single hollow needle in the first predetermined reservoir chamber position; and an actuator having a plunger operably coupled thereto and terminating in a stopper, the stopper having formed therein a frusto-concical depression; the frusto-concical depression having a depth corresponding to the length of the upper non-skin contacting end of the single hollow needle disposed within the interior of the reservoir chamber; the plunger adapted to be in slidable communication within the reservoir chamber via the reservoir open top such that, in use, the stopper can communicate with the flexible filled reservoir body with a portion of the flexible filled reservoir body being received in the frusto-conical depression when in the second predetermined reservoir chamber position, wherein a force being applied to the actuator causes the lower end of the single hollow needle to enter the skin to the second position and further force causes the upper non-skin contacting end of the single hollow needle to pierce the reservoir body and puts the upper non-skin contacting end of the single hollow needle into fluid communication with the contents of the flexible filled reservoir body such that continuous force being applied to the actuator causes the stopper to compress the flexible filled reservoir body and expel the fluid drug through the single hollow needle and wherein the upper non-skin contacting end of the single hollow needle is located within a portion of the flexible filled reservoir body received in the frusto-concical depression once substantially all of the fluid drug is expelled.

2. The device as defined in claim 1, wherein abutment of the housing bottom base with the reservoir chamber bottom base in the second predetermined reservoir chamber position acts to provide a predetermined length of travel of the single hollow needle through the aperture.

3. The device as defined in claim 1, wherein the biasing means is located within the inner chamber between the housing bottom base and the reservoir bottom base so as to bias the reservoir chamber in the initial reservoir chamber position.

4. The device as defined in claim 1, wherein the length of travel of the single hollow needle in the second predetermined reservoir chamber position is from about 0.5 mm to about 10 mm extending through the aperture.

5. The device as defined in claim 1, wherein the length of travel of the single hollow needle in the second predetermined reservoir chamber position is from about 1.5 mm to about 8 mm extending through the aperture.

6. The device as defined in claim 1, wherein the length of travel of the single hollow needle in the second predetermined reservoir chamber position is from about 3 mm to about 8 mm extending through the aperture.

7. The device as defined in claim 3, wherein the biasing means is a spring.

8. A process for producing a flexible fluid filled reservoir body comprising: aligning and contacting a first surface of a first plastics material sheet with a second surface of second plastics material sheet; applying a first mold half to the exterior side of the first plastics material sheet and a second mold half to the exterior of the second plastics material sheet, at least one of the first mold half and the second mold half having a depression formed therein with an open vertical path extending outwardly of the first mold half and the second mold half; sandwiching the first plastics material sheet and the second plastics material sheet between the first mold half and the second mold half; applying a vacuum to the first mold half and the second mold half so as to form a bubble into the depression between the first surface and the second surface and produce a fluid filling path; sealing the first surface to the second surface about the perimeter of the bubble and the fluid filling path; filling a fluid into the bubble through the fluid filling path; sealing the fluid filling path; and trimming about the sealed perimeter of the bubble and the fluid filling path.

9. The process as defined in claim 8, wherein the first surface and the second surface are provided by folding a single sheet of a plastics material in half.

10. The process for producing a flexible fluid filled reservoir body as defined in claim 8, wherein the first plastics material sheet and the second plastics material sheet are provided as a thermoplastics material and the first plastics material sheet and the second plastics material sheet are heated prior to sandwiching.

11. The process for producing a flexible fluid filled reservoir body as defined in claim 8, wherein at least one of the first mold half and the second mold half are heatable for softening and/or bonding the first surface to the second surface.

12. The process for producing a flexible fluid filled reservoir body as defined in claim 8, wherein the first plastics material sheet and the second plastics material sheet are provided in a colour and said colour corresponds to a particular fluid.

13. The process for producing a flexible fluid filled reservoir body as defined in claim 8, wherein the fluid is provided a liquid drug.

14. The device for administering to an animal a fluid drug as defined in claim 1, wherein the flexible fluid filled reservoir body is produced by: aligning and contacting a first surface of a first plastics material sheet with a second surface of second plastics material sheet; applying a first mold half to the exterior side of the first plastics material sheet and a second mold half to the exterior of the second plastics material sheet, at least one of the first mold half and the second mold half having a depression formed therein with an open vertical path extending outwardly of the first mold half and the second mold half; sandwiching the first plastics material sheet and the second plastics material sheet between the first mold half and the second mold half; applying a vacuum to the first mold half and the second mold half so as to form a bubble into the depression between the first surface and the second surface and produce a fluid-filling path, the bubble correspondingly sized to fit within the reservoir chamber; sealing the first surface to the second surface about the perimeter of the bubble and the fluid filling path; filling the fluid drug into the bubble through the fluid filling path; sealing the fluid filling path; and trimming about the sealed perimeter of the bubble and the fluid-filling path so as to produce the flexible fluid filled reservoir body.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] These and other features of the invention will become more apparent from the following description in which reference is made to the appended drawings wherein:

[0023] FIGS. 1A to 1G illustrate the steps in the manufacture of a drug reservoir according to the present invention;

[0024] FIGS. 2A to 2J Illustrate the operation of one embodiment of a delivery device of the invention;

[0025] FIGS. 3A and 3B illustrate another embodiment of a delivery device; and;

[0026] FIGS. 4A to 4C illustrate yet another embodiment of a delivery device.

DETAILED DESCRIPTION

[0027] The following description is of preferred embodiments.

[0028] In one aspect of the present invention a novel type of drug reservoir is provided. The drug reservoir comprises a fillable bladder. The reservoir is formed between two layers of plastic film. The two layers can be formed from two sheets or from one sheet folded in half. When two sheets are used, the sheets may comprise the same material, thickness, etc. or they may be two different types of sheets.

[0029] The present invention provides for a drug delivery device incorporating a disposable reservoir. The device may be provided as a single-use, disposable device or a multi-use device. The device comprises a housing that has an upper end and a lower end. As used herein, the term upper is used to refer to the surface furthest away from an individual skin and the term lower is used to refer to the part of the device that contacts a patient's skin. An actuator is mounted at the top of the housing. The actuator is used to activate a drive mechanism. One example of a drive mechanism is a plunger that travels up and down within the housing. A reservoir chamber is slideably mounted within the housing. The reservoir chamber holds a reservoir filled with a liquid. The reservoir chamber is operatively linked to the drive mechanism. The reservoir chamber has a micro needle mounted on the lower surface of the chamber. When the plunger is depressed, the reservoir housing travels downward within the housing until it stops when the bottom of the reservoir housing hits the bottom of the outer housing.

[0030] A process for the manufacture of one embodiment of the reservoir is shown in FIGS. 1A-G. In FIG. 1A, a sheet of thermoplastic material 10 is folded in half to provide a first surface 12 and a second surface 14. Referring to FIG. 1B, the sheet 10 is folded so that the first surface and the second surface overlap each other. Then the sheet is heated to soften the film. FIG. 1C illustrates a mold 18 applied to each of the surfaces 12, 14. The mold for each side may be of similar or different shapes. As a vacuum is applied to the mold halves, a bubble 20 is formed and at the same time the boundary 22 of the reservoir shape is sealed. A vertical path 24 is left open for filling of the reservoir. As shown in FIG. 1D, the mold halves 18 are removed and the sheet 10 including the bubbles 20 are cooled to room temperature. The filling process is demonstrated in FIG. 1E. The film is preferably oriented with the vertical path 24 open at the top for filling to avoid the formation of air pockets during the filling process. A fine dispensing nozzle 26 is inserted into the vertical path 24 and a controlled amount of drug 27 is inserted into the reservoir. The open end 30 of the vertical path 24 is then heat sealed as shown in FIG. 1F. The bubble shaped reservoir 20 can then be trimmed as shown in FIG. 1G from the remaining sheets of plastic film or the bubble shapes can be partially trimmed and the bubbles can be stored in a roll format.

[0031] In another embodiment, the reservoir is formed by preparing a sheet of material having a series of wells or depressions. The wells are filled with a drug and then an upper sheet is applied to cover and seal the open end of the wells. In both embodiments the reservoir comprises a fillable, sealable bladder of thermoplastic material.

[0032] Various colors and shapes of reservoirs can be used for different drugs. For example, a round, blue bubble may indicate that the reservoir contains insulin and a square pink bubble may indicate a DPT vaccine. The reservoir of the present invention can be used to store many different kinds of active agents. Color coding can be used to identify the agent and/or dose strength.

[0033] The present invention also provides a device and method for delivery of the drug stored in the reservoir to an animal, preferably a human. The device comprises an outer housing. The outer housing can be made of any durable material, preferably a hard plastic. The outer housing can take various shapes, e.g. it can be round, oval, hexagonal, square etc. The outer housing can incorporate various colours to identify the agent and/or dose strength. The outer housing defines an internal chamber that includes an open top at the upper end and a base having an aperture at the lower end. A reservoir chamber is fitted inside the housing. The reservoir chamber is adapted to receive a disposable reservoir such as that described above. A microneedle is mounted in the bottom platform of the reservoir chamber with its upper (non-skin contacting) end protruding upward and just below the reservoir and the skin-contacting tip extending beyond the bottom of the chamber. The reservoir chamber frictionally engages the internal wall(s) of the housing. A drug reservoir or bubble is contained within the reservoir chamber. A drive actuator is operatively linked to the reservoir chamber. The drive actuator may include a flexible dome or an upper casing. The reservoir chamber typically comprises an open upper end, an internal chamber to hold the reservoir and a base platform with the needle mounted so that it transects the base. A retraction mechanism such as a vacuum bulb or a spring is also optionally included.

[0034] In use, the delivery device is placed on the skin with the lower end of the housing touching the skin. The drive mechanism is then actuated to drive the reservoir chamber downwards until the base platform of the reservoir chamber hits the base of the housing. This causes the needle to exit through the aperture in the base of the housing a predetermined distance and enter into the skin to a predetermined depth. Further downward pressure on the plunger compresses the drug filled reservoir and causes it to be pierced by the upper end of the needle. This puts the cannula of the needle in fluid communication with the contents of the reservoir and as the downward pressure continues until the tip of the plunger bottoms on the base platform of the reservoir chamber, the contents of the reservoir are passed through the cannula of the needle to the skin of an animal or human subject. When the pressure on the drive mechanism is released, retraction means cause the needle to be retracted back into the housing for disposal.

[0035] One preferred embodiment of the device and its operation is shown in FIGS. 2A-J. The device 50 comprises housing 52. The housing has an open upper end 54 and a bottom base 56 defining an interior chamber 58 that optionally includes a spring. The bottom base comprises an aperture 60. The interior of the housing is adapted to receive a reservoir chamber 62 having a chamber ledge 62A circumferentially disposed around the interior of the upper end of the chamber 62. The reservoir chamber comprises a base 64 and a surrounding wall 66 extending upwards from the base defining a chamber 62 with an open top 68. A filled reservoir body 70 is located in the reservoir chamber.

[0036] A single hollow needle 72 is associated with the reservoir chamber 62. The needle 72 extends through the base 64 of the chamber 62 and has a cannula with an upper end 74 communicating with the interior 75 of the reservoir chamber and a lower end 78 projecting out of the chamber and down a predetermined distance. The open top 68 of the reservoir chamber is adapted to receive an actuator 80. In the illustrated embodiment, the actuator comprises a plunger 82 having an activation flange 84 at one end and a stopper 86 at the other end. In the initial position of the device as provided and as shown in FIGS. 2A and 2B, the base 64 of the reservoir chamber 62 is held at a predetermined distance from the interior surface 88 of the base 56 of the housing by at least one releasable latch 90 which retains the chamber in position by the interaction of the latch 90 with a latch retainer 92. The latch 90 includes a notch 91.

[0037] In one preferred embodiment an upper housing 96 encases the plunger 80.

[0038] It is clearly apparent that the distance the needle travels can be varied depending on the desired application and on the bubble position and the length of the needle. For example, the device can be adapted to have the needle travel a distance between about 0.5 mm to about 10 mm. Thus, the device of the invention can be adapted for intradermal, subcutaneous or intramuscular injections. The needle preferably travels from about 3 mm to 8 mm. The needle gauge is preferably 25 to 84 gauge although different gauge needles can be used.

[0039] The operation of the device is illustrated sequentially in FIGS. 2A to 2J. FIGS. 2A and 2B illustrate the device in the initial state as described above. Referring now to FIGS. 2C and 2D for use, the base 56 of the housing 52 is placed against the skin. When pressure is exerted on the actuator 80, the latch 90 is released from the retainer 92. The actuator 80 is connected to the reservoir chamber 62 via a notch 100 and tab 102 connector and the reservoir chamber will be forced down until the base 64 of the reservoir chamber 62 hits the interior surface 88 of the housing base 56 and the chamber is stopped from any further downward movement. By adjusting the relative sizes and positions of the components, the length of the travel of the needle through the aperture into the skin can be tightly controlled. The distance that the needle extends is about 0.5 to 10 mm, preferably 0.5 to 5 mm, more preferably from about 3 mm to about 5 mm, even more preferably from about 1.5 to 3 mm. The outer layer of skin, the epidermis typically has a thickness of about 0.5 to 2 mm. and the inner layer, the dermis, has a thickness of about 1.5 to 3 mm. The dermis comprises two layers, the papillary layer and the reticular layer. The reticular layer contains many blood vessels and lymph vessels, making it a desirable area for delivery of active agents. Below the dermis is the subcutaneous layer and then muscle. In a preferred embodiment, the distance that the tip of the needle can extend beyond the lower outer surface of the housing is selected to be optimum for insertion in the dermis or subcutaneous layer. As the reservoir chamber 62, carrying the needle 72 descends, the lower tip of the needle 78 exits the aperture 60. The downward travel of the reservoir chamber 62 is limited when the base 64 of the chamber contacts the base 56 of the housing. In this way the travel of the needle through the aperture 60 is also limited so as to limit the depth of penetration of the needle into the skin. The components of the device have been configured so that the distance that the bottom of the chamber travels is translated into a predetermined travel for the needle through the aperture in the bottom of the housing to provide a certain skin penetration.

[0040] Referring now to FIGS. 2E and 2F, as continued pressure is applied to the actuator 80, the tab 102 is released from the notch 100 and the plunger 82 descends within the reservoir chamber forcing the filled reservoir 70 downwards until it contacts the base 64 of the reservoir chamber 62. As the actuator 80 exerts pressure on the reservoir 70, the reservoir 70 contacts the upper end 74 of the needle 72 and is punctured. The cannula of the needle 72 is now in fluid communication with the contents of the reservoir.

[0041] Referring now to FIGS. 2G and 2H, continued pressure on the actuator 80 compresses the reservoir 70 and forces all the contents to flow through the needle 72 and into the patient. The downward travel of the actuator 80 is stopped when the plunger stopper 86 contacts the base 64 of the reservoir chamber 62.

[0042] After use, the needle is preferably retracted back into the housing 52 as illustrated in FIGS. 2I and 2J. The position of the reservoir chamber 62 carrying the needle 72 is preferably biased to the pre-activation position by biasing means such as a spring, a vacuum bulb or a moldable bulb. Once pressure is released on the actuator 80, the base 64 of the reservoir chamber moves up in the housing thus automatically retracting the used needle into the housing. This provides for safe disposal of the device. In a preferred embodiment, the needle is preferably locked in the retracted position. FIG. 2J shows a retracted reservoir chamber that is locked in position when tab 102 slides into indent 104.

[0043] In the embodiment illustrated in FIGS. 3A and 3B, an actuator 106 is continuous with an upper casing 108 that fits over a housing 110. The housing 110 receives a reservoir chamber 112 that has a needle 114 transversely mounted through its base 116. A drug reservoir 118 is contained within the chamber 112. As shown in FIG. 3B, pressure on the actuator 106 causes the reservoir chamber 112 to descend until it abuts the base 120 of the housing 110. As the chamber 112 descends, it drives the tip 122 of the needle 114 through an aperture 124 in the housing 110. Further pressure causes the rear 126 of the needle to puncture the reservoir 118. Upon continued pressure, the contents of the reservoir are expelled through the needle.

[0044] In another embodiment, a flexible dome fits over the plunger rod and activation flange. It is also clearly apparent the manual activation flange can be exposed. The device also optionally includes a spring that is located around or below the reservoir chamber base such that when pressure on the activation flange is released the compressive energy of the spring causes the needle to be retracted back into the housing.

[0045] FIGS. 4A to 4C illustrate another embodiment of the device. The device 130 includes a housing 132 and an upper casing 134. An actuator 136 is operably linked to a reservoir chamber 138 disposed within the housing 132. For use, a drug filled reservoir 140 is placed in the reservoir chamber 138. A needle 142 is mounted so as to transverse the base 144 of the chamber 138. The device also includes a spring 146 that biases the reservoir chamber 138 upwards in the housing 132. Upon pressure on the actuator 136, the spring compresses and the reservoir chamber travels downward carrying the needle and the needle tip 148 exits the housing 132. Upon further pressure, the actuator 136 compresses the drug filled reservoir 140 until the back 150 of the needle punctures the reservoir and the contents flow through the needle as shown in FIG. 4C.

[0046] In another aspect of the invention, a method for delivering an effective amount of a liquid active agent to an animal, preferably a human, is provided. The method comprises providing a drug delivery device according to the present invention, said device containing a reservoir filled with the desired drug; applying the bottom surface of the drug delivery device of the invention to the skin of an animal, applying pressure on the actuator to cause the needle to enter the skin, applying continued pressure to puncture the reservoir and deliver the contents of the reservoir through the cannula of the needle.

[0047] The device of the present invention can be used to deliver a variety of active agents. The term drug is used loosely herein to refer to prophylactic as well as therapeutic agents. For example, vaccines may be delivered using the device. In addition, the term refers broadly to active agents, such as nucleic acids, small molecules, therapeutic proteins, hormones, analgesics, etc. in additional to traditional pharmacologic agents. Typical drugs include peptides, proteins or hormones such as insulin, calcitonin, calcitonin gene regulating protein, atrial natriuretic protein, colony stimulating factor, betaseton, erythropoietin (EPO), interferons such as , , or interferon, somatropin, somatotropin, somatostatin, insulin-like growth factor (somatomedins), luteinizing hormone releasing hormone (LHRH), tissue plasminogen activator (TPA), growth hormone release hormone (GHRH), oxytocin, estradiol, growth hormones, leuprolide acetate, factor VIII, interleukins such as interleukin-2, and analogues thereof; analgesics such as fentanyl, sufentanil, butorphanol, buprenorphine, levorphanol, morphine, hydromorphone, hydrocodone, oxymorephone, methadone, lidocaine, bupivacaine, diclofenac, naproxen, pavefin, and analogues thereof; anti-migraine agents such as sumatriptan, ergot alkaloids, and analogues thereof, anti-coagulant agents such as hepafin, hirudin, and analogues thereof; anti-emetic agents such as scopolamine, ondansetron, domperidone, metoclopramide, and analogues thereof; cardiovascular agents, anti-hypertensive agents and vasodilator such as diltiazem, clonidine, nifedipine, verapamil, isosorbide-5-mononitrate, organic nitrates, agents used in treatment of heart disorders, and analogues thereof; sedatives such as benzodiazepines, phenothiozines, and analogues thereof; narcotic antagonists such as naltrexone, naloxone, and analogues thereof; chelating agents such as deferoxamine, and analogues thereof; anti-diuretic agents such as desmopressin, vasopressin, and analogues thereof; antineoplastics such as 5-fluorouracil, bleomycin, and analogues thereof; prostaglandins and analogues thereof; and chemotherapy agents such as vincristine, and analogues thereof. Stabilized preparations of drugs that can be stored at room temperature are particularly preferred for use in the device and method.

[0048] The term fluid refers to any fluid containing an active agent or communication of agents that can pass through the cannula of the microneedle. This includes a liquid, a solution, a gel, a dispersion or a fine suspension.

[0049] All citations are hereby incorporated by reference.

[0050] The present invention has been described with regard to one or more embodiments. However, it will be apparent to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as defined in the claims.