Implantable solid dosage form

Abstract

A solid dose for insertion into the skin of a patient wherein the solid dose has a hollow core. There is also provided a solid dose carrier, a device, a method of manufacturing the solid dose and a method of delivering a solid dose transdermally to a human or animal.

Claims

1. A solid dose for insertion into the skin of a patient wherein the solid dose is a pellet having a hollow core, wherein the solid dose comprises a proximal end and a distal end, wherein the hollow core extends completely from the proximal end to the distal end of the solid dose, wherein the solid dose is configured to be seated around a carrier, wherein the proximal end of the solid dose detachably rests on the carrier, wherein the carrier is capable of penetrating the surface of the skin of a patient to allow for the solid dose to be delivered instantly without the need for any residence time of the carrier inside the skin once the solid dose has been inserted; and wherein the solid dose is configured to remain substantially undissolved upon retraction of the carrier.

2. The solid dose according to claim 1 wherein the solid dose has a shape which allows delivery of the solid dose into the skin, wherein the shape is conical, frustoconical, cylindrical or a cuboid.

3. The solid dose according to claim 1 wherein the distal end of the solid dose is tapered.

4. The solid dose according to claim 1 wherein the solid dose is elongated with an aspect ratio of greater than 1.

5. The solid dose according to claim 1 wherein the solid dose comprises at least one active ingredient.

6. The solid dose according to claim 1 wherein the solid dose comprises at least one excipient.

7. The solid dose according to claim 1 wherein the solid dose consists of an active ingredient.

8. The solid dose according to claim 1 wherein the length of the solid dose is less than 1000 microns, or wherein the length of the solid dose is between 10 microns to 20 mm in length.

9. The solid dose according to claim 1 wherein the solid dose is coated with a biodegradable polymer or a carbohydrate.

10. The solid dose according to claim 1 wherein the solid dose is soluble or biodegradable.

11. A method of manufacturing a solid dose as defined in claim 1 comprising the following steps: (i) providing the solid dose ingredients; and (ii) shaping the solid dose.

12. The method according to claim 11 wherein the shaping step involves using a method selected from wet casting, direct compression molding or extrusion.

13. The method according to claim 11 wherein the shaping step involves compression molding using a multipart tool.

14. The method according to claim 13 further comprising a step of forming a hollow core of the solid dose.

15. The method according to claim 14 wherein the method further comprises the steps of (i) placing the solid dose ingredients into a multipart die; (ii) pressing a punch section comprising a pin into the die section to form the hollow core of the solid dose; (iii) optionally rotating either the pin or the die multiparts; and (iv) ejecting the formed solid dose from the die.

Description

BRIEF DESCRIPTION OF FIGURES

(1) FIG. 1—Schematic of the device and solid dose delivery process.

(2) FIG. 2—Illustration of the device indicating an upper portion for pressing down with palm, and lower portion with a needle indicated as the carrier of the solid dose (solid dose not shown).

(3) FIG. 3—Schematic representation of the device.

(4) FIG. 4—Cross section of the carrier portion of the device.

(5) FIG. 5—Schematic representation of various shapes of the solid dose.

(6) FIG. 6—Schematic illustration of a three-part mold tool for producing the solid dose.

(7) FIG. 7—Schematic illustration of the mold tool and pin associated with the compression die.

(8) FIG. 8—Schematic illustration of the device within an outer case which provides resistance to the movement of the solid dose/carrier.

(9) FIG. 9—A graph showing the release of diclofenac sodium in a pellet, formed according to the present invention, wherein the pellet comprises 40% diclofenac sodium and 60% sucrose.

(10) The device (20) according to the present invention is shown in FIG. 1 in use and illustrates the solid dose delivery process. A solid dose carrier (3) is shown as carrying the solid dose (5) and a sleeve (4) (indicated as an insertion rod) is shown shrouding the upper proximal portion of the carrier, and the solid drug pellet shown shrouding the distal portion of the carrier, with a sharp tip from the carrier protruding out from the base of the solid drug pellet. This is then shown inserted inside the skin followed by further insertion of the solid dose using the sleeve, and retraction of the device with the solid dose remaining inside the skin. Protrusion of the tip of the carrier may be tens to several thousand micrometers, preferably 10 to 5,000 micrometers, more preferably 20 to 2,000 micrometers and more preferably 50 to 1,000 micrometers.

(11) The depth of insertion is dependent upon the size of the solid dose. In one aspect wherein the dose is a large dose of approximately >1 mm in length, then the solid dose will be required to be pushed deeper into the skin, than if it is a smaller solid dose, of approximately <1 mm length. The depth is determined such that it is sufficient to ensure the pellet does not protrude back out of the skin. In accordance with the present invention, the solid dose is pushed to a depth of at least 0.5 mm into the skin, preferably the solid dose is pushed to a depth of about 0.5 mm to about 1 mm.

(12) In FIG. 2, the device of the present invention is shown with an upper surface (100) for pressing down with the palm, and lower portion (110) with a needle (120) indicated as the carrier of the solid dose (solid dose not shown). The device (20) is shown as a single use disposable component without any moving parts whereby a single motion of pushing the carrier/solid dose into the skin leads to delivery of the solid dose into the skin to a pre-defined depth.

(13) In FIG. 3, the device (20) of the present Invention is shown having an upper surface (100) which is used to apply the device by applying manual pressure to this portion. The carrier (3) with a sharp tip is shown attached to a platform (2) which is intended to define the maximum depth of penetration of the solid dose carrier.

(14) In FIG. 4 the cross-section of the carrier portion of the device is shown with the carrier (3), solid dose insertion sleeve (movable relative to the carrier) or restraint sleeve (fixed position relative to the carrier) (4) and solid dose (5) shown as a hollow conical dose.

(15) FIG. 5 illustrates that the solid dose can comprise of various shapes and dimensions which include, but are not limited to the shape of a hollow cone, hollow cocoon and hollow rectangular shape with smoothed edge profile. It will be appreciated that these are mere representations of the shapes and dimensions of the solid dose that can be produced and is not intended to be an all-encompassing representation.

(16) The three-part mold tool for producing the solid dose is shown in FIG. 6, with each of the three parts (8) shown in the open position, with the block arrows intended to indicate the movement of the parts together. After compression the three parts are moved apart leading to the dose being readily ejected from the die. It will be appreciated that the three-part tool is a representation of a multi-part tool system, and the tooling may contain one or more parts for the die section according to the needs based on the solid dose size and geometry,

(17) Release agents may be used to assist in removing the formed solid dose from the die. A suitable release agent is magnesium stearate.

(18) FIG. 7 shows a multi-part mold tool die (8) and punch (9), and pin (13) which can be used to prepare the solid dose of the present invention. The arrow shown next to the punch is intended to indicate the punch rotating as well as moving down vertically to compact the mass into a solid dose. The arrow indicated next to the die section is intended to indicate the rotation of the die before. This rotation may be during and possibly after the die section has closed together to form the desired cavity.

(19) The device (20) is shown in FIG. 8 within an outer case (40) which provides resistance to the movement of the solid dose/carrier. The upper surface (100) of the main body (30) of the device (20) is shown at an elevated position relative to the outer case (40). The body (30) of the device is also shown with protrusions (10) on the surface to provide resistance to movement of the device as it is pushed into the skin. The body (30) of the device can comprise one or more protrusions (10). The outer case (40) has a corresponding cavity in the case wall (11) which will seat the protrusion(s) (10) on the main device housing once the latter has been depressed far enough. The outer casing (40) is shown with a bottom rib (12) which seats against the skin.

(20) This embodiment of the device provides a means to fix the pressure that is applied to the device to ensure insertion. By designing the one or more protrusions (10) on the main device body (30), and flexibility into the outer case (40) such that for the drug carrier (3) to move down and into the skin a defined force must be applied to overcome the resistance from the protrusion to enable the inner main device body (30) to move relative to the outer case (40).

(21) An added benefit of this is that once the force threshold has been reached the carrier (3) and solid dose (5) will rapidly enter the skin thus avoiding the possibility of an operator mis-dosing due to inadequate penetration of the solid dose into the skin. This also provides a means of ensuring the same device cannot be used twice on a patient, by ensuring the outer and inner case lock together at this point of insertion.

(22) The present invention provides an enlarged surface area through a combination of the surface and the inner walls of the hollow core of the dosage, into which fluid from the skin will diffuse and provide rapid dissolution where desired, depending on the formulation of the dose. The larger surface area from which gradual erosion can occur provides a greater degree of control over the controlled or sustained release from the solid dose by virtue of the surface area to volume ratio i.e., the variability of release profile for a given surface area will be reduced with an increase in surface area.

(23) As the skilled person will appreciate there are a wide range of formulations known in this particular field that provide a dynamic range over which drug release occurs. The dose may be delivered for localised drug delivery to the extent that it does not release fast enough for systemic absorption, or it may be released within tens of seconds (as demonstrated by recent dissolution studies illustrated in FIG. 9) for rapid systemic absorption.

EXAMPLE

(24) A typical solid dose prepared according to the present invention contains the following ingredients:

(25) Formulation A: Microcrystalline cellulose as key bulking agent (80% by weight), and 20% Bovine Serum Albumin, (up to 20% by weight).

(26) The above formulation was also prepared using Pearlitol (direct compression mannitol) and sodium carboxy methyl cellulose in replacement of microcrystalline cellulose.

(27) It was found that for the above tested formulations, the compressed solid dose mechanical properties were acceptable for skin insertion.