COMPACTED POWDER

Abstract

The present invention is directed towards a compacted powder shaped to comprise: a) a substantially annular girdle having opposing circumferential edges, the girdle having a diameter (x); and b) a dome protruding from each of the opposing circumferential edges of the girdle, wherein the height of each dome (hd) from the circumferential edge is, individually, about 0.18x to about 0.28x.

Claims

1. A tablet formed from a compacted powder and shaped to comprise: a) a substantially annular girdle having opposing circumferential edges, the girdle having a diameter (x); and b) a dome protruding from each of the opposing circumferential edges of the girdle, wherein the height of each dome (hd) from the circumferential edge is, individually, about 0.18x to about 0.28x.

2. A tablet according to claim 1 comprising a pharmaceutical composition.

3. A tablet comprising a pharmaceutical composition and formed from a compacted powder and shaped to comprise: a largest cross section which is substantially circular in form and having a diameter x and at least one circumferential edge; and a pair of opposing domes extending from the circumferential edge, wherein the total height (hp) of the tablet in a direction perpendicular to the plane of the largest cross section is less than 0.95x and equal to or greater than 0.86x.

4. A tablet according to claim 3, wherein hp is less than 0.95x and equal to or greater than 0.89x, optionally wherein hp is less than 0.94x and equal to or greater than 0.89x, for example wherein hp is less than 0.94x and equal to or greater than 0.92x, preferably wherein hp is 0.93x.

5. A tablet according to claim 3 wherein the largest cross section comprises part of a substantially cylindrical girdle having a pair of opposed circumferential edges, wherein each of the opposed domes extends from one of the opposed circumferential edges.

6. A tablet according to claim 5, wherein the height of each dome (hd) from the circumferential edge is, individually, about 0.18x to about 0.28x.

7. A tablet according to claim 1 wherein the hd is between about 0.18x to about 0.27x, such as wherein the hd is between about 0.22x to about 0.27x, optionally wherein the hd is between about 0.23x to about 0.26x, for example wherein the hd is between about 0.22x to about 0.25x, preferably wherein hd is about 0.25x, optionally wherein hd is either different or the same for each of the dome protrusions, preferably wherein hd is the same.

8. A tablet according to claim 1, wherein the girdle has a height (hg) of about 0.27x to about 0.7x, for example wherein hg is about 0.37x to about 0.7x, such as between about 0.4x to about 0.7x, optionally wherein hg is between about 0.43 to about 0.62x, for example wherein the hg is between about 0.43x to about 0.54x, such as wherein hg is about 0.5x, preferably wherein hg is about 0.43x.

9. A tablet according to claim 8, wherein hd is between about 0.18x to about 0.28x and hg is between about 0.36x to about 0.62x, such as wherein hd is between about 0.18x to about 0.25x and hg is between about 0.43x to about 0.62x, for example, hd is between about 0.22x to about 0.25x and hg is between about 0.43x to about 0.54x, preferably, hd is about 0.25x and hg is about 0.43x.

10. A tablet according to claim 1, wherein hd is between about 0.55 mm to about 0.85 mm, such as wherein hd is between about 0.55 mm to about 0.80 mm, optionally wherein hd is between about 0.65 mm to about 0.78 mm, preferably wherein hd is about 0.75 mm.

11. A tablet according to claim 1, wherein the total height of the compacted powder (hp) is between about 0.8x to about 1.3x, for example wherein hp is between about 0.8x to about 1.03x, such as wherein hp is between about 0.8x to about 1x, for example wherein hp is between about 0.86x to about 1x, optionally wherein hp is between about 0.86x to about 0.97x, for example wherein hp is between about 0.89x to about 0.97x, optionally wherein hp is between about 0.93x to about 1.03x, for example hp may be about 0.93x, preferably hp is about 1x.

12. A tablet according to claim 2, wherein hp is between about 2.4 mm to about 3.9 mm, for example wherein hp is between about 2.4 mm to about 3.2 mm such as wherein hp is between about 2.6 mm to about 3.1 mm, for example wherein hp is between about 2.7 mm to about 3.1 mm, for example wherein hp is about 2.8 to 3.1 mm, optionally wherein hp is between about 2.8 mm to about 2.9 mm.

13. A tablet according to claim 1 having a hardness of greater than about 2 kPa, for example greater than 3 kPa, such as greater than 4 kPa.

14. A tablet according to claim 1 having a hardness of between about 2 kPa and about 6 kPa, optionally wherein the compacted powder has a hardness of between about 2.5 kPa to about 5.0 kPa, such as wherein the compacted powder has a hardness of between about 3 kPa and about 4.5 kPa, preferably wherein the compacted powder has a hardness of between about 4 kPa and about 4.5 kPa.

15. A tablet according to claim 1, wherein x is between about 1 mm to about 5 mm, such as wherein x is between about 2 to about 4 mm, preferably wherein x is about 3 mm.

16. A tablet according to claim 1, wherein the compacted powder is in a pseudo-spherical or modified ball shape.

17. A tablet according to claim 1, wherein the total mass of the powder is between about 5 mg to about 100 mg, such as wherein the total mass is about 10 mg to about 80 mg, optionally wherein the total mass is about 15 mg to about 50 mg, preferably wherein the total mass is about 20 mg.

18. A tablet according to claim 1 comprising a medicament selected from one or more of levodopa/carbidopa or levodopa/benserazide, morphine, oxikodone or methadone, pregabaline, diazepam, oxazepam or alprazolam, methylfenidate, acarbose, metformine, glibenclamide or glipizide, atomoxetine, capecitabine, pyridostigmine, warfarin, valproate or quetiapine.

19. A mould configured to produce a tablet as defined in claim 1.

20. A mould according to claim 19 comprising two opposing halves.

21. A mould according to claim 20, wherein each half of the mould is configured to correspond to one half of the shaped tablet according to any one of claims 1 to 18.

22. A method for preparing a tablet according to claim 1 comprising the steps of: a) providing a powder composition; and b) shaping the powder.

23. A method according to claim 22, wherein the powder composition comprises a pharmaceutical composition.

24. A method according to claim 22 comprising the use of a mould.

25. A method according to claim 24, wherein the powder components are placed into a first mould half, wherein the second mould half is compressed on top of the first mould half.

26. The method according to claim 22, wherein the shaping step comprises the method of direct compression moulding.

27. The use of a device to dispense a plurality of the compacted powder tablets according to claim 1 to provide a single patient with a prescribed dose of medication.

28. The use according to claim 27, wherein the device comprises a removable cassette, the tablets being stored in the removable cassette.

29. The use according to claim 28, wherein the removable cassette comprises between about 50 to about 1500 tablets, such as between about 250 to about 750 tablets, optionally between about 500 to about 750 tablets, preferably wherein the cassette comprises about 750 tablets.

30. The use according to claim 27, wherein the probability of encountering a dispensing error is equal to or less than about 2%, optionally wherein the probability is equal to or less than about 1%, such as wherein the probability is equal to or less than 0.5%, for example wherein the probability is equal to or less than about 0.05%, preferably wherein the probability is equal to or less than 0.13% or equal to or less than about 0.013%.

31. A device for dosing and/or dispensing medication, the device comprising a storage chamber containing a plurality of tablets according to claim 1.

32. A device according to claim 31, wherein the storage chamber is comprised in a removable cassette.

33. A device according to claim 31, wherein the device or cassette comprises between about 50 to about 1500 tablets, such as between about 250 to about 750 tablets, optionally between about 500 to about 750 tablets, preferably wherein the cassette comprises about 750 tablets.

34. A cassette configured to be releasably engageable with a device for dosing and/or dispensing medication, the cassette comprising a storage chamber containing a plurality of tablets according to claim 1, such that the tablets may be dispensed from the storage chamber by the device.

35. The device or cassette according to claim 32 comprising a feed assembly for dispensing tablets from the storage chamber, the feed assembly comprising a plurality of movable feed pockets for transporting the tablets, for example in the form of a feed wheel which comprises a plurality of the feed pockets about its circumference.

36. The device or cassette according to claim 35, wherein the feed pockets are configured to receive a single tablet.

37. The device or cassette according to claim 35, wherein the depth of the feed pockets is between about x and about 1.3x, for example between about x and about 1.1x e.g. is substantially equal to x

38. The cassette according to claim 34, wherein the cassette is for single use.

39. The cassette according to claim 34, comprising between about 50 to about 1500 tablets, such as between about 250 to about 750 tablets, optionally between about 500 to about 750 tablets, preferably wherein the cassette comprises about 750 tablets.

40. A compacted powder tablet as herein described with reference to the accompanying drawings.

41. A method of forming a compacted powder tablet as herein described.

Description

[0054] Preferred embodiments of the invention will now be described by reference to the following drawings.

[0055] FIGS. 1 and 2 show a device for dispensing tablets according to the present invention;

[0056] FIG. 3 shows a cassette for use with a device for dispensing tablets according to the present invention;

[0057] FIG. 4 shows a tablet according to the invention.

[0058] Embodiments of the present invention relate to tablets for use with medicine dispensing devices. An example of a medicine dosing and dispensing device 10 is shown in FIGS. 1 and 2.

[0059] The dosing and dispensing device 10 may be comparable in size with hand held devices such as, for example, mobile telephones, thereby rendering the dosing and dispensing device 10 suitable for use as a hand held device. It is envisaged that in other embodiments the size and shape of the dosing and dispensing device 10 may be varied to render the dosing and dispensing device 10 suitable for users having limited dexterity, for example. The device 10 may also be sized and designed to be used in a fixed location.

[0060] The dosing and dispensing device 10 includes a housing 12 including a storage chamber 14 to store discrete units or tablets of medicine 16 and a feed assembly 18 located between the storage chamber 14 and a dispenser 20. In some embodiments, the dosing and dispensing device 10 also includes an impacter 22 (see FIG. 3) that is operably associated with the storage chamber 14 to agitate units of medicine 16 stored in the storage chamber 14.

[0061] As can be seen from FIG. 3, the impacter 22 includes a rigid element 24 fixedly connected at one end 26 to a wall 28 inside of the storage chamber 14. The impacter 22 is operably associated at a second end 30 with an actuating mechanism 32 that deflects the second end 30 of the impacter 22 towards the wall 28 of the storage chamber 14 to strain the impacter 22 such that, when released, the strained impacter 22 moves towards the interior 34 of the storage chamber 14 and impacts again units of medicine 16 stored therein.

[0062] The example dosing and dispensing device 10 includes a storage chamber 14 provided in a removable cassette 36 that is releasably engageable with the housing 12.

[0063] In other embodiments of the invention it is envisaged that the storage chamber 14 may be permanently located within the housing 12, the housing 12 including an opening to permit access to the storage chamber 14 to permit refilling thereof.

[0064] The housing 12 and cassette 36 may include mutually engageable latch members that interengage on insertion of the cassette 36 into the housing 12 to retain the cassette 36 within the housing 12. The dosing and dispensing device 10 also includes an ejection mechanism that is selectively operable to disengage the latch members and allow removal of the cassette 36 from the housing 12.

[0065] This allows the provision of a cassette 36 that, when received in the housing 12, has an external surface 38 that sits flush with an adjacent outer surface 40 of the housing 12, which enhances the appearance of the dosing and dispensing device 10.

[0066] The latch members include elongate projections 42 provided on an upper face 44 of the cassette 36 and extending in the direction in which the cassette 36 is inserted into and withdrawn from the housing 12.

[0067] The latch members also include correspondingly shaped and sized openings 46 (FIGS. 9 and 10) provided on an inner surface 48 of an upper face 50 of the housing 12. The openings 46 are located on the inner surface 48 so as to be aligned with the projections 42 provided on the cassette 36. When the cassette 36 is fully inserted into the housing 12, an interference fit is formed to prevent sliding withdrawal of the cassette 36 from the housing 12.

[0068] In other embodiments, alternative means of securing the cassette 36 into the device 10 as may be known in the art may be utilized.

[0069] The feed assembly 18 includes a feed wheel 94 (FIG. 3) defining a plurality of feed pockets 96 about its circumference. The feed wheel 94 is located in the cassette 36 between the storage chamber 14 and the dispenser 20 and comprises seven pockets 96 and one blank pocket 97. The feed wheel comprises a central hub and pairs of equally spaced parallel radially extending fingers to form the pockets 96 therebetween. The pockets 96 are sized so as to contain a single tablet 16. The blank pocket 97 is of similar dimensions as the pockets 96 but is formed from a pair of radially extending lugs 99 which acts as a baffle to the receipt and/or containment of a tablet 16 in that part of the feed wheel 94.

[0070] The feed wheel 94 is mounted to rotate so that rotation in a first direction moves the feed pockets 96 sequentially into alignment with a feed channel of the storage chamber 14 to each receive a unit of medicine 16.

[0071] On further rotation of the feed wheel 94 in the first direction, the feed pockets 96 are moved sequentially into alignment with an inlet of the dispensing chamber 72 of the dispenser 20 to feed the respective units of medicine 16 into the dispensing chamber 72 dispenser 20.

[0072] Typically, the device 10 will contain a system of sensors and a controller (not shown) for operating the feed wheel 94 to dispense a quantity of tablets as programmed and/or for counting the number of tablets which are dispensed by the device to ensure that a particular dispensing program is properly executed.

[0073] Spherical or pseudo-spherical tablets have been found to be suitable for use in such devices, which are ideal for tailoring doses of pharmaceuticals by the person requiring the treatment rather than a trained medical practitioner. Depending on a person's weight, severity of condition etc. the required dose of a pharmaceutical medicament for that person will be specific to them. As each tablet contains only a small amount of the pharmaceutical dose, the dose to be taken by the person in need thereof may be made more exact by using tablets according to the invention. As such, depending on the dose required, a relatively large number of tablets may need to be dispensed and administered to the patient per dose cycle, such as 5, 10, 15, 20 or 25 units, or any discrete number between these values. Indeed, the number of tablets to be dispensed and administered to the patient per dose cycle may be greater than 25, greater than 50 or greater than 100. Therefore, at each interval of administration, a relatively large number of tablets will need to be dispensed from the device at any one time.

[0074] As a number of tablets may need to be dispensed from the device at each dosing time, a large number of tablets are required to be stored within the device. For ease of use and to lower the occurrence of cross-contamination, it is desirable that these tablets be stored in a removable cassette. Ideally, each cassette will house a relatively large number of tablets so as to reduce the frequency of changing the cassette. Preferably, the removable cassette is configured to be able to store between about 50 to about 1500 tablets, such as between about 250 to about 750 tablets, optionally between about 500 to about 750 tablets, preferably wherein the cassette is configured to store about 750 tablets.

[0075] However, when such a large number of tablets are stored together the chances of forming bridges of tablets or other jams within the device are increased, which leads to blockages within the storage chamber and therefore potentially inaccurate and/or incomplete dosing or malfunctioning of the device.

[0076] Spherical or pseudo-spherical tablets are produced via a number of methods. However, an effective and efficient process is to place the powder in a lower mould and place an opposing upper mould on top. These moulds are then compacted together at a desired force after which, the upper mould is removed. A mechanical arm then sweeps across the upper surface of the lower mould essentially knocking the compacted powder out of the mould.

[0077] Sometimes, when being removed from the mould the tablets break or crumble, which leads to a less efficient manufacturing process, wasted material and higher manufacturing costs.

[0078] It has been surprisingly found that the dimensions and hardness of the tablets have been found to significantly influence the number of breakages occurring during their production via the method as detailed above.

[0079] The breaking of tablets has two significant drawbacks. Firstly, broken tablets will comprise less mass, and therefore less pharmaceutical dose, than required and predicted. As such, this can lead to dosing errors, particularly under dosing, when administering such tablets to a patient. Secondly, when the tablets are broken during production, a large amount of the powder residue remains in the lower mould. As a result, these moulds need to be cleaned and emptied manually before they can be used again. Therefore, as the number of breakages occurring during manufacture increases, the costs of manufacture increase and the efficiency decreases.

[0080] The present invention addresses these problems by providing a formed from a compacted powder as shown in FIG. 4, being shaped to comprise: a substantially annular girdle having opposing circumferential edges, the girdle having a diameter (x); and a dome protruding from each of the opposing circumferential edges of the girdle, wherein the height of each dome (h.sub.d) from the circumferential edge is, individually, about 0.18x to about 0.28x. The values of h.sub.d and the overall height of the tablet (h.sub.p) and the girdle (h.sub.g) are variable as is described herein.

[0081] The tablets of the invention preferably comprise a pharmaceutical dose. In order to tailor the dose of a pharmaceutical dose to a patient, it is desirable that each tablet comprises only a small portion of the required dose. For example, drug therapies used to treat Parkinson's disease, epilepsy, cancer, depression, schizophrenia, attention deficit-hyperactivity disorder (ADHD) as well as other neurobehavioural disorders, diabetes, arthritis and asthma and diseases requiring anti-coagulants, anti arrhythmics and/or analgesia, often have a narrow therapeutic window and produce significant side effects when dosing is non-optimal. Accordingly, the tablets of the invention may include medicaments such as levodopa/carbidopa or levodopa/benserazide, morphine, oxikodone or methadone, pregabaline, diazepam, oxazepam or alprazolam, methylfenidate, acarbose, metformine, glibenclamide or glipizide, atomoxetine, capecitabine, pyridostigmine, warfarin, valproate or quetiapine (as appropriate, i.e. depending on the disease to be treated).

[0082] As such, it is preferable for each tablet to comprise only a small amount of the total pharmaceutical dose to be administered. For example, the amount of pharmaceutical dose comprised in each tablet may be between about 1 wt % to about 20 wt % of the total dose required, such as between about 1 wt % to about 10 wt %, for example between about 2 wt % to about 5 wt %.

[0083] The invention will now be illustrated by the following non-limiting Examples.

EXAMPLES

Example 1

[0084] The dispensing of various compacted powders was assessed using a MyFID (Sensidose AB, Sollentuna, Sweden) device.

[0085] The tablets were composed of levodopa (5 mg), carbidopa (1.25 mg) and excipients in an amount sufficient to bring the total weight of each tablet to 20 mg.

[0086] Various compacted powders were tested for their efficacy when in use in the MyFID device (see Table 1). Discrete units of the compacted powders were loaded into a removable cassette, which was inserted into the MyFID device. The device was then set to dispense the discrete units of compacted powder. The dispensing order was random and in each round 5, 10, 15 or 20 units of compacted powder were dispensed. The number of compacted powder units actually dispensed was compared to the number of units programmed to be dispensed. The number of broken compacted powder units or number of occasions where dispensing could not be performed by the device due to the tablet causing technical faults such as bridging, were also counted. The breaking of compacted powder units occurs during the manufacture of the units and is dependent on the dimensions and hardness of the units. In all of the compacted powders x is 3 mm. The average weight of each of the compacted powders is 201 mg.

[0087] The results of the assessment are detailed below in Table 1.

TABLE-US-00001 TABLE 1 h.sub.d [as h.sub.p [as Occurrence function function Hardness Bridging Occurrence of wrong of x] of x (kPa) Occasions of breaking dosing 0.18x 0.97x 2 56.9% 22.2% 8.3% 0.18x 0.86x 4.2 23.8% 28.6% 3.2% 0.22x 0.97x 2.5 28% 14.6% 6.7% 0.22x 0.89x 3.9 9.6% 0% .sup.0% 0.25x 0.93x 4.3 1.8% 0% .sup.0% 0.29x* 0.85x 4.3 8.7% 0.3% 0.3% *Comparative example

[0088] These results show that for compacted powders having a h.sub.d of 0.18x, the occurrence of breakages is not significantly influenced when the hardness is increased from 2 kPa to 4.2 kPa. However, the bridging occurrence is reduced when the hardness is increased.

[0089] For compacted powders having a h.sub.d of 0.22x, the occurrence of breakages is significantly reduced when the hardness is increased from 25 kPa to 39 kPa. Similarly, the occurrence of bridging is also reduced.

[0090] Increasing the h.sub.d from 0.22x to 0.25x and keeping the hardness at around 40 kPa, the occurrence of bridging increases even further leading to highly accurate dispensing of the compacted powders.

[0091] Increasing the h.sub.d further from 0.25x to 0.29x leads to an increase in the number of breakages, which in turn would lead to an inaccurate dosing of any pharmaceutical composition comprised within the compacted powder unit.

[0092] As the hardness of the compacted powder increases from about 20 kPa to about 40 kPa, the occurrence of tablets breaking significantly lowers for compacted powders having a hd of between about 0.22x and about 0.75x.

[0093] However, the dimensions of the compacted powders appear to be the primary influence of the number of breakages that occur. For compacted powders having a h.sub.d of 0.18, it was found that then number of breakages was not significantly influenced by the hardness of the powders and that the number of breakages was, therefore, due to the dimensions of the compacted powders rather than their hardness. Without wishing to be bound by any particular theory, it is postulated that reductions of breakages would be shown for tablets having dimensions of the invention when compared to the prior art, notwithstanding any change in hardness.

[0094] Surprisingly, it was found that for the production of compacted powders having a h.sub.d of 0.29x, the number of breakages increases compared to compacted powders having the same hardness but lower h.sub.d, particularly a h.sub.d of 0.25x. Without wishing to be bound by theory, it is believed that as the compacted powders pass a certain h.sub.d value and become more spherical, the portion of powder encased by the lower mould increases to the overall volume of the compacted powder. This means that the compacted powders require more force to remove them from the moulds and this, in turn, leads to a large number of breakages.

[0095] These results also show that the dimensions of the tablets influence the occurrence of the formation of tablet bridges within the storage cassette. In particular, it has been found that as h.sub.d increases from 0.18x to 0.25x, the number of bridging occasions decreases to 1.8%. However, as h.sub.d increases further to 0.29x the number of bridging occasions increases to 8.7%. Therefore, it has been found that when using tablets having a h.sub.d of 0.25x, the number of bridging occasions significantly decreases. However, as h.sub.d is increased further, and thus making the tablets more spherical, the number of bridging occasions surprisingly begins to rise.

[0096] No doubt many other effective alternatives will occur to the skilled person. It will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the spirit and scope of the invention.