WO2001000176A1

WO2001000176A1 - Divisible tablets

Info

Publication number: WO2001000176A1
Application number: PCT/GB2000/002438
Authority: WO
Inventors: Malcolm Clark
Original assignee: EU Pharma Ltd
Current assignee: EU Pharma Ltd
Priority date: 1999-06-23
Filing date: 2000-06-22
Publication date: 2001-01-04
Anticipated expiration: 2001-12-23
Also published as: AU5551800A

Abstract

A divisible tablet of the type having readily severable sections which may be divided accurately and separated into multi-sectional subunits, the tablet comprising a unitary tablet body having a bottom surface, i.e. suitably initially downwardly facing, in use, with at least a first concavity therein, wherein the tablet further has a second concavity in its upper surface, i.e. the initially upwardly facing, in use, surface, at a location that is longitudinally displaced relative to the first and any further concavities of the bottom surface whereby a compressive force applied to the tablet on the upper surface over the first concavity enables division of the tablet at the first concavity and a compressive force applied to the tablet on the bottom surface over the second concavity enables division of the tablet at the second concavity. This enables all divisions to be carried out singlehandedly by pressing the tablet against a support surface and inverting the tablet following the first division(s). The tablet may also suitably be fragmented by squeezing between thumb and forefinger at the appropriate points along the tablet.

Description

DIVISIBLE TABLETS

Field of the Invention

The present invention relates to divisible tablets and more particularly although not necessarily exclusively to divisible pharmaceutical tablets of the type that are scored to enable accurate fragmentation into multiple sub-dosage units for patient consumption. As used herein, the term "pharmaceutical" is not to be interpreted in the narrowest sense but is to be read to encompass so-called nutraceuticals and other formulations that are consumed in tablet form.

Background to the Invention

Divisible or "fractionable" pharmaceutical tablets have become increasingly wide-spread in recent years, partly in view of the advancements in pharmaceutical research that have enabled medicaments to be administered at greatly reduced daily dosages and whereby patients may have more control over the dosage taken to suit the severity of their illness. The ability to divide tablets accurately into sub-dosage units greatly facilitates tailoring of a drug regime to a particular patient's needs.

In view of the widespread usage of divisible tablets, a number of proposals have been made in the prior art for tablets designed to facilitate the division into the sub- dosage units. In the majority of cases, the division involves a simple halving of the tablet by snapping along a single "score-line" where the tablet is weakened by a sharp furrow. However, for increased versatility in drug dosage, the ability to divide into a greater number of sub-dosage units is desirable and multiple score lines are required.

A discussion of several prior art approaches to providing suitable multi- fractionable tablets is provided in UK Patent GB 2 047 095 B.

The prior art tablet designs, including that espoused by GB 2 047 095 B, provide proposals for scoring of the tablets at selected intervals to enable fragmentation into multiple sub-dosage units. However, a problem that has not been adequately addressed in the prior art, to the best of the applicant's knowledge, is ensuring that the user may easily break the tablet into the further sub-divisions once the initial division has been made.

In GB 2 047 095 B the tablets have breakage score-lines on their respective opposing major faces and also on the opposing side edges/faces of the tablet. This does not, however, render fragmentation uniformly straightforward, particularly in view of the multiple planes in which the score-lines are provided. Furthermore, the configuration does not allow for simple one-handed fragmentation.

In other prior art proposals such as, for example, US Patent US 5 061 494, the tablet design enables fragmentation into multiple sub-dosage units with each tablet having a pair of concavities on its undersurface and score-lines or "breaking grooves", one centrally between the concavities and the others at the centres of the respective concavities extending laterally across the width of the tablet. With this prior proposal selection and control of the fragmentation into the required sub-dosage units is not optimally straightforward and again there is not allowance for single-handed fragmentation.

Summary of the Invention

According to a first aspect of the present invention there is provided a divisible tablet of the type having readily severable sections which may be divided accurately and separated into multi-sectional sub units, the tablet comprising a unitary tablet body having a bottom surface, i.e. suitably initially downwardly facing, in use, with at least a first concavity therein, wherein the tablet further has a second concavity in its upper surface, i.e the initially upwardly facing, in use, surface, at a location that is longitudinally displaced relative to the first and any further concavities of the bottom surface whereby a compressive force applied to the tablet on the upper surface over the first concavity enables division of the tablet at the first concavity and a compressive force applied to the tablet on the bottom surface over the second concavity enables division of the tablet at the second concavity. This enables all divisions to be carried out singlehandedly by pressing the tablet against a support surface and inverting the tablet following the first division(s). The tablet may also suitably be fragmented by squeezing between thumb and forefinger at the appropriate points along the tablet.

In one preferred embodiment the fragmentation may be assisted by provision of breakage score lines on the tablet. Such score lines may most suitably be provided at each of the concavities and most preferably extending laterally across the width of the tablet. In one preferred embodiment, to further assist clean breakage, a score line is also provided at each apex of the tablet and extending substantially parallel to the score line at each concavity.

Suitably each part of the tablet that forms a sub unit is marked with its dosage, weight or other indentifier.

Preferably the tablet has two or more concavities on its bottom surface. The term concavity is not intended to imply that the recessed surface is necessarily curved. It may be triangular. The precise shape of the concavity may be selected dependent upon the extent of hardness of the tablet and whether score lines are provided or not.

Particularly preferably, the tablet has a concavity on its upper surface corresponding to a region intermediate the concavities of the bottom surface.

In one particularly preferred embodiment the tablet has two concavities on its bottom surface, one on its upper surface corresponding to a region intermediate the concavities of the bottom surface and thereby defines a generally M-shaped profile when viewed from the side.

The concavities are suitably angular and the angles of the concavities are obtuse, whereby when the tablet has the form with a generally M-shaped profile this is a flattened M-shape.

Where there is a concavity in the upper surface intermediate the concavities of the bottom surface, the concavity of the upper surface suitably has a greater obtuse angle than the concavities of the bottom surface.

Preferably the tablet is of the order of 20 to 30 mm long and of the order of 5 to

10 mm wide.

Suitably each score line comprises a furrow and the furrow of each score line that defines an end fragment of the tablet is formed asymmetrically having a greater slant of one side wall of the furrow relative to the other.

Suitably each score line comprises a channel that has side walls that are less than one millimeter apart and preferably narrow toward the floor of the channel. Suitably each score line comprises a furrow and the furrow has a curved floor with a radius of curvature that is less than 0.5 mm and preferably is of the order of 0.25 to 0.3 mm.

To assist purchase of the tablet against the support surface for fragmentation, the ends of the tablet are suitably relatively flattened on the bottom surface.

For comfort and ease of swallowing, where the tablet has apices corresponding to the concavities, the apices are each suitably rounded.

The side edges of the tablet are, furthermore, preferably bevelled or rounded.

In a further aspect of the present invention there is provided a method of forming a tablet of the aforementioned type, wherein the tablet is press formed using a punch that has an undulating profile of working surface with one or more concavities and apices to define the undulating profile of the tablet.

The further aspect of the present invention provides a punch for use in this method of forming the tablet and which has an undulating profile of working surface with one or more concavities and apices to define the undulating profile of the tablet.

Brief Description of the Drawings

Three preferred embodiments of the present invention will now be more particularly described, by way of example, with reference to the accompanying drawings, wherein:

Figures 1 and 2 are, respectively, a side elevation of a first preferred embodiment of tablet and a plan view of the same; and Figures 3 and 4 are, respectively, a side elevation view of a second preferred embodiment of tablet and plan view thereof;

Figures 5, 6 and 7 are, respectively a side elevation of the second preferred embodiment similar to Figure 1 but showing preferred dimensions and angles, a plan view and an end view thereof;

Figures 8, 9 and 10 are, respectively, a side elevation of a third preferred embodiment, a plan view and an end view thereof; and

Figure 11 is a longitudinal sectional view of the working profile of a punch for forming the tablet of the third preferred embodiment.

Description of the Preferred Embodiments

Referring to Figure 1 , in the simplest embodiment of the present invention the tablet is a divisible pharmaceutical tablet that comprises three sub dosage units 1 , 2, 3 for patient consumption.

The tablet as a whole comprises a unitary elongated tablet body with a length greater than its width and having a bottom facing surface 4 that, for the initial break, suitably faces downwardly and an upper facing surface 5 being the obverse to the bottom surface 4. The profile (cross section) of the tablet is suitably flattened but may be generally elliptical, for example.

The bottom surface 4 is provided with a single concavity 6, extending laterally across the width of the tablet. This concavity may be substantially triangular of a suitable angle to provide for ease of breakage without compromising overall integrity of the tablet, but may alternatively be curved and possibly arcuate. The upper most point, or apex 7 of the concavity 6 corresponds to a breakage zone at which the tablet may be fragmented.

Fragmentation of the tablet at the breakage zone may be achieved by pressing down on the upper surface 5 of the tablet above the apex 7 of the concavity 6 while the tablet is resting on its bottom surface 4 on a suitable support surface such as a table.

To further assist this initial fragmentation there is a breakage score line 8, extending laterally across the width of the tablet at the apex 7 of the concavity 6.

In order that the tablet may be further fragmentated into equal sub dosage units the alternate surface of the tablet, hereinbefore described as the upper surface 5 is further provided with a concavity 8 that is longitudinally displaced from the longitudinal position of the concavity of the bottom surface 4. By inverting the tablet so that the bottom facing surface 4 then becomes uppermost, or farthest from the supporting surface, the tablet may then be further divided by pressing down on the tablet to break the tablet at the additional concavity 8. As with the concavity 6 of the "bottom" surface 4, the concavity 8 of the "upper" surface 5 suitably also has a breakage score line extending transversely across it.

The breakage score lines 7, 9 are preferably positioned at the apical breakage zones and most suitably are equidistantly spaced apart. However, since the ends of the tablet may be relatively rounded it may be desirable to adjust the spacing of the breakage score lines to ensure that the end fragments have the required unit dosage content. Turning to the second illustrated embodiment in Figures 3 and 4, this is divisible into up to four sub dosage units/fragments, having a pair of concavities 6, 10 on its bottom surface 4 and one 8 on its upper surface 5 intermediate the longitudinal positions of the pair of concavities 6, 10 on the bottom surface 4.

The terms "upper" and "bottom" with respect to the surfaces of the tablet are used for convenience and are not intended to imply that any given face of the tablet is, or remains, uppermost in use. Indeed, the tablet is fundamentally reversible and the tablet may, of course, be pressed against an inclined or even vertical support surface to be broken, and even broken between thumb and forefinger. For the tablet with the two concavities 6, 10 in the so-called bottom surface 4 and one in the upper surface 5 and with the bottom surface 4 resting upon a support surface (e.g. a table), pressure may be applied over one or both of the concavities 6, 10 in the bottom surface 4 to fragment the tablet into either %: fragments or VA.VΪ.VA fragments.

If the intact tablet is inverted so that the "upper surface" 5 of the tablet rests downwardly against the support surface this enables pressure to be applied over the third concavity 8 to break the tablet substantially centrally, i.e. into halves. Accordingly the nature of the division can be selected simply and conveniently by the user, depending upon which face of the tablet is pressed against a support surface.

Furthermore, the tablet can be fully fragmented by the user single-handedly. This may be of great value to the disabled and especially those who are arthritic. The tablet of the present invention may be of particular benefit in delivery of NSAIDS to patients with arthritis, for example.

Although the preferred forms of the tablet are adapted to fragment into three or four pieces and having two or three concavities, the pattern may further be extended to include one or more further concavities with or without scorelines within the limits of tabletting technology to provide further fragmenting options.

Referring now to Figures 5 to 7, these demonstrate example preferred dimensions and angles for the second embodiment of tablet. This, as will be seen, has a length of the order of 25.1 mm and "depth" dimension of the order of 7 mm from apex of "upper" surface 5 to lowest point of "bottom" surface 4. The concavities 6 and 10 each subtend an angle of approximately 118° and the concavity 8 subtends an angle of approximately 131° and all concavities have a score line 7, 9 that is formed as a furrow with a cross-sectional radius of approximately 0.3 mm and an angle of approximately 40° between the walls, 30, 40 of the furrow 7, 9. However as can be further seen in Figure 5, although the furrow 9 of the upper surface 5 is substantially symmetrical in cross section, the furrows 7 of the bottom surface 4 have an asymmetrical cross section with the walls 30 of the furrows nearest the ends of the tablet being more inclined and thereby deeper than those walls 40 of the furrows nearest the center of the tablet. This asymmetry of the furrows 7 of the bottom surface 4 that define the end fragments of the tablet is a measure to assist breaking whilst ensuring that the fragments formed by breakage of the illustrated shape of tablet are substantially equal in size and, therefore, in dose.

Further notable from Figures 5 to 7 are the 2 mm radii of curvature of the two apices of the upper surface 5 and single central apex of the bottom surface 4; and the 1.5 mm radii of curvature of the upper part of the ends of the tablet and the greater (3 mm) radii of curvature of the lower part of the ends of the tablet, increasing the area of contact of the tablet ends with the support surface against which the tablet is to be pressed to break it.

The curvature of the apices and ends of the tablets improve comfort of handling and swallowing of the tablets. The side edges of the tablets are also beveled for this reason, having a 0.5 mm deep and 30° slanted bevelled periphery.

In practice it has been found, that surprisingly, a tablet of the general shape and size illustrated in Figures 5 to 7 and 8 to 10 is, indeed easy and comfortable to handle and, furthermore, swallow even when undivided. Despite the undulating configuration of the tablet, testing has demonstrated that it is easily ingested. This could perhaps be as a result of the concavities reducing contact with the mucosa of the oesophagus.

Tablets having the general shape and size of the Figure 7 to 9 embodiment were formulated using broadly conventional ingredients including approximately 90% granulated paracetamol and the majority of the balance made up of pre-gelatinised starch and minor amounts of one or more other binding agents, lubricants and/or disintegrants, substantially in accordance with conventional tablet formulation practice.

The formulation was compressed into the required tablet form by a punch having an undulating working surface profile corresponding to the generally M-shaped profile of the tablet. The use of an undulating profiled punch to form the tablets proved, unexpectedly, to be the most efficient and effective way to form the tablets as against, for example, pressing the tablets laterally. A punch profile of the general type is illustrated in Figure 11.

In practice, punching forces of the order of 6.5 kN proved useful. The punch design is, however, capable of applying forces of substantially greater than this - forces greater than 20 kN being easily achievable. Tabletting rates in excess of 1000 tablets per minute were easily achieved and with the tablets being accurately formed and accurately and easily divisible into two or four substantially equal parts while having sufficient integrity not to break accidentally with normal handling.

Referring to Figures 8, 9 and 10, these illustrate a further embodiment of the invention which is which is similar to that of Figures 5 to 7 but differs in having score lines 17 provided at the apices of the tablet corresponding to the concavities 6, 8, 10 of the other surface of the tablet. These additional score lines 17 provided at the apices further improve the ease and accuracy of division of the tablets.

To aid the user in identification of the respective sub dosage units the dosage amount of each unit is suitably marked on the respective subunits. The tablet may be coated in a suitable coating, eg cellulose-based, to be marked by ink jet printing or may be embossed, for example.

Claims

1. A divisible tablet of the type having readily severable sections which may be divided accurately and separated into multi-sectional sub units, the tablet comprising a unitary tablet body having a bottom surface, i.e. suitably initially downwardly facing, in use, with at least a first concavity therein, wherein the tablet further has a second concavity in its upper surface, i.e the initially upwardly facing, in use, surface, at a location that is longitudinally displaced relative to the first and any further concavities of the bottom surface whereby a compressive force applied to the tablet on the upper surface over the first concavity enables division of the tablet at the first concavity and a compressive force applied to the tablet on the bottom surface over the second concavity enables division of the tablet at the second concavity.

2. A divisible tablet as claimed in claim 1 , wherein a breakage score line is provided on the tablet at each of the concavities.

3. A divisible tablet as claimed in claim 2 wherein the scoreline extends laterally across the width of the tablet.

4. A divisible tablet as claimed in claim 2 or 3 wherein a score line is provided at each apex of the tablet and extending substantially parallel to the score line of the corresponding concavity.

5. A divisible tablet as claimed in any preceding claim, wherein each part of the tablet that forms a sub unit is marked with its dosage, weight or other indentifier.

6. A divisible tablet as claimed in any preceding claim, wherein the tablet has two or more concavities on its bottom surface.

7. A divisible tablet as claimed in claim 6 wherein the tablet has a concavity on its upper surface corresponding to a region intermediate the concavities of the bottom surface.

8. A divisible tablet as claimed in claim 7 wherein the tablet has two concavities on its bottom surface, one on its upper surface corresponding to a region intermediate the concavities of the bottom surface and thereby defines a generally M-shaped profile when viewed from the side.

9. A divisible tablet as claimed in any preceding claim, wherein the concavities are angular and the angles of the concavities are obtuse, whereby when the tablet has the form with a generally M-shaped profile this is a flattened M-shape.

10. A divisible tablet as claimed in claim 9, wherein where there is a concavity in the upper surface intermediate the concavities of the bottom surface, the concavity of the upper surface has a greater obtuse angle than the concavities of the bottom surface.

11. A divisible tablet as claimed in any preceding claim, wherein the tablet is of the order of 20 to 30 mm long and of the order of 5 to 10 mm wide.

12. A divisible tablet as claimed in claim 2, wherein the or each score line comprises a furrow and the furrow of each score line that defines an end fragment of the tablet is formed asymmetrically having a greater slant of one side wall of the furrow relative to the other.

13 A divisible tablet as claimed in claim 2, wherein the or each score line comprises a channel that has side walls that are less than one millimeter apart.

14. A divisible tablet as claimed in claim 2 wherein the or each score line comprises a channel that has sidewalls that converge toward the floor of the channel.

15. A divisible tablet as claimed in claim 2, wherein the or each score line comprises a furrow and the furrow has a curved floor with a radius of curvature that is less than 0.5 mm and preferably is of the order of 0.25 to 0.3 mm.

16. A divisible tablet as claimed in any preceding claim, wherein to assist purchase of the tablet against the support surface for fragmentation, the ends of the tablet are relatively flattened on the bottom surface.

17. A divisible tablet as claimed in any preceding claim wherein the tablet has apices corresponding to the concavities and, the apices are each rounded.

18. A divisible tablet as claimed in any preceding claim wherein the side edges of the tablet are bevelled or rounded.

19. A divisible tablet substantially as hereinbefore described with reference to any suitable combination of the accompanying drawings.

20 A method of forming a tablet of any of claims 1 to 19, wherein the tablet is press formed using a punch that has an undulating profile with one or more concavities and apices to define the undulating profile of the tablet.

21. A punch for use in the method of forming a tablet of claim 20 and which has an undulating working profile with one or more concavities and apices to define the undulating profile of the tablet.