WO2001000176A1 - Comprimes secables - Google Patents

Comprimes secables Download PDF

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Publication number
WO2001000176A1
WO2001000176A1 PCT/GB2000/002438 GB0002438W WO0100176A1 WO 2001000176 A1 WO2001000176 A1 WO 2001000176A1 GB 0002438 W GB0002438 W GB 0002438W WO 0100176 A1 WO0100176 A1 WO 0100176A1
Authority
WO
WIPO (PCT)
Prior art keywords
tablet
divisible
concavity
concavities
score line
Prior art date
Application number
PCT/GB2000/002438
Other languages
English (en)
Inventor
Malcolm Clark
Original Assignee
Eu Pharma Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9914620.1A external-priority patent/GB9914620D0/en
Application filed by Eu Pharma Ltd. filed Critical Eu Pharma Ltd.
Priority to AU55518/00A priority Critical patent/AU5551800A/en
Publication of WO2001000176A1 publication Critical patent/WO2001000176A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B30—PRESSES
    • B30B—PRESSES IN GENERAL
    • B30B15/00—Details of, or accessories for, presses; Auxiliary measures in connection with pressing
    • B30B15/06—Platens or press rams
    • B30B15/065—Press rams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms

Definitions

  • 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.
  • 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.
  • 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.
  • the tablet 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.
  • the fragmentation may be assisted by provision of breakage score lines on the tablet.
  • score lines may most suitably be provided at each of the concavities and most preferably extending laterally across the width of the tablet.
  • a score line is also provided at each apex of the tablet and extending substantially parallel to the score line at each concavity.
  • each part of the tablet that forms a sub unit is marked with its dosage, weight or other indentifier.
  • the tablet has two or more concavities on its bottom surface.
  • 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.
  • the tablet has a concavity on its upper surface corresponding to a region intermediate the concavities of the bottom surface.
  • 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.
  • the concavity of the upper surface suitably has a greater obtuse angle than the concavities of the bottom surface.
  • the tablet is of the order of 20 to 30 mm long and of the order of 5 to
  • 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.
  • 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.
  • 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.
  • the ends of the tablet are suitably relatively flattened on the bottom surface.
  • the apices are each suitably rounded.
  • the side edges of the tablet are, furthermore, preferably bevelled or rounded.
  • 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.
  • 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;
  • Figure 11 is a longitudinal sectional view of the working profile of a punch for forming the tablet of the third preferred embodiment.
  • 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.
  • breakage score line 8 extending laterally across the width of the tablet at the apex 7 of the concavity 6.
  • 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.
  • the tablet may then be further divided by pressing down on the tablet to break the tablet at the additional concavity 8.
  • the concavity 8 of the "upper” surface 5 suitably also has a breakage score line extending transversely across it.
  • 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.
  • 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.V ⁇ .VA fragments.
  • 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.
  • 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.
  • FIGS. 5 to 7 demonstrate example preferred dimensions and angles for the second embodiment of tablet.
  • This 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.
  • 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.
  • Figures 5 to 7 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.
  • 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.
  • 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.
  • FIGs 8, 9 and 10 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.
  • 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.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un comprimé sécable pourvu de sections facilement séparables pouvant être coupées de manière précise, puis séparées en sous-unités à multiples sections. Le comprimé comprend un corps unitaire possédant une surface inférieure, au départ convenablement orientée vers le bas au cours de son utilisation, pourvue d'au moins une première concavité. Le comprimé comprend également une seconde concavité dans sa surface supérieure, c'est-à-dire la surface au départ orientée vers le haut au cours de son utilisation, sur un emplacement longitudinalement déplacé par rapport à la première et à toute autre concavité de la surface inférieure. Une force de compression exercée sur le comprimé, sur la surface supérieure au-dessus de la première concavité, permet ainsi de couper le comprimé au niveau de la première concavité, et une force de compression exercée sur le comprimé, sur la surface inférieure au-dessus de la seconde concavité, permet de couper le comprimé au niveau de la seconde concavité. Ceci permet de procéder à toutes les divisions d'une seule main en appuyant le comprimé contre une surface de support et en renversant le comprimé suite à la(aux) première(s) division(s). Le comprimé peut également être convenablement fragmenté en le pressant entre le pouce et l'index, au niveau des points appropriés sur le comprimé.
PCT/GB2000/002438 1999-06-23 2000-06-22 Comprimes secables WO2001000176A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU55518/00A AU5551800A (en) 1999-06-23 2000-06-22 Divisible tablets

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9914620.1A GB9914620D0 (en) 1999-06-23 1999-06-23 Divisible tablets
GB9914620.1 1999-06-23
GB0010840A GB2351234B (en) 1999-06-23 2000-05-05 Divisible tablets
GB0010840.7 2000-05-05

Publications (1)

Publication Number Publication Date
WO2001000176A1 true WO2001000176A1 (fr) 2001-01-04

Family

ID=26244220

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/002438 WO2001000176A1 (fr) 1999-06-23 2000-06-22 Comprimes secables

Country Status (2)

Country Link
AU (1) AU5551800A (fr)
WO (1) WO2001000176A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2859632A1 (fr) * 2003-09-15 2005-03-18 Arrow Generiques Comprime multisecable a observance amelioree.
WO2006105350A1 (fr) * 2005-03-31 2006-10-05 Advancis Pharmaceutical Corporation Comprime pharmaceutique et appareil et procede de fabrication
WO2007021033A1 (fr) 2005-08-18 2007-02-22 Teijin Pharma Limited Comprime comportant de multiples segments contenant des medicaments

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3336200A (en) * 1963-05-28 1967-08-15 Warner Lambert Pharmaceutical Tablet structure
US4353887A (en) * 1979-08-16 1982-10-12 Ciba-Geigy Corporation Divisible tablet having controlled and delayed release of the active substance
US5061494A (en) * 1990-06-14 1991-10-29 The Upjohn Comany Tri-scored drug tablet
DE19837684A1 (de) * 1998-08-19 2000-02-24 Knoll Ag Exakt teilbare Tablette

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3336200A (en) * 1963-05-28 1967-08-15 Warner Lambert Pharmaceutical Tablet structure
US4353887A (en) * 1979-08-16 1982-10-12 Ciba-Geigy Corporation Divisible tablet having controlled and delayed release of the active substance
US5061494A (en) * 1990-06-14 1991-10-29 The Upjohn Comany Tri-scored drug tablet
DE19837684A1 (de) * 1998-08-19 2000-02-24 Knoll Ag Exakt teilbare Tablette

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2859632A1 (fr) * 2003-09-15 2005-03-18 Arrow Generiques Comprime multisecable a observance amelioree.
WO2006105350A1 (fr) * 2005-03-31 2006-10-05 Advancis Pharmaceutical Corporation Comprime pharmaceutique et appareil et procede de fabrication
WO2007021033A1 (fr) 2005-08-18 2007-02-22 Teijin Pharma Limited Comprime comportant de multiples segments contenant des medicaments

Also Published As

Publication number Publication date
AU5551800A (en) 2001-01-31

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