EP1140479B1 - Appareil et procede de fabrication d'articles moules - Google Patents

Appareil et procede de fabrication d'articles moules Download PDF

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Publication number
EP1140479B1
EP1140479B1 EP99972151A EP99972151A EP1140479B1 EP 1140479 B1 EP1140479 B1 EP 1140479B1 EP 99972151 A EP99972151 A EP 99972151A EP 99972151 A EP99972151 A EP 99972151A EP 1140479 B1 EP1140479 B1 EP 1140479B1
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EP
European Patent Office
Prior art keywords
zirconia
shaped member
moulded
die
part according
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
EP99972151A
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German (de)
English (en)
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EP1140479A1 (fr
Inventor
Ronald Stevens
Michael Tobyn
John Nicholas Staniforth
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University of Bath
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University of Bath
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Priority claimed from GBGB9825309.9A external-priority patent/GB9825309D0/en
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Publication of EP1140479A1 publication Critical patent/EP1140479A1/fr
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Publication of EP1140479B1 publication Critical patent/EP1140479B1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B30—PRESSES
    • B30B—PRESSES IN GENERAL
    • B30B15/00—Details of, or accessories for, presses; Auxiliary measures in connection with pressing
    • B30B15/0005—Details of, or accessories for, presses; Auxiliary measures in connection with pressing for briquetting presses
    • B30B15/0011—Details of, or accessories for, presses; Auxiliary measures in connection with pressing for briquetting presses lubricating means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B30—PRESSES
    • B30B—PRESSES IN GENERAL
    • B30B11/00—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses
    • B30B11/02—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses using a ram exerting pressure on the material in a moulding space
    • B30B11/08—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses using a ram exerting pressure on the material in a moulding space co-operating with moulds carried by a turntable
    • 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

Definitions

  • the invention relates to the manufacture of moulded products, especially tablets and powder plugs for encapsulation, for example, produced by the compression of particulate material, for example, powders and granules.
  • tablette includes pharmaceutical tablets, vitamin and/or mineral tablets and confectionery.
  • Pharmaceutical tablets are usually prepared by the instantaneous compression of a powder, comprising the active ingredient and an excipient, between two punches in a die.
  • the force for compression may be supplied by either the upper punch or by both the upper and lower punches, but in neither case does all of the applied force go into compressing the powder. Although some of the force is lost in heat and sound energy a major proportion is absorbed in overcoming die wall friction. These frictional forces are sometimes so great as to prevent tablet compression altogether, and in other cases the appearance of the tablets is unacceptable; for example the tablets may be chipped, capped or laminated rendering them unsuitable for further processing.
  • a lubricant especially magnesium stearate
  • magnesium stearate lubricant has, however, given rise to a number of problems, especially in the production of pharmaceutical tablets but also for other moulded products.
  • the principal problems are
  • the punches and the dies of the moulding devices previously used for the manufacture of tablets are typically formed of steel. Because of the repeated reciprocation of the punches within their associated die, on the repeated compression of the material to be formed into tablets, both the punches and the die are subjected to a high degree of wear. In practice, a hardened steel has been used for the manufacture of the punches and dies. Even with such hardened steel materials, lubricated in the manner described above, the severe abrasion to which the parts are subjected in use results in wear, and may result in the shedding of small amounts of the metal into the substrate. The presence of that material in the resulting tablets, albeit being substantially non-toxic in the amounts obtaining in normal practice, is undesirable.
  • Powder plugs for incorporation into hard gelatin capsules may be made using a dosator.
  • Dosators of the type conventionally used to make such plugs include a cylindrical casing ("dosage tube"), defining a cylindrical bore in which is located a piston ("dosage punch").
  • the dosage tube is lowered downwardly into a hopper containing the powder to be compressed by means of relative vertical movement of the hopper and the dosage tube the dosage punch lightly compressing the powder to form a plug which remains within a lower portion of the dosage tube when that is lifted out of the surrounding powder, and can subsequently be ejected from the tube into an open capsule body by operation of the dosage punch.
  • DE 298 078 40U describes a part for use in a tablet-moulding apparatus, the part having an adhesion-reducing coating.
  • EP 0 841 153A describes a part for a tablet-moulding apparatus with an adhesion-reducing coating which may comprise zirconia.
  • EP 0 883 389A describes tablets for use in bacterial sensitivity testing, the tablets comprising an oxide of one or more of the metals titanium, zirconium, hafnium, thorium and cerium and an antibiotic or chemotherapeutic agent.
  • the invention provides a part for use in a moulding apparatus, the part comprising a shaped member consisting of stabilised zirconia.
  • Zirconia has been found to have particularly suitable properties for use in those parts in tabletting machines that will be in contact with the material to be moulded. It is a very hard material, and thus resistant to abrasion. The use of zirconia offers significant advantages in terms of wear resistance, and thus in terms of the length of the useful life of the parts. Zirconia is substantially non-toxic when ingested in small quantities so that, should any abraded material from the shaped part enter the moulded tablet, that will not detrimentally affect the acceptability of the tablets, whether for pharmaceutical or other use.
  • zirconia offers a low coefficient of friction in the context of moulding. It is thought that this unexpectedly low coefficient of friction is accounted for by the fact that the surface of the zirconia attracts a monolayer of water molecules, which acts as a lubricant during the manufacturing process. The present inventors have thus found that zirconia has an advantageous spectrum of properties which, in combination, make it especially effective in the moulding of tablets.
  • zirconia in the devices for use in the manufacture of lightly compressed plugs for incorporation in capsules will offer similar advantages.
  • the part is a punch.
  • the shaped member may constitute the whole punch. If preferred, however, the shaped member may constitute a component of the punch, the punch comprising at least one further component, which may be of zirconia or of any other suitable material, for example steel. In that case, it will be appreciated that at least that portion of the surface of the punch that in use contacts the material to be moulded will be constituted by the shaped member consisting of stabilised zirconia.
  • the shaped member consisting of stabilised zirconia may include a surface having at least one protrusion arranged to form, in use, a corresponding recess or recesses in an article moulded using the part.
  • the shaped member consisting of stabilised zirconia may include a surface having at least one recessed region arranged to form, in use, a corresponding embossed region or regions on an article moulded using the part. Said at least one protrusion or at least one recessed region may be in the form of one or more letters of the alphabet.
  • a punch according to the invention enables there to be formed embossed region(s) and/or recess(es) on the surface of the moulded article, for example, tablet, in reproducible fashion, even after many thousands of moulding cycles.
  • the shaped member consisting of stabilised zirconia may be configured and dimensioned to impart to an article to be moulded a feature or features of configuration that is or are substantially invisible to the naked eye.
  • the shaped member consisting of stabilised zirconia may be configured to impart to an article to be moulded a feature of configuration which is suitable for distinguishing the article from a counterfeited article.
  • a unique pattern which may for example be in the form of a letter or letters of the alphabet identifying the manufacturer or constituting a trade mark associated with the articles, in the form of braille letters enabling blind consumers reliably to distinguish the articles from other similar articles, or in the form of a distinctively shaped design, such as a logo.
  • Incorporation of such a unique pattern may have a number of advantages from the point of view of distinguishing the articles from other articles of similar type, but may especially be useful in enabling genuine articles to be distinguished from counterfeit articles.
  • the punches of the invention may have a recessed region for generating a complementary embossed region on a moulded article. It has not been possible using the previously known punches to generate such embossed regions satisfactorily and reproducibly on certain types of moulded article, especially tablets. Further, in the case of impressed patterns formed in the tablet surface, such patterns may be deeper than those generally formed in the use of the previously known punches. That is because of the reduced adhesion in the case of the surface of the shaped member, which reduces the tendency of the upper portion of the tablet to be removed when impressing such patterns.
  • lubricant in use of the shaped members of the invention, it is possible to use a relatively small amount of lubricant in the moulding process, or even to use no added lubricant. It may also in appropriate formulations be acceptable to reduce or even eliminate the amounts of flow aid and/or anti-adherent additives required.
  • the part is a die.
  • the shaped member may constitute the entire die. It may be preferred, however, for the die to comprise at least one further component (which may be of zirconia or may be of any other suitable material, for example, steel) as well as the shaped member consisting of stabilised zirconia. In that case, at least that portion of the die that in use contacts the material to be moulded will be constituted by the shaped member consisting of stabilised zirconia.
  • the shaped member may be a liner for the interior of the die.
  • the invention further provides a tabletting machine, which comprises a moulding apparatus according to claim 19, in which the shaped member is a cylindrical tube.
  • the shaped member consists essentially of zirconia.
  • the shaped member advantageously contains at least 90%, preferably 95%, and more preferably 97%, by weight, based on the total weight of the member, of zirconia.
  • One or more suitable compounds selected from yttria and other metal oxides may advantageously be present in small amounts, for example, up to 10%, preferably up to 5% by weight based on the total weight of the member to stabilise the lattice structure of the zirconia.
  • the shaped member may be of zirconia and another suitable material.
  • it may be of a blend comprising zirconia and alumina. In that case, the shaped member may comprise, for example, from 5 to 20% by weight zirconia in admixture with alumina.
  • the tabletting machine comprises at least one pair of punches and a die which are each so configured that they cooperate to form, in use, a moulded article having a plurality of edges and corners.
  • Tabletting machines comprising punches and dies consisting wholly or in part of zirconia as described above offer particular advantages in the manufacture of embossed tablets.
  • the use of zirconia parts of suitable configuration will also facilitate the manufacture of tablets of given desired configurations, and may be especially advantageous in the manufacture of tablets having more than the usual number of edges or of unusual shapes, enabling a wider range of tablet shapes to be generated satisfactorily.
  • the tabletting machine is a rotary press.
  • a multiplicity of pairs of punches operate sequentially and the pressing cycle is initiated by a cam mechanism which acts on a portion of each punch (that portion being referred to below as a "cam follower").
  • cam follower it may be advantageous for the cam follower to comprise zirconia, rendering the cam follower more resistant to wear. It may also be advantageous for the cam to comprise zirconia.
  • a moulding apparatus comprising a said shaped member may be suitable for use in the manufacture of powder plugs for encapsulation in gelatin capsules, for example, it may be a device of the type known as a dosator.
  • the shaped member advantageously constitutes the dosage tube of the dosator. It may be preferred, however, for merely the tip of the dosage tube, in particular the portion that in normal use comes into contact with the composition to be compressed, to consist of stabilised zirconia.
  • the invention provides a method of making a moulded article, which is administrable to a human or animal, especially an ingestible article, comprising introducing a zirconium-containing compound into a mould with the material to be moulded, the zirconium-containing compound being present in an amount of 0.05 to 20% by weight.
  • the lubricating properties of the zirconium-containing compound may render the use of other lubricating materials unnecessary (although the presence of such other lubricants is not excluded, if desired).
  • zirconium-containing compounds especially zirconia
  • a lubricating ingredient offers advantages over conventional lubricants, such as magnesium stearate, in particular in that it has a lesser effect on the solubility characteristics of the other ingredients of the moulded article.
  • the zirconium-containing compound should be a physiologically tolerable compound.
  • the zirconium-containing compound may be introduced into the mould in admixture with the material to be moulded. As well, or instead, the zirconium-containing compound may be introduced into the mould in advance of the material to be moulded.
  • the zirconium-containing compound may be zirconia, but is preferably zirconium hydroxide or a physiologically tolerable zirconium salt.
  • Zirconium-containing compounds for use in the manufacture of moulded articles according to the invention will advantageously be in the form of powders, of which the maximum particle size is not more than 10 ⁇ m.
  • Zirconia powder for use in the manufacture of the moulded articles may be made by calcination of finely divided zirconia.
  • the moulded article is a tablet.
  • the moulded article is a pharmaceutical tablet.
  • the invention further includes a tablet comprising a zirconium-containing compound in an amount of from 0.05 to 20% by weight, based on the total weight of the tablet.
  • moulded articles administrable to a human or animal that may be made by the said method include powder plugs for encapsulation in gelatin capsules.
  • the invention thus further provides for the manufacture of hard gelatin capsules including an encapsulated composition comprising a zirconium-containing compound.
  • the zirconium-containing compound to be incorporated in the moulded article may be in the form of a gel or of small particle size particulates, which may be obtained for example by means of spray drying, lyophilisation or size reduction from larger particles.
  • the zirconium-containing compound is incorporated in mixtures of drugs or drug formulations in amounts of 0.05% to 20%, and preferably not more than 10%, more preferably not more than 5%, by weight based on the total weight of the combined components.
  • the presence of the zirconium-containing compound may improve the flow, adherence and lubrication properties of such mixtures.
  • the zirconium-containing compounds may be used in combination with, or as alternatives to, materials currently used for flow improvement, adherence or lubrication.
  • the rotary press shown in the drawing is entirely conventional, except for the punches and dies which, as described further below, are in accordance with the invention.
  • the rotary press may, for example, be a rotary press of the Type RB3 (trade mark) manufactured by Manesty Machines Ltd.
  • the press has a circular die table 1 mounted for rotation about its central axis.
  • a plurality of dies 2 are located in the table 1.
  • Above and aligned with each die 2 is an associated upper punch 3 mounted for sliding movement into and away from the die in an upper punch holder 4 which, in turn, is arranged for rotation with the die table 1.
  • each die 2 below and aligned with each die 2 is an associated lower punch 5 mounted for sliding movement into and away from the die in a lower punch holder 6 which, in turn, is arranged for rotation with the die table 1.
  • Each of the upper punches 3 has a cam follower 7 at its upper end and similarly each of the lower punches 5 has a cam follower 8 at its lower end.
  • the cam followers 7 rest on a stationary fixed upper cam track 9 while the cam followers 8 rest on a stationary fixed lower cam track 10.
  • the die table 1, dies 2, punches 3, 5 and punch holders 4, 6 are made of metal.
  • the lower cam track 10 is interrupted at one position by a ramp 11 the height of which can be screw-adjusted and at another position by the head of an ejection knob 12 which is also screw-adjustable.
  • a pair of compression rolls 13 are also associated with the upper and lower cam tracks 10 and 11.
  • the press has a main hopper 14 for feeding the powder or granules to be tabletted.
  • this powder would include lubricant particles but in the described apparatus that may not be necessary (although it is not excluded).
  • the hopper 14 has an outlet leading to a stationary feed frame or a force feeder with moving paddles 15 immediately about the die table 1.
  • the base of the frame 15 lies immediately adjacent to the top of the die table 1 and has apertures which allow powder or granules to pass from the compartment into the dies 2.
  • a stationary blade 16 is provided for scraping excess powder or granules away from the dies 2.
  • a given die 2 having an associated lower punch 5 and upper punch 3 moves to a position underneath the feed frame 15 where the die is filled with powder.
  • the cam follower 8 is caused to move down by the downwardly sloping cam track 10 so that the lower punch 5 only just projects into the die and the die is therefore almost entirely filled with powder.
  • the cam follower 8 subsequently reaches the ramp 11 and is driven upwardly thereby expelling powder.
  • the cam follower 8 subsequently reaches the ramp 11 and is driven upwardly thereby expelling powder from the die. While the cam follower 8 is on the top of the ramp 11 the blade 16 scrapes away excess powder from above the die.
  • a punch 3 suitable for use in the machine of Fig. 1 may have a steel body 17, to which is fixedly attached a tip 18, which is of zirconia. If desired, the end portion of the punch opposed to the tip 17 (which opposed end portion includes at least the cam follower surface 7) may also be of zirconia, although such a construction is not illustrated in Fig. 2. The punch 3 may, instead, be wholly of zirconia, and may then be monolithic.
  • a die 2 suitable for use in the machine may have an outer casing 19 of steel and a lining 20 of zirconia defining a cylindrical bore 21.
  • the die may, however, be wholly of zirconia and may then be monolithic.
  • the punch tip diameter and the die internal diameter may each be 10 mm.
  • a die or punch or a shaped die lining or punch tip according to the invention may be of stabilised zirconia which may be manufactured from a tetragonal zirconia powder which may contain for example 3mol% yttria in solid solution, the presence of yttria contributing to the stability of the tetragonal phase.
  • yttria or instead, other additives, for example one or more other oxides, may be used to stabilise the zirconia product.
  • the powder, including any additives may then be pressed into shape by any suitable technique, for example, die pressing or hydrostatic pressing or both of those techniques used sequentially. Other methods such as slip casting may be used.
  • the green body (that is, the shaped powder compact) may then be sintered, for example, by heating in a furnace under a controlled heating cycle to a maximum temperature between 1300°C and 1600°C, preferably in the range 1400°C to 1500°C, and maintaining this temperature for 2 to 12 hours. The temperature may then be lowered slowly co room temperature.
  • the shaped member so obtained may then be machined to the precise final configuration and dimensions required, to give a close fit between the cooperating punch and die, for example, using diamond grinding techniques. It is in particular desirable to ensure that sharp edges are removed by imparting in their place a small radius of curvature as the presence of sharp edges would lead to regions of stress concentration in use.
  • the desired pattern may be generated on the punch tip by any suitable method, for example, by machining the tip using suitable diamond tooling, or by appropriate modification of the method of manufacture of the tip.
  • the pattern may be introduced during manufacture by green machining the pattern onto the tip surface to a calculated shape and size and subsequently sintering (the densification on sintering causing shrinkage of dimensions with the pattern being essentially retained), or by impressing the pattern, to a calculated shape and size, into the powder compact and sintering to full density. It will be appreciated that, in each case, when calculating the appropriate shape and size, allowance will have to be made for the shrinkage that will occur on sintering.
  • the patterns so produced are of relatively high definition.
  • the liner in the form of a thin walled cylinder is, after sintering, diamond machined such that its diameter is slightly larger than the internal diameter of the outer die casing.
  • the casing which may be of, for example, tooled steel, may be heated to expand its internal diameter and the zirconia insert may then be inserted and the casing shrink fitted onto the liner, imposing compressive stresses on the liner, both holding it in place and strengthening it.
  • the inner diameter of the lining may then be diamond honed to give it the desired final dimensions.
  • the tip may be held in place by any suitable means, for example, mechanical means, any suitable adhesive or metallic braze, or a suitable combination of one or more of those means.
  • suitable mechanical means may include the provision of cooperating means on the tip and the punch body, for example, means permitting an interlocking fit or a screw fit.
  • Suitable adhesives are preferably organic-based adhesives. Because the stresses on the tip are mainly compressive in nature, it is in general unnecessary to take any special measures to ensure that the affixment of the tip to the remainder of the punch is of very high strength.
  • Fig. 4 is a graph of the ejection force required to eject from a die a compressed portion of microcrystalline cellulose powder against the compaction force previously applied to the compressed portion to be ejected.
  • the powder did not contain any conventional lubricant additives.
  • the upper line represents measurements made using as the die a steel die
  • the lower line represents measurements made using as the die a zirconia die according to the invention.
  • the lower opening of the die is closed by a lower punch, arranged to be stationary, and the material is compacted by an upper, vertically movable punch.
  • the upper and lower punches are, in each case, of the same material as the die, that is, of steel or zirconia, respectively.
  • Fig. 4 is a graph of the ejection force required to eject from a die a compressed portion of microcrystalline cellulose powder against the compaction force previously applied to the compressed portion to be ejected.
  • the powder did not contain any conventional lubricant additives.
  • the ejection force required in the case of the steel die is significantly greater than in the case of the zirconia die.
  • the measurements were obtained by compressing a portion of the microcrystalline cellulose in the die by advancing the upper punch downwardly at a speed of 10 mm per minute until the desired compaction force is reached and thereafter inverting the die together with the compressed portion contained therein and advancing the punch downwardly onto the compressed portion and determining the ejection force required to eject it.
  • the compaction force and ejection force were measured using an Instron tensile testing machine, having a load cell arranged to measure the force transmitted through the punch.
  • the compaction force and the ejection force are the peak force, determined in each case by the load cell, during compaction and ejection, respectively.
  • Fig. 5 is a corresponding graph of the ejection force against compaction force for compressed portions of silicified microcrystalline cellulose, without added lubricant and Fig. 6 is an analogous graph for compressed portions of lactose containing 1% by weight magnesium stearate as added lubricant.
  • the upper line represents measurements made using as the die a steel die
  • the lower line represents measurements made using as the die a zirconia die according to the invention
  • the relative positions of the lines show that the ejection force required in the case of the steel die is significantly greater than in the case of the zirconia die.
  • diluents selected from microcrystalline cellulose, silicified microcrystalline cellulose and lactose, and Figs. 4 to 6 demonstrate the benefit of the advantageous frictional behaviour of zirconia in the manufacture of tablets. In the presence of added lubricant, the superior performance of zirconia will still be observable, at a given lubricant content.
  • Figs. 7a to 7e are graphs showing the relationship between ejection force and ejection time for a microcrystalline cellulose tablet, incorporating 0.5 wt % magnesium stearate as added lubricant, the tablet having previously been compacted in the compaction simulator.
  • Compaction of the tablets was accomplished using a sawtooth profile compaction cycle, with a punch tip velocity of 100mm per second, at a selected compaction force. (Punch tip velocity in the compaction simulator may be determined using a linear variable displacement transducer.)
  • Fig. 7a relates to tablets previously compacted at compaction force 2kN
  • Fig. 7b to tablets compacted at 4kN
  • Fig. 7c to tablets compacted at 8kN
  • Fig. 7d to tablets compacted at 12kN
  • Fig. 7e to tablets compacted at 16kN.
  • each curve represents the averaged results for at least five tablets.
  • the area under each curve represents the work needed to overcome die wall friction during ejection, and it will be seen that, in each of Figs. 7a to 7e, the area under the curve representing tablets ejected from zirconia tools is less than that under the curve representing tablets ejected from steel tools, indicating a significant reduction in ejection forces.
  • Microcrystalline cellulose used in the above methods was of the type known as EMCOCEL 90M, obtainable from Mendell UK Ltd. Where magnesium stearate was used as an additive, it was incorporated in the powder before compaction by mixing for five minutes in a Turbula mixer at slow speed. All powders were stored before use for at least one day in the desiccator at room temperature and relative humidity 44%. Where used, the compaction simulator was fitted with 10mm diameter flat-faced round F-tooling manufactured from zirconia or steel. The compaction speed used was 100mm/sec corresponding to the main compaction time of 0.345 seconds. A single saw-tooth control profile was chosen to provide the main compaction pressures. The die was filled manually, sufficient powder being used to produce a tablet thickness of about 2.5mm at zero porosity. During tableting, relative humidity was within the range of 35 to 45% and temperature within the range 20 to 25°C.
  • the punches and dies used in the Instron tester and in the compaction simulator were all of type suitable for use in the press of Fig. 1.
  • Shaped members comprising zirconia according to the invention have also been found to exhibit excellent wear resistance, and have high strength, high fracture toughness and high hardness.
  • Other properties of zirconia which it is thought may contribute to its excellent performance in the manufacture of tablets are its anti-static properties, non-magnetic nature, low thermal conductivity and good corrosion resistance.
  • a consequence of the advantageous combination of properties is that the amounts of material shed into the tablet formulation are likely to be considerably reduced as compared with the steel parts conventionally used, and may be substantially eliminated.
  • the tablets manufactured using zirconia members according to the invention may, moreover, be of improved strength.
  • a part comprising a shaped member comprising zirconia in a device for moulding powder plugs for subsequent encapsulation.
  • the forces to which the part will be subjected in use will be lower than in a tabletting machine.
  • a moulding device of the type known as a dosator it may be appropriate to use a single walled cylindrical tube of zirconia, for example of wall thickness 1mm, as the dosage tube itself or as the tip portion of the dosage tube.
  • the zirconia in the form of particles of diameter less than 10 ⁇ m and obtainable by calcination of the fine oxide, are mixed with the other ingredients by tumbling for 5 minutes and the particulate mixture is introduced into a hopper of a rotary press such as that shown in Fig. 1 and pressed therein to produce 160 mg tablets without the use of conventional lubricants such as magnesium stearate.
  • determination of particle size may be carried out by any method suitable having regard to the material and particle size, for example, by low angle laser light scattering using an apparatus such as the Malvern Mastersizer X (trade mark).
  • zirconia in the above formulations (or in any other formulation according to the invention) any zirconium-containing compound that is pharmaceutically acceptable.

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  • Engineering & Computer Science (AREA)
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  • Medicinal Preparation (AREA)
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Claims (29)

  1. Pièce devant être utilisée dans un appareil de moulage, la pièce comprenant un élément formé réalisé en zircone stabilisée.
  2. Pièce selon la revendication 1, qui est un poinçon.
  3. Pièce selon la revendication 2, dans laquelle l'élément formé constitue le poinçon complet
  4. Pièce selon la revendication 2, dans laquelle l'élément formé constitue une partie du poinçon, le poinçon comprenant au moins une autre partie.
  5. Pièce selon la revendication 4, dans laquelle ladite ou lesdites autres parties sont en zircone ou autre matériau approprié.
  6. Pièce selon la revendication 5, dans laquelle ladite ou lesdites parties de la surface du poinçon qui, en utilisation, contactent le matériau à mouler sont constituées de l'élément formé réalisé en zircone stabilisée.
  7. Pièce selon l'une quelconque des revendications 2 à 6, dans laquelle l'élément formé réalisé en zircone stabilisée comporte une surface ayant au moins une saillie agencée pour former, en utilisation, un ou plusieurs creux dans un article moulé utilisant la pièce.
  8. Pièce selon l'une quelconque des revendications 2 à 7, dans laquelle l'élément formé réalisé en zircone stabilisée comporte une surface ayant au moins une zone en creux agencée pour former, en utilisation, une ou plusieurs zones en saillie correspondantes sur un article moulé utilisant la pièce.
  9. Pièce selon la revendication 7 ou 8, dans laquelle ladite ou lesdites saillies ou ladite ou lesdites zones en creux ont la forme d'une ou plusieurs lettres de l'alphabet
  10. Pièce selon l'une quelconque des revendications 2 à 9, dans laquelle l'élément formé réalisé en zircone est configuré et dimensionné pour conférer à un article à mouler une ou plusieurs caractéristiques de configuration essentiellement invisibles à l'oeil nu.
  11. Pièce selon l'une quelconque des revendications 2 à 10, dans laquelle l'élément formé réalisé en zircone stabilisée est configuré pour conférer à un article à mouler une caractéristique de configuration qui permet de distinguer l'article d'un article contrefait.
  12. Pièce selon la revendication 1, qui est une matrice.
  13. Pièce selon la revendication 12, dans laquelle l'élément formé constitue la matrice entière.
  14. Pièce selon la revendication 13, dans laquelle l'élément formé constitue une partie de la matrice, la matrice comprenant au moins une autre partie.
  15. Pièce selon la revendication 14, dans laquelle ladite ou lesdites autres parties peuvent être en zircone ou autre matériau approprié.
  16. Pièce selon la revendication 14 ou la revendication 15, dans laquelle l'élément formé est une doublure pour l'intérieur de la matrice.
  17. Pièce devant être utilisée dans un appareil de moulage, la pièce comprenant un élément formé constitué d'alumine et de 5 à 20% en poids de zircone stabilisée.
  18. Appareil de moulage comprenant au moins une pièce selon l'une quelconque des revendications 1 à 17.
  19. Appareil de moulage selon la revendication 18, qui convient à l'utilisation dans la fabrication des obturateurs de poudre pour l'encapsulation dans des capsules de gélatine.
  20. Appareil de moulage selon la revendication 19, dans lequel l'élément formé est un tube cylindrique.
  21. Machine à fabriquer les comprimés qui comprend au moins un poinçon comprenant un élément formé réalisé essentiellement en zircone et/ou au moins une matrice comprenant un élément formé réalisé essentiellement en zircone.
  22. Machine à fabriquer les comprimés selon la revendication 21, qui comprend au moins une paire de poinçons et une matrice qui sont configurés chacun de manière à coopérer pour former, en utilisation, un article moulé ayant une pluralité de bords et d'angles.
  23. Elément constitué de zircone stabilisée, l'élément convenant à l'utilisation dans un appareil pour la fabrication de comprimés.
  24. Procédé de fabrication d'un article moulé, qui peut être administré à un humain ou à un animal, comprenant l'introduction d'un composé contenant du zirconium dans un moule avec le matériau à mouler, le composé contenant du zirconium étant présent à raison de 0,05 à 20% en poids.
  25. Procédé selon la revendication 24, dans lequel la zircone est introduite dans le moule en mélange avec le matériau à mouler.
  26. Procédé selon la revendication 24, dans lequel la zircone est introduite dans le moule avant le matériau à mouler.
  27. Procédé selon l'une quelconque des revendications 24 à 26, dans lequel l'article moulé est un comprimé.
  28. Procédé selon la revendication 27, dans lequel l'article moulé est un comprimé pharmaceutique.
  29. Comprimé pharmaceutique comprenant un composé contenant du zirconium à raison de 0,05 à 20% en poids, sur la base du poids total du comprimé.
EP99972151A 1998-11-18 1999-11-18 Appareil et procede de fabrication d'articles moules Expired - Lifetime EP1140479B1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB9825309 1998-11-18
GBGB9825309.9A GB9825309D0 (en) 1998-11-18 1998-11-18 Improvements in or relating to the manufacture of moulded products
GB9908440 1999-04-13
GBGB9908440.2A GB9908440D0 (en) 1998-11-18 1999-04-13 Improvements in or relating to the manufacture of moulded products
PCT/GB1999/003853 WO2000029205A1 (fr) 1998-11-18 1999-11-18 Appareil et procede de fabrication d'articles moules

Publications (2)

Publication Number Publication Date
EP1140479A1 EP1140479A1 (fr) 2001-10-10
EP1140479B1 true EP1140479B1 (fr) 2003-04-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP99972151A Expired - Lifetime EP1140479B1 (fr) 1998-11-18 1999-11-18 Appareil et procede de fabrication d'articles moules

Country Status (6)

Country Link
EP (1) EP1140479B1 (fr)
JP (1) JP2002529255A (fr)
AT (1) ATE236009T1 (fr)
DE (1) DE69906577D1 (fr)
GB (1) GB2343862A (fr)
WO (1) WO2000029205A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10064639C2 (de) * 2000-12-22 2003-01-30 Henkel Kgaa Tablettenpreßstempel mit Kugelgewindetrieb
DE10064640C2 (de) * 2000-12-22 2003-01-09 Henkel Kgaa Tablettenpreßstempel-Anordnung
JP2009539966A (ja) * 2006-06-13 2009-11-19 セーエスウーエム、サントル、スイス、デレクトロニック、エ、ド、ミクロテクニック、ソシエテ、アノニム 回折性微小構造を有する薬学的錠剤およびそのような錠剤を製造するための圧縮ダイ
CH699631B1 (de) * 2007-01-12 2010-04-15 Suisse Electronique Microtech Realisieren einer diffraktiven Mikrostruktur in eine Pillenoberfläche.
US10363221B2 (en) 2007-10-17 2019-07-30 I-Property Holding Corp. Manufacturing solid pharmaceutical dosage forms with visible micro- and nanostructured surfaces and micro- and nanostructured pharmaceutical dosage form
FR2933897B1 (fr) * 2008-07-18 2011-05-20 Eurotab Dispositif pour former des tablettes par compaction a volume constant
FR2946916B1 (fr) * 2009-06-17 2012-11-16 Eurotab Procede et dispositif de fabrication de produits compactes par compaction lente
EP2607067B1 (fr) * 2011-12-21 2014-06-25 I Holland Limited Poinçon pour une presse à comprimés et son procédé de fabrication
DE102014209661A1 (de) * 2014-05-21 2015-11-26 Bundesdruckerei Gmbh Presswerkzeug und Verwendung einer Keramikfolie als Presswerkzeug sowie Verfahren zur Herstellung einer Keramikfolie

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB883389A (en) * 1959-07-31 1961-11-29 Evans Medical Ltd Improvements in or relating to bacteriological testing
JPS61143552A (ja) * 1984-12-14 1986-07-01 Matsushita Electric Ind Co Ltd 光学ガラス素子のプレス成形用型
JPS61249735A (ja) * 1985-04-30 1986-11-06 Toyo Soda Mfg Co Ltd プラスチック成形用ダイス
GB8530365D0 (en) * 1985-12-10 1986-01-22 Univ Bath Manufacture of moulded products
JP2526869B2 (ja) * 1986-08-07 1996-08-21 東ソー株式会社 打錠機用粉体成形用型
JPH0230663A (ja) * 1988-07-20 1990-02-01 Sumitomo Chem Co Ltd ジルコニア質焼結体およびその製造方法
US5232878A (en) * 1989-06-30 1993-08-03 Hoya Corporation Process for producing inorganic biomaterial
US5308556A (en) * 1993-02-23 1994-05-03 Corning Incorporated Method of making extrusion dies from powders
JPH09174661A (ja) * 1995-12-25 1997-07-08 Tosoh Corp ポリスチレン系樹脂発泡シート製造用ダイス及びポリスチレン系樹脂発泡シートの製造方法
EP0838329A1 (fr) * 1996-10-28 1998-04-29 Eastman Kodak Company Elément de transport de matériaux
DE19646475A1 (de) * 1996-11-11 1998-05-14 Notter Werkzeugbau Gmbh Tablettierwerkzeug mit adhäsionshemmender Beschichtung
DE29807840U1 (de) * 1998-04-30 1998-09-03 Notter GmbH Werkzeugbau, 75248 Ölbronn-Dürrn Tablettierwerkzeug, insbesondere Tablettierstempel oder Tablettiermatritze

Also Published As

Publication number Publication date
GB2343862A (en) 2000-05-24
JP2002529255A (ja) 2002-09-10
DE69906577D1 (de) 2003-05-08
WO2000029205A1 (fr) 2000-05-25
GB9927318D0 (en) 2000-01-12
EP1140479A1 (fr) 2001-10-10
ATE236009T1 (de) 2003-04-15

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