AU705657B2 - Molding belt calender - Google Patents

Description

MOLDING BELT CALENDER The present invention relates to a machine and a process for producing flat moldings, in particular tablets, from a product composition containing active ingredients.

A known process for producing tablets is melt calendering. A process of this type is described, for example, in DE-A 17 66 546 and US-A 4,880,585. The principle of this process is the embedding of an active ingredient in a melt of a carrier, for example fatty substances or water-soluble, thermoplastic polymers. The melt is produced by the mixture of active ingredient, polymer and, where appropriate, other ancillary substances being melted, for example in an extruder, and being shaped as melt in a downstream molding calender to tablets, which harden by cooling. The molding calender comprises a pair of counter-rotating molding rolls which have on their surface engravings (depressions) which correspond to the shape of one half of the required tablet. The 20 tablet molding takes place in the region of contact of the two rolls by combination of the tablet compositions in the depressions in one roll with those in the opposite depressions in the other roll.

However, this process for producing tablets has disadvantages.

Thus, for example, construction of the rolls is very complicated.

The depressions are cut into the rolls and must in most cases be subsequently polished in order to obtain a tablet surface of maximum smoothness. The production of such rolls is very costly beeoe 30 cause the depressions must be introduced with great precision.

S"This is because the rolls must be adjusted so that two depres- 1I sions are always opposite as accurately as possible. This condition is particularly difficlt to achieve when the depressions are very small.

In addition, such a machine is inflexible because, for example, if it is wished to produce different tablet shapes and/or sizes with the same machine, this is possible only by complete replacement of the rolls and elaborate readjustment. However, great flexibility in respect of different tablet sizes and shapes is required of machines for tablet production, especially in the drugs sector.

From CH-A 530 944 a machine for producing flat moldings is known, having at least one charging means for supplying a product composition, at least one pair of rolls consisting of two counterrotatable calender rolls, where the machine comprises a circulat-

I

ing molding belt, preferably a continuous belt, which passes between the two rolls of a pair of rolls, the molding belt having recesses on its surface to receive the product composition. The known machine is used to produce relatively large moldings.

It is an object of the present invention to indicate a machine for producing flat moldings from a product composition containing an active ingredient which, on the one hand, is less costly than known machines, and, on the other hand, provides greater flexibility. It is also an object of the invention to provide a simple and flexible process for tablet production.

We have found that this object is achieved by a machine for producing flat moldings from a product composition containing an active ingredient, having at least one charging means for supplying the product composition, at least one pair of rolls consisting of two counter-rotatable calender rolls, where the machine comprises a circulating molding belt, preferably as continuous belt, which passes between the two rolls of a pair of rolls, the molding belt 20 having recesses on its surface to receive the product composition characterized in that the recesses are continuous apertures in the moldinq belt.

ooThe rolls are arranged so that they have, between their outer surfaces, a slit-like passage. Moreover, the smallest distance between the outer surfaces of the pair of rolls essentially corresponds to the thickness of the molding belt. The product composition is supplied, preferably as broad product ribbon, parallel to the direction of movement of the molding belt to the trough-like hollow between the two rolls. The molding belt and *product composition are passed further into the increasingly narrow region between the calender rolls, with the product composition being forced into the recesses in the molding belt. The spacing between the rolls moreover essentially determines the pressure exerted on the product composition and thus the thickness of the moldings produced in this way.

The use of a molding belt leads to a considerably greater flexibility in the production of tablets. Different tablet shapes or sizes can now be produced by merely exchanging the molding belt in the machine, while the same pressure rolls can be used for different tablet sizes. The machine can, moreover, be produced at lower cost because the recesses in the molding belt no longer have to be introduced with high precision because only one recess is now necessary per tablet. Elaborate adjustment of components movable in opposite directions is dispensed with.

S OZ 0480/01154 3 In a particularly simple and economical embodiment, the recesses are continuous apertures in the molding belt. In this embodiment, the apertures are preferably produced by punching, it being possible to produce any desired tablet shapes depending on the punching tool used. The product composition forced into the molds during the tablet production comes into contact with both outer surfaces of the pair of calender rolls in this embodiment, so that in this case the tablets which are produced have two flat surfaces.

It is self-evident that the recesses or the apertures in the molding belt are introduced in such a way that the product composition can be converted into the product moldings with minimum loss.

Recesses or apertures which are preferably used are those having a circular, oval or hexagonal shape when viewed from above.

The apertures may also have, for example, bars on their peripheral surface which are produced by corresponding notches in the punch shape, so that tablets with scores can be produced.

The molding belt can consist of any desired material, but preferably of metal, particularly preferably of steel, plastic or rubber. If a molding belt of relatively rigid material is used, the thickness of the belt essentially corresponds to the desired thickness of the tablets. Thicker tablet shapes thus require a thicker belt which can, where appropriate, be in the form of an articulated belt so that it can more easily be passed around the deflecting rollers of the machine. However, it is also possible to use molding belts of flexible material, which can then also be thicker than the desired thickness of the tablets. In this case, the molding belt is, in particular, thicker than the slit between the calender rolls. When fed between the rolls, the molding belt is increasingly compressed so that a different pressure can be exerted on the tablet moldings depending on the distance apart of the calender-rolls.

The calender rolls preferably have smooth outer surfaces. If tablet moldings with an increased surface area are required, however, calender rolls whose surface has a certain roughness are also conceivable, for example.

Temperature-controllable calender rolls are advantageously used.

This is because if a product composition which is plastic at high temperature and becomes solid on cooling is used, it will be preferable to employ cooled calender rolls. On the other hand, M/35193 SOz 0480/01154 4 product compositions which are plastic in the moist state and solid in the dry state are also known, so that in this case heatable calender rolls will preferably be employed. The rolls are accordingly used to cool or to dry the product composition. The product composition is in thermal contact with these rolls for different lengths of time depending on the diameter of the rolls.

The pressure rolls are all-purpose tools which are preferably thermally conducting, stable to compressive force and inert to the substances used. The distance between the rolls can be adjusted to produce different contact pressures.

In a simple embodiment, the machine has only one charging means for the product composition. However, it may also be desired to produce, for example, multilayer tablets so that other embodiments may also have a plurality of charging means which produce a plurality of product ribbons. The product ribbons can be supplied simultaneously to one pair of rolls. However, it is also possible to pass the molding belt through a plurality of pairs of rolls, in which case the different product ribbons are supplied successively in the individual pairs of rolls. The distance between the pairs of rolls in this case will preferably be adjusted so that the contact pressure is lowest for the first pair of rolls and highest for the last pair of rolls. The tablets produced in this way are then multilayer tablets.

However, it is also conceivable to coat tablets with a thin protective film, for example a diffusion-resistant polymer, to achieve a specific release of active ingredient. It is possible to produce protective films which dissolve, and release the active ingredient, only under specific environmental conditions (for example in respect of pH or temperature). The coating can also serve as taste mask or light stabilizer. If the complete tablet is to be coated with a protective film, this will in general be carried out in a separate subsequent step using known coating processes. However, it is also possible according to the invention to feed one or two film webs together with the melt into the roll arrangement in such a way that the melt is located between the two film webs. This results in tablets which are provided on their upper and/or lower side with suitable protective films. The protective films on the upper and lower sides need not be identical. In the case of multilayer tablets the protective films may, for example, lead to a different release of active ingredient.

Extruders and/or heatable filling wedges are the preferred charging means used.

M/35193 OZ 0480/01154 The machine according to the invention can be used to produce tablets or pellet-like moldings continuously. The machine is extremely all-purpose because the basic roll equipment remains unchanged and it is necessary to exchange only the molding belt.

Depending on the molding belt used and the dimensions of the recesses or of the apertures, the range of products which can be produced extends from very small pellet-like products to tablet weights of 1 gram and more. The moldings have edge angles of 900 or less, which facilitates deflashing of the tablets, especially with brittle product compositions. The apertures in the molding belt are preferably spaced apart so that no formation of twinned tablets occurs during production. Subsequent singling of the tablets is therefore unnecessary.

The frictional coupling with a pressure roll drive means that a separate drive of the molding belt is unnecessary. The length of the molding belt can be varied within wide limits. It proves to be particularly advantageous that this makes it possible to extend the residence time of the tablets in the molds as much as required so that ejection of tablets which have not yet cooled (not yet hardened) is avoided.

After leaving the calender roll, removal of the products from the molding belt is possible in a simple manner through deflection of the roller or, where appropriate, through use of a spiked roll.

This particularly applies to the case of molding belts with continuous apertures because in this case the tablets are accessible from the upper and lower sides and can easily be pushed out of the belt.

The flat moldings obtainable with the molding belt calender are particularly suitable for use as tablets. Suitable in this connection are, in particular, IR tablets, that is to say tablets which release the active ingredient rapidly (instant release), SR tablets, ie. tablets with slow release of active ingredient (slow release), delayed action tablets, ie. tablets with delayed release of active ingredient, sublingual tablets whose active ingredients are absorbed through the oral mucosa and which are therefore intended to dissolve "under the tongue", pastilles or soluble tablets.

The tablets which can be produced in this way can be used, of course, in the drugs sector or the food sector (eg. in the form of vitamin tablets), but applications in crop protection and in many industrial sectors are also conceivable.

M/35193 OZ 0480/01154 6 The present invention also relates to a process for producing flat moldings from a product composition containing an active ingredient, where a molding belt provided with recesses is passed between the counter-rotating rolls of a pair of calender rolls, at least one product strand consisting of the composition containing active ingredient is formed, preferably as broad ribbon, this product strand is supplied to the pair of rolls, with the product composition being, when fed between the rolls of the pair of rolls, forced into the recesses, and the moldings being removed from the recesses after passing through the pair of rolls.

The required contact pressure with which the product composition is compressed is fixed beforehand by adjusting the distance of the two rolls apart. The distance apart of the rolls, ie. the smallest distance between their outer surfaces, should preferably not be larger than the thickness of the molding belt used. In the case of a particularly elastic molding belt it is possible for the slit between the rolls to be chosen to be distinctly smaller than the thickness of the belt so that a higher pressure can be exerted on the product composition.

In another embodiment of the process according to the invention, the product ribbon is passed through a plurality of consecutive pairs of rolls. It is also possible to form a plurality of different product strands which are supplied simultaneously to one pair of rolls or successively to a plurality of pairs of rolls.

As a variant of this embodiment, a multilayer melt having the required sequence of layers of the later tablet even in the melt can be produced by coextrusion.

The product composition is plastic when hot or when moist, depending on the required tablet. Depending on the mode of production, the pair of rolls will be either heated or cooled in order to obtain, solid, dimensionally stable tablets.

The tablets are produced from a mixture which contains one or more pharmaceutical active ingredients and one or more conventional ancillary substances and which, owing to melting or softening of at least one component, becomes pasty or viscous and therefore extrudable.

This comprises, in particular, mixtures which contain pharmacologically acceptable polymers (with the glass transition temperature of the mixture being below the decomposition temperature of all the components in the mixture), for example polyvinylpyrrolidone (PVP), copolymers of N-vinylpyrrolidone (NVP) and vinyl acetate, copolymers of vinyl acetate and crotonic acid, partially hydrolyzed polyvinyl acetate, polyvinyl alcohol, ethylene/vinyl M/35193 OZ 0480/01154 7 acetate copolymers, polyhydroxyethyl methacrylate, copolymers of methyl methacrylate and acrylic acid, cellulose esters, cellulose ethers, polyethylene glycol or polyethylene. The K values (according to H. Fikentscher, Cellulose-Chemie 13 (1932), 58-64 and 71 and [sic] 74) of the polymers are in the range from 10 to 100, preferably 12 to 70, in particular 12 to 35, and for PVP preferably 12 to 35, in particular 12 to 17.

The polymeric binder must soften or melt in the complete mixture of all the components in the range from 50 to 180, preferably to 130°C, so that the composition is extrudable. The glass transition temperature of the mixture must therefore be below 180, preferably below 130, If necessary, it is reduced by conventional pharmacologically acceptable plasticizing ancillary substances such as long-chain alcohols, ethylene glycol, propylene glycol, trimethylolpropane, triethylene glycol, butanediols, pentanols, hexanols, polyethylene glycols, silicones, aromatic carboxylic esters (eg. dialkyl phthalates, trimellitic esters, benzoic esters, terephthalic esters) or aliphatic dicarboxylic esters (eg. dialkyl adipates, sebacic esters, azelaic esters, citric and tartaric esters) or fatty acid esters.

Examples of conventional pharmaceutical ancillary substances, whose total amount can be up to 100 of the weight of the polymer, are extenders or bulking agents, such as silicates or diatomaceous earth, magnesium oxide, aluminum oxide, titanium oxide, stearic acid or salts thereof, eg. the magnesium or calcium salt, methylcellulose, sodium carboxymethylcellulose, talc, sucrose, lactose, cereal starch or corn starch, potato flour, polyvinyl alcohol, especially in a concentration of from 0.02 to 50, preferably 0.20 to 20, of the total weight of the mixture are preferred [sic]; lubricants such as aluminum and calcium stearates, talc and silicones, in a concentration of from 0.1 to 5, preferably 0.1 to 3, of the total weight of the mixture are preferred [sic]; dyes, such as azo dyes, organic or inorganic pigments or dyes of natural origin, with inorganic pigments [lacuna] in a concentration of from 0.001 to 10, preferably 0.5 to 3, of the total weight of the mixture; flow aids such as animal or vegetable fats, especially in hydrogenated form and those which are solid at room temperature. These fats preferably have a melting point of 50°C or above. Triglycerides of C 12 C14, C 16 and C 18 fatty acids are preferred. It is also M/35193 oz 0480/01154 8 possible to use waxes such as carnauba wax. These fats and waxes can advantageously be admixed alone or together with mono- and/or diglycerides or phosphatides, especially lecithin. The mono- and diglycerides are preferably derived from the abovementioned fatty acid types. The total amount of fats, waxes, mono- and diglycerides and/or lecithins is from 0.1 to 30, preferably 0.1 to of the total weight of the composition for each layer; stabilizers such as antioxidants, light stabilizers, hydroperoxide destroyers, radical scavengers and stabilizers against microbial attack.

It is furthermore possible to add wetting agents, preservatives, disintegrants, adsorbents, mold release agents and propellants for example, H. Sucker et al., Pharmazeutische Technologie, Thieme-Verlag, Stuttgart 1978).

Ancillary substances also mean for the purpose of the invention substances for producing a solid solution with a pharmaceutical active ingredient. Examples of these ancillary substances are pentaerythritol and pentaerythritol tetracaetate, polymers such as polyethylene and polypropylene oxides and their block copolymers (poloxamers), phosphatides such as lecithin, homo- and copolymers of vinylpyrrolidone, surfactants such as polyoxyethylene 40 stearate, and citric and succinic acids, bile acids, sterols and others as indicated, for example, in J. L. Ford, Pharm. Acta Helv. 61 (1986) 69-88.

Also regarded as pharmaceutical ancillary substances are additions of bases and acids to control the solubility of an active ingredient (see, for example, K. Thoma et al., Pharm. Ind. 51 (1989) 98-101).

The only prerequisite for suitability of ancillary substances is an adequate thermal stability.

Pharmaceutical active ingredients for the purpose of the invention mean all substances with any pharmaceutical effect and minimal side effects as long as they do not decompose under the processing conditions. The amount of active ingredient per dose unit and the concentration may vary within wide limits depending on the efficacy and rate of release. The only condition is that they suffice to achieve the desired effect. Thus, the concentration of active ingredient can be in the range from 0.1 to 95, preferably from 20 to 80, in particular 30 to 70, by weight. It is also possible to employ combinations of active ingredients, eg. ibuprofen/caffeine. Active ingredients for the purpose of the inven- M/35193 OZ 0480/01154 9 tion are also vitamins and minerals, as well as crop treatment agents and insecticides. The vitamins include the vitamins of the A group, of the B group, by which is meant, besides B 1

B

2

B

6 and

B

12 and nicotinic acid and nicotinamide, also compounds with vitamin B properties, such as adenine, choline, pantothenic acid, biotin, adenylic acid, folic acid, orotic acid, pangamic acid, carnitine, p-aminobenzoic acid, myo-inositol and lipoic acid, and vitamin C, vitamins of the D group, E group, F group, H group, I and J group, K group and P group. Active ingredients for the purpose of the invention also include peptide therapeutic agents.

The process according to the invention is suitable for processing the following active ingredients, for example: acebutolol, acetylcysteine, acetylsalicylic acid, acyclovir, albrazolam [sic], alfacalcidol, allantoin, allopurinol, ambroxol, amikacin, amiloride, aminoacetic acid, amiodarone, amitriptyline, amlodipine, amoxicillin, ampicillin, ascorbic acid, aspartame, astemizole, atenolol, beclomethasone, benserazide, benzalkonium hydrochloride, benzocaine, benzoic acid, betamethasone, bezafibrate, biotin, biperiden, bisoprolol, bromazepam, bromhexine, bromocriptine, budesonide, bufexamac, buflomedil, buspirone, caffeine, camphor, captopril, carbamazepine, carbidopa, carboplatin, cefachlor, cefalexin, cefatroxil, cefazolin, cefixime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, celediline [sic], chloramphenicol, chlorhexidine, chlorpheniramine, chlortalidone, choline, cyclosporin, cilastatin, cimetidine, ciprofloxacin, cisapride, cisplatin, clarithromycin, clavulanic acid, clomibramine [sic], clonazepam, clonidine, clotrimazole, codeine, cholestyramine, cromoglycic acid, cyanocobalamin, cyproterone, desogestrel, dexamethasone, dexpanthenol, dextromethorphan, dextropropoxiphen, diazepam, diclofenac, digoxin, dihydrocodeine, dihydroergotamine, dihydroergotoxin, diltiazem, diphenhydramine, dipyridamole, dipyrone, disopyramide, domperidone, dopamine, doxocycline [sic], enalapril, ephedrine, epinephrine, ergocalciferol, ergotamine, erythromycin-, estradiol, ethinylestradiol, etoposide, Eucalyptus Globulus, famotidine, felodipine, fenofibrate, fenoterol, fentanyl, flavine-mononucleotide, fluconazole, flunarizine, fluorouracil, fluoxetine, flurbiprofen, furosemide, gallopamil, gemfibrozil, gentamicin, Ginkgo Biloba, glibenclamide, glipizide, clozapine, Glycyrrhiza glabra, griseofulvin, guaifenesin, haloperidol, heparin, hyaluronic acid, hydrochlorothiazide, hydrocodone, hydrocortisone, hydromorphone, ipratropium hydroxide, ibuprofen, imipenem, indomethacin, iohexol, iopamidol, isosorbide dinitrate, isosorbide mononitrate, isotretinoin, ketotifen, ketoconazole, ketoprofen, ketorolac, labatalon [sic], M/35193 SOZ 0480/01154 lactulose, lecithin, levocarnitine, levodopa, levoglutamide, levonorgestrel, levothyroxine, lidocaine, lipase, lipramine [sic], lisinopril, loperamide, lorazepam, lovastatin, medroxyprogesterone, menthol, methotrexate, methyldopa, methylprednisolone, metoclopramide, metoprolol, miconazole, midazolam, minocycline, minoxidil, misoprostol, morphine, multivitamin mixtures or combinations and mineral salts, N-methylephedrine, naftidrofuryl, naproxen, neomycin, nicardipine, nicergoline, nicotinamide, nicotine, nicotinic acid, nifedipine, nimodipine, nitrazepam, nitrendipine, nizatidine, norethisterone, norfloxacin, norgestrel, nortriptyline, nystatin, ofloxacin, omeprazole, ondansetron, pancreatin, panthenol, pantothenic acid, paracetamol, penicillin G, penicillin V, phenobarbital, phenoxifylline [sic], phenoxymethylpenicillin, phenylephrine, phenylpropanolamine, phenytoin, piroxicam, polymyxin B, povidone-iodine, pravastatin, prazepam, prazosin, prednisolone, prednisone, promocriptine [sic], propafenone, propranolol, proxyphylline, pseudoephedrine, pyridoxine, quinidine, ramipril, ranitidine, reserpine, retinol, riboflavin, rifampicin, rutoside, saccharin, salbutamol, salcatonin, salicylic acid, simvastatin, somatropin, sotalol, spironolactone, sucralfate, sulbactam, sulfamethoxazole, sulfasalazine, sulpiride, tamoxifen, tegafur, teprenone, terazosin, terbutaline, terfenadine, tetracycline, theophylline, thiamine, ticlopidine, timolol, tranexamic acid, tretinoin, triamcinolone acetonide, triamterene, trimethoprim, troxerutin, uracil, valproic acid, vancomycin, verapamil, vitamin E, volinic [sic] acid, zidovudine.

Preferred active ingredients are ibuprofen (as racemate, enantiomer or enriched enantiomer), ketoprofen, flurbiprofen, acetylsalicylic acid, verapamil, paracetamol, nifedipine or captopril.

In a few cases, solid solutions may form. The term "solid solutions" is familiar to the skilled person, for example from the literature cited at the outset. In solid solutions of pharmaceutical active ingredients in polymers, the active ingredient is present in a molecular dispersion in the polymer.

The pharmaceutical mixture is then melted in a conventional way, preferably in an extruder, and supplied to the molding belt calender as described, for example, in US-A 4,880,585. If necessary, the tablets are cooled after the calendering, eg. in an air or cooling bath.

M/35193 tical active ingredients in polymers, the active ingredient is present in a molecular dispersion in the polymer.

The pharmaceutical mixture is then melted in a conventional way, preferably in an extruder, and supplied to the molding belt calender as described, for example, in US-A 4,880,585. If necessary, the tablets are cooled after the calendering, eg. in an air or cooling bath.

In the case of sticky or highly viscous materials which are detached from the mold only with difficulty or not at all, it is expedient to use a mold release agent, for example a silicone oil or a silicone paint.

Preferred embodiments of the machine according to the invention are explained hereinafter by means of the appended drawing. In this: 2- Figure 1 shows a diagrammatic view of the molding belt calender according to the invention, i- Figure 2 shows a detailed view in longitudinal section of a molding belt known in the art which is passed between the calender rolls of the machine from Figure 1, 2- Figure 3 shows a view as in Figure 2 of an embodiment of the molding belt of the present invention.

Figure 1 shows the molding belt calender 10 according to the invention, with a molding belt 12 being passed between calender "i rolls 14, 16 over deflecting rolls 18. An extruder 20 is used to produce the plastic product composition, which is preferably produced as a wide product ribbon 22. The calendar rolls 14, 16, the S molding belt 12 and the product ribbon 22 preferably have essentially the same width. The direction of circulation of the molding belt 12, and the direction of rotation of the rolls 14 and 16 are indicated by arrows. The product ribbon 22 is fed, parallel to the direction of movement of the molding belt 12, into the trough-like depression 26 between the rolls 14 and 16.

The molding belt 12 has on its surface depressions 24 or apertures 30 as depicted, in particular, in Figures 2 and 3.

Figure 2 shows a molding belt 12 of prior art having depressions 24. Molding belt 12 and product composition 22 are passed together into the increasingly narrow slit between the two rolls 14 and 16, with the product composition 22 being forced into the reoz 0480/01154 12 Figure 3 shows the same detail as Figure 2 of a molding belt calender according to the invention as shown in Figure i, with the molding belt 12 in Figure 3 having, according to another embodiment of the invention, continuous apertures 30 into which the product composition 22 is forced on passing between the rolls 14 and 16 of the machine. The moldings 28 produced in this case have two smooth surfaces. The apertures 30 in the molding belt 12 are preferably produced by punching out the molding belt. As is evident from Figure 3, thd resulting moldings 28 have edge angles which are essentially 900. Any protruding product composition can easily be deflashed in the case of tablets molded in this way.

M/35193

Claims (16)

1. A machine for producing flat moldings from a product composition containing an active ingredient, having at least one charging means for supplying the product composition, at least one pair of rolls consisting of two counter-rotatable calender rolls, and a circulating molding belt which is passed between the two rolls, the molding belt having on its surface recesses to receive the product composition characterized in that said recesses are continuous apertures.

2. A machine as claimed in claim 1, wherein the apertures have on their 0 periphery bars which point inward to form scores in the moldings.

3. A machine as claimed in claim 1, wherein the thickness of the molding belt is at least as large as the required thickness of the moldings. 9* 0

4. A machine as claimed in claim 1, wherein the calender rolls have smooth outer surfaces.

A machine as claimed in claim 1, wherein the temperature of the calender rolls can be controlled. 9

6. A machine as claimed in claim 1, wherein the spacing of the rolls of a pair of rolls can be altered.

7. A machine as claimed in claim 1, wherein the machine has a plurality of charging means for different product compositions.

8. A machine as claimed in claim 1, wherein the charging means is an extruder and/or a heatable filling wedges. 14

9. A process for producing flat moldings from a product composition which contains an active ingredient, wherein a molding belt with recesses formed as continuous apertures is passed between the counter-rotating rolls of a pair of calender rolls, the required contact pressure of the two rolls is set, at least one product strand consisting of the composition containing active ingredient is formed, this product strand is supplied to the pair of rolls, with the product composition being forced into the apertures, the moldings are removed from the apertures.

10. A process as claimed in claim 9, wherein the product strand is passed between a plurality of pairs of rolls.

11. A process as claimed in claim 9, wherein a plurality of product strands is formed, and these are supplied simultaneously to a pair of rolls or successively to a plurality of pairs of rolls. 9 SS

12. A process as claimed in claim 9, wherein a product composition which is plastic when hot and becomes solid when cold is supplied.

13. A process as claimed in claim 12, wherein at least one pair of rolls is s cooled.

14. A process as claimed in claim 9, wherein a product composition which is plastic when moist and becomes solid on drying is used.

I A process as claimed in claim 14, wherein at least one pair of rolls is heated.

16. A machine as claimed in claim 1 substantially as hereinbefore described with reference to the figures. DATED this 23rd day of March 1998 WATERMARK PATENT TRADEMARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA DOC 22 AU7491196.WPC LCG/KMH/RES *9 S S S S S.