WO2006065141A2

WO2006065141A2 - Method and device for manufacturing products comprising medication

Info

Publication number: WO2006065141A2
Application number: PCT/NL2005/050086
Authority: WO
Inventors: Antonio Giuseppe Perra
Original assignee: 4Sight Innovation B.V.
Priority date: 2004-12-17
Filing date: 2005-12-16
Publication date: 2006-06-22
Also published as: WO2006065140A1; WO2006065141A3; NL1027807C1

Abstract

A method for manufacturing products comprising medication, comprising: A) moistening a carrier material; B) mixing the moistened carrier material with at least one medicine; C) arranging at least a part of said mixture in at least one mould cavity; D) removing the mixture from the mould cavity, and E) extracting moisture from the mixture while forming an at least partly porous product comprising at least one medicine. A device for manufacturing products by applying said method, comprising: moistening means for moistening a carrier material, at least one mixing unit for mixing the moistened carrier material and the medicine, at least one mould provided with at least one mould cavity for receiving the mixture of the moistened carrier material and the medicine, manipulating means for removing the mixture from the mould cavity, and means for extracting moisture from the mixture while forming an at least partially porous product .

Description

Method and device for manufacturing products comprising medication

The invention relates to a method for manufacturing products comprising medication. The invention also relates to a device for manufacturing products comprising medication by applying the method according to the invention. The invention further relates to a product comprising medication, which product is manufactured by means of the method according to the invention.

Medicines are biologically active substances which at relatively low concentrations are designed to cause a pharmacological effect in humans or animals. The medicines can be administered to the body in diverse ways. It is known here to compress the medication into a tablet, which tablet can then be administered orally. Tablets are manufactured by compressing a measured quantity of medication in a mould, usually together with a measured quantity of filler. Lactose, sucrose or starch can herein be used as filler. At present there are two methods of increasing the disintegration rate of the tablets. A first known method of increasing the disintegration rate of the tablets is formed by adding a gas-generating component to the tablet to enable an effervescent effect to be generated. Although it is claimed that tablets with an improved disintegration rate can be provided using this method, the tablets disintegrate relatively slowly in water. In general, known effervescent tablets disintegrate only after 5 to 10 minutes. The consumer perception that the known effervescent tablets disintegrate relatively rapidly in water is in fact psychological in nature; this perception is caused particularly because a consumer can observe the escape of gas bubbles ftom the drink, which creates the perception that the effervescent tablet in question is therefore also disintegrating relatively rapidly, which is not the case. A second known method is formed by manufacturing tablets by means of a fteeze-drying process. Although a somewhat improved disintegration rate of the tablets can be achieved using this second method, a significant drawback of this second method is that the physical integrity of the tablets is relatively poor. Manufacturing the tablets in this manner is furthermore relatively expensive, all the more so as each production process cycle takes a relatively long time (generally between 24 and 48 hours) and is accompanied by relatively high energy costs and a relatively limited production capacity. There is a need for the development of products comprising medication which on the one hand disintegrate relatively rapidly during contact with a liquid, whereby a consumer can ingest the medication relatively quickly, and which on the other hand can be manufactured relatively inexpensively and quickly.

The invention has for its object to provide a method for manufacturing in relatively inexpensive and rapid manner products comprising medication, which disintegrate relatively rapidly during contact with a liquid.

The invention provides for this purpose a method of the type stated in the preamble, comprising the steps of: A) moistening a carrier material, B) mixing the moistened carrier material with at least one medicine, C) arranging at least part of the mixture of the moistened carrier material and the medicine in at least one mould cavity, D) removing the mixture from the mould cavity, and E) extracting moisture from the mixture while forming an at least partly porous product comprising at least one medicine. Application of the method according to the invention provides an at least partly porous product which disintegrates relatively rapidly during contact with a liquid, i.e. within about 10 seconds, since the porosity of the product, or at least a part of the product, results in a relatively short penetration time for the liquid to be able to substantially fully penetrate the product. The product can form an orodispersible product, wherein the product will fall apart on the tongue of a person during contact with saliva, and will be swallowed with the saliva. The product can however also be disintegrable in water or any other ingesting liquid, whereafter the product dispersed in water can be ingested together with the water. What is special about the method according to the invention is that use is made of a carrier material which is moistened, whereafter the medication is added to the moistened carrier material. Tests have shown that moistening of the carrier material (and the medication) after mixing of the carrier material and the medication does not result in a satisfactory end product that can disintegrate relatively rapidly, since the medication usually becomes lumpy during manufacture of the product, which is disadvantageous for the desired relatively rapid disintegration of the final product. It has been found that a product with a relatively short disintegration time can only be obtained by performing steps A) and B) sequentially before the mixture of the carrier material and the at least one medicine is arranged in the at least one mould cavity. The product formed during step E) is formed by a substantially solid, compressed mass, this mass comprising the carrier material and at least one medicine. Each product comprises a measured quantity of medicine, wherein the product falls apart (disintegrates) substantially completely and preferably dissolves after the product is brought into contact with a liquid such as saliva or a separate ingesting liquid. The design of the final product depends particularly on the design of the mould cavity. The moist mixture can for instance be given the form of a pill, a tablet or a granule by means of the mould cavity. The final product can optionally comprise a (small) fraction of liquid or gel-like material but will generally consist substantially of a mixture of solid materials (at room temperature). Products comprising medication can moreover be manufactured relatively rapidly and, above all, relatively inexpensively by means of the method according to the invention, since the production time per product can be significantly shortened. It is noted that the product obtained by applying the method according to the invention will generally contain one or more human medicines, wherein ingestion of the product by persons is intended. It is however also possible to envisage the product comprising one or more veterinary medicines (animal medicines). These animal medicines are mainly antibiotics and antiparasitics, which are used as group medication in domestic and farm animals. Antibiotics are also applied frequently in (tropical) fish culture. The products formed by applying the method will generally only be ingested orally. It is not however precluded that these products can also be administered rectally.

In a preferred embodiment the at least one medicine comprises at least one (biologically) active pharmacological substance. The at least one active pharmacological substance or active substance preferably forms part of at least one of the following substance groups: The active pharmaceutical ingredient belongs to a class of medicines chosen from the group which comprises: anti-migraines, anti-rheumatics, nonsteroidal anti-infiammatories, nsaids, opioids, antimycobacterials, anti-parasites, antivirals, beta-lactams, macrolide antibiotics, fluoroquinolones, tetracyclines, alkylating agents, anti-metabolites, hormonal drugs and antagonists, mitotic inhibitors, imraunosupressants, anti-arrhythmics, antihypertensives, beta-adrenergic blockers, calcium channel blockers, hypolipidemics, nitrates, anticonvulsants, anti-depressants, anxiolitics, sedatives, hypnotics, neurodegenerative disease drugs, ophthalmic drugs, antipeptics, bismuth salts, anti-emetics, laxatives, coagulants, anti-coagulants, hemotopoietics, anti-diabetics, contraceptives, thyroid and anti-thyroid drugs, diuretics, electrolytes, gout therapy drugs, anti-asthmatics, antihistamines, medicines against coughs, colds and flu, and nutritional supplements. The at least one medicine preferably also comprises one or more other active substances, such as for instance a flavouring, an aromatic substance and a colouring agent, in order to improve and/or characterize the taste, smell and/or colour of the product. It is however also possible to envisage the medication, optionally additionally, comprising other active substances, such as for instance a substance, usually a complex, for improving or masking the taste of other active substances, a substance for controlled release of other active substances, a substance for generating a gas which generates an effervescent effect, and/or a substance for improving the disintegration rate of other active components. By applying a gas-generating component a gas can be generated in an ingesting drink after the product is brought into contact with the drink, whereby the drink will begin to effervesce. The turbulence which the effervescence causes in the drink due to the created gas bubbles results in a somewhat improved mixing of the medication with the ingesting drink, although it is noted that the substantially reduced disintegration time of the product is caused by the selective porosity of the product obtained by applying the method according to the invention. The gas-generating agents preferably comprise at least one carbonate salt and/or one nutrient acid such as citric acid. After bringing a carbonate salt-citric acid mixture into contact with the ingestion drink the product will dissolve, whereafter the carbonate group will be chemically converted and form gaseous carbon dioxide.

The at least one medicine added during step B) is preferably pre-treated, more preferably pre-dried and/or compressed. Advantages of drying the medicine prior to adding the at least one medicine to the moistened carrier material is that the medicine can be preserved (significantly) longer without the properties of the medicine being affected. The mass of the medication can moreover be reduced considerably by pre- drying and/or compressing the medicine, which is generally also advantageous from financial and logistical viewpoint; in general only four to seven percent of the original moisture content remains after drying of the medication. Pre-compressing the at least one medicine can take place in a number of ways. The medication can for instance be compressed by means of particle size manipulation during the production process, in particular by limiting the particle size to atypical particle size between 50 micrometers and 600 micrometers, more preferably between 50 micrometers and 300 micrometers. Pre-drying of the at least one medicine can take place in a number of ways. The medication can for instance be dried by means of vacuum-drying, puff-drying or trehalose, although in a particular preferred embodiment the at least one medicine added during step B) is spray-dried and/or fieeze-dried. The advantage of spray-drying and freeze-drying (or a combination thereof) is that the product in great measure regains the properties of the original medicine after rehydration. After bringing the medicine into contact with a liquid the rehydration of the medication moreover takes place relatively quickly, whereby the medicine can be ingested relatively quickly by a person. Diverse active pharmacological substances which have been developed recently are relatively unstable (proteins, gene therapeutics) and/or relatively lipophilic. Both types of substance require an advanced formulation technique, which on the one hand has a stabilizing effect and on the other improves the solubility. A solution of the active substance is therefore preferably mixed with a sugar solution so that one single solution is obtained of both the active substance and sugar. The solvent, or at least a substantial part hereof, is then removed from the solution, preferably via spray-drying, fteeze- drying or spray-freeze-drying, whereby a solid granulate is obtained. In this granulate, usually a powder, the active substance will generally be distributed homogeneously over the (amorphous) sugar matrix. For the two stated types of medication, the unstable and the lipophilic, the use of a sugar matrix has many advantages. For the unstable active substances (including proteins, gene therapeutics, strongly oxidizing substances) the transition from a solution to dry powder is relatively favourable; diverse decomposition reactions are greatly inhibited (molecular mobility) and diverse formulations become possible. While in the past it was only possible to administer this group of substances parenterally, for instance via injection, it has now become possible to incorporate the unstable active components incorporated in a sugar matrix in a product suitable for oral ingestion.

The medicine is preferably formed by a solid substance (at room temperature and atmospheric pressure). More preferably, the at least one medicine added during step B) is formed substantially by a granulate consisting of (powder) particles or granules. It is possible to envisage a plurality of medicines being mixed with the moistened carrier material during step B).

The moist mixture will generally first be removed from the mould cavity (step D)) before moisture is extracted from the mixture (step E)). It is however also possible to envisage extracting moisture from the mixture while the mixture is still arranged in the mould cavity, whereby the final product can already be formed in the mould cavity. The extraction of moisture or drying of the moist mixture can take place in diverse ways. In the case that steps D) and E) are performed at least partly simultaneously it is possible here to envisage the mould cavity being heated, for instance electrically, whereby at least part of the moisture present in the mixture evaporates. In a preferred embodiment the mixture arranged in the mould cavity is irradiated with electromagnetic radiation during step D). The electromagnetic radiation can be formed by infrared radiation, but is preferably formed by microwave radiation in order to allow extraction of the moisture from the mixture arranged in the mould cavity in relatively effective manner and without affecting the porous product structure then formed. Since step E) will generally take place after step D), in a preferred embodiment the mixture is first removed from the mould cavity, whereafter the mixture can be irradiated with electromagnetic radiation, and in particular infrared radiation and/or microwave radiation. It is also possible to envisage, as optional addition, guiding a (relatively dry) airflow along the moist mixture in order to extract moisture from the mixture. The airflow can herein also be heated to a temperature which is higher than room temperature.

The carrier material for the medication is preferably relatively rapidly disintegrable, and more preferably relatively easily soluble, in an ingestion drink such as water, whereby (residues of) the carrier material staying behind (discernibly) in the drink can be prevented. In this manner no residues remain in the drink container after the drink is consumed. Nor in this case will a person swallow any solid particles of the carrier material during consumption of the drink.

In a preferred embodiment the carrier material comprises at least one polyol, more preferably at least one hydrogenated sugar. A polyol forms an organic chemical compound provided with a plurality of alcohol groups. Hydrogenated sugars such as erythritol, isomalt, lactitol, sorbitol, xylitol, maltitol, and mannitol (or a combination hereof) are particularly suitable for use as carrier material. Erythritol, isomalt, lactitol and xylitol are particularly well soluble in water, which makes these polyols particularly suitable for application as (at least a part of the) carrier material. Erythritol (E-number: E968) originates from an extract of fermented corn/wheat sugar. Isomalt (E-number: E953) is resistant to heating and acids and moreover does not cause tooth decay, and possibly protects against cavities (tooth decay). In addition to being readily soluble in water, lactitol (E-number: E966) is also resistant to heating. Nor furthermore does lactitol cause cavities. Sorbitol (E-number: E420) occurs naturally in fruits, is resistant to heating and moreover has a preserving and stabilizing effect. In addition, sorbitol does not cause tooth decay. Xylitol (E-number: E967) occurs naturally in fruit and vegetables in small quantities (<1%) and has almost the same properties as sugar. Xylitol probably has the effect of protecting against cavities, and inhibits in particular the growth of bacteria which cause cavities. Maltitol (E-number: E965) and mannitol (E-number: E421) are both resistant to heating and do not cause cavities. It is also conceivable to use polydextrose (also a polyol). Polydextrose (E-number: E 1200) has preserving properties. Polydextrose also prevents drying out and protects against freeze damage during freezing. It is however noted that the carrier material can also comprise a plurality of types of polyol to be able to optimize the properties of the carrier material.

The carrier material is selected particularly from the group comprising: dextrates, dextrins, dextrose, fructose, lactitol, lactose, maltitol, maltose, mannitol, mannose, sorbitol, sucrose, erythritol, xylitol, starch, gelatines, acacia preparations, alginate acid, sodium alginate, cellulose, carboxy methyl cellulose, ethyl cellulose, hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polydextrose, polyacrylic acid, carbomer, polyethylene oxide and povidone.

In order to stabilize the cohesion of the mixture arranged in the mould cavity the method preferably also comprises step F), comprising of exerting a pressure on the mixture subsequent to arranging at least part of the mixture of the moistened carrier material and the medicine in the at least one mould cavity as according to step C). In this manner a relatively stable product can be obtained during step E). Exerting the pressure on the mixture must take place such that on the one hand the pressure is sufficiently high to be able to realize a stable product with a predefined form, but wherein the pressure is on the other hand low enough that the porosity of the product to be finally formed, and thereby a rapid disintegration of the product, remains ensured. An optimal pressure must be determined subject to the situational conditions, which are determined by, among other factors, the nature and quantity of the carrier material and the at least one medicine. While a pressure is being exerted on the mixture, a determined form can also be imparted to the mixture, and thereby to the product to be finally formed. The form can herein be of aesthetic, but also functional nature. After all, an increase in the area to volume ratio of the finally formed product will generally enhance the disintegration rate of the product. The product is preferably embodied in tablet form. The tablet form provides a conveniently rounded product, wherein the tablet is generally formed by a disc with a height of three to four millimetres and a diameter of six to ten millimetres. It will however be apparent that this dimensioning is in no way limitative. The area to volume ratio of the tablet form can optionally be increased by arranging one or more cavities in the tablet form, by rounding off edges of the (cylindrical) tablet form and/or by otherwise profiling the external surface of the - preferably substantially tablet-like - product. After arranging one or more cavities in the product, these (unfilled) cavities thus contain neither carrier material nor medication. The cavity can for instance be formed by a recess or a channel passing through the product. The cavity also makes it possible to manipulate the product more easily by using the cavity as a point of engagement, for instance for a finger, spoon or stirring stick. . . hi a preferred embodiment the mixture of the moistened carrier material and the medicine is arranged in a plurality of mould cavities during step B). In this manner a plurality of products can be manufactured simultaneously.

Between 0.5 and 7% by mass, more preferably between 0.5 and 5% by mass and in a particular preferred embodiment between 0.5 and 3% by mass of water is preferably added to the carrier material during step A). In this manner the final mixture of the moistened carrier material and the at least one medicine will be moistened with a mass percentage lying substantially between 0.5 and 2% by mass. At a lower moisture percentage it will generally not be possible to realize a porous structure of the final product cohering in stable manner, and at a higher percentage the mixture to be arranged in the mould cavity will generally be too liquid, wherein the chance of premature disintegration of the carrier material and/or the at least one medicine is considerable. During step E) (only) a part of the moisture absorbed in the mixture is preferably extracted from the mixture. The advantage of only partial extraction from the mixture of the moisture absorbed therein is the most favorable from a practical viewpoint, since the remaining moisture contributes toward the stability of the product and in particular to the cohesion between the carrier material and the at least one medicine of the final product. The quantity of carrier material preferably lies substantially between 30 and 95% by mass, more preferably between 30 and 50% by mass, of the product formed during step E). At lower mass percentages of carrier material it will generally not be possible to realize a porous structure of the final product cohering in stable manner, and higher mass percentages of carrier material will result in a relatively compressed product with too low a porosity, wherein the chance of fusing of the carrier material and the chance of an unacceptably long disintegration time of the product is considerable. The quantity of the medicine added during step B) preferably lies substantially between 0.5 and 80% by mass, more preferably between 0.5 and 70, and in a particular preferred embodiment between 0.5 and 60% by mass of the product formed during step E), depending on the nature of the medication.

In a preferred embodiment the carrier material moistened during step A) has a substantially granular form, wherein the grain size of the carrier material lies between 100 and 600 micrometers. The grain size of the grains can herein be substantially uniform, but the carrier material preferably has a grain size distribution lying between 100 and 500 micrometers. By selectively having the grains vary in size in accordance with a pre-defined grain size distribution suitable for the relevant medication, a relatively homogeneous mixture can be obtained with an effective (internal) surface of the porous product, which considerably enhances the disintegration of the product after the product is brought into contact with a liquid. A varying grain size will generally result in insufficient binding or decomposition, wherein the chance of varying product- related experiences by a user, such as a discernibly different taste and/or a discernibly different disintegration, is considerable.

The invention also relates to a device for manufacturing products comprising at least one medication by applying the method according to the invention, comprising: moistening means for moistening a carrier material, at least one mixing unit for mixing the moistened carrier material and at least one medicine, at least one mould provided with at least one mould cavity for receiving the mixture of the moistened carrier material and the at least one medicine, manipulating means for removing the mixture from the mould cavity, and moisture extracting means for extracting moisture from the mixture while forming an at least partially porous product comprising at least one medicine. Advantages of applying the device according to the invention have already been comprehensively discussed in the foregoing. The device will generally also comprise a plurality of supply containers, wherein at least one supply container is adapted to hold a supply of carrier material and wherein at least one other supply container is adapted to hold a supply of at least one medicine. The supply containers can herein each be formed by a hopper (supply hopper). The device preferably also comprises transport means for transporting the moist, though formed mixture removed from the mould cavity in the direction of the moisture extracting means. The transport means are preferably provided here with an endless conveyor belt.

As moistening means can be used: dextrate, dextrin, dextrose, fructose, lactitol, lactose, maltitol, maltose, mannitol, mannose, sorbitol, sucrose, erythritol, xylitol, microcrystalline cellulose, silicated microcrystalline cellulose, powdered cellulose, cellulose acetate, calcium sulphate, calcium carbonate, dicalcium phosphate, tricalcium phosphate, carboxymethyl cellulose-calcium salts and combinations thereof.

The device preferably comprises pressing means for pressing the mixture arranged in the mould cavity. The pressing means can herein be provided with an optionally specially formed closing element which can be received (temporarily) with clamping fit in the mould cavity for the purpose of compressing the moist mixture.

The moisture extracting means preferably comprise heating means. The heating means can be adapted to generate direct heat (by means of infrared radiation) or to generate indirect heat (by means of microwave radiation) to allow heating and therefore extraction of moisture from the mixture arranged in the mould cavity while forming the actual product.

In a preferred embodiment the mould is provided with a plurality of mould cavities to enable simultaneous forming of a plurality of products. In a particular preferred embodiment the mould cavities arranged in the mould are ordered substantially in the form of a matrix. The mould is preferably arranged rotatably in the device in order to enable filling, emptying and optional cleaning of the mould cavity or cavities arranged in the mould in relatively efficient manner. The manipulating means comprise at least one ejecting member for pushing the mixture out of the mould cavity. The ejecting member, or at least a part thereof, can herein form part of the mould and in particular can define the design of the mould cavity. Removal of the mixture from the mould cavity will generally take place by means of pushing the mixture out of the mould cavity. In an alternative embodiment variant however, it is also possible to envisage removing the mixture from the mould cavity by means of applying an underpressure to the mixture.

The device preferably comprises at least one packing station for packing the formed products. Each formed product can herein be provided with a separate packaging. In general however a packaging will be arranged round an assembly of products. The device preferably comprises displacing means for displacing the at least one formed product to the packing station. Owing to the 'pick and place' functionality of the displacing means the products can be picked up in relatively efficient manner and displaced to the packing station. The displacing means generally comprise engaging members for engaging on one or (simultaneously) on a plurality of products, which can be further displaced in the direction of a finishing unit, such as for instance a packing station.

The invention further relates to a product comprising at least one medicine, which product is manufactured by means of the method according to the invention and comprises a substantially porous structure, which porous structure comprises a carrier material and at least one medicine. An advantage of the product according to the method of the invention, and using the device according to the invention, is that the product can be penetrated relatively easily by a liquid, such as an ingestion drink or saliva, particularly due to the (selectively) porous structure, and can therefore disintegrate relatively rapidly in the liquid. The presence of the carrier material herein facilitates the disintegration. In this way a medicine can thus be ingested by a person, or possibly an animal, in relatively rapid, simple, efficient, controllable and measured manner.

The carrier material preferably comprises at least one polyol, further preferred embodiments of which have already been described in the foregoing. The at least one medicine preferably comprises a mixture of active substances. In a particular preferred embodiment at least one active pharmacological substance forms part of at least one of the following substance groups: beta-blockers, antiepileptics, analgesics, cytostatics, antibiotics, psychopharmaceuticals, bronchospasmolytics, X-ray contrast agents, hormonal substances, vasodilatants, antilipemics, gastrointestinal medicines and sleep- inducing medication. In a preferred embodiment the medication (additionally) comprises a flavouring, an aromatic substance and/or a colouring agent. It is however also possible to envisage other active components being incorporated in the product. The active components can herein be adapted to impart particular properties to the product, such as for instance improving the disintegration of the product

The grain size of the carrier material preferably lies between 100 and 600 micrometers. The carrier material preferably has a grain size distribution lying between 100 and 600 micrometers. A selective composition of grains with different, predetermined grain sizes can contribute significantly toward optimizing the construction of the porous, preferably crystalline or at least semi-crystalline product structure, whereby penetration of the structure by a liquid can also be optimized, which results in minimizing of the disintegration time of the product. It is noted that the grain size of the medicine can be very diverse and depends on the nature of the medicine.

The quantity of carrier material preferably lies substantially between 30 and 95% by mass and depends on the nature of the medicine. The quantity of medicine preferably lies substantially between 0.5 and 70% by mass, as already specified above. The total weight of the final product is preferably less than 5 grams, more preferably between 1 and 3 grams, and amounts in particular to substantially 2 grams.

In addition, the invention relates to a packaging provided with at least one product according to the invention. The packaging will generally take a disposable form. It is however also possible to envisage providing a durable packaging for the product. In this case however, the packaging will generally be adapted to contain a plurality of products optionally in tablet form.

The invention will be elucidated on the basis of non-limitative exemplary embodiments shown in the following figures. Herein: figure 1 shows a perspective view of a device according to the invention, figure 2a shows a detailed cross-section of a part of the device according to figure 1, figure 2b shows a detailed cross-section of a part of an alternative device according to the invention, figure 3 shows a schematic representation of a method according to the invention, figure 4 shows a perspective view of a product manufactured by means of the method according to the invention, figure 5 shows a product according to the invention provided with a packaging, and figures 6a and 6b show a packaging in which a plurality of products according to the invention are arranged.

Figure 1 shows a perspective view of a device 1 according to (he invention. Device 1 is adapted to allow continuous manufacture of products comprising at least one medication, wherein each product disintegrates relatively rapidly after the product is brought into contact with a liquid, whereafter the product, and in particular the at least one medicine, can be ingested relatively quickly and effectively by a person. Device 1 comprises a first hopper 2 for holding a supply of a medicine 3. In order to manufacture the products a measured quantity of medicine 3 (preferably between 0.5 and 70% by mass of the product for manufacturing) is collected in a first metering container 4. In addition, device 1 comprises a second hopper 5 for holding a supply of a carrier material 6, in particular carrier material comprising a polyol, more particularly carrier material comprising a hydrogenated sugar. A measured quantity of carrier material 6 (preferably between 30 and 95% by mass of the product for manufacturing) will be collected in a second metering container 7, to which second metering container 7 a measured quantity of water 9 (preferably between 0.5 and 7% by mass of the moistened carrier material 6) is also added via a water conduit 8. Medicine 3 and moistened carrier material 6 are added to a mixing unit 10 in which medicine 3 and moistened carrier material 6 are mixed intensively and to a substantially homogeneous mixture. By means of a screw conveyor 11, in particular a trough conveyor, the moist mixture is displaced and arranged via a feed unit 12 in mould cavities 14 arranged in a rotating mould 13. Mould cavities 14 are arranged in a matrix structure in an external side of mould 13. Rotating mould 13 co-acts with a compression roller 15 for the purpose of compressing to some extent the moist mixture arranged in mould cavities 14. As soon as a mould cavity 14 (at least partly) filled with the moist mixture has reached a lowest orientation, the formed mixture 16 is forcibly removed from mould cavity 14 and thereby arranged on an endless, perforated conveyor 17. After emptying of mould cavities 14, the relevant mould cavities 14 are guided along a cleaning roller 18 in order to clean mould 13 at the position of the relevant mould cavities 14. A detailed view of mould 13 and compression roller 15 is shown in figure 2a. Since an upper part of conveyor 17 moves in a direction away from mould 13 (see arrow A), the moist mixtures 16 deposited on conveyor 17 and formed in the mould cavities can be guided through an irradiation chamber 19 in which a plurality of electromagnetic radiation sources 20 are disposed. Radiation sources 20 are preferably adapted to generate microwave radiation (see arrow B) with a wavelength lying substantially between 1 mm (300 GHz) and 30 cm (1 GHz), whereby the moisture present in the individualizable mixtures 16 preformed in mould cavities 14 can be at least partially extracted from mixtures 16 while forming the actual, at least partly porous product comprising one or more medicines. The moisture 21 extracted from mixtures 16 (see arrow C) is actively discharged from irradiation chamber 19 via one or more fans 22. In order to complete the moisture-removing process the products situated on perforated conveyor 17 are guided through one or more ventilation chambers 23, in which a relatively warm airflow (see arrow D) is guided along and optionally partly through products 16, whereafter the airflow humidified by products 16 is discharged from ventilation chambers 23 via fans 24 (see arrow E). After drying of products 16 the products can be ingested by persons (or animals). Products 16 will generally be packaged individually or together after drying in order to be able to facilitate transport and storage of products 16.

Figure 2a shows a detailed cross-section of a part of device 1 according to figure 1. Figure 2a clearly shows that feed unit 12 connects to the rotating hollow mould 13. Mould 13 is provided on an external side with a plurality of mould cavities 14 ordered in rows for receiving the mixture 16 supplied via feed unit 12. Each mould cavity 14 is herein bounded by, among other things, an ejecting member 25 which co-acts with an irregular external surface of a guide cam 26 positioned in mould 13. In this manner the relative orientation of ejecting member 25 and mould 13 can be changed subject to the situation and the orientation of mould cavity 14 which is partly bounded by the relevant ejecting member 25. Figure 2a in particular shows that the volume of mould cavities 14 is minimized in a lowest orientation, whereby the moist mixtures 16 are there pressed out of mould cavities 14. This minimized state of mould cavities 14 is maintained while mould cavities 14 are guided along cleaning roller 18 for brushing clean both ejecting member 25 and an outer side of mould 13, whereafter the volume of mould cavities 14 is increased once again to allow a fresh quantity of mixture 16 to be received. Compression roller 15 is disposed for rotation (in opposing direction) and is provided with a plurality of protruding pressing elements 27 ordered in rows for the purpose of compressing to some extent the mixture 16 arranged in mould cavities 14 in order to be able to increase the stability of the final product 16, but wherein the porosity of the final product 16 is guaranteed. Figure 2a also shows that feed unit 12 is provided with a plurality of rotating stirring elements 28 to prevent the mixture 16 from becoming lumpy and/or settling out.

Figure 2b shows a detailed cross-section of a part of an alternative device 29 according to the invention. The shown part of device 29 comprises a feed unit 30, a mould 31 provided with mould cavities 32, and a cleaning roller 33, which are structurally identical to feed unit 12, mould 13 and cleaning roller 18 as shown in figure 2a. A moist mixture 34 of one or more medicines and pre-moistened carrier material is arranged in mould cavities 32, whereafter the mould cavities 32 rilled with mixture 34 are rotated in downward direction. Device 29 also comprises a rotatable, hollow compression roller 35 for compressing the mixture 34 received in the relevant mould cavities 32 at a predetermined pressure. Compression roller 35 is provided for this purpose with a plurality of pressing members 36 which are accommodated displaceably in compression roller 35. Pressing members 36 herein co-act with a guide cam 37 which is arranged displaceably in compression roller 35 and which hi the shown orientation is accommodated eccentrically (non-concentrically) in compression roller 35. By displacing guide cam 37 relative to compression roller 35 the pressure exerted by pressing members 36 on the mixtures 34 received in mould cavities 32 can be regulated, and in particular optimized for the nature of the mixtures 34 received in mould cavities 32. This is because tests have shown that a different optimal bias must usually be exerted on a first mixture containing medication than the optimal bias which must be exerted on a second mixture containing medication, whereby the ability to regulate the bias by displacing guide cam 37 relative to compression roller 35 is particularly advantageous.

Figure 3 shows a schematic representation of a method according to the invention. According to the method a measured quantity of carrier material and a measured quantity of water are first combined (step A). The moistened carrier material is then combined with a measured quantity of medicine, wherein the moist mixture is mixed intensively (step B) to form a substantially homogeneous mass. The moistened mixture is then arranged in one or more mould cavities with a predefined volume (step C). The mixture arranged in the mould cavities is then compressed to some extent by exerting a pressure on the mixture (step D). Each mixture arranged in the relevant mould cavity is then removed from the mould cavity (step E), whereafter the moist mixture is at least partially dried (step F) while forming the final products. It is noted that step E) and step F) can also take place in reverse sequence, or even at least partly simultaneously. After steps A)-F) have been performed, the products are preferably provided with a packaging (step G).

Figure 4 shows a perspective view of a product 38 manufactured by means of the method according to the invention. Product 38 has a substantially cylindrical design and has a height of three to four millimetres and a diameter of six to ten millimetres. The mass of product 38 lies between 1 and 3 grams. The area to volume ratio of the cylindrical product is now (slightly) increased by rounding off the edges 39 of the cylinder form, which to some extent enhances the disintegration rate of product 38. Product 38 is provided with information 40 enabling designation of the type and/or the dosage of the medicine forming part of product 38.

Figure 5 shows a product according to the invention provided with a packaging 41. The packaging is manufactured from a packaging material 42 which can be readily opened by tearing, for instance paper or plastic, or a laminate thereof. The packaging material preferably comprises at least one medium-tight layer so as to prolong the shelf-life of the product. The packaging can be provided with graphic information 43, such as information relating to the nature of the product.

Figures 6a and 6b show a packaging in which a plurality of products according to the invention are arranged. Packaging 44 takes the form of a press-through strip in which a plurality of products 45 in tablet form according to the invention are each held in separate receiving spaces 46. Receiving spaces 46 are manufactured from a relatively flexible material which can be pressed in such that, when receiving space 46 is pressed down as according to arrow A, a product 45 is pressed through a breakable layer 47 of packaging 44 and thus released as according to arrow B. Pressing-out is further elucidated in figure 6b, in which a user presses on a receiving space 46 with finger 48, whereby this receiving space is deformed and wherein product 45 tears the breakable layer 47 locally, whereby the user gains access to product 45, whereafter product 45 can be ingested by persons (or animals).

It will be apparent that the invention is not limited to the exemplary embodiments shown and described here, but that numerous variants, which will be self-evident to the skilled person in this field, are possible within the scope of the appended claims.

Claims

1. Method for manufacturing products comprising medication, comprising the steps of: A) moistening a carrier material,

B) mixing the moistened carrier material with at least one medicine,

C) arranging at least a part of the mixture of the moistened carrier material and the medicine in at least one mould cavity,

D) removing the mixture from the mould cavity, and E) extracting moisture from the mixture while forming an at least partly porous product comprising at least one medicine.

2. Method as claimed in claim 1 , characterized in that the at least one medicine comprises at least one active pharmacological substance.

3. Method as claimed in claim 2, characterized in that at least one active pharmacological substance forms part of at least one of the following substance groups: beta-blockers, antiepileptics, analgesics, cytostatics, antibiotics, psychopharmaceuticals, bronchospasmolytics, X-ray contrast agents, hormonal substances, vasodilatants, antilipemics, gastrointestinal medicines and sleep-inducing medication.

4. Method as claimed in any of the foregoing claims, characterized in that the medicine comprises at least one of the following substances: a flavouring, an aromatic substance and a colouring agent.

5. Method as claimed in any of the foregoing claims, characterized in that the at least one medicine added during step B) is pre-dried.

6. Method as claimed in claim 5, characterized in that the at least one medicine added during step B) is spray-dried and/or freeze-dried.

7. Method as claimed in either of the claims 5 or 6, characterized in that the pre- dried medicine is mixed with sugar.

8. Method as claimed in any of the foregoing claims, characterized in that the at least one medicine added during step B) is formed substantially by a granulate.

9. Method as claimed in any of the foregoing claims, characterized in that a plurality of medicines are mixed with the moistened carrier material during step B).

10. Method as claimed in any of the foregoing claims, characterized in that the mixture is irradiated with electromagnetic radiation during step E).

11. Method as claimed in any of the foregoing claims, characterized in that the carrier material is formed by a substantially water-soluble material.

12. Method as claimed in any of the foregoing claims, characterized in that the carrier material comprises at least one polyol, in particular a hydrogenated sugar. . . ^{■ ■}

13. Method as claimed in any of the foregoing claims, characterized in that the method also comprises step F), comprising of exerting a pressure on the mixture subsequent to arranging at least part of the mixture of the moistened carrier material and the medicine in the at least one mould cavity as according to step C).

14. Method as claimed in any of the foregoing claims, characterized in that the mixture of the moistened carrier material and the medicine is arranged in a plurality of mould cavities during step B).

15. Method as claimed in any of the foregoing claims, characterized in that the at least one mould cavity has at least substantially the form of a pill.

16. Method as claimed in any of the foregoing claims, characterized in that between 0.5 and 7% by mass of water is added to the carrier material during step A).

17. Method as claimed in any of the foregoing claims, characterized in that a part of the moisture absorbed in the mixture is extracted from the mixture during step E).

18. Method as claimed in any of the foregoing claims, characterized in that the quantity of the carrier material moistened during step A) lies substantially between 30 and 95% by mass of the product formed during step E).

19. Method as claimed in any of the foregoing claims, characterized in that the quantity of the medicine added during step B) lies substantially between 0.5 and 70% by mass of the product formed during step E).

20. Method as claimed in any of the foregoing claims, characterized in that the carrier material moistened during step A) has a substantially granular form, wherein the grain size of the carrier material lies between 100 and 600 micrometers.

21. Method as claimed in any of the foregoing claims, characterized in that the carrier material has a grain size distribution lying between 100 and 600 micrometers.

22. Device for manufacturing products comprising medication by applying the method as claimed in any of the claims 1-21, comprising: . . .

- moistening means for moistening a carrier material,

- at least one mixing unit for mixing the moistened carrier material and at least one medicine, - at least one mould provided with at least one mould cavity for receiving the mixture of the moistened carrier material and the at least one medicine,

- manipulating means for removing the mixture from the mould cavity, and

- moisture extracting means for extracting moisture from the mixture while forming an at least partially porous product comprising at least one medicine.

23. Device as claimed in claim 22, characterized in that the device comprises pressing means for pressing the mixture arranged in the mould cavity.

24. Device as claimed in claim 22 or 23, characterized in that the moisture extracting means comprise heating means.

25. Device as claimed in any of the claims 22-24, characterized in that the mould is provided with a plurality of mould cavities.

26. Device as claimed in claim 25, characterized in that the mould cavities arranged in the mould are ordered substantially in the form of a matrix.

27. Device as claimed in any of the claims 22-26, characterized in that the mould is arranged rotatably in the device.

28. Device as claimed in any of the claims 22-27, characterized in that the manipulating means comprise at least one ejecting member for pushing the formed product out of the mould cavity.

29. Device as claimed in any of the claims 22-28, characterized in that the device comprises at least one packing station for providing a formed product with a packaging.

30. Device as claimed in claim 29, characterized in that the device comprises displacing means for displacing the at least one formed product to the packing station.

31. Product comprising medication, which product is manufactured by means of the method as claimed in any of the claims 1-21, comprising a substantially porous structure, which porous structure comprises a carrier material and at least one medicine.

32. Product as claimed in claim 31 , characterized in that the carrier material comprises at least one polyol, in particular a hydrogenated sugar.

33. Product as claimed in claim 31 or 32, characterized in that the at least one medicine comprises a mixture of active pharmacological substances.

34. Product as claimed in claim 33, characterized in that at least one active pharmacological substance forms part of at least one of the following substance groups: beta-blockers, antiepileptics, analgesics, cytostatics, antibiotics, psychopharmaceuticals, bronchospasmolytics, X-ray contrast agents, hormonal substances, vasodilatants, antilipemics, gastrointestinal medicines and sleep-inducing medication.

35. Product as claimed in any of the claims 31 -34, characterized in that at least one active component is formed by at least one of the following substances: a flavouring, an aromatic substance and a colouring agent.

36. Product as claimed in any of the claims 31 -35, characterized in that the grain size of the carrier material lies between 100 and 600 micrometers.

37. Product as claimed in any of the claims 31-36, characterized in that the carrier material has a grain size distribution lying between 100 and 600 micrometers.

38. Product as claimed in any of the claims 31-37, characterized in that the quantity of carrier material lies substantially between 30 and 95% by mass.

39. Product as claimed in any of the claims 31-38, characterized in that the quantity of medicine lies substantially between 0.5 and 70% by mass.