EP1848394B1 - Production de formes posologiques à partir de substances actives fondues - Google Patents

Production de formes posologiques à partir de substances actives fondues Download PDF

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Publication number
EP1848394B1
EP1848394B1 EP06707060.7A EP06707060A EP1848394B1 EP 1848394 B1 EP1848394 B1 EP 1848394B1 EP 06707060 A EP06707060 A EP 06707060A EP 1848394 B1 EP1848394 B1 EP 1848394B1
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EP
European Patent Office
Prior art keywords
melt
separating
films
separating films
film
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EP06707060.7A
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German (de)
English (en)
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EP1848394A1 (fr
Inventor
Jörg Rosenberg
Norbert Steiger
Harald Hach
Jörg Breitenbach
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AbbVie Deutschland GmbH and Co KG
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Abbott GmbH and Co KG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets
    • 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
    • B30B11/16—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses using pocketed rollers, e.g. two co-operating pocketed rollers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J2200/00—General characteristics or adaptations
    • A61J2200/20—Extrusion means, e.g. for producing pharmaceutical forms

Definitions

  • the present invention is a process for the preparation of dosage forms from a drug-containing melt.
  • WO 9707786 describes the use of lipids as an aid in the preparation of solid dosage forms by the melt extrusion process. Between 0.1-10 wt .-% lipids are added to the extrusion mixture as a mold release agent.
  • DE 4446467 describes a process for producing lenticular tablets by melt calendering. It is referred to in this document that molding rolls can be used, which are provided with a release agent.
  • a release agent for example, a silicone varnish is suitable.
  • the EP 0358105 describes a method for shaping extrudate masses. Here are two elastic bands with opposite recesses, which determine the tablet shape used.
  • the WO 9619963 describes a process for the production of coated tablets by melt calendering in which the active substance-containing melt is introduced into the calender forming rolls between two sheets of the wrapping material.
  • the SU 1824158 describes an apparatus for molding viscoplastic praline masses.
  • the device comprises a hopper with two chambers. Under the hopper, a molding roll with cells for receiving and shaping the candy mass is arranged. The forming roll is covered with an elastic band. Under pressure, a first mass is forced out of the first chamber into the cells, whereby the elastic band is partially deflected. The forming roll continues to rotate and a second mass is forced out of the second chamber into the cells, with maximum deflection of the elastic band. Upon further rotation of the chocolate mass molding is ejected by the elasticity of the tape from the cells.
  • the JP 02 063699 A discloses a Druckgranuliervorraum with two counter-rotating rollers and two elastic films which rest on the rollers at least in the contact area of the rollers. Recesses are provided on the surface of the rollers or films. A powder is compressed between the rollers and maintains the shape of the recesses.
  • the invention is based on the object to provide a universally applicable method that allows the formation of active ingredient-containing melts without the problems occurring by sticking the melt on or in the mold.
  • the present invention relates to a process in which two release films are brought together in a defined region, an active-substance-containing melt is introduced between the release films so that a pocket for receiving a portion of the melt is formed in at least one of the release films and the release films are separated from one another to demold the portion.
  • the release film is expediently brought into contact with the heat-sink, at least in the area of the pocket, with the side facing away from the melt. Heat is removed from the melt via the release film and the melt solidifies. In addition, the thermal load on the release film is reduced and increases its life.
  • the incoming melt usually has a temperature of more than 70 ° C, usually more than 80 ° C, for. B. 80 to 180 ° C.
  • the release films are brought into contact with each other in the nip of two counterrotating molding rolls, at least one of which has depressions into which the release film can be pressed to form pockets.
  • both forming rollers on their surface on opposite recesses into which the release films can be pressed to form pockets are particularly preferably, both forming rollers on their surface on opposite recesses into which the release films can be pressed to form pockets.
  • the release film is deformed by the introduced into the trough-shaped space between the mold rolls melt and to the surfaces the wells pressed.
  • the release film prevents direct contact of the melt with the roll surface, so that any adhesion / adhesion of the melt to the surface of the roll can be excluded.
  • the forming rollers also act as heat sinks and are for this purpose made of a highly thermally conductive material, preferably a metal, such as stainless steel or non-ferrous alloys.
  • the heat dissipation can passively be effected by heat radiation from the forming rolls to the environment or by active cooling of the forming rolls, e.g. B. by circulating a coolant through holes in the interior of the molding rolls. Only when the release film is completely pressed into the recess of the mold roll and the bag formed is completely filled with melt, the release film touches the surface of the mold roll. Only then begins a noticeable cooling and solidification of the melt. Premature solidification, which could lead to incomplete filling of the wells with melt, is largely avoided. This gives moldings which are very uniform in their shape and mass.
  • the thickness of the release films used is generally in the range of 0.05 to 1.6 mm, preferably 0.1 to 1 mm and particularly preferably 0.1 to 0.5 mm.
  • the release films of an elastically deformable material since in this case by the relaxation of the release film when leaving the nip, a force occurs, which pushes the molding out of the cavity, so practically ejects the molding.
  • release films with low or negligible elasticity is preferred.
  • the formation of the pockets in the release films can be promoted by a slight softening of the films at the temperatures in the nip.
  • the softening point can be adjusted by the content of plasticizers in the release films.
  • the films are made of an elastomer, they have a tensile strength measured in accordance with DIN EN ISO 527-1 in the range from 3 to 40 MPa, preferably 7 to 30 MPa.
  • the elongation at break according to DIN EN ISO 527-1 is at least 200%, preferably at least 400%.
  • the release films may be passed through the nip by unwinding the film from a roll and winding it onto a second roll after passing through the nip.
  • the release film can be passed behind the roller through a scraper or a cleaning bath.
  • the release films are each closed to form an endless belt, which allows continuous process control.
  • the release film can rest on the outer surface of the forming rollers at the peripheries of the forming roller recesses
  • a variant of the method is to lead one or both release films spaced from the nip to the forming rollers and z. B. to lead over adjustable guide rollers in the gap.
  • tensioning screws which are attached to the guide rollers also permit precise adjustment of the thickness of the film in the calendering gap and thus the specific influence on the ejection forces with which the shaped bodies are pressed out of the cavities of the shaping roller.
  • the invention also relates to a device with a mixing and plasticizing unit for the formation of an active ingredient-containing melt and shaping means, which consist of two molding rolls, which have at least one recess for receiving a melt containing active substance.
  • the device is characterized in that the depression comprises a release film which can be reversibly transferred from a rest position into a deflected position by introducing the active substance-containing melt into the depression.
  • the material of the release films may be selected from elastomers and / or water-insoluble thermoplastic polymers.
  • elastomers such as silicone elastomers, acryllyl rubber, polyester urethane rubber, brominated butyl rubber, polybutadiene, chlorinated butyl rubber, chlorinated polyethylene, epichlorohydrin homo- / copolymer, polychloroprene, sulfurized polyethylene, ethylene-acrylate rubber, ethylene Propylene terpolymer, ethylene-propylene copolymer, polyether-urethane rubber, ethylene-vinyl acetate copolymer, fluororubber, fluorosilicone rubber, hydrogenated nitrile rubber, butyl rubber, dimethylpolysiloxane, nitrile rubber (low, medium, high ACN content , Natural rubber, thioplast, polyfluorophosphazenes, polynorbonene, styrene-butadiene rubber and carboxy group-containing nitrile rubbers or mixtures thereof.
  • silicone elastomers such as silicone
  • elastomers that are accepted as product-contacting materials in pharmaceutical manufacturing processes, e.g. Silicones. These silicone materials can be produced by addition-curing, condensation-curing or free-radical crosslinking. Other preferred materials are natural rubber and synthetic rubber, with natural rubber being particularly preferred.
  • Preferred release film materials have one or more, preferably all of the following properties:
  • property unit preferably particularly preferred hardness Shore A 35 - 90 45 - 75 tear strength [N / mm 2 ] 15 - 30 15 - 30 elongation at break [%] 100 - 900 200 - 900 Tear strength [N / mm] ⁇ 3,2
  • property unit preferably particularly preferred hardness Shore A 35 - 95 45 - 75 tear strength [N / mm 2 ] 6 - 50 8 - 50 elongation at break [%] 100 - 800 200 - 800 Tear resistance [N / mm] > 25
  • property unit preferably particularly preferred hardness Shore A 5 - 80 45 - 75 tear strength [N / mm 2 ] 2.4 - 9.5 6 - 9.5 elongation at break [%] 100 - 600 200 - 600 Tear strength [N / mm] 4.4 - 52.5
  • polyolefins and polyolefin derivatives or copolymers for example polyethylene, polypropylene, polyisobutylene, poly-4-methylpentene and vinyl acetate, vinyl alcohol, acrylic or methacrylic copolymers
  • vinyl polymers eg polystyrene and polystyrene ter and block polymers, eg copolymers of styrene, acrylonitrile and butadiene
  • polyvinyl chloride and copolymers for example copolymers of vinyl chloride and vinyl acetate, methacrylate or acrylonitrile
  • polyvinyl acetate polyvinyl alcohol
  • Polyvinyl methyl ether fluoropolymers such as polytetrafluoroethylene, polyvinyldiene fluoride, polyvinyl fluoride, polyacrylates and methacrylates such as polyacrylonitrile, polymethyl methacrylate, poly
  • thermoplastic polymers whose softening point is above the temperature of the active substance-containing melt when it enters the calendering gap.
  • preference is given to guiding the film as an endless belt through the calendering gap, since this does not result in any film waste.
  • profiled foils e.g. Noppenfolien
  • geometries of the dosage forms can be further changed.
  • the preparation of the dosage forms is carried out starting from a mixture containing one or more active pharmaceutical ingredients and one or more auxiliaries and which is doughy or viscous by melting or softening at least one component and therefore extrudable.
  • N-vinyl lactams especially homopolymers and copolymers of N-vinyl pyrrolidone, e.g. As polyvinylpyrrolidone (PVP), copolymers of N-vinylpyrrolidone and vinyl acetate or vinyl propionate,
  • PVP polyvinylpyrrolidone
  • Cellulose esters and cellulose ethers in particular methylcellulose and ethylcellulose, hydroxyalkylcelluloses, in particular hydroxypropylcellulose, hydroxyalkylalkylcelluloses, in particular hydroxypropylmethylcellulose, cellulose phthalates or succinates, in particular cellulose acetate phthalate and hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose succinate or hydroxypropylmethylcellulose acetate succinate,
  • High molecular weight polyalkylene oxides such as polyethylene oxide and polypropylene oxide and copolymers of ethylene oxide and propylene oxide,
  • Polyacrylates and polymethacrylates such as methacrylic acid / ethyl acrylate copolymers, methacrylic acid / methyl methacrylate copolymers, butyl methacrylate / 2-dimethylaminoethyl methacrylate copolymers, poly (hydroxyalkyl acrylates), poly (hydroxyalkyl methacrylates),
  • Vinyl acetate polymers such as copolymers of vinyl acetate and crotonic acid, partially hydrolyzed polyvinyl acetate (also referred to as partially saponified polyvinyl alcohol),
  • Oligo- and polysaccharides such as carrageenans, galactomannans and xanthans, or mixtures of one or more thereof.
  • homopolymers or copolymers of vinylpyrrolidone are particularly preferred, for.
  • active substances are to be understood as meaning all substances having a desired physiological action on the human or animal body or plants. These are in particular pharmaceutical active ingredients.
  • the amount of active ingredient per unit dose can vary within wide limits. It is usually chosen so that it is sufficient to achieve the desired effect. Also drug combinations can be used.
  • Active substances within the meaning of the invention are also vitamins and minerals.
  • the vitamins include the vitamins of the A group, the B group, which in addition to B 1 , B 2 , B 6 and B 12 and nicotinic acid and nicotinamide and compounds with vitamin B properties are understood, such.
  • adenine 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 substances within the meaning of the invention also include peptide therapeutics and proteins.
  • For plant treatment agents include, for. Vinclozolin, epoxiconazole and quinmerac.
  • the process according to the invention is suitable, for example, for processing the following active substances:
  • the mass may also include various optional adjuvants.
  • optional adjuvants are:
  • Plasticizers such.
  • the concentration of plasticizer if present, is generally 0.5 to 30, preferably 0.5 to 10,% by weight, based on the total weight of polymer and plasticizer.
  • the amount of plasticizer is advantageously at most 30% by weight, based on the total weight of polymer and plasticizer, in order to form storage-stable formulations and dosage forms, which do not show any cold flow, in the area of solid forms.
  • Sugar alcohols such as sorbitol, xylitol, mannitol, maltitol; or sugar alcohol derivatives such as isomalt or hydrogenated condensed palatinose as in DE 102 62 005 described.
  • Solubilizers such as sorbitan fatty acid esters, polyalkoxylated fatty acid esters, such as. B polyalkoxylated glycerides, polyalkoxylated sorbitan fatty acid esters or fatty acid esters of polyalkylene glycols; or polyalkoxylated ethers of fatty alcohols.
  • a fatty acid chain in these compounds usually comprises 8 to 22 carbon atoms.
  • the polyalkylene oxide blocks comprise on average from 4 to 50 alkylene oxide units, preferably ethylene oxide units, per molecule.
  • Suitable sorbitan fatty acid esters are sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan tristearate, sorbitan trioleate, sorbitan monostearate, sorbitan monolaurate or sorbitan monooleate.
  • Suitable polyalkoxylated sorbitan fatty acid esters are, for example, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan tristearate, Polyoxyethylene (20) sorbitan trioleate, polyoxyethylene (4) sorbitan monostearate, polyoxyethylene (4) sorbitan monolaurate or polyoxyethylene (4) sorbitan monooleate.
  • Suitable polyalkoxylated glycerides are z. B. obtained by alkoxylation of natural or hydrogenated glycerides or by transesterification of natural or hydrogenated glycerides with polyalkylene glycols.
  • Commercially available examples are Polyoxyethylenglycerolricinoleat-35, Polyoxyethylenglyceroltrihydroxystearat-40 (Cremophore RH40, BASF AG) and polyalkoxylated glycerides as they are available under the trade names Gelucire® and Labrafil® from Gattefosse, z.
  • Gelucire® 44/14 (lauroyl-macrogol-32-glycerides prepared by transesterification of hydrogenated palm kernel oil with PEG 1500), Gelucire® 50/13 (stearoyl macrogol-32-glycerides prepared by transesterification of hydrogenated palm oil with PEG 1500 ) or Labrafil M1944 CS (oleoyl-macrogol-6-glycerides prepared by transesterification of apricot kernel oil with PEG 300).
  • a suitable fatty acid ester of polyalkylene glycols is e.g. B. PEG-660-hydroxystearic acid (polyglycol ester of 12-hydroxystearic acid (70 mol%) with 30 mol% ethylene glycol).
  • Suitable polyalkoxylated ethers of fatty alcohols are, for. Macrogol 6 cetyl stearyl ether or Macrogol 25 cetyl stearyl ether
  • Solubilizers are typically included in the powder mixture in an amount of 0.1 to 15% by weight, preferably 0.5 to 10% by weight.
  • Disintegrants such as crosslinked polyvinylpyrrolidone and crosslinked sodium carboxymethylcellulose.
  • Extenders or fillers such as lactose, cellulose, silicates or silica
  • Lubricants such as magnesium and calcium stearate, sodium stearyl fumarate,
  • Dyes such as azo dyes, organic or inorganic pigments or dyes of natural origin
  • Stabilizers such as antioxidants, light stabilizers, hydroperoxide destroyers, radical scavengers, stabilizers against microbial attack.
  • the components or a part of the components of the melt are mixed before heating to form a powder mixture.
  • Mixing the components for powder mixing takes place in conventional mixers, such as plowshare mixers, shaker or free-fall mixers and the like.
  • the heating of the powder mixture takes place in a mixing and plasticizing unit customary for this purpose.
  • heatable extruders or kneaders such as mixing kneaders (eg ORP, CRP, AP, DTB from List or Reactotherm from Krauss-Maffei or Ko-Kneader from Buss), Doppelmulden kneaders (tray mixers) and die kneaders (Internal mixer) or rotor / stator systems (eg Dispax from IKA).
  • the residence time of the mass in the extruder is preferably less than 5 minutes, in particular less than 3 minutes.
  • twin-screw extruders rotating in the same direction or in opposite directions and optionally equipped with kneading disks.
  • co-rotating twin screw extruders are particularly preferred.
  • the feeding of the extruder or kneader takes place, depending on their design, continuously or discontinuously in the usual way.
  • the powder mixture is preferably in the free feed, z. B. be introduced via a differential dosing.
  • the pulverulent mixture of the polymer and the active ingredient is introduced at an inlet end into an elongate extruder housing; heats the mixture to obtain a melt; moves the melt through the extruder barrel to an exit end of the extruder barrel; and generates sufficient back pressure in the extruder barrel to allow the melt to exit from an exit end of the extruder barrel as a continuous extrudate.
  • the resulting composition is then subjected to shaping according to the invention.
  • shaping according to the invention In this case, a variety of shapes, depending on the tool and type of molding, can be generated.
  • these forms can also be ground to powder and then compressed in the usual way to tablets.
  • tabletting aids such as colloidal silica, calcium hydrogen phosphate, lactose, microcrystalline cellulose, starch or magnesium stearate can be used.
  • the molding rolls usable in the invention for shaping the melt can be cooled or heated in a manner known per se, and the optimum surface temperature of the molding roll for the respective processing can be adjusted in this manner.
  • the invention is based on the FIGS. 1 and 2 and illustrated by the examples below.
  • Fig. 1a shows a device 1 suitable for carrying out the method according to the invention with counter-rotating forming rollers 2 and 3.
  • the forming rollers 2 and 3 have recesses 4 and 5 on their surface.
  • On the lateral surface of the forming rollers 2 and 3 is a release film 7.
  • the release film 7 is pressed in the nip in the wells 4 and 5. After leaving the nip, the portions of the melt 6 are removed from the mold.
  • Fig. 1 b is an enlarged section of the gap between the forming rollers 2 and 3 from Fig. 1a and shows the release film 7 in its rest position 8 and its deflected position.
  • Fig. 2 shows a further suitable for carrying out the method device 1 with counter-rotating forming rollers 2 and 3.
  • the forming rollers 2 and 3 have recesses 4 and 5 on its surface.
  • Adjustable guide rollers 10 allow the separating films 7 to be guided at a distance from the forming rollers 2 and 3 outside the nip.
  • On the guide rollers 10 mounted screws 11 and 12 (in the Fig. 2 not shown) allow the distance between the guide rollers 10 to vary and thus adjust the tension of the release film 7, when using elastic bands an accurate adjustment of the thickness of the release film 7 in the nip
  • a mixture containing 50% by weight of verapamil hydrochloride, 32% by weight of hydroxypropylcellulose (Klucel EF, Aqualon) and 18% by weight of hydroxypropylmethylcellulose (Methocel K4M; Colorcon) was used in a co-rotating twin-screw extruder at a screw speed of 80 U / min and a melt product temperature of 110 - 120 ° C extruded into a homogeneous extrudate melt.
  • the melt came directly after exiting the extruder head between a pair of counter-rotating mold rolls, the molding rolls each had recesses on their surface, with the help of which in the nip from the melt directly tablets could be formed.
  • the forming rolls were coated with an annular elastomeric film which had been cut out of the gum area of a rubber glove (Duo-Nit Co., material: latex mix, film thickness: 0.4 mm).
  • This elastomeric ring had a slightly smaller diameter than the forming rolls in the unstretched state and therefore sat firmly on the forming roll surface in a slightly stretched state.
  • a Formwalzentemperatur of 10 ° C could with this process from the active ingredient-containing melt directly elongated tablets of about 1000 mg in weight are produced. There were no problems with melt sticking in the cavities of the forming rolls.
  • Example 2 The procedure was as in Example 1, but without using the elastomeric film on the rollers. The melt adhered too much to the calender roll surfaces, i. a demolding of the tablets did not succeed.
  • Example 2 The procedure was as described in Example 1, but with a mixture consisting of 50 wt .-% verapamil hydrochloride, 40 wt .-% hydroxypropyl cellulose (Klucel EF, Aqualon) and 10 wt .-% hydroxypropyl methylcellulose (Methocel K100M; Colorcon ).
  • the calendering was carried out with an elastomer ring (elastomeric film from the cuff area of a rubber glove, Berner, cytostatic rubber glove BI-4021, material: natural latex, film thickness: 0.26 mm). There were no problems with melt sticking in the cavities of the forming rolls.
  • Example 3 The procedure was as in Example 3, but without the use of the rollers on the elastomeric film. The melt adhered too much to the calender roll surfaces, i. a demolding of the tablets did not succeed.
  • Example 2 The procedure was as described in Example 1, but with a mixture consisting of 55 wt .-% hydroxypropyl cellulose (Klucel EF, Aqualon) and 45 wt .-% mannitol (Merck).
  • the calendering was carried out using an elastomer ring (elastomeric film from the cuff area of a rubber glove, Reichelt Chemie-Technik, Thomastat-HSR-2020 15 MIL black gloves, material: soft plastic, film thickness: 0.15 mm). There were no problems with melt sticking in the cavities of the forming rolls.
  • Example 5 The procedure was as in Example 5, but without the use of the rollers on the elastomeric film. The melt adhered too much to the calender roll surfaces, i. a demolding of the tablets did not succeed.
  • a mixture containing 40% by weight of ibuprofen, 20% by weight of sodium carbonate, 10.2% by weight, isomaltol (isomalt F), 23.8% by weight of polyvinylpyrrolidone (Kollidon K30, BASF), 5% by weight cross-linked polyvinylpyrrolidone (Kollidon Cl, BASF), 1 wt .-% Aerosil 200 was extruded in a co-rotating twin-screw extruder at a screw speed of 100 U / min and a melt product temperature of 120 - 130 ° C to form a homogeneous extrudate melt.
  • the melt came directly after exiting the extruder head between a pair of counter-rotating mold rolls, the molding rolls each had depressions on their surface, with the help of which in the nip from the melt directly tablets could be formed.
  • the tablets were readily demoulded using the elastomeric film specified in Example 1. There were no problems with melt sticking in the cavities of the forming rolls.
  • Example 7 The procedure was as in Example 7, but without the use of the rollers on the elastomeric film. The melt adhered too much to the calender roll surfaces, i. a demolding of the tablets did not succeed.

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Claims (18)

  1. Procédé de fabrication de formes de dosage, dans lequel
    i. on amène deux feuilles de séparation l'une contre l'autre dans une zone définie,
    ii. on introduit entre les feuilles de séparation une masse fondue contenant la substance active de telle sorte que dans au moins une des feuilles de séparation il se forme une poche pour recevoir une portion de la masse fondue, on met en contact avec un dissipateur thermique la feuille de séparation dans la zone de la poche avec le côté éloigné de la masse fondue,
    iii. on sépare l'une de l'autre les feuilles de séparation afin de démouler la portion.
  2. Procédé selon la revendication 1, dans lequel on respecte une différence de température d'au moins 30 °C, entre la masse fondue à introduire et le dissipateur thermique.
  3. Procédé selon la revendication 1 ou 2, dans lequel on amène l'une contre l'autre les feuilles de séparation dans l'interstice de deux rouleaux de formage qui tournent en sens contraire et qui présentent sur leur surface des creux qui sont situés de façon opposée les uns aux autres et dans lesquels les feuilles de séparation peut être pressées pour la formation de poches.
  4. Procédé selon une des revendications précédentes, dans lequel les feuilles de séparation sont fermées respectivement pour réaliser une bande sans fin.
  5. Procédé selon la revendication 4, dans lequel les feuilles de séparation reposent sur les périmètres des creux sur les rouleaux de formage.
  6. Procédé selon une des revendications précédentes, dans lequel les feuilles de séparation présentent une épaisseur de 0,05 à 1,6 mm.
  7. Procédé selon une des revendications précédentes, dans lequel les feuilles de séparation sont déformables de façon élastique.
  8. Procédé selon la revendication 7, dans lequel les feuilles de séparation présentent une résistance à la traction de 3 à 40 Mpa selon DIN EN ISO 527-1.
  9. Procédé selon la revendication 7 ou 8, dans lequel les feuilles de séparation sont réalisées en caoutchouc naturel, en caoutchouc synthétique ou en élastomères de silicone.
  10. Procédé selon une des revendications 1 à 6, dans lequel la feuille de séparation est réalisée en polymère thermoplastique insoluble dans l'eau.
  11. Procédé selon une des revendications précédentes, dans lequel au moins une des feuilles de séparation présente une surface structurée.
  12. Procédé de fabrication de formes de dosage avec une unité de mélangeage et de plastification pour la formation d'une masse fondue contenant la substance active et avec des moyens de façonnage (1), composés de deux rouleaux de formage (2) et (3) qui présentent au moins un creux (4), (5) pour recevoir la masse fondue (6) contenant la substance active, le creux (4) (5) comprenant une feuille de séparation (7) qui, par la mise en place de la masse fondue contenant la substance active dans le creux, peut être transposée de façon réversible d'une position de repos (8) vers une position déviée (9), caractérisé en ce que les rouleaux de formage sont constitués en tant que dissipateurs thermiques.
  13. Dispositif selon la revendication 12, caractérisé en ce que la feuille de séparation (7) dans la position déviée est adaptée à la forme du creux (4), (5).
  14. Dispositif selon une des revendications 12 ou 13, caractérisé en ce que la feuille de séparation (7) est déformable de façon élastique.
  15. Dispositif selon une des revendications 12 à 14, caractérisé en ce que les moyens de façonnage (1) comprennent deux rouleaux de formage (2), (3) tournant en sens contraire, au moins un des rouleaux de formage présentant sur sa surface des creux (4) destinés à recevoir la masse fondue contenant la substance active.
  16. Dispositif selon la revendication 15, caractérisé en ce que les deux rouleaux de formage (2), (3) présentent sur leurs surfaces des creux (4), (5) disposés de façon opposée l'un à l'autre.
  17. Dispositif selon la revendication 16, caractérisé en ce que les feuilles de séparation (7) sont respectivement fermées pour réaliser une bande sans fin.
  18. Dispositif selon la revendication 17, caractérisé en ce que chaque rouleau de formage (2) (3) est entouré d'une feuille de séparation (7).
EP06707060.7A 2005-02-17 2006-02-17 Production de formes posologiques à partir de substances actives fondues Active EP1848394B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP06707060.7A EP1848394B1 (fr) 2005-02-17 2006-02-17 Production de formes posologiques à partir de substances actives fondues

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP05003457A EP1693045A1 (fr) 2005-02-17 2005-02-17 Production de formes posologiques à partir de substances actives fondues
PCT/EP2006/001475 WO2006087218A1 (fr) 2005-02-17 2006-02-17 Production de formes de dosage a partir de matieres fondues contenant un principe actif
EP06707060.7A EP1848394B1 (fr) 2005-02-17 2006-02-17 Production de formes posologiques à partir de substances actives fondues

Publications (2)

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EP1848394A1 EP1848394A1 (fr) 2007-10-31
EP1848394B1 true EP1848394B1 (fr) 2013-10-09

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EP05003457A Withdrawn EP1693045A1 (fr) 2005-02-17 2005-02-17 Production de formes posologiques à partir de substances actives fondues
EP06707060.7A Active EP1848394B1 (fr) 2005-02-17 2006-02-17 Production de formes posologiques à partir de substances actives fondues

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP05003457A Withdrawn EP1693045A1 (fr) 2005-02-17 2005-02-17 Production de formes posologiques à partir de substances actives fondues

Country Status (7)

Country Link
US (1) US20090050262A1 (fr)
EP (2) EP1693045A1 (fr)
JP (1) JP2008529852A (fr)
CA (1) CA2598168C (fr)
DK (1) DK1848394T3 (fr)
ES (1) ES2445828T3 (fr)
WO (1) WO2006087218A1 (fr)

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US20090317355A1 (en) * 2006-01-21 2009-12-24 Abbott Gmbh & Co. Kg, Abuse resistant melt extruded formulation having reduced alcohol interaction
TW200950776A (en) * 2008-01-24 2009-12-16 Abbott Gmbh & Co Kg Abuse resistant melt extruded formulation having reduced alcohol interaction
JP2011511782A (ja) 2008-02-12 2011-04-14 アボット・ラボラトリーズ 長期放出性ヒドロコドンアセトアミノフェンならびにその関連方法および用途
CN108309796A (zh) * 2018-01-17 2018-07-24 刘雅文 一种压缩中药饮片及其制备方法
KR102585933B1 (ko) * 2022-09-21 2023-10-06 주식회사 태성공영 구형 성형체 제조장치
CN117698024A (zh) * 2023-12-18 2024-03-15 青岛环球输送带有限公司 一种节能式橡胶硫化机

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DE4446468A1 (de) * 1994-12-23 1996-06-27 Basf Ag Verfahren zur Herstellung von umhüllten Tabletten

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Publication number Priority date Publication date Assignee Title
JPS5722900A (en) * 1980-07-12 1982-02-05 Kurosaki Refract Co Ltd Pocket structure in roll or the like for briquetting machine
SU1600670A2 (ru) * 1987-12-03 1990-10-23 Кемеровский технологический институт пищевой промышленности Устройство дл формовани конфетных масс
JPH0263699A (ja) * 1988-08-29 1990-03-02 Fuji Paudaru Kk 圧縮造粒装置
DE3830353A1 (de) 1988-09-07 1990-03-15 Basf Ag Verfahren zur kontinuierlichen herstellung von festen pharmazeutischen formen
RU1824158C (ru) * 1991-03-11 1993-06-30 Кемеровский технологический институт пищевой промышленности Устройство дл формовани конфетных масс
DE4446467A1 (de) 1994-12-23 1996-06-27 Basf Ag Verfahren zur Herstellung von linsenförmigen Tabletten durch Schmelzkalandrierung
DE19531277A1 (de) 1995-08-25 1997-02-27 Basf Ag Verwendung von Lipiden als Hilfsmittel bei der Herstellung von festen Arzneiformen nach dem Schmelzextrusionsverfahren
DE10242062B4 (de) 2002-09-11 2007-02-15 Südzucker Aktiengesellschaft Mannheim/Ochsenfurt Hydrierte kondensierte Palatinose, Verfahren zu deren Herstellung und deren Verwendung

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Publication number Priority date Publication date Assignee Title
DE4446468A1 (de) * 1994-12-23 1996-06-27 Basf Ag Verfahren zur Herstellung von umhüllten Tabletten

Also Published As

Publication number Publication date
ES2445828T3 (es) 2014-03-05
EP1848394A1 (fr) 2007-10-31
CA2598168C (fr) 2014-09-23
EP1693045A1 (fr) 2006-08-23
CA2598168A1 (fr) 2006-08-24
JP2008529852A (ja) 2008-08-07
US20090050262A1 (en) 2009-02-26
WO2006087218A1 (fr) 2006-08-24
DK1848394T3 (da) 2014-01-20

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