EP1133271B1 - Procede de fabrication de moules de dosage compacts - Google Patents

Procede de fabrication de moules de dosage compacts Download PDF

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Publication number
EP1133271B1
EP1133271B1 EP99959299A EP99959299A EP1133271B1 EP 1133271 B1 EP1133271 B1 EP 1133271B1 EP 99959299 A EP99959299 A EP 99959299A EP 99959299 A EP99959299 A EP 99959299A EP 1133271 B1 EP1133271 B1 EP 1133271B1
Authority
EP
European Patent Office
Prior art keywords
dosage forms
annular groove
acid
solid dosage
molding
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP99959299A
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German (de)
English (en)
Other versions
EP1133271A1 (fr
Inventor
Jörg Rosenberg
Werner Maier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott GmbH and Co KG
Original Assignee
Abbott GmbH and Co KG
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Publication date
Application filed by Abbott GmbH and Co KG filed Critical Abbott GmbH and Co KG
Publication of EP1133271A1 publication Critical patent/EP1133271A1/fr
Application granted granted Critical
Publication of EP1133271B1 publication Critical patent/EP1133271B1/fr
Anticipated expiration legal-status Critical
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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
    • B30B11/165—Roll constructions

Definitions

  • the present invention relates to a process for the preparation of solid dosage forms by making a plastic Mixture containing at least one active ingredient and at least one polymeric Contains binder, and forms of the plastic mixture to the solid dosage forms in a two-way mold calender rotating forming rollers.
  • Such a method is e.g. from US-A-4,880,585.
  • a drug and binder-containing Mass plasticized with an extruder, and the resulting Melt is subjected to shaping in a mold calender.
  • the forming rollers of the mold calender have depressions on their surface with mutually corresponding outlines.
  • the wells on the surfaces of the forming rollers occur at the contact line the forming rollers for a short time to forms for the active ingredient Melt together and strive in the further rotation of the Forming rollers then apart again, with the molded Dosage forms are released. This procedure has certain Disadvantages.
  • DE4446470A discloses a process for producing divisible Tablets by melt calendering, wherein two molding rolls combined, of which at least one well Has at least one bridge, extending to the generatrix the forming roll extends and the formation of a breaking groove causes.
  • a mold calender with two counter-rotating molding rolls, along their circumference extending annular grooves and along Wraparound rings from radially outward having extending teeth which engage in the annular grooves is known from WO97 / 36722A for briquette production.
  • the present invention is therefore based on the object simple and inexpensive process for the production of solid To provide dosage forms with no problems with respect to an offset of upper and lower half of the dosage forms occur.
  • Form rolls to be used according to the invention are known as "prism rolls” known from compacting technology. It will be on B. Pietsch, Processing Technique 3 (1970) pp. 128-138. There, the use of such rolls for solidifying flowable Bulk goods to granules described. Problems of a possible offset between the upper and lower half of the formed Comprimate are not addressed in this context.
  • roller pairs to be used according to the invention allow, in spite of simple roll construction a considerable variety of shapes the solid dosage forms so prepared.
  • the variations concern primarily the formation of the annular groove and the formation of the gap between successive ones Teeth of a wreath. So the ring groove can be a number of different Cross-sectional profiles (projection onto a plane, the the roll axis contains).
  • the annular groove can be a rectangular, triangular, rounded or any other cross-section respectively. In general, it is preferred that the annular groove for easier to demould the shaped dosage forms into a rounded one Has cross-sectional profile.
  • the longitudinal profile of the spaces between successive Teeth of a wreath (i.e., the projection of the gap on a plane perpendicular to the roll axis) is also subject to one Variation.
  • the spaces between triangular, parallelogram have rounded or another longitudinal profile.
  • the resulting dosage forms can be prepared in this way e.g. Prism shape, Prismatic stump shape, tetrahedral shape or caliper shape have, wherein the caliper shape is preferred.
  • a circumferential ridge and the teeth have a corresponding recess.
  • the individual dosage forms can, especially when the plastic mixture after the complete Cooling shows a higher brittleness, slightly separated from each other become. It may be appropriate to the dosage forms obtained then deburr.
  • the dosage forms are allowed to cool and solid be, e.g. on a cooling belt.
  • the present process for the preparation of solid dosage forms involves the production of a plastic mixture. This is usually done by mixing and melting of at least a pharmacologically acceptable polymeric binder, at least one pharmaceutical agent and, where appropriate customary pharmaceutical additives in the presence or absence of a solvent. These process steps can be based on known Way to be done.
  • the components can first be mixed and then melted and homogenized. Especially when using sensitive However, active ingredients have proven to be preferred First, the polymeric binder, optionally together with conventional pharmaceutical additives, melt and premix, wherein the stirred tank, stirrers, solid mixers, etc. optionally be operated alternately, and then the (the) sensitive Active substance (s) in "intensive mixers" in plastic Phase at very small residence times (homogenize).
  • the active ingredient (s) may be in solid form or be used as a solution or dispersion.
  • suitable Devices are for example described in "Mixing in the production and processing of plastics ", H. Pahl, VDI-Verlag, 1986.
  • Particularly suitable mixing apparatuses are extruders and dynamic and static mixers, as well as stirred tank, single-shaft Stirrers with stripping devices, in particular so-called Paste agitators, multi-shaft agitators, in particular PDSM mixers, Solid mixers and preferably mixing kneading reactors (e.g., ORP, CRP, AP, DTB from List or Reactotherm Company) Krauss-Maffei or Ko-Kneader Fa. Buss), Doppelmuldenkneter (Trough mixer) and stamp mixer (internal mixer) or rotor / stator systems (e.g., Dispax from IKA).
  • kneading reactors e.g., ORP, CRP, AP, DTB from List or Reactotherm Company
  • the first is preferably the first Melting of the polymeric binder in an extruder and then admixing the active ingredient in a mixing-kneading reactor.
  • the charging of the mixing device takes place depending on their design continuously or discontinuously in the usual way.
  • Powdered components may be in free feed, e.g. over a Differential dosing be introduced.
  • Plastic masses can fed directly from an extruder or via a gear pump, especially at high viscosities and high pressures is beneficial to be fed.
  • Liquid media can over a suitable pump unit are metered.
  • the active ingredient and optionally the additive or additives Mixture is doughy to viscous (thermoplastic) and therefore also extrudable.
  • the glass transition temperature of the mixture is below the decomposition temperature of all contained in the mixture Components.
  • the binder should preferably be in physiological Environment be soluble or swellable. Examples for suitable binders are:
  • PVP Polyvinylpyrrolidone
  • NVP
  • the K values (after H. Fikentscher, Cellulose Chemistry 13 (1932), pages 58-64, 71, 74) of the polymers are in the range of 10 to 100, preferably 12 to 70, in particular 12 to 35, for PVP> 17, in particular 20 to 35.
  • Preferred polymeric binders are polyvinylpyrrolidone, copolymers of N-vinylpyrrolidone and vinyl esters, polyhydroxyalkyl acrylates, Polyhydroxyalkyl methacrylates, polyacrylates, polymethacrylates, Alkylcelluloses and hydroxyalkylcelluloses.
  • the polymeric Binder must be in the total mixture of all components in the Range from 50 to 180 ° C, preferably 60 to 130 ° C soften or melt.
  • the glass transition temperature of the mixture must therefore below 180 ° C, preferably below 130 ° C. if necessary It is made by usual, pharmacologically acceptable softening Reduced excipients.
  • the amount of plasticizer is at most 30 wt .-%, based on the total weight of binder and plasticizers to form storage-stable dosage forms, that show no cold flow.
  • the mixture contains no plasticizer.
  • plasticizers examples include:
  • long-chain alcohols ethylene glycol, propylene glycol, glycerol, Trimethylolpropane, triethylene glycol, butanediols, pentanols, such as Pentaerythritol, hexanols, polyethylene glycols, polypropylene glycols, Polyethylene propylene glycols, silicones, aromatic carboxylic acid esters (e.g., dialkyl phthalates, trimellitic acid esters, benzoic acid esters, Terephthalic acid ester) or aliphatic dicarboxylic acid esters (e.g., dialkyl adipates, sebacic acid esters, azelaic acid esters, citric acid).
  • aromatic carboxylic acid esters e.g., dialkyl phthalates, trimellitic acid esters, benzoic acid esters, Terephthalic acid ester
  • aliphatic dicarboxylic acid esters e.g., dialkyl a
  • fatty acid esters such as glycerol mono-, Glycerine di- or Glycerintriacetat or Natriumdiethylsulfosuccinat.
  • concentration of plasticizer is generally 0.5 to 15, preferably 0.5 to 5 wt .-%, based on the total weight of the mixture.
  • Usual galenic adjuvants their total amount up to 100 % By weight, based on the polymer, are e.g. Extenders or fillers, such as silicates or silica, magnesium oxide, Alumina, titania, stearic acid or their Salts, e.g. the magnesium or calcium salt, methyl cellulose, sodium carboxymethyl cellulose, Talc, sucrose, lactose, cereal or corn starch, potato flour, polyvinyl alcohol, in particular in a concentration of 0.02 to 50, preferably 0.20 to 20 wt .-%, based on the total weight of the mixture.
  • Lubricants such as aluminum and calcium stearate, talc and silicones, in a concentration of 0.1 to 5, preferably 0.1 to 3 wt .-%, based on the total weight of the mixture.
  • Plasticizers such as animal or vegetable fats, in particular in hydrogenated form and those which are solid at room temperature. These fats preferably have a melting point of 50 ° C or higher. Preferred are triglycerides of C 12 , C 14 , C 16 and C 18 fatty acids. Even waxes, such as carnauba wax, are useful. These fats and waxes may advantageously be admixed alone or together with mono- and / or diglycerides or phosphatides, in particular lecithin. The mono- and diglycerides are preferably derived from the fatty acid types mentioned above. The total amount of fats, waxes, mono-, diglycerides and / or lecithins is 0.1 to 30, preferably 0.1 to 5 wt .-%, based on the total weight of the mass for each layer;
  • Dyes such as azo dyes, organic or inorganic pigments or dyes of natural origin, with inorganic Pigments in a concentration of 0.001 to 10, preferably 0.5 to 3 wt .-%, based on the total weight of the mixture is preferred are;
  • Stabilizers such as antioxidants, light stabilizers, hydroperoxide destroyers, Radical scavengers, stabilizers against microbial Infestation.
  • excipients according to the invention are also substances for preparing a solid solution with the pharmaceutical To understand the active substance.
  • these adjuvants are for example Pentaerythritol and pentaerythritol tetracaetate, polymers such as e.g. Polyethylene or polypropylene oxides and their block copolymers (Poloxamers), phosphatides such as lecithin, homo- and copolymers of Vinylpyrrolidones, surfactants such as polyoxyethylene-40-stearate and citric and succinic acid, bile acids, sterols and others like e.g. in J.L. Ford, Pharm. Acta Helv. 61 (1986) pp. 69-88.
  • auxiliaries also additives of bases and Acids to control the solubility of an active agent (see for example, K. Thoma et al., Pharm. Ind. 51 (1989) 98-101).
  • compositions in the context of the invention are to be understood as meaning all substances having a pharmaceutical action and the lowest possible side effects, provided that they do not decompose under the processing conditions.
  • the amount of active ingredient per unit dose and the concentration can vary within wide limits depending on the efficacy and rate of release. The only condition is that they are sufficient to achieve the desired effect.
  • the concentration of active ingredient in the range of 0.1 to 95, preferably from 20 to 80, in particular 30 to 70 wt .-% are.
  • Active substances within the meaning of the invention are also vitamins and minerals, as well as plant treatment agents and insecticides.
  • 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 compounds with vitamin B properties are understood, such as adenine, choline, pantothenic acid , Biotin, adenylic acid, folic acid, orotic acid, pangamic acid, carnitine, p-aminobenzoic acid, myo-inositol and lipoic acid as well as 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.
  • the inventive method is for example for processing suitable for the following active substances:
  • Preferred active ingredients are ibuprofen (as racemate, enantiomer or enriched enantiomer), ketoprofen, flurbiprofen, acetylsalicylic acid, Verapamil, paracetamol, nifedipine or captopril.
  • solid solutions can lead to the formation of solid solutions.
  • solid solutions is familiar to the person skilled in the art, for example from the literature cited above.
  • active ingredients in polymers is the Active ingredient molecular dispersion in the polymer before.
  • the resulting mixture is preferably solvent-free, i. it contains neither water nor an organic solvent.
  • the obtained Mixture is then placed in a mold calender discussed above introduced.
  • compositions can also be used in conventional Be provided with film coatings, which the drug release control or cover the taste.
  • suitable Materials for such coatings are polyacrylates, such as the Eudragit types, Cellulose esters, such as the hydroxypropylmethylcellulose phthalates, and cellulose ethers such as ethyl cellulose, hydroxypropylmethyl cellulose or hydroxypropylcellulose.
  • the ring groove can be rectangular (a), triangular (b) or rounded (c) have cross-sectional profile.
  • the annular groove On the ground the annular groove may be a circumferential web (d), the leads to solid dosage forms on one side of their surface have a breaking notch.
  • FIG. 3 illustrates the design principle of a pair of rollers with two tracks, one roller having two circumferential annular grooves having rounded cross-sectional profile and the other roller two circumferential rings extending radially outward Having teeth, wherein the spaces between successive Teeth have a rounded longitudinal profile.
  • Figure 3 shows above a cross section of the roller pair through the roller axes.
  • Figure 3 shows below a cross section of the roller pair perpendicular to the roll axes.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (5)

  1. Procédé de fabrication de formes galéniques solides consistant à
    a) préparer un mélange plastique contenant au moins un agent actif et au moins un liant polymère et
    b) mouler le mélange plastique en formes galéniques solides dans une calandre de moulage ayant deux rouleaux de moulage tournant en sens inverse, caractérisé en ce qu'un rouleau de moulage présente au moins une rainure annulaire le long de sa périphérie et l'autre rouleau de moulage au moins une couronne de dents s'étendant radialement vers l'extérieur le long de sa périphérie, qui peuvent s'engager dans la rainure annulaire.
  2. Procédé selon la revendication 1, caractérisé en ce que la rainure annulaire présente un profil de section arrondi.
  3. Procédé selon la revendication 1 ou 2, caractérisé en ce que les espaces intermédiaires entre les dents successives d'une couronne présentent un profil longitudinal arrondi.
  4. Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce qu'une entretoise périphérique se trouve sur le fond de la rainure annulaire et en ce que les dents présentent un évidement correspondant.
  5. Procédé selon l'une quelconque des revendications précédentes, caractérisé en ce que les formes galéniques obtenues sont ébavurées.
EP99959299A 1998-11-23 1999-11-22 Procede de fabrication de moules de dosage compacts Expired - Lifetime EP1133271B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19853985 1998-11-23
DE19853985A DE19853985A1 (de) 1998-11-23 1998-11-23 Verfahren zur Herstellung von festen Dosierungsformen
PCT/EP1999/008995 WO2000030586A1 (fr) 1998-11-23 1999-11-22 Procede de fabrication de moules de dosage compacts

Publications (2)

Publication Number Publication Date
EP1133271A1 EP1133271A1 (fr) 2001-09-19
EP1133271B1 true EP1133271B1 (fr) 2004-09-01

Family

ID=7888719

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99959299A Expired - Lifetime EP1133271B1 (fr) 1998-11-23 1999-11-22 Procede de fabrication de moules de dosage compacts

Country Status (8)

Country Link
US (1) US6737005B1 (fr)
EP (1) EP1133271B1 (fr)
JP (1) JP4488143B2 (fr)
AT (1) ATE274896T1 (fr)
CA (1) CA2351484C (fr)
DE (2) DE19853985A1 (fr)
ES (1) ES2226469T3 (fr)
WO (1) WO2000030586A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7364752B1 (en) 1999-11-12 2008-04-29 Abbott Laboratories Solid dispersion pharamaceutical formulations
DE60028754T2 (de) * 1999-11-12 2007-05-31 Abbott Laboratories, Abbott Park Feste dispersion mit ritonavir, fenofibrat oder griseofulvin
DE10026698A1 (de) * 2000-05-30 2001-12-06 Basf Ag Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung
US7122143B2 (en) 2001-09-28 2006-10-17 Mcneil-Ppc, Inc. Methods for manufacturing dosage forms
US7838026B2 (en) 2001-09-28 2010-11-23 Mcneil-Ppc, Inc. Burst-release polymer composition and dosage forms comprising the same
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
US8377952B2 (en) * 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
CA2649372A1 (fr) * 2006-06-07 2007-12-13 Novartis Ag Procede de fabrication de multiparticules utilisant un rouleau compacteur
US20100040721A1 (en) * 2008-08-12 2010-02-18 Dec Roman T Roller press for high pressure briquetting of biomass, low rank coals and other fibrous materials
FR2936811B1 (fr) * 2008-10-08 2012-07-27 Crea Bloc allume-feu, procede de fabrication de celui-ci et dispositif pour la mise en oeuvre du procede
GB0915389D0 (en) 2009-09-03 2009-10-07 Sericol Ltd Printing ink

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3890080A (en) * 1974-01-22 1975-06-17 Iu Conversion Systems Roll-pelletizer for making uniform particle size pellets
DE3612211A1 (de) 1986-04-11 1987-10-15 Basf Ag Kontinuierliches verfahren zum tablettieren
DE3612212A1 (de) * 1986-04-11 1987-10-15 Basf Ag Verfahren zur herstellung von festen pharmazeutischen formen
DE3830353A1 (de) * 1988-09-07 1990-03-15 Basf Ag Verfahren zur kontinuierlichen herstellung von festen pharmazeutischen formen
US5049333A (en) * 1990-09-17 1991-09-17 The Clorox Company Briquet forming apparatus and method
DE4446470A1 (de) 1994-12-23 1996-06-27 Basf Ag Verfahren zur Herstellung von teilbaren Tabletten
AU2554597A (en) * 1996-03-29 1997-10-22 Startec, Inc. Briquet forming machine
US20010001670A1 (en) * 1997-03-31 2001-05-24 Kenneth A. Krismanth Briquet forming machine and feeder system therefor
DE19753298A1 (de) * 1997-12-01 1999-06-02 Basf Ag Verfahren zur Herstellung von festen Dosierungsformen
DE19840256A1 (de) * 1998-09-03 2000-03-09 Basf Ag Verfahren zur Herstellung von beschichteten festen Dosierungsformen
DE19843904A1 (de) * 1998-09-24 2000-03-30 Basf Ag Feste Dosierungsform mit polymerem Bindemittel
DE19847618A1 (de) * 1998-10-15 2000-04-20 Basf Ag Verfahren zur Herstellung von festen Dosierungsformen

Also Published As

Publication number Publication date
ES2226469T3 (es) 2005-03-16
JP4488143B2 (ja) 2010-06-23
EP1133271A1 (fr) 2001-09-19
WO2000030586A1 (fr) 2000-06-02
US6737005B1 (en) 2004-05-18
DE59910408D1 (de) 2004-10-07
DE19853985A1 (de) 2000-05-25
ATE274896T1 (de) 2004-09-15
CA2351484C (fr) 2008-10-21
JP2002530155A (ja) 2002-09-17
CA2351484A1 (fr) 2000-06-02

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