WO2012119997A1 - Composition pharmaceutique pour la fabrication de comprimés à délitement rapide - Google Patents

Composition pharmaceutique pour la fabrication de comprimés à délitement rapide Download PDF

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Publication number
WO2012119997A1
WO2012119997A1 PCT/EP2012/053771 EP2012053771W WO2012119997A1 WO 2012119997 A1 WO2012119997 A1 WO 2012119997A1 EP 2012053771 W EP2012053771 W EP 2012053771W WO 2012119997 A1 WO2012119997 A1 WO 2012119997A1
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WO
WIPO (PCT)
Prior art keywords
film
forming
sugar
weight
tablets
Prior art date
Application number
PCT/EP2012/053771
Other languages
German (de)
English (en)
Inventor
Karl Kolter
Silke Gebert
Sandra Kruse
Michael SCHÖNHERR
Original Assignee
Basf Se
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Basf Se filed Critical Basf Se
Priority to BR112013022017A priority Critical patent/BR112013022017A2/pt
Priority to CN201280012068.0A priority patent/CN103415284B/zh
Priority to EP12706862.5A priority patent/EP2683365A1/fr
Priority to JP2013557067A priority patent/JP2014507454A/ja
Publication of WO2012119997A1 publication Critical patent/WO2012119997A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Definitions

  • the present invention relates to pharmaceutical formulations in the form of granules for the preparation of rapidly disintegrating tablets containing non-film-forming sugars or sugar alcohols, film-forming sugars or sugar alcohols, cross-linked polyvinylpyrrolidone and water-insoluble polymers.
  • Rapidly disintegrating in the mouth and / or rapidly dissolving tablets are becoming increasingly important for the oral administration of drugs.
  • Such tablets must taste pleasant within a short time, preferably within 30 seconds in the oral cavity, and must not leave a sandy feeling.
  • the direct tabletting offers considerable advantages over the wet granulation, and have a high mechanical strength, so they survive packaging procedures, transport and also the squeezing out of packaging unscathed.
  • Fast disintegrating tablets often consist of sugars and sugar alcohols, effervescent systems, microcrystalline cellulose and other non-water-soluble fillers such as calcium hydrogen phosphate, cellulose derivatives, corn starch, or polypeptides.
  • water-soluble polymers conventional disintegrants (crosslinked PVP, Na and Ca salt of crosslinked carboxymethylcellulose, sodium salt of carboxymethyl starch, low-substituted hydroxypropylcellulose L-HPC) and essentially inorganic water-insoluble components (silicas, silicates, inorganic pigments) Commitment.
  • the tablets may also contain surfactants.
  • WO 2003/051338 describes a direct tabletting and readily compressible excipient formulation which contains mannitol and sorbitol.
  • an auxiliary premix is prepared by dissolving mannitol and sorbitol in water followed by spray drying (ordinary spray drying and SBD). Mannitol can additionally be added to this coprocessed mixture. Tablets which additionally contain disintegrants, release agents, pigment and an active ingredient should disintegrate within 60 seconds in the oral cavity.
  • a tablet which disintegrates within 60 seconds in the oral cavity and is mainly formulated from a physical mixture of spray-dried mannitol and a coarse cross-linked polyvinylpyrrolidone as well as a limited selection of active ingredients. These tablets have a breaking strength of about 40N and produce an unpleasant, sandy mouthfeel.
  • a type C methacrylic acid copolymer is to be used as disintegrant.
  • the methacrylic acid copolymer type C is a gastric juice-resistant polymer, which is not soluble in the acidic pH range, in the pH range of 7, as it is in the oral cavity, but is water-soluble.
  • the tablets In addition to a low breaking strength ( ⁇ 20N), the tablets have a high friability (> 7%) and contain a high proportion in the range of
  • EP 0839526 A2 describes a pharmaceutical dosage form consisting of an active ingredient, erythritol, crystalline cellulose and a disintegrant. Furthermore, mannitol is incorporated and crosslinked as disintegrants polyvinylpyrrolidone used, so that a physical mixture is formed. The tablets should disintegrate within 60 seconds in the oral cavity.
  • a disintegrating in the mouth within 60 seconds tablet consisting of an active ingredient, a water-soluble polyvinyl alcohol-polyethylene glycol copolymer, sugar / sugar alcohol (mannitol) and disintegrants is described.
  • WO 2007071581 describes preparations which consist of a sugar or sugar alcohol and cross-linked polyvinylpyrrolidone which are agglomerated with an aqueous dispersion of a water-insoluble polymer.
  • a disadvantage of these preparations is that tablets produced therefrom undergo considerable prolongations of the disintegration time when stored at elevated temperature and elevated humidity.
  • the preparations require relatively high amounts of lubricant in the tableting and they tend to stick to the punches.
  • the object of the present invention was to find quickly disintegrating tablets in the mouth, which leave a pleasant mouthfeel, are mechanically very stable, experience no disintegration prolongations when stored at elevated humidity and temperature and show no tendency to stick in the tableting.
  • rapidly disintegrating tablets containing such preparations were found in the mouth.
  • the tablets disintegrate in the mouth or in an aqueous medium within 40 seconds, preferably within 30 seconds, more preferably within 20 seconds.
  • a sugar or sugar alcohol is then called when an aqueous solution gives a film-like, smooth coating when dried at 45 ° C.
  • Non-film-forming sugars or sugar alcohols show a powdery or crystalline structure after drying.
  • the pharmaceutical preparations contain as component a) 60-96 wt .-% of at least one non-film forming sugar or sugar alcohol, more preferably 80 to 90 wt .-% non-film-forming sugars, sugar alcohols or mixtures thereof.
  • non-film-forming sugars or sugar alcohols are mannitol, erythritol, or xylitol.
  • the sugar or sugar alcohol components are preferably finely divided, with mean particle sizes of from 5 to 100 ⁇ m. preferably 10 to 80 ⁇ . If desired, the particle sizes can be adjusted by grinding.
  • Mannitol, xylitol, erythritol or mixtures thereof are preferably used. Very particularly preferred is mannitol.
  • Component b) used is 1 to 10% by weight of film-forming sugars or sugar alcohols, particularly preferably 2 to 6% by weight of film-forming sugars or sugar alcohols or mixtures thereof.
  • the film-forming sugars or sugar alcohols include: sucrose, glucose, for example in the form of glucose syrup, fructose, lactose, trehalose, sorbitol, maltitol, lactitol, palatinit® (isomalt) and glucose syrup.
  • a film-drawing device for example, is a commercial device such as the Coatmaster 509 MC.
  • film-forming refers to the products that are present as a clear film or coating after the drying process.When crystals are visible or the mass appears powdery, the substances are classified as "non-film-forming". Accordingly, for example, a clear film / coating: sorbitol, lactitol maltitol, palatinite, lactose, sucrose, trehalose or glucose. Crystals or a powdery structure form, for example, mannitol, xylitol or erythritol.
  • disintegrants in amounts of 3 to 25 wt .-%, preferably, 4 to 20 wt .-%, particularly preferably 5 to 15 wt .-%, are used.
  • Suitable disintegrants are cross-linked polyvinylpyrrolidones, sodium croscarmellose, cross-linked Na-carboxymethyl starch or L-hydroxypropylcellulose (L-HPC).
  • L-HPC is a low substituted hydroxypropyl cellulose with a degree of substitution of 5 to 16% (after drying for 1 h at 105 ° C). It is also possible to use mixtures of these disintegrating agents.
  • Preferred disintegrants are cross-linked polyvinylpyrrolidones.
  • Such crosslinked polyvinylpyrrolidones are water-insoluble (less than 1 part in 10,000 parts solvent), but not film-forming.
  • the crosslinked polyvinylpyrrolidone may have an average particle size (volume average) of from 2 to 60 ⁇ m, preferably from 2 to less than 50 ⁇ m, particularly preferably from 2 to less than 30 ⁇ m.
  • Very particular preference is given to cross-linked polyvinylpyrrolidones having a hydration capacity of greater than 6.5 g / g.
  • the hydration capacity is determined by the following method:
  • water-insoluble film-forming polymers in amounts of 0 to 10% by weight, preferably 0 to 6% by weight, particularly preferably 1 to 5% by weight, can be used as component d).
  • the polymers should be film-forming polymers.
  • film-forming means that the polymers in aqueous dispersion have a minimum film-forming temperature of -20 to + 150 ° C., preferably 0 to 100 ° C.
  • Suitable polymers are polyvinyl acetate, ethyl cellulose, methyl methacrylate-ethyl acrylate copolymers, Ethylaci lat-methyl methacrylate-trimethylammoniumethyl methacrylate terpolymers, or Butylmethaci lat-methyl methacrylate-dimethylaminoethyl methacrylate terpolymers
  • the acrylate-methacrylate copolymers are described in detail in the European Pharmacopoeia as Polyacrylate Dispersion 30%, in the USP as Ammonio Methacrylate Copolymer and in JPE as Aminoalkyl-Methacrylate Copolymer E.
  • the preferred component d) is ethylcellulose.
  • Suitable ethylcelluloses usually have an ethoxyl content of 45 to 50%.
  • Such ethylcelluloses and also the determination of the ethoxyl content are described in various pharmacopoeias such as e.g. the USP 34 (201 1) described.
  • the viscosity of the ethyl cellulose measured as a 5% strength by weight solution in toluene / ethanol 8: 2, is 3 to 400 mPas, preferably 4 to 200 and particularly preferably 5 to 100 mPas. The measurement is carried out at 25 ° C in a Ubbelohde viscometer.
  • the taste and appearance of the tablets obtained from the formulations can be further improved by addition of pharmaceutically customary auxiliaries (components e) in amounts of from 0 to 15% by weight, for example as acidifiers, buffer substances, sweeteners, flavors, flavor enhancers and colorants ,
  • auxiliaries for example as acidifiers, buffer substances, sweeteners, flavors, flavor enhancers and colorants .
  • the following substances are particularly suitable here: citric acid, tartaric acid, ascorbic acid, sodium dihydrogen phosphate, cyclamate, saccharin sodium, aspartame, menthol, peppermint flavor, fruit flavors, vanilla flavor, glutamate, riboflavin, beta carotene, water-soluble dyes, finely divided lakes.
  • Suitable substances are, for example, polyvinylpyrrolidones, vinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohols, polyvinyl alcohol-polyethylene glycol graft copolymers, polyethylene glycols, ethylene glycol-propylene glycol block copolymers, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carragenans, pectins, xanthans, alginates.
  • surfactants can also be added as components e).
  • Suitable surfactants are, for example, sodium lauryl sulfate, dioctylsulfosuccinate, alkoxylated sorbitan esters such as polysorbate 80, polyalkoxylated derivatives of castor oil or hydrogenated castor oil, for example Cremophor® RH 40, alkoxylated fatty acids, alkoxylated hydroxyfatty acids, alkoxylated fatty alcohols, alkali metal salts of fatty acids and lecithins.
  • finely divided pigments can be added to further improve the disintegration because they increase the internal interfaces and thus water can penetrate faster in the tablet.
  • these pigments such as iron oxides, titanium dioxide, colloidal or precipitated silica, calcium carbonates, calcium phosphates must be very finely divided, otherwise a grainy taste is produced.
  • the formulations according to the invention in the form of granules can be prepared by built-up agglomeration in mixers, fluidized bed apparatus, paddle dryers or spray towers. In this case, solid starting materials and granulation are first brought together and dried the moist material simultaneously or subsequently.
  • the granulating liquid used is an aqueous solution of component b), the film-forming sugar or sugar alcohol.
  • an aqueous solution of the powdered film-forming sugar or sugar alcohol which is a fluidized mixture of non-film forming sugar or sugar alcohol and crosslinked PVP, and optionally further polymers or adjuvants, is sprayed, thereby agglomerating the fine particles ,
  • a disintegrant preferably crosslinked PVP, is suspended in the aqueous granulating liquid containing the film-forming sugars or sugar alcohols.
  • insoluble film-forming polymer is suspended in the aqueous granulating liquid containing the film-forming sugars or sugar alcohols.
  • a disintegrating agent preferably crosslinked PVP, and insoluble film-forming polymer are suspended.
  • the so-called FSD or SBD fluidized spray drying
  • a solution of the non-film-forming sugar or sugar alcohol in water is first spray-dried, in the lower part of the spray dryer or in a connected fluidized bed is the addition of crosslinked PVP and the injection of an aqueous solution of the film-forming sugar or sugar alcohol as a spray solution, whereby the particles agglomerate , Fine particles can also be blown again in front of the spray nozzle of the sugar or sugar alcohol solution and additionally agglomerated.
  • FSD or SBD process control starting from the crystalline form of non-film-forming sugar or non-film-forming sugar alcohol.
  • the crystalline sugar or sugar alcohol is added at the top of the spray tower or in the fine material recycling stream.
  • the crystalline solid of the non-film-forming sugar (alcohol) is agglomerated in the tower to give granules.
  • the spray-drying of the non-film-forming sugar (alcohol) s usually takes place from aqueous solutions with a concentration of 10 to 50 wt .-%.
  • the film-forming sugar alcohol is usually used in the form of aqueous solutions with a concentration of 1 to 40 wt .-%.
  • the concentration of the film-forming sugar alcohol in the aqueous spray solution can also be varied in two or more process steps.
  • a relative exhaust air humidity of greater than 85% is set by adjusting the spray rate, the supply air temperature, the supply air volume and the humidity of the supply air.
  • the two main parameters are the spray rate and the supply air temperature. An increase in the spray rate and a reduction in the supply air temperature lead to an increase in the exhaust air humidity.
  • the spray rate can be selected in the range of 3 g to 35 g per minute per kg of powder, preferably 5 g to 30 g per minute per kg of powder.
  • the supply air temperatures are 20 to 80 ° C, preferably 30 to 60 ° C.
  • the exhaust air temperatures are 10 to 60 ° C, preferably 10 to 40 ° C and particularly preferably 15 to 30 ° C.
  • the granulation is preferably carried out at a spray rate of 5 g to 30 g per minute per kg Pulvervor- läge in combination with a supply air temperature of 30 to 60 ° C and an exhaust air temperature of 10 to 40 ° C.
  • the granulation is carried out at a spray rate of 6 g to 18 g per minute per kg powder template in combination with a supply air temperature of 35 to 50 ° C and an exhaust air temperature of 15 to 25 ° C.
  • the supply air humidity can be up to 99.5% r.F. be.
  • the concentration of the aqueous spray solution of the film-forming sugar or sugar alcohol is varied in several steps. Initially, the concentration is kept very low - it may even be 0% by weight (spraying water) - to humidify the submitted materials and to set a high exhaust air humidity. This does not involve agglomeration into granules. Thereafter, the concentration of the aqueous spray solution of the film-forming sugar or sugar alcohol is increased, whereby the submitted materials agglomerate into granules. In the individual stages, the process conditions can be varied within the given limits.
  • the mass ratio of the spray solutions of the first and second stages may be varied from 1 to 5 to 5 to 1, preferably 1 to 2 to 2 to 1.
  • the granule size can be controlled by the amount of film-forming sugar or sugar alcohol in the product. The more of this substance is introduced, the larger the granules.
  • the fineness of the spray droplet of the binder solution (adjustable via the atomizing gas pressure), the nozzle geometry and the distance of the nozzle from the product bed can be considered.
  • the finer and more uniformly sprayed, the finer and more uniform the granules result.
  • the atomization gas pressure is usually in the range from 0.5 to 5 bar, preferably from 1.0 to 3.0 bar.
  • nozzles usually two-fluid nozzles are used.
  • the nozzle diameters are usually in the range of 0.5 to 4.0 mm, preferably 0.8 to 3.0 mm.
  • the distance of the nozzles from the product bed depends on the size of the atomizer. Which distances are suitable in the individual case can be determined by the person skilled in the art by means of a few customary tests.
  • the moist material is dried.
  • the intake air temperature is increased in order to accelerate the drying process. Typical temperatures are 30-100 ° C.
  • the materials submitted are sprayed with a solution of the film-forming sugar or sugar alcohol in water and dried simultaneously or subsequently.
  • the granules can also be prepared in a mixer by means of a continuously guided mixture aggregation.
  • a continuously guided mixture aggregation is the so-called “Schugi granulation.”
  • Solid starting materials and the granulating liquid containing the film-forming sugar or sugar alcohol are intensively mixed in a continuously operating, vertically arranged high-speed mixer (see also M. Bohnet, "Mechanical Process Engineering”). , Wiley VCH Verlag, Weinheim 2004, p. 198 ff.)
  • the granules thus obtained have an average particle size (volume average) of 100-600 ⁇ , preferably 120-500 ⁇ and particularly preferably 140-400 ⁇ on.
  • the film-forming sugar or sugar alcohol serves as an agglomerating agent to agglomerate the fine non-film-forming sugars or sugar alcohol crystals and the particles of crosslinked PVP.
  • the granules according to the invention can be tabletted with small amounts of lubricant, which results in no significant influence on the disintegration time. Furthermore, the granules according to the invention do not stick to the punches, whereby higher tabletting speeds and shorter tableting processes are achieved.
  • the formulations according to the invention are preferably suitable for the preparation of tablets rapidly disintegrating in the mouth.
  • the formulations according to the invention can advantageously also be used for the production of tablets which are allowed to disintegrate in a glass of water before use.
  • the production of tablets, which are swallowed intact, is of course possible.
  • the usual methods can be used, wherein the direct tabletting and roll compaction offer particular advantages. Due to the special properties of the formulations according to the invention, generally only the active ingredient, the formulation according to the invention and a lubricant are required.
  • the tablet formulation is thus very simple, very reproducible and easy to validate the procedure.
  • a film-forming sugar or sugar alcohol can function as a very effective binder with appropriate process control, which also significantly accelerates the disintegration of tablets.
  • the production of granules is possible which contain neither a water-soluble polymer nor a water-insoluble polymer as a binder.
  • the use of water-soluble polymers leads to significantly longer disintegration times of tablets, and the use of water-insoluble polymers gives rise to quickly disintegrating tablets, which, however, exhibit considerable disintegration prolongations when stored at elevated temperature and / or elevated humidity.
  • the disintegration time of the preparations according to the invention is not influenced by increased temperature and humidity.
  • the preparations according to the invention have exceptionally good flowability and compressibility, which lead to very stable tablets.
  • the breaking strength of the tablets produced with the aid of the pharmaceutical formulations according to the invention is> 50 N. Frequently, the breaking strengths are above 80 N, even when using difficult to press active ingredients.
  • the friability is ⁇ 0.2%. Damage to the usual tablet handling thus does not occur. Due to the fine cross-linked polyvinylpyrrolidone, the tablets show almost no changes in the tablet surface upon moist storage. In contrast to coarse cross-linked polyvinylpyrrolidone, there is no pilling due to highly swollen particles. The formulations according to the invention are thus very stable on storage and retain their attractive appearance.
  • Examples A-H show the agglomerating effect of film-forming sugars or sugar alcohols.
  • Non-film-forming sugar / sugar alcohol and cross-linked PVP and other auxiliaries were introduced in a fluidized bed and with a 3 wt .-% aqueous solution of film-forming sugar or sugar alcohol, in the fluidized bed granulator (Glatt, GPCG 3.1) by top spray method were sprayed, agglomerated.
  • Table 1 Formulation composition of granules A to H in% by weight AB c DEFGHI
  • Kollicoat® MAE 100 P powder, 97% by weight of methacrylic acid-ethyl acrylate copolymer (1: 1), 2.3% by weight of polysorbate 80, 0.7% by weight of sodium lauryl sulfate
  • Ethyl cellulose 7 mPas, ethoxyl content 48.0 - 49.5%
  • Kollicoat® IR Graft copolymer of 25% by weight of PEG6000 and 75% by weight of polyvinyl alcohol side chains, MW 45,000 D.
  • the granules produced had the following properties: Mean particles
  • the particle size was determined by light diffraction and used as average particle size (volume average) of the D (4,3) value.
  • the granules thus prepared were mixed with 2.0% by weight of lubricant (sodium stearyl fumarate) in a Turbula mixer for 5 minutes. Subsequently, these mixtures were tabletted on a fully instrumented rotary tablet press (Korsch XL 100/8) at a speed of 40 rpm.
  • the rotary tablet press was equipped with 8 punches (10 mm, biplan, faceted). The tablet weight was adjusted to 300 mg. The pressing force was adjusted so that the breaking strength of the tablets was 50 N.
  • the tablets were tested for breaking strength (tablet tester HT-TMB-CI-12 F, Messrs. Kraemer), friability (Roche Friabilator, Erweka) and disintegration time in phosphate buffer pH 7.2 (disintegration tester ZT 74, Erweka).
  • the preparation was carried out analogously to Example B, but instead of a sorbitol solution, a xylitol solution was used.
  • Example B The preparation was carried out analogously to Example B, but the spray rate was adjusted so that a relative exhaust air humidity of 70% resulted.
  • Example L (Comparative Example to Example H of WO 2007/071581)
  • the disintegration time of the tablets directly after preparation was 30 s.
  • the tablets were then stored at 40 ° C./75% RH and at 60 ° C. for 4 weeks.
  • the disintegration time increased to 180s or 204s. Examples M - P
  • Examples M to P show the suitability of a fast disintegrating excipient in a drug formulation.
  • the rapidly disintegrating excipient is prepared by agglomeration in the fluidized bed analogously to Example C.
  • the direct tabletting agent thus prepared was mixed with active ingredient and 0.5 to 1.0% by weight of lubricant (Mg stearate) and then pressed on a rotary tablet press (Korsch PH 100/6) into tablets having a breaking strength of 50 N.
  • Table 3 Active ingredient, amount of active ingredient, tablet weight and diameter of the active ingredient formulations M - P
  • the tablets were tested for breaking strength (tablet tester HT-TMB-CI-12 F, Messrs. Kraemer), friability (Roche Friabilator, Erweka) and disintegration time in phosphate buffer pH 7.2 (disintegration tester ZT 74, Erweka).
  • Non-film-forming sugar / sugar alcohol and crosslinked PVP and other auxiliaries were introduced in a fluidized bed and first with demineralized water and then with a 6 wt .-% aqueous solution of the film-forming sugar or sugar alcohol in the fluidized bed granulator (Glatt, GPCG 3.1) sprayed by topspray method, agglomerated.
  • the following manufacturing conditions were used:
  • Table 1 Formulation composition of the granules Q to S in% by weight
  • the particle size was determined by means of light diffraction and used as average particle size (volume average) of the D (4,3) value.

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Abstract

L'invention concerne une composition pharmaceutique sous forme de granulés contenant a) 60 - 96 % en poids de sucres ou d'alcools de sucre non filmogènes, b) 1 - 10 % en poids de sucres ou d'alcools de sucre filmogènes, c) 3 - 25 % en poids d'un délitant, d) 0 - 10 % en poids de polymères filmogènes insolubles dans l'eau, e) 0 - 15 % en poids d'autres adjuvants pharmaceutiquement courants, la somme totale des composants a) à e) étant égale à 100 %.
PCT/EP2012/053771 2011-03-09 2012-03-06 Composition pharmaceutique pour la fabrication de comprimés à délitement rapide WO2012119997A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR112013022017A BR112013022017A2 (pt) 2011-03-09 2012-03-06 formulação farmacêutica, comprimido, e, método para produzir uma formulação farmacêutica
CN201280012068.0A CN103415284B (zh) 2011-03-09 2012-03-06 用于制备快速崩解的片剂的药物配制物
EP12706862.5A EP2683365A1 (fr) 2011-03-09 2012-03-06 Composition pharmaceutique pour la fabrication de comprimés à délitement rapide
JP2013557067A JP2014507454A (ja) 2011-03-09 2012-03-06 速崩錠を製造するための医薬製剤

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EP11157458.8 2011-03-09
EP11157458 2011-03-09

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023099532A1 (fr) * 2021-12-02 2023-06-08 Basf Se Composition auxiliaire de compression directe

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19615418A1 (de) * 1996-04-22 1997-10-23 Merck Patent Gmbh Polyol-Zusammensetzung
EP0839526A2 (fr) 1996-10-31 1998-05-06 Takeda Chemical Industries, Ltd. Préparation pharmaceutique solide à dissolution ou désintégration buccale rapide
US20020071864A1 (en) 1999-03-25 2002-06-13 Yuhan Corporation Rapidly disintegrable tablet for oral administration
WO2003051338A1 (fr) 2001-12-17 2003-06-26 Spi Pharma, Inc. Systeme glucidique co-traite utilise en tant que matrice a dissolution rapide pour formes posologiques solides
US6696085B2 (en) 1998-07-20 2004-02-24 Antares Pharma Ipl Ag Use of an acrylic type polymer as disintegrating agent
JP2004265216A (ja) 2003-03-03 2004-09-24 Seiko Epson Corp 印刷装置、受信装置、中継装置、印刷システムおよび印刷方法
CN1732905A (zh) * 2004-08-09 2006-02-15 赵力 可直接压片的木糖醇颗粒及其制法
WO2007071581A2 (fr) 2005-12-21 2007-06-28 Basf Se Formulation pharmaceutique destinee a la fabrication de comprimes a desintegration rapide
EP1852109A1 (fr) * 2005-05-08 2007-11-07 Beijing Jianli Pharmaceutical Co. Ltd. Granules de xylitol pouvant etre transformes directement en comprimes et procede de preparation associe

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1020380A (ja) * 1996-07-05 1998-01-23 Minolta Co Ltd カメラ
IN234086B (fr) * 2003-10-15 2009-05-29 Fuji Chem Ind Co Ltd
CN101360480B (zh) * 2005-12-21 2015-04-08 巴斯夫欧洲公司 用于制备快速崩解片剂的药物配制剂
WO2008140772A2 (fr) * 2007-05-08 2008-11-20 Hercules Incorporated Formulation de comprimés robustes à désintégration rapide
CN102046147B (zh) * 2007-06-06 2013-03-20 巴斯夫欧洲公司 用于制备快速崩解的片剂的药物配制剂

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19615418A1 (de) * 1996-04-22 1997-10-23 Merck Patent Gmbh Polyol-Zusammensetzung
EP0839526A2 (fr) 1996-10-31 1998-05-06 Takeda Chemical Industries, Ltd. Préparation pharmaceutique solide à dissolution ou désintégration buccale rapide
US6696085B2 (en) 1998-07-20 2004-02-24 Antares Pharma Ipl Ag Use of an acrylic type polymer as disintegrating agent
US20020071864A1 (en) 1999-03-25 2002-06-13 Yuhan Corporation Rapidly disintegrable tablet for oral administration
WO2003051338A1 (fr) 2001-12-17 2003-06-26 Spi Pharma, Inc. Systeme glucidique co-traite utilise en tant que matrice a dissolution rapide pour formes posologiques solides
JP2004265216A (ja) 2003-03-03 2004-09-24 Seiko Epson Corp 印刷装置、受信装置、中継装置、印刷システムおよび印刷方法
CN1732905A (zh) * 2004-08-09 2006-02-15 赵力 可直接压片的木糖醇颗粒及其制法
EP1852109A1 (fr) * 2005-05-08 2007-11-07 Beijing Jianli Pharmaceutical Co. Ltd. Granules de xylitol pouvant etre transformes directement en comprimes et procede de preparation associe
WO2007071581A2 (fr) 2005-12-21 2007-06-28 Basf Se Formulation pharmaceutique destinee a la fabrication de comprimes a desintegration rapide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
M. BOHNET: "Mechanische Verfahrenstechnik", 2004, WILEY VCH VERLAG, pages: 198 FF

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023099532A1 (fr) * 2021-12-02 2023-06-08 Basf Se Composition auxiliaire de compression directe

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