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WO1998036737A1 - Procede de granulation par voie humide - Google Patents

Procede de granulation par voie humide Download PDF

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Publication number
WO1998036737A1
WO1998036737A1 PCT/US1997/002830 US9702830W WO9836737A1 WO 1998036737 A1 WO1998036737 A1 WO 1998036737A1 US 9702830 W US9702830 W US 9702830W WO 9836737 A1 WO9836737 A1 WO 9836737A1
Authority
WO
WIPO (PCT)
Prior art keywords
mixture
granules
granulating fluid
granulating
group
Prior art date
Application number
PCT/US1997/002830
Other languages
English (en)
Inventor
Ashok Premchand Luhadiya
Original Assignee
The Procter & Gamble Company
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 The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to PCT/US1997/002830 priority Critical patent/WO1998036737A1/fr
Priority to AU19707/97A priority patent/AU1970797A/en
Priority to JP10512609A priority patent/JPH11506473A/ja
Priority to IDP980300A priority patent/ID19965A/id
Publication of WO1998036737A1 publication Critical patent/WO1998036737A1/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
    • A61K9/14—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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Definitions

  • the present invention relates to a method of preparing granules comprising an active ingredient and a carrier.
  • the present method is suitable for preparing granule compositions.
  • Granulating techniques are widely used in various industries, for example, in the manufacture of pharmaceutical products, food products, and washing and cleaning agents.
  • a starting material comprises a mixture of particles of varying sizes, or small particles (such as powder)
  • these materials are typically granulated to facilitate subsequent handling in an industrial process.
  • a tablet is a typical product formed by compressing granules into a predetermined shape.
  • Granule properties play an important role in the overall dissolution and/or disintegration property of a tablet formed from the granules.
  • the dissolution and/or disintegration property of a tablet can be of critical importance in, e.g., a pharmaceutical product.
  • wet granulating methods
  • dry granulating methods
  • ingredients e.g., active ingredients, carriers, flavors, coloring agents, and the like
  • wet granulation method is widely used and usually produces the most satisfactory results in pharmaceutical products.
  • wet granulating methods known in the art for preparing granules include: mixing or blending ingredients; treating the mixture with an amount of solution comprising, for example, binding agents, to obtain a mass which is forced through a screen having openings of a predetermined size; drying on trays, in drying machines, and the like; and re-grinding and re-screening to obtain granules having suitable size such as those used for compression into tablets.
  • known wet granulating methods may not be suitable for some medicinal agents which are sensitive to moisture.
  • Medical agents and granulating mass used for known wet granulating methods may also be sensitive to exposure to high temperature even over a short time and/or exposure to lower temperature for a long time at the drying step, when granulating fluids are removed. Extended granule drying time is also costly, even if the resulting quality of granules is acceptable.
  • the known wet granulating methods can produce undesirably hard granules.
  • the hardness of a granule may be caused by using excessive levels of granulating fluids and/or excessive levels of binding agent and/or over mixing (e.g., for an extended period of time) of the components, and/or slow evaporation of any excess granulating fluid from the final products. If the granulating fluid is allowed to evaporate during storage, the granules may become undesirably hard. Consequently, tablets comprising such hard granules may also be undesirably hard. Such hardness can result in poor dissolution and/or disintegration of the tablet when contacted with saliva or water in the mouth.
  • the present invention is directed to a method for making granules comprising the steps of: (a) applying a granulating fluid onto a mixture of an active ingredient and a carrier; (b) heating the mixture of step (a) in an air-tight container; and (c) drying the mixture of step (b); wherein the resulting mixture is in the form of a granule having an average particle size of from about 150 microns to about 850 microns and comprising no more than about 1.5% of the granulating fluid.
  • a method satisfies the need for a wet granulating method which provides granules having improved dissolving and/or disintegrating properties when contacted with water.
  • the granules obtained by the method of the present invention may further be tabletted to provide a tablet which is smooth, soft and chewable.
  • the present invention is further directed to a composition comprising the granules of the present invention.
  • Such a composition satisfies the need for, e.g., a tablet which is readily chewable and/or readily dissolves and/or disintegrates in one's mouth.
  • the present invention relates to a method of making granules comprising:
  • the resulting mixture of the present invention is in the form of a granule having an average particle size of from about 150 microns to about 850 microns and comprising no more than about 1.5% of the granulating fluid.
  • the granulating method of the present invention can be used for a variety of products in different industrial areas wherein conventional wet granulating methods have been useful.
  • Example products include pharmaceuticals; food, animal feed, seasoning, and beverage preparations; cleaning powders; fertilizers; pesticides; and cosmetics.
  • the method of the present invention is particularly useful for granules for use in pharmaceutical products which are designed to readily dissolve and/or disintegrate upon contact with water or saliva.
  • the method of the present invention is particularly useful for granules for pharmaceutical products which are subjected to tabletting.
  • the first step (“step (a)"), of the present invention comprises applying a granulating fluid onto a mixture of an active ingredient and a carrier.
  • the active ingredient and the carrier useful herein may be in solid or liquid form; preferably one or both are in a solid form.
  • a more uniform mixture of the active ingredient and the carrier can be obtained by pre-mixing these components prior to applying the granulating fluid. Such pre-mixing of these components prior to applying the granulating fluid will result in a more uniform distribution of the active ingredient and carrier in the subsequently formed mixture.
  • Any equipment which is generally used for mixing or blending ingredients such as powders are acceptable for mixing the ingredients so long as it provides generally uniform mixing, yet produce minimal dust generation.
  • Equipment useful in the present method include planetary mixer, sigma mixer, mass mixer, Hobart mixer, ribbon blender, V-blender, processall mixer, and the like; preferably the planetary mixer.
  • the equipment comprises a spraying system.
  • the conditions for mixing ingredients and the pre-mixing, if needed, can be selected depending on the property of ingredients which are mixed.
  • Active Ingredient refers to the material intended to be delivered to (e.g. ingested by) the user, via the medium of the granules of the present invention.
  • the active ingredient may be any compound, preferably solid and not heat- sensitive, and thus stable under the below mentioned process conditions.
  • suitable active ingredients include pharmaceuticals and health supplements, main components of food, animal feed, seasoning, and beverage preparations, surfactants for cleaning powders and effervescent tablets, fertilizing agents for fertilizers, bioactive ingredients for pesticides, and pigments for cosmetics.
  • Example pharmaceuticals and health supplements which can be used as active ingredients include antacids, analgesics, anti-histamines, decongestants, herb powders, laxatives, vitamins, minerals, and mixtures thereof.
  • the method of the present invention is particularly useful for making granules or tablets comprising an antacid, as antacids are generally stable to heat.
  • Antacids which can be used in the present invention include those selected from the group consisting of a metal carbonate compound, a metal hydroxide compound, a metal oxide compound, a bismuth subsalicylate, and mixtures thereof.
  • Nonlimiting examples of the antacids include, for example, aluminum carbonate, calcium carbonate, magnesium carbonate, aluminum hydroxy- carbonate, dihydroxy aluminum sodium carbonate, aluminum hydroxide, magnesium hydroxide, aluminum phosphate, calcium phosphate, aluminum magnesium glycinate, magnesium glycinate, dihydroxy aluminum amino acetate, dihydroxy aluminum aminoacetic acid, aluminum magnesium hydrated sulfate, magnesium aluminate, magnesium oxide, magnesium alumino silicate, magnesium trisilicate, sucralfates, and mixtures thereof.
  • Preferred antacids are selected from the group consisting of calcium carbonate, dihydroxy aluminum sodium carbonate, aluminum hydroxide, magnesium hydroxide, and mixtures thereof; more preferably calcium carbonate.
  • the resulting mixture of step (a) comprises an effective amount of an antacid, preferably from about 20% to about 95%, more preferably from about 35% to about 70%, more preferably still from about 40% to about 60% by weight of the mixture of the active ingredient and the carrier.
  • Carrier preferably from about 20% to about 95%, more preferably from about 35% to about 70%, more preferably still from about 40% to about 60% by weight of the mixture of the active ingredient and the carrier.
  • Carriers useful in the present method can be any compound which are not heat-sensitive, not moisture-sensitive, and useful for conventional wet granulating methods.
  • the carrier is selected depending upon the compatibility with the active ingredient, and the desired characteristic of the product. It is recognized that some carriers may also have properties as a binding agent. These carriers may be useful for providing improved binding within the mixture of step (a), and the final mixture of the present invention.
  • the carrier is in a solid form.
  • the carrier may be added with the granulating fluid as described hereinafter.
  • Example carriers useful in combination with active ingredients for pharmaceutical products include those selected from the group consisting of sugar, sugar alcohols, and mixtures thereof.
  • Nonlimiting examples of sugars useful herein include lactose, glucose, maltodexthns, and sucrose.
  • Sugar alcohols useful herein include sorbitol, xylitol, mannitol and maltitol.
  • a preferred carrier of the present invention is selected from the group consisting of sucrose, mannitol, and mixtures thereof.
  • a more preferred carrier is sucrose, which is generally used for antacid products.
  • the carrier is present in the final mixture resulting from the method at an effective level, preferably at a level of from about 5% to about 80%, more preferably from about 35% to about 70%, more preferably still from about 40% to about 60% by weight of the mixture of the active ingredient and the carrier.
  • Granulating fluid means a fluid which is suitable for making granules, wherein the granulating fluid is applied onto a mixture of the active ingredient and the carrier at step (a), then removed during a drying step to form granules.
  • the hardness of the granule is caused by using excessive levels of granulating fluids and/or excessive levels of binding agent and/or over mixing (e.g., for an extended period of time) of the components, and/or slow evaporation of any excess granulating fluid from the final products. If the granulating fluid is allowed to evaporate during storage, the granules and/or the resulting tablets may become undesirably hard.
  • Suitable granulating fluids useful herein include water, a mixture of water and ethyl alcohol, and isopropyl alcohol; more preferably water.
  • the total amount of the granulating fluid added at step (a) is selected depending upon the wetting capacity of the mixture of the active ingredient and the carrier.
  • the viscosity and binding capability of binding agents which may be added if needed, may also affect the total amount of the granulating fluid to be used.
  • the amount of granulating fluid added to the active ingredient and the carrier is from about 2% to about 5.5% by weight of the active ingredient and the carrier.
  • the total amount of the granulating fluid used in the present invention is from about 20% to about 80 % less than the granulating fluid used in conventional wet granulating methods. Consequently, the method can reduce drying time for making granules.
  • the granulating fluid can further comprise other ingredients.
  • additional ingredients are neither heat sensitive nor moisture sensitive.
  • These ingredients can be either solid or liquid in form.
  • Example ingredients include sorbitol and xylitol.
  • the granulating fluid may also comprise a binding agent.
  • a binding agent is particularly useful when a carrier, such as mannitol, may have a limited ability to bind the components of step (a) and/or the final resulting granules of the present method.
  • the levels and types of binding agent are selected depending upon the character of the carriers, compatibility with other components, and desired characteristic of the final product.
  • binding agents examples include sugar, sugar alcohols, starches such as starch paste and pregelatinized starch, poiyvinylpyrrolidone, cellulose derivatives, gelatin, gums, and mixture thereof.
  • Preferred binding agents include sucrose, glucose, and mixtures thereof.
  • the binding agent and the carrier may be made of the same material (e.g., a sugar carrier, and a granulating fluid comprising water and sugar as the binding agent).
  • the binding agent and the carrier may be altogether different.
  • mannitol may be used as a carrier.
  • sugar may be used as a binding agent.
  • their use as a carrier may negate the need to add a binding agent to the granulating fluid (e.g., granulating fluid may merely be water).
  • the mixture of step (a) comprises an effective amount of the binding agents, preferably from about 0.1% to about 10% by weight, more preferably from about 0.2% to about 5%, more preferably still from about 0.5% to about 3%.
  • the granulating fluid may further comprise a coloring agent.
  • a coloring agent is added with the granulating fluid to facilitate a uniform distribution and mixing.
  • the coloring agent is present at an effective level, preferably from about 10ppm to about 500ppm, more preferably from about 20ppm to about 250ppm by weight.
  • step (b) comprises heating the mixture of step (a) in an air-tight container.
  • Air-tight container refers to a container having an airproof condition (i.e., completely sealed without any leaks) during the heating step, to facilitate or favor the process of making granules
  • the temperature and time period used for heating the mixture of step (a) is selected depending upon the desired characteristics of the resulting mixture (such as crystal structure and chemical property) so long as the temperature is distributed uniformly without overheating.
  • the higher the temperature the shorter the time required for heating or drying the mixture of ingredients. Higher temperatures however, may cause melting, browning, undesirable chemical reaction between ingredients, and/or degradation of the ingredients or the resulting mixture. A higher temperature may even change the crystal structure of the ingredients in the resulting mixture. A higher temperature may also result in a non-uniform distribution of heat. A lower temperature requiring increased time at the heating step may cause similar interactions.
  • the temperature for heating the mixture of step (a) is from about 50°C to about 100°C.
  • the mixture of step (a) is heated from about 5 minutes to about 180 minutes. More preferably the mixture of step (a) is heated at, at least about 50°C for about 55 to about 135 minutes; more preferably at least about 70°C for about 20 to about 45 minutes; more preferably still at least about 80°C for about 5 to about 20 minutes in an air-tight container.
  • the method further comprises drying the mixture of step (b).
  • the resulting mixture of the present invention hereinafter called a "resulting granule,” is in the form of a granule comprising no more than about 1.5% by weight of the granulating fluid.
  • the resulting granules have an average particle size of from about 150 microns to about 850 microns.
  • the resulting granules can comprise less than about 10% particles which are above about 1200 microns or below about 50 microns.
  • the resulting granules of the present invention can provide excellent properties such as improved dissolving and/or disintegrating and softness in the mouth when contacted with water or saliva.
  • the granules made by the method of the present invention are bound by the combination of absorbed layer bonding and liquid bridge bonding mechanisms.
  • the granules made by the method may further provide a good free flowing benefit and thereby easily processed.
  • any conventional drying equipment is acceptable.
  • Useful equipment includes for example, fluidized bed drier, vacuum drier, and the like.
  • the temperature and time period used for drying the mixture of step (b) is selected depending upon the characteristics of the active ingredients, carriers, and the resulting granules.
  • Preferably granules to be used for pharmaceuticals are dried at a temperature of from about 60°C to about 80 O C.
  • the dried granules are, then passed through sieves #14 to have a desirable granule size.
  • the sieves used herein are corresponded to those proposed as an international standard (ISO; International Standardization Organization).
  • ISO International Standardization Organization
  • a particle that passes through sieves #14 s e.g., U.S. Series Alternate Sieve Designation with 1400 micron opening
  • the method for making granules of the present invention may be useful in a variety of industrial areas such as pharmaceutical, food and beverage, detergent, fertilizer, pesticide, and cosmetic areas, wherein a conventional wet granulation method has previously been useful.
  • Example products made from the resulting granules of the present invention include tablet or granules (e.g., powder) for hot or cold drink mixes; pharmaceuticals; salt, animal feed, seasoning preparations; cleansing powders; detergents; fertilizer; pesticides; and cosmetics.
  • the granules made by the method can be formulated into tablets, filled in capsules, or packed in sachets.
  • the resulting granules of the present invention are used to make a pharmaceutical tablet composition.
  • the pharmaceutical tablet composition made by the granules may further comprise from about 3% to about 30%, by weight of the tablet, of one or more other ingredients such as tableting aids, flavors, sweetening agents, and ingredients used in conventional pharmaceutical tablets.
  • Tabletting aids refers to an ingredient that is added to the granules in small quantities to provide flowability to granules, to reduce friction, and/or to ease removal of the tablets from the tableting machine.
  • the tableting aids useful herein include, for example, magnesium stearate, stearic acid, aerosil, talc, and mixtures thereof. Excess amount of other ingredients other than those added during making granules prepared as mentioned may not be distributed uniformly.
  • the other ingredients are in a solid form to facilitate operating flowability and product stability.
  • ingredients for tableting useful herein include, for example, diluents such as glucose, mannitol and direct compressible sugar; flavoring agents; sweetening agents; coloring agents; stabilizing agents such as agar, pectin, gums and starches; antioxidants such as ascorbic acid and BHA; cooling agents such as TK-10, WS-3 and WS-23; preservatives such as potassium sorbate and Sodium benzoate, and the like, referred to in U.S. Patent number 5,244,670, issued September 14, 1993 to Upson et. al; as well as other non-toxic compatible substances used in pharmaceutical formulation.
  • the resulting tablets dissolve and/or disintegrate smoothly when contacted with water or saliva and produce little to no gritty sensation in the user's mouth.
  • Examples I - V For Examples I through V, the sugar and CaC ⁇ 3 are mixed in a planetary mixer bowl (Rama Pharma, India). Water containing a dye is sprayed onto the mixture in the planetary mixer bowl during blending. The mixture is blended about 5 minutes at 60rpm. After the mixing is completed, the planetary mixer bowl is closed. The planetary mixer bowl is then heated to a temperature of at least about 80°C for about 20 minutes to agglomerate the mixture. The resulting agglomerates are dried at about 60°C in a tray drier to reduce the granulating fluids to levels below about 1.5% by weight of the resulting granules. The dried agglomerates are passed through #14 sieves. The resulting granules provide a soft mouth feel with minimal to no grittiness.
  • the granules are mixed with glucose and blended for about 4 minutes. Flavor is then added and blended for about 4 more minutes. Magnesium stearate and Talc (in 1 :1 ratio) is added, the ingredients are mixed for another 2 minutes. The mixture is fed into a tableting machine to be compressed into tablets.
  • a 20% sugar solution is prepared. Mannitol and CaC ⁇ 3 are mixed in a planetary mixer bowl (Rama Pharma, India). The 20% sugar solution is sprayed onto the mixture in the bowl during blending. The mixture is blended for about 5 minutes at 60rpm. After the mixing is completed, the planetary mixer bowl is closed. The planetary mixer bowl is then heated to a temperature of at least about 80°C for about 20 minutes to agglomerate the mixture. The resulting agglomerates are dried at about 60°C in a tray drier to reduce the granulating fluids to levels below about 1.5% by weight of the resulting granules. The dried agglomerates are passed through #14 sieves.
  • the resulting granules are mixed with a direct compressible sugar and blended for about 4 minutes. Flavor is then added, the mixture is blended for about 4 more minutes. Magnesium stearate and Talc (in a 1 :1 ratio) is added, followed by an additional 2 minutes of mixing. The resulting mixture is fed into a tableting machine to be compressed into tablets.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un procédé de production de granulés consistant (a) à appliquer un fluide de granulation sur un mélange constitué d'un principe actif et d'un excipient; (b) à chauffer le mélange de l'étape (a) dans un contenant étanche; et (c) à sécher le mélange de l'étape (b). Le mélange obtenu se présente sous la forme de granulés présentant une taille moyenne de particules comprise entre environ 150 microns et environ 850 microns, et comprenant une proportion inférieure ou égale à environ 1,5 % du fluide de granulation. L'invention concerne également des compositions contenant lesdits granulés obtenus selon ce procédé.
PCT/US1997/002830 1997-02-25 1997-02-25 Procede de granulation par voie humide WO1998036737A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
PCT/US1997/002830 WO1998036737A1 (fr) 1997-02-25 1997-02-25 Procede de granulation par voie humide
AU19707/97A AU1970797A (en) 1997-02-25 1997-02-25 Wet granulating method
JP10512609A JPH11506473A (ja) 1997-02-25 1997-02-25 湿式粒状化方法
IDP980300A ID19965A (id) 1997-02-25 1998-02-27 Metoda pembutiran basah

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1997/002830 WO1998036737A1 (fr) 1997-02-25 1997-02-25 Procede de granulation par voie humide

Publications (1)

Publication Number Publication Date
WO1998036737A1 true WO1998036737A1 (fr) 1998-08-27

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ID=22260415

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/002830 WO1998036737A1 (fr) 1997-02-25 1997-02-25 Procede de granulation par voie humide

Country Status (4)

Country Link
JP (1) JPH11506473A (fr)
AU (1) AU1970797A (fr)
ID (1) ID19965A (fr)
WO (1) WO1998036737A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003092658A1 (fr) * 2002-04-29 2003-11-13 Egis Gyógyszergyár Rt Procede de preparation de comprimes a partir de substances, actives sur le plan pharmaceutique, ne possedant pas de proprietes favorables a la mise en comprime, avec un liquide de granulation contenant de la cellulose microcristalline

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3315800A1 (de) * 1983-04-30 1984-10-31 Merck Patent Gmbh, 6100 Darmstadt Verfahren zur herstellung eines granulats
EP0330284A2 (fr) * 1988-02-25 1989-08-30 Yamanouchi Europe B.V. Procédé de préparation d'un granulé pharmaceutique
EP0368682A1 (fr) * 1988-11-11 1990-05-16 Euroceltique S.A. Composition pharmaceutique à base d'une résine d'échange ionique
JPH05105636A (ja) * 1991-10-14 1993-04-27 Lion Corp 制酸剤組成物
WO1996017611A1 (fr) * 1994-12-07 1996-06-13 The Wellcome Foundation Limited Composition pharmaceutique contenant de la lamotrigine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3315800A1 (de) * 1983-04-30 1984-10-31 Merck Patent Gmbh, 6100 Darmstadt Verfahren zur herstellung eines granulats
EP0330284A2 (fr) * 1988-02-25 1989-08-30 Yamanouchi Europe B.V. Procédé de préparation d'un granulé pharmaceutique
EP0368682A1 (fr) * 1988-11-11 1990-05-16 Euroceltique S.A. Composition pharmaceutique à base d'une résine d'échange ionique
JPH05105636A (ja) * 1991-10-14 1993-04-27 Lion Corp 制酸剤組成物
WO1996017611A1 (fr) * 1994-12-07 1996-06-13 The Wellcome Foundation Limited Composition pharmaceutique contenant de la lamotrigine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch Week 9321, Derwent World Patents Index; Class B06, AN 93-172631, XP002045396 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003092658A1 (fr) * 2002-04-29 2003-11-13 Egis Gyógyszergyár Rt Procede de preparation de comprimes a partir de substances, actives sur le plan pharmaceutique, ne possedant pas de proprietes favorables a la mise en comprime, avec un liquide de granulation contenant de la cellulose microcristalline

Also Published As

Publication number Publication date
JPH11506473A (ja) 1999-06-08
ID19965A (id) 1998-08-27
AU1970797A (en) 1998-09-09

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