EP0809487A1 - Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose - Google Patents

Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose

Info

Publication number
EP0809487A1
EP0809487A1 EP96902968A EP96902968A EP0809487A1 EP 0809487 A1 EP0809487 A1 EP 0809487A1 EP 96902968 A EP96902968 A EP 96902968A EP 96902968 A EP96902968 A EP 96902968A EP 0809487 A1 EP0809487 A1 EP 0809487A1
Authority
EP
European Patent Office
Prior art keywords
hydroxypropyl cellulose
preparations
mixture
acid
active
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.)
Withdrawn
Application number
EP96902968A
Other languages
German (de)
English (en)
Inventor
Joerg Rosenberg
Sven Grabowski
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.)
BASF SE
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
Publication of EP0809487A1 publication Critical patent/EP0809487A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing

Definitions

  • the present invention relates to solid preparations containing active ingredients, obtainable by melt extrusion of a mixture of
  • the invention relates to a method for producing such preparations and pharmaceutical forms from them
  • JP-A 58-79915 and JP-A 58-192817 disclose the production of rod-shaped dosage forms by melt extrusion of water-soluble polymers such as, for example
  • HPC Hydroxypropyl cellulose
  • EP-A 596 203 describes active substance-containing preparations which are obtained by mixing the active substance with a water-soluble melt of two polymers with different viscosities, for example polymer mixtures of hydroxypropyl cellulose and hydroxypropyl methyl cellulose.
  • Known active ingredient preparations generally have relatively high polymer contents. High polymer contents result in good processability, but the inevitably resulting lower active substance contents, that is to say a low active substance dose with a high tablet weight, can make the entire production process uneconomical. For example, if the active substance content of one tablet is originally 40% by weight, the tablet weight could be halved with the same dosage when the active substance content was doubled. With a given melt output of an extruder, the production capacity of the extruder could be doubled.
  • Dosage form would be difficult. In such cases, however, it would also make sense to limit the proportion of the relatively high-priced polymers. In order not to fall below the minimally sensible weight of the pharmaceutical forms, it would make sense to replace a part of the more expensive polymer component by inexpensive, not necessarily meltable, auxiliary substances.
  • the object of the present invention was to find preparations which, with a low polymer content, permit thermoplastic processing of the preparation, so that the highest possible proportion of the preparation can consist of active ingredient or active ingredient and inexpensive auxiliaries.
  • a water-soluble, thermoplastically processable hydroxypropyl cellulose is used as component A), which preferably has a molar degree of substitution of 3.0 to 4.4.
  • “Molar degree of substitution” refers to the average number of moles of propylene oxide converted per glucose unit of the cellulose.
  • the hydroxypropyl celluloses can have melt viscosities according to DIN 53735 in the range from 0.075 to 54.8 g / 10 mm.
  • the molecular weight of the hydroxypropyl cellulose can be varied within a wide range, depending on whether a slower or a faster release of active ingredient is desired.
  • High molecular weight hydroxypropyl cellulose with molecular weights in the range from 200,000 to 1,500,000 is particularly suitable for the production of pharmaceutical forms in which slow release of active ingredients is desired, for example in the case of sustained release forms, since the high molecular weight polymers dissolve less well and only with swelling in water .
  • the use of low molecular weight polymers that are readily water-soluble is recommended, in which case hydroxypropyl celluloses with a molecular weight of 60,000 to 200,000, preferably 60,000 to 100,000, can be used.
  • the preparation of the hydroxypropyl celluloses used according to the invention is generally known.
  • the proportion of hydroxypropyl cellulose in the total amount of the preparation is 10 to 30% by weight, preferably 20 to 30% by weight.
  • component B) of the preparations active substances or mixtures of active substances are considered which are thermally stable under the processing conditions.
  • suitable active ingredients are, for example:
  • Plant protection agents are also suitable as active ingredients.
  • the amount of active ingredient component B) in the overall preparation can vary within wide limits depending on the effectiveness.
  • the content of B) can be from 0.1 to 90% by weight, based on the overall preparation.
  • preparations according to the invention can also contain conventional pharmaceutical auxiliaries as components C), provided that they are thermally stable under the processing conditions, e.g. Fillers or extenders, lubricants, plasticizers, stabilizers, dyes or pigments, disintegrants, preservatives or
  • Suitable fillers are, for example, organic compounds such as lactose or mannitol or inorganic Substances such as silica or silicates, oxides of magnesium, aluminum or titanium.
  • Well water-soluble fillers such as lactose or mannitol are suitable, for example, for the preparation of preparations with accelerated release of active ingredients.
  • the proportion of fillers in the preparation depends on the dosage of the active ingredient. In the case of active ingredients with a low dosage, a higher tablet weight can be achieved according to the invention by means of higher filler contents without the thermoplastic processability being impaired. In the case of active ingredients to be dosed very low, the amount of filler can be up to approximately 90% by weight.
  • glidant can the long-chain fatty acids such as C ⁇ 2, such as the mono-, di- and triglycerides -, C ⁇ 4 -, C ⁇ 6 - and Ci ß fatty acid or waxes such as carnauba wax are used in the usual amounts.
  • C ⁇ 2 such as the mono-, di- and triglycerides -, C ⁇ 4 -, C ⁇ 6 - and Ci ß fatty acid or waxes such as carnauba wax are used in the usual amounts.
  • plasticizers e.g. in addition to low molecular weight
  • Polyalkylene oxides such as polyethylene glycol, polypropylene glycol and polyethylene propylene glycol also called polyhydric alcohols such as propylene glycol, glycerin, pentaerythritol and sorbitol as well as sodium diethylsulfosuccinate, mono-, di- and triacetate of glycerol and polyethyleneglycol stearic acid ester.
  • the amount of plasticizer is about 0.5 to 15, preferably 0.5 to 5 parts by weight.
  • lubricants e.g. Stearates of aluminum or calcium, as well as talc and silicones, the amount of which is approximately 0.1 to 5, preferably 0.1 to 3% by weight.
  • Stabilizers which may be mentioned are, for example, light stabilizers, antioxidants, radical scavengers and stabilizers against microbial attack which can be used in the customary amounts.
  • the active ingredient component can either be melted directly in the form of a physical mixture with the polymer A) or mixed with the polymer melt already present.
  • the component is mixed with the melt in a manner known per se in extruders, preferably in single- or twin-screw extruders, in a temperature range between 50 and 200.degree.
  • the shaping of the polymer melt containing the active substance into the preparations according to the invention can for example, by calendering the extrudate according to the method described in EP-A 240 906 and according to the processing method known from DE-A 38 30 355 by comminuting the extrudate with rotating knives into equal-volume - still deformable - pieces.
  • the cooled melt can also be processed into granules.
  • auxiliaries can be incorporated into the polymer melt together with the active ingredient. Mixtures of auxiliaries, the active ingredient and the polymer A) can also be melted directly. In general, it is common to fuse together a physical mixture of auxiliaries, active ingredients and polymers.
  • preparations according to the invention are used as pharmaceuticals in the form of tablets, granules or as pellets in capsules.
  • the solid pharmaceutical form can also be provided with a conventional coating to improve the appearance and / or taste (dragee) or to delay the release of the active ingredient.
  • the present invention makes it possible to produce solid active substance preparations by melt extrusion in a simple manner, the proportion of polymer being able to be kept low by using a special polymer component without impairing the thermoplastic processability of the preparation.
  • a large proportion of the recipe can consist of an active ingredient and inexpensive auxiliary substances.
  • medicament sizes which are easy to handle according to the invention can be produced by melt extrusion of the preparations without having to use a relatively large proportion of the comparatively high-priced polymer.
  • the throughput was 20 kg / h (feed weigher feed).
  • the hard, homogeneous melt was pressed directly into tablets weighing 500 mg in a molding calender located in front of the extruder head.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des préparations contenant des principes actifs, que l'on obtient par extrusion d'un mélange en fusion comprenant A) une hydroxypropylcellulose thermoplastique, soluble dans l'eau, B) un ou plusieurs principes actifs, C) si on le désire, des produits auxiliaires pharmaceutiques, la proportion de A) représentant de 10 à 30 % en poids par rapport à l'ensemble de la préparation.
EP96902968A 1995-02-14 1996-02-01 Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose Withdrawn EP0809487A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19504831 1995-02-14
DE19504831A DE19504831A1 (de) 1995-02-14 1995-02-14 Feste Wirkstoffzubereitungen enthaltend Hydroxypropylcellulose
PCT/EP1996/000418 WO1996025149A1 (fr) 1995-02-14 1996-02-01 Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose

Publications (1)

Publication Number Publication Date
EP0809487A1 true EP0809487A1 (fr) 1997-12-03

Family

ID=7753889

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96902968A Withdrawn EP0809487A1 (fr) 1995-02-14 1996-02-01 Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose

Country Status (9)

Country Link
EP (1) EP0809487A1 (fr)
JP (1) JPH11501618A (fr)
CN (1) CN1174502A (fr)
AU (1) AU4717096A (fr)
CA (1) CA2211671A1 (fr)
DE (1) DE19504831A1 (fr)
IL (1) IL117050A0 (fr)
WO (1) WO1996025149A1 (fr)
ZA (1) ZA961138B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012126813A1 (fr) 2011-03-21 2012-09-27 Boehringer Ingelheim International Gmbh Préparation solide contenant de l'ambroxol

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19536387A1 (de) * 1995-09-29 1997-04-03 Basf Ag Verfahren zur Herstellung von vitaminhaltigen festen Zubereitungen
DE19710009A1 (de) * 1997-03-12 1998-09-24 Knoll Ag Mehrphasige wirkstoffhaltige Zubereitungsformen
IT1298574B1 (it) * 1998-02-06 2000-01-12 Vectorpharma Int Composizioni farmaceutiche in forma di microparticelle a base polimerica ottenute mediante estrusione e sferonizzazione
US6787157B1 (en) 1998-03-10 2004-09-07 Abbott Laboratories Multiphase active ingredient-containing formulations
DE19842753A1 (de) 1998-09-18 2000-03-23 Bayer Ag Agitationsunabhängige pharmazeutische Retardzubereitungen und Verfahren zu ihrer Herstellung
DE19934610A1 (de) * 1999-07-23 2001-01-25 Bayer Ag Schnellfreisetzende Extrudate und Verfahren zu ihrer Herstellung sowie daraus erhältliche Zubereitungen
GB0102342D0 (en) 2001-01-30 2001-03-14 Smithkline Beecham Plc Pharmaceutical formulation
US7842308B2 (en) 2001-01-30 2010-11-30 Smithkline Beecham Limited Pharmaceutical formulation
US7883721B2 (en) 2001-01-30 2011-02-08 Smithkline Beecham Limited Pharmaceutical formulation
JP4310605B2 (ja) * 2001-05-25 2009-08-12 大塚製薬株式会社 医薬用組成物
TW200526274A (en) 2003-07-21 2005-08-16 Smithkline Beecham Plc Pharmaceutical formulations
TW201240679A (en) 2004-03-12 2012-10-16 Capsugel Belgium Nv Pharmaceutical formulations
MX2007014041A (es) * 2005-05-10 2008-02-11 Novartis Ag Proceso de extrusion para preparar composiciones con compuestos terapeuticos poco comprimibles.
CN100448432C (zh) * 2006-10-26 2009-01-07 徐竹青 高溶出度尼莫地平分散片的制备方法
JP2011503048A (ja) 2007-11-08 2011-01-27 グラクソ グループ リミテッド 医薬製剤
WO2018219801A1 (fr) 2017-06-02 2018-12-06 Bayer Pharma Aktiengesellschaft Extrudats à libération immédiate

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3769029A (en) * 1971-05-26 1973-10-30 Hercules Inc Method of making a thermoplastic food product
US4014675A (en) * 1974-12-05 1977-03-29 Hercules Incorporated Fertilizer stick
JPS5879915A (ja) * 1981-11-09 1983-05-13 Nippon Soda Co Ltd 棒状薬剤の製造方法
JPS58192817A (ja) * 1982-05-06 1983-11-10 Nippon Soda Co Ltd 棒状製剤の製造方法
JPH03145418A (ja) * 1989-10-27 1991-06-20 Sumitomo Pharmaceut Co Ltd 塩基性薬物塩酸塩の徐放性製剤
DE4226753A1 (de) * 1992-08-13 1994-02-17 Basf Ag Wirkstoffe enthaltende Zubereitungen in Form fester Teilchen
AU679937B2 (en) * 1992-11-18 1997-07-17 Johnson & Johnson Consumer Products, Inc. Extrudable compositions for topical or transdermal drug delivery

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9625149A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012126813A1 (fr) 2011-03-21 2012-09-27 Boehringer Ingelheim International Gmbh Préparation solide contenant de l'ambroxol

Also Published As

Publication number Publication date
CN1174502A (zh) 1998-02-25
CA2211671A1 (fr) 1996-08-22
DE19504831A1 (de) 1996-09-05
AU4717096A (en) 1996-09-04
IL117050A0 (en) 1996-06-18
ZA961138B (en) 1997-08-13
JPH11501618A (ja) 1999-02-09
WO1996025149A1 (fr) 1996-08-22

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