WO1996025149A1 - Solid active agent preparations containing hydroxypropyl cellulose - Google Patents
Solid active agent preparations containing hydroxypropyl cellulose Download PDFInfo
- Publication number
- WO1996025149A1 WO1996025149A1 PCT/EP1996/000418 EP9600418W WO9625149A1 WO 1996025149 A1 WO1996025149 A1 WO 1996025149A1 EP 9600418 W EP9600418 W EP 9600418W WO 9625149 A1 WO9625149 A1 WO 9625149A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydroxypropyl cellulose
- preparations
- mixture
- acid
- active
- Prior art date
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
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8524616A JPH11501618A (en) | 1995-02-14 | 1996-02-01 | Solid active agent formulation containing hydroxypropylcellulose |
EP96902968A EP0809487A1 (en) | 1995-02-14 | 1996-02-01 | Solid active agent preparations containing hydroxypropyl cellulose |
AU47170/96A AU4717096A (en) | 1995-02-14 | 1996-02-01 | Solid active agent preparations containing hydroxypropyl cellulose |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19504831A DE19504831A1 (en) | 1995-02-14 | 1995-02-14 | Solid active substance preparations containing hydroxypropyl cellulose |
DE19504831.8 | 1995-02-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996025149A1 true WO1996025149A1 (en) | 1996-08-22 |
Family
ID=7753889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1996/000418 WO1996025149A1 (en) | 1995-02-14 | 1996-02-01 | Solid active agent preparations containing hydroxypropyl cellulose |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0809487A1 (en) |
JP (1) | JPH11501618A (en) |
CN (1) | CN1174502A (en) |
AU (1) | AU4717096A (en) |
CA (1) | CA2211671A1 (en) |
DE (1) | DE19504831A1 (en) |
IL (1) | IL117050A0 (en) |
WO (1) | WO1996025149A1 (en) |
ZA (1) | ZA961138B (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997012604A1 (en) * | 1995-09-29 | 1997-04-10 | Basf Aktiengesellschaft | Process for producing solid vitamin preparations |
EP0864326A2 (en) * | 1997-03-12 | 1998-09-16 | Knoll Ag | Multiphasic preparation comprising an active agent |
WO1999039692A2 (en) * | 1998-02-06 | 1999-08-12 | Eurand International S.P.A. | Pharmaceutical compositions in form of polymeric microparticles obtained by extrusion and spheronization |
WO2001007015A2 (en) * | 1999-07-23 | 2001-02-01 | Bayer Aktiengesellschaft | Quick-release extrudates, method for preparing the same and compositions obtained from said extrudates |
US6787157B1 (en) | 1998-03-10 | 2004-09-07 | Abbott Laboratories | Multiphase active ingredient-containing formulations |
US6805881B1 (en) | 1998-09-18 | 2004-10-19 | Bayer Aktiengesellschaft | Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same |
WO2018219801A1 (en) | 2017-06-02 | 2018-12-06 | Bayer Pharma Aktiengesellschaft | Immediate-release extrudates |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7883721B2 (en) | 2001-01-30 | 2011-02-08 | Smithkline Beecham Limited | Pharmaceutical formulation |
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 |
JP4310605B2 (en) * | 2001-05-25 | 2009-08-12 | 大塚製薬株式会社 | Pharmaceutical composition |
TW200526274A (en) | 2003-07-21 | 2005-08-16 | Smithkline Beecham Plc | Pharmaceutical formulations |
TW200539903A (en) | 2004-03-12 | 2005-12-16 | Smithkline Beecham Plc | Pharmaceutical formulations |
BRPI0608609A2 (en) * | 2005-05-10 | 2010-01-19 | Novartis Ag | extrusion process for preparing compositions with poorly compressible therapeutic compounds |
CN100448432C (en) * | 2006-10-26 | 2009-01-07 | 徐竹青 | Method for preparing nimodipine dispersible tablet with high dissolution |
JP2011503048A (en) | 2007-11-08 | 2011-01-27 | グラクソ グループ リミテッド | Pharmaceutical formulation |
BR112013023879B1 (en) | 2011-03-21 | 2022-08-30 | Boehringer Ingelheim International Gmbh | SOLID PREPARATIONS CONTAINING AMBROXOL, ITS PREPARATION METHOD, PHARMACEUTICAL DOSAGE FORM AND THEIR USES |
Citations (7)
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 (en) * | 1981-11-09 | 1983-05-13 | Nippon Soda Co Ltd | Preparation of rod-shaped drug |
JPS58192817A (en) * | 1982-05-06 | 1983-11-10 | Nippon Soda Co Ltd | Production of stick-like drug preparation |
EP0425298A2 (en) * | 1989-10-27 | 1991-05-02 | Sumitomo Pharmaceuticals Company, Limited | Sustained-release preparation of basic medical agent hydrochloride |
EP0596203A1 (en) * | 1992-08-13 | 1994-05-11 | BASF Aktiengesellschaft | Preparations in solid particle form containing active and water-soluble polymers |
EP0598606A1 (en) * | 1992-11-18 | 1994-05-25 | JOHNSON & JOHNSON CONSUMER PRODUCTS, INC. | Extrudable compositions for topical or transdermal drug delivery |
-
1995
- 1995-02-14 DE DE19504831A patent/DE19504831A1/en not_active Withdrawn
-
1996
- 1996-02-01 JP JP8524616A patent/JPH11501618A/en active Pending
- 1996-02-01 EP EP96902968A patent/EP0809487A1/en not_active Withdrawn
- 1996-02-01 CA CA002211671A patent/CA2211671A1/en not_active Abandoned
- 1996-02-01 AU AU47170/96A patent/AU4717096A/en not_active Abandoned
- 1996-02-01 CN CN96191927A patent/CN1174502A/en active Pending
- 1996-02-01 WO PCT/EP1996/000418 patent/WO1996025149A1/en not_active Application Discontinuation
- 1996-02-06 IL IL11705096A patent/IL117050A0/en unknown
- 1996-02-13 ZA ZA9601138A patent/ZA961138B/en unknown
Patent Citations (7)
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 (en) * | 1981-11-09 | 1983-05-13 | Nippon Soda Co Ltd | Preparation of rod-shaped drug |
JPS58192817A (en) * | 1982-05-06 | 1983-11-10 | Nippon Soda Co Ltd | Production of stick-like drug preparation |
EP0425298A2 (en) * | 1989-10-27 | 1991-05-02 | Sumitomo Pharmaceuticals Company, Limited | Sustained-release preparation of basic medical agent hydrochloride |
EP0596203A1 (en) * | 1992-08-13 | 1994-05-11 | BASF Aktiengesellschaft | Preparations in solid particle form containing active and water-soluble polymers |
EP0598606A1 (en) * | 1992-11-18 | 1994-05-25 | JOHNSON & JOHNSON CONSUMER PRODUCTS, INC. | Extrudable compositions for topical or transdermal drug delivery |
Non-Patent Citations (3)
Title |
---|
DATABASE WPI Section Ch Week 8325, Derwent World Patents Index; Class A96, AN 83-59971K, XP002006072 * |
DATABASE WPI Section Ch Week 8351, Derwent World Patents Index; Class A96, AN 83-847162, XP002006073 * |
NICOLAS FOLLONIER: "Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials", J.CONTROLLED RELEASE, vol. 36, no. 3, 1995, pages 243-250, XP002006071 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997012604A1 (en) * | 1995-09-29 | 1997-04-10 | Basf Aktiengesellschaft | Process for producing solid vitamin preparations |
EP0864326A2 (en) * | 1997-03-12 | 1998-09-16 | Knoll Ag | Multiphasic preparation comprising an active agent |
EP0864326A3 (en) * | 1997-03-12 | 2000-11-22 | Knoll Ag | Multiphasic preparation comprising an active agent |
WO1999039692A2 (en) * | 1998-02-06 | 1999-08-12 | Eurand International S.P.A. | Pharmaceutical compositions in form of polymeric microparticles obtained by extrusion and spheronization |
WO1999039692A3 (en) * | 1998-02-06 | 1999-09-23 | Vectorpharma S P A | Pharmaceutical compositions in form of polymeric microparticles obtained by extrusion and spheronization |
AU738029B2 (en) * | 1998-02-06 | 2001-09-06 | Adare Pharmaceuticals S.R.L. | Pharmaceutical compositions in form of polymeric microparticles obtained by extrusion and spheronization |
US6787157B1 (en) | 1998-03-10 | 2004-09-07 | Abbott Laboratories | Multiphase active ingredient-containing formulations |
US6805881B1 (en) | 1998-09-18 | 2004-10-19 | Bayer Aktiengesellschaft | Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same |
WO2001007015A2 (en) * | 1999-07-23 | 2001-02-01 | Bayer Aktiengesellschaft | Quick-release extrudates, method for preparing the same and compositions obtained from said extrudates |
WO2001007015A3 (en) * | 1999-07-23 | 2001-12-06 | Bayer Ag | Quick-release extrudates, method for preparing the same and compositions obtained from said extrudates |
US6569455B1 (en) * | 1999-07-23 | 2003-05-27 | Bayer Aktiengesellschaft | Quick-release extrudates, method for preparing the same and compositions obtained from said extrudates |
WO2018219801A1 (en) | 2017-06-02 | 2018-12-06 | Bayer Pharma Aktiengesellschaft | Immediate-release extrudates |
Also Published As
Publication number | Publication date |
---|---|
AU4717096A (en) | 1996-09-04 |
JPH11501618A (en) | 1999-02-09 |
CN1174502A (en) | 1998-02-25 |
IL117050A0 (en) | 1996-06-18 |
ZA961138B (en) | 1997-08-13 |
DE19504831A1 (en) | 1996-09-05 |
CA2211671A1 (en) | 1996-08-22 |
EP0809487A1 (en) | 1997-12-03 |
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