CA2213719C - Transparent rapid-release preparation of non-steroid analgesics - Google Patents
Transparent rapid-release preparation of non-steroid analgesics Download PDFInfo
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- CA2213719C CA2213719C CA002213719A CA2213719A CA2213719C CA 2213719 C CA2213719 C CA 2213719C CA 002213719 A CA002213719 A CA 002213719A CA 2213719 A CA2213719 A CA 2213719A CA 2213719 C CA2213719 C CA 2213719C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
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- 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
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- 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
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- 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
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- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
Transparent rapid-release active agent preparations obtainable by the extrusion of melts containing non-steroid analgesics, homopolymers of N-vinyl pyrrolidone, saccharides or sugar alcohols and sodium or potassium salts.
Description
Transparent rapid release preparation of non-steroidal analgesics The present invention relates to transparent rapid release compositions of non-steroidal analgesics with antipyretic and antiinflammatory action, obtainable by extrusion of a melt comprising, besides one or more active substances, a) 50-100% by weight of homopolymers of N-vinylpyrrolidone with a Fikentscher K value of 30, b) 0-30% by weight of water-soluble saccharides or sugar alcohols or mixtures thereof, and c), 0-20% by weight of one or more physiologically acceptable salts of sodium or of potassium, where the stated amounts are based on the total of a), b) and c), and subsequent shaping.
The invention furthermore relates to a process for producing such compositions.
Rapid release of the active substance is of crucial importance particularly with analgesics in order to achieve a rapid onset of the pain-relieving action.
In the case of active substances with low solubility in water, as represented, for example, by the organic acids with analgesic activity, rapid release of sufficient doses is often not simple to achieve.
EP-A 607 467 proposes to promote rapid release of ibuprofen by adding basic salts which are applied during the pelleting process in the form of aqueous solutions to the active substance which has previously been mixed with an ancillary substance. The pellets are subsequently compressed to tablets in a conventional way. However, this procedure is relatively elaborate and therefore rather unfavorable economically.
It is furthermore known that drug forms can be produced in a very economic manner by extrusion of polymer melts which contain active substances, with subsequent continuous shaping.
The invention furthermore relates to a process for producing such compositions.
Rapid release of the active substance is of crucial importance particularly with analgesics in order to achieve a rapid onset of the pain-relieving action.
In the case of active substances with low solubility in water, as represented, for example, by the organic acids with analgesic activity, rapid release of sufficient doses is often not simple to achieve.
EP-A 607 467 proposes to promote rapid release of ibuprofen by adding basic salts which are applied during the pelleting process in the form of aqueous solutions to the active substance which has previously been mixed with an ancillary substance. The pellets are subsequently compressed to tablets in a conventional way. However, this procedure is relatively elaborate and therefore rather unfavorable economically.
It is furthermore known that drug forms can be produced in a very economic manner by extrusion of polymer melts which contain active substances, with subsequent continuous shaping.
EP-B 240 904 describes such a process for producing solid pharmaceutical forms by extrusion of polymer melts which contain active substances, using as polymers homo- or copolymers of N-vinylpyrrolidone.
However, a fundamental problem in the process of this type is that the matrix-forming polymers on the one hand are sufficiently melt-processible, or become processible by addition of a plasticizing substance, at the processing temperatures but, on the other hand, lead to stable drug forms under the usual storage conditions, with which no cold flow occurs.
This problem is all the more difficult to solve when the intention is to produce rapid release drug forms. Normally suitable for this purpose are, in particular, relatively low molecular weight polymers which rapidly dissolve in the digestive juices. However, it is precisely these which show the phenomenon of cold flow of the finished drug forms to a pronounced extent.
High molecular weight polymers do not usually show rapid release and can scarcely be extruded without plasticizers because the glass transition temperature (DIN 52324) is considerably higher.
An additional problem arises when the intention is to produce transparent drug forms by melt extrusion. The active substance is completely uniformly distributed without compartmentalization only in transparent forms. This is indispensable for rapid release. In addition, the use of transparent forms simplifies quality control and patient compliance.
It is an object of the present invention to find transparent rapid release compositions of non-steroidal analgesics which can be produced in a simple. manner by melt extrusion with subsequent shaping' and have good storage stability.
We have found that this object is achieved by the compositions defined at the outset.
Suitable active substances according to the invention are non-steroidal analgesics with antipyretic and antiinflammatory effect, as also used for symptomatic antirheumatic therapy.
Suitable active substances are, accordingly, derivatives of salicylic acid such as acetylsalicylic acid and derivatives of other organic acids and pyrazole derivatives. Thus, suitable active substances are aryl acid derivatives such as diclofenac, tolmetin or zomepirac, also arylpropyl acid derivatives such as ibuprofen, naproxen, fenoprofen, flurbiprofen or ketoprofen, or else indole- and indeneacetic acid derivatives such as indometacin or sulindac. Examples of suitable pyrazole derivatives are for example phenazone, aminophenazone, metamizole, propyphenazone, phenylbutazone or oxyphenbutazone.
Preferred active substances are ibuprofen, acetylsalicylic acid and ketoprofen, sulindac, indometacin, flurbiprofen.
It is also possible to use mixtures of active substances.
The compositions according to the invention contain as component a) a homopolymer of N-vinylpyrrolidone with a Fikentscher K value of 30 (for the definition of the K value see "H. Fikentscher, Cellulose-Chemie" 13 (1932), 58-64 and 71-74). This homopolymer is readily soluble in water, where "soluble in water" means that at least 0.5 g, preferably at least 2 g, of the polymer dissolves in 100 g of water at 20°C, where appropriate as colloidal solution. The preparation of the homopolymer is generally known.
Suitable as components b) are water-soluble saccharides or sugar alcohols or mixtures thereof. Suitable saccharides are, in particular, mono- or disaccharides such as galactose, fructose, dextrose, mannose, maltose, isomaltulose (palatinose), lactose or sucrose.
Examples of suitable sugar alcohols are mannitol, xylitol, sorbitol, adonitol, dulcitol and generally pentitols and hexitols.
Suitable as components c) are physiologically tolerated sodium and/or potassium salts, for example sodium acetate, potassium acetate, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium chloride or potassium chloride, with sodium acetate being preferred.
The ratios of the amounts of components a), b) and c) are chosen according to the invention so that the compositions comprise a) 50-100% by weight, preferably 60-90% by weight, of component a), b) 0-30% by weight, prefearbly 5-20% by weight, of component b), and c) 0-20% by weight, preferably 5-20% by weight, of component c), where the stated amounts are based on the total of a), b) and c).
Preferred compositions contain 80-95% by weight of component a) and 5-20% by weight of component c), based on the total of a) and c).
The total content of active substance in the compositions may vary within wide limits depending on the dose required and the release rate. Thus, the content of active substance can be from 0.1 to 90, preferably 0.5 to 60, % by weight of the complete composition.
The compositions. according to the invention may additionally contain conventional pharmaceutical ancillary substances and in the usual amounts.
The mixing of the active substance or active substances with the polymeric binders and, where appropriate, pharmaceutical additives can take place before or after the melting of the polymeric binder by processes customary in the art. The mixing is preferably carried out in an extruder, preferably a twin screw extruder or a single screw extruder with mixing compartment.
The melts are solvent-free. This means that no water and no organic solvent is added.
Production takes place by extrusion at 50-180°C, preferably 60-150°C, and subsequent shaping of the still plastic extrudate, eg. by shaping to tablets, for example as described in EP-A 240 906 by passing the extrudate between two rolls which are driven in opposite directions and have mutually opposite depressions in the casing, whose design determines the shape of the tablets. Cold cutting is also suitable.
The hot-cut method is preferred. This entails the extrudates being palletized immediately after emergence from the die arrangement on the extruder, for example by rotating knives or another suitable arrangement, expediently to pellets whose length is about the same as the diameter of the extrudate. These cut-off pellets are cooled in the stream of air or gas to such an extent that the surface is tack-free even before contact with other pellets or a vessel wall but, on the other hand, the pellets are still sufficiently plastic that they acquire a spherical shape by impacts, for example with the wall of a subsequent cyclone. This results in a simple manner in pellets which are sustantially spherical or lentil-shaped and have diameters of from 0.5 to 4, preferably 0.8 to 2, mm. The preferred smaller particles are primarily suitable for filling capsules.
The solid drug forms can also be provided with a conventional 5 coating to improve the appearance and/or the taste (sugar-coated tablet).
The compositions according to the invention of non-steroidal analgesics with antipyretic and antiinflammatory action are transparent, stable on storage and display rapid release. "Rapid release" means that the release of the active substance measured by the USP XXII paddle method after 30 min is at least 70%.
Surprisingly, despite the use of a relatively high molecular weight polymer, even drug forms with high weights, such as 1000 mg, showed rapid release. It is also advantageous that large tablets can be used as pastilles without being swallowed, and the addition of sugar alcohols also means that no taste problems occur. The swallowing of large tablets is often associated with difficulty in particular for elderly patients or patients with dysphagia, so that rapid release pastilles have great advantages.
Examples The compositions indicated in each of the examples were premixed and introduced into the feed section of a twin screw extruder (Werner & Pfleiderer, 2SK 30). The melt extrusion took place with a product throughput of 3-4 kg/h. The temperatures in the individual zones ("sections") of the extruder, and the temperature of the heated die strip are stated for each of the tests. Bolus tablets weighing 1000 mg were produced from the extrudate by the calendering process described in EP-B 240 906.
The release of active substance was measured by the USP XXIII
paddle method. This in vitro test method is used to determine the rate of dissolution of shaped articles containing active substances, eg. tablets.
This was done by equilibrating 900 ml of a phosphate buffer with a pH of 6.8, with addition of 0.1% sodium lauryl sulfate, in a 1 1 round-bottom vessel at 37°C. An appropriate amount of the drug form was weighed in. The release of active substance from the boli was determined in this USP XXI no-change test at a paddle speed of 100 rpm after.30 min in each case by UV spectroscopy.
However, a fundamental problem in the process of this type is that the matrix-forming polymers on the one hand are sufficiently melt-processible, or become processible by addition of a plasticizing substance, at the processing temperatures but, on the other hand, lead to stable drug forms under the usual storage conditions, with which no cold flow occurs.
This problem is all the more difficult to solve when the intention is to produce rapid release drug forms. Normally suitable for this purpose are, in particular, relatively low molecular weight polymers which rapidly dissolve in the digestive juices. However, it is precisely these which show the phenomenon of cold flow of the finished drug forms to a pronounced extent.
High molecular weight polymers do not usually show rapid release and can scarcely be extruded without plasticizers because the glass transition temperature (DIN 52324) is considerably higher.
An additional problem arises when the intention is to produce transparent drug forms by melt extrusion. The active substance is completely uniformly distributed without compartmentalization only in transparent forms. This is indispensable for rapid release. In addition, the use of transparent forms simplifies quality control and patient compliance.
It is an object of the present invention to find transparent rapid release compositions of non-steroidal analgesics which can be produced in a simple. manner by melt extrusion with subsequent shaping' and have good storage stability.
We have found that this object is achieved by the compositions defined at the outset.
Suitable active substances according to the invention are non-steroidal analgesics with antipyretic and antiinflammatory effect, as also used for symptomatic antirheumatic therapy.
Suitable active substances are, accordingly, derivatives of salicylic acid such as acetylsalicylic acid and derivatives of other organic acids and pyrazole derivatives. Thus, suitable active substances are aryl acid derivatives such as diclofenac, tolmetin or zomepirac, also arylpropyl acid derivatives such as ibuprofen, naproxen, fenoprofen, flurbiprofen or ketoprofen, or else indole- and indeneacetic acid derivatives such as indometacin or sulindac. Examples of suitable pyrazole derivatives are for example phenazone, aminophenazone, metamizole, propyphenazone, phenylbutazone or oxyphenbutazone.
Preferred active substances are ibuprofen, acetylsalicylic acid and ketoprofen, sulindac, indometacin, flurbiprofen.
It is also possible to use mixtures of active substances.
The compositions according to the invention contain as component a) a homopolymer of N-vinylpyrrolidone with a Fikentscher K value of 30 (for the definition of the K value see "H. Fikentscher, Cellulose-Chemie" 13 (1932), 58-64 and 71-74). This homopolymer is readily soluble in water, where "soluble in water" means that at least 0.5 g, preferably at least 2 g, of the polymer dissolves in 100 g of water at 20°C, where appropriate as colloidal solution. The preparation of the homopolymer is generally known.
Suitable as components b) are water-soluble saccharides or sugar alcohols or mixtures thereof. Suitable saccharides are, in particular, mono- or disaccharides such as galactose, fructose, dextrose, mannose, maltose, isomaltulose (palatinose), lactose or sucrose.
Examples of suitable sugar alcohols are mannitol, xylitol, sorbitol, adonitol, dulcitol and generally pentitols and hexitols.
Suitable as components c) are physiologically tolerated sodium and/or potassium salts, for example sodium acetate, potassium acetate, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium chloride or potassium chloride, with sodium acetate being preferred.
The ratios of the amounts of components a), b) and c) are chosen according to the invention so that the compositions comprise a) 50-100% by weight, preferably 60-90% by weight, of component a), b) 0-30% by weight, prefearbly 5-20% by weight, of component b), and c) 0-20% by weight, preferably 5-20% by weight, of component c), where the stated amounts are based on the total of a), b) and c).
Preferred compositions contain 80-95% by weight of component a) and 5-20% by weight of component c), based on the total of a) and c).
The total content of active substance in the compositions may vary within wide limits depending on the dose required and the release rate. Thus, the content of active substance can be from 0.1 to 90, preferably 0.5 to 60, % by weight of the complete composition.
The compositions. according to the invention may additionally contain conventional pharmaceutical ancillary substances and in the usual amounts.
The mixing of the active substance or active substances with the polymeric binders and, where appropriate, pharmaceutical additives can take place before or after the melting of the polymeric binder by processes customary in the art. The mixing is preferably carried out in an extruder, preferably a twin screw extruder or a single screw extruder with mixing compartment.
The melts are solvent-free. This means that no water and no organic solvent is added.
Production takes place by extrusion at 50-180°C, preferably 60-150°C, and subsequent shaping of the still plastic extrudate, eg. by shaping to tablets, for example as described in EP-A 240 906 by passing the extrudate between two rolls which are driven in opposite directions and have mutually opposite depressions in the casing, whose design determines the shape of the tablets. Cold cutting is also suitable.
The hot-cut method is preferred. This entails the extrudates being palletized immediately after emergence from the die arrangement on the extruder, for example by rotating knives or another suitable arrangement, expediently to pellets whose length is about the same as the diameter of the extrudate. These cut-off pellets are cooled in the stream of air or gas to such an extent that the surface is tack-free even before contact with other pellets or a vessel wall but, on the other hand, the pellets are still sufficiently plastic that they acquire a spherical shape by impacts, for example with the wall of a subsequent cyclone. This results in a simple manner in pellets which are sustantially spherical or lentil-shaped and have diameters of from 0.5 to 4, preferably 0.8 to 2, mm. The preferred smaller particles are primarily suitable for filling capsules.
The solid drug forms can also be provided with a conventional 5 coating to improve the appearance and/or the taste (sugar-coated tablet).
The compositions according to the invention of non-steroidal analgesics with antipyretic and antiinflammatory action are transparent, stable on storage and display rapid release. "Rapid release" means that the release of the active substance measured by the USP XXII paddle method after 30 min is at least 70%.
Surprisingly, despite the use of a relatively high molecular weight polymer, even drug forms with high weights, such as 1000 mg, showed rapid release. It is also advantageous that large tablets can be used as pastilles without being swallowed, and the addition of sugar alcohols also means that no taste problems occur. The swallowing of large tablets is often associated with difficulty in particular for elderly patients or patients with dysphagia, so that rapid release pastilles have great advantages.
Examples The compositions indicated in each of the examples were premixed and introduced into the feed section of a twin screw extruder (Werner & Pfleiderer, 2SK 30). The melt extrusion took place with a product throughput of 3-4 kg/h. The temperatures in the individual zones ("sections") of the extruder, and the temperature of the heated die strip are stated for each of the tests. Bolus tablets weighing 1000 mg were produced from the extrudate by the calendering process described in EP-B 240 906.
The release of active substance was measured by the USP XXIII
paddle method. This in vitro test method is used to determine the rate of dissolution of shaped articles containing active substances, eg. tablets.
This was done by equilibrating 900 ml of a phosphate buffer with a pH of 6.8, with addition of 0.1% sodium lauryl sulfate, in a 1 1 round-bottom vessel at 37°C. An appropriate amount of the drug form was weighed in. The release of active substance from the boli was determined in this USP XXI no-change test at a paddle speed of 100 rpm after.30 min in each case by UV spectroscopy.
Example 1 Temperatures of the extruder zones (sections 1-5) 20, 80, 140, 130, 130°C, temperature of extruder head 130°C, temperature of die strip 130°C
Active substance component a Ibuprofen 20% by weight polyvinylpyrrolidone K value 30, 80% by weight Release after 30 min 82%
Example 2 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 110, 120°C, temperature of extruder head 130°C, temperature of die strip 120°C
Active substance component a component b Ibuprofen 20% by weight polyvinylpyrrolidone D-mannitol 10% by weight K value 30, 70% by weight Release after 30 min 72%
Example 3 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 120, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component b Ibuprofen 20% by weight polyvinylpyrrolidone D-~nannitol 20% by weight K value 30, 60% by weight Release after 30 min 70%
Example 4 Temperatures of the extruder zones (sections 1-5) 70, 130, 130, 140, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a Ibuprofen 20% by weight polyvinylpyrrolidone K value 30, 80% by weight Release after 30 min 82%
Example 2 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 110, 120°C, temperature of extruder head 130°C, temperature of die strip 120°C
Active substance component a component b Ibuprofen 20% by weight polyvinylpyrrolidone D-mannitol 10% by weight K value 30, 70% by weight Release after 30 min 72%
Example 3 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 120, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component b Ibuprofen 20% by weight polyvinylpyrrolidone D-~nannitol 20% by weight K value 30, 60% by weight Release after 30 min 70%
Example 4 Temperatures of the extruder zones (sections 1-5) 70, 130, 130, 140, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component c Ibuprofen 20% by weight polyvinylpyrrolidone Na acetate 13.5%
by weight K value 30, 66.5% by weight Release after 30 min 95%
Example 5 Temperatures of the extruder zones (sections 1-5) 70, 130, 130, 140, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component c Ibuprofen 20% by weight polyvinylpyrrolidone Na acetate 5%
by weight K value 30, 75% by weight Release after 30 min 95%
Example 6 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 120, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component b component c Ibuprofen 20% by weight polyvinylpyrrolidone D-mannitol Na acetate K value 30, 5% by weight 5% by weight 70% by weight Release after.30 min 80%.
by weight K value 30, 66.5% by weight Release after 30 min 95%
Example 5 Temperatures of the extruder zones (sections 1-5) 70, 130, 130, 140, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component c Ibuprofen 20% by weight polyvinylpyrrolidone Na acetate 5%
by weight K value 30, 75% by weight Release after 30 min 95%
Example 6 Temperatures of the extruder zones (sections 1-5) 60, 120, 120, 120, 130°C, temperature of extruder head 130°C, temperature of die strip 160°C
Active substance component a component b component c Ibuprofen 20% by weight polyvinylpyrrolidone D-mannitol Na acetate K value 30, 5% by weight 5% by weight 70% by weight Release after.30 min 80%.
Claims (5)
1. A transparent rapid release composition of a non-steroidal analgesic with antipyretic and antiinflammatory action, obtained by extrusion of a melt comprising, besides one or more active substances, a) 50-100% by weight of homopolymers of N-vinylpyrrolidone with a Fikentscher K value of 30, b) 0-30% by weight of water-soluble saccharides or sugar alcohols or mixtures thereof, and c) 0-20% by weight of one or more physiologically acceptable salts of sodium or of potassium, where the stated amounts are based on the total of a), b) and c), and subsequent shaping.
2. A composition as claimed in claim 1, comprising 5-20% by weight of component c).
3. A composition as claimed in claim 1 or 2, comprising ibuprofen as active substance.
4. A composition as claimed in any one of claims 1 to 3, comprising sodium acetate as component c).
5. A process for producing a transparent rapid release composition as claimed in any one of claims 1 to 4, which comprises extrusion of a melt comprising, besides one or more active substances, a) 50-100% by weight of homopolymers of N-vinylpyrrolidone with a Fikentscher K value of 30, b) 0-30% by weight of water-soluble saccharides or sugar alcohols or mixtures thereof, and c) 0-20% by weight of one or more physiologically acceptable salts of sodium or of potassium, where the stated amounts are based on the total of. a), b) and c), at 50-180°C, and subsequent shaping.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19509805.6 | 1995-03-21 | ||
| DE19509805A DE19509805A1 (en) | 1995-03-21 | 1995-03-21 | Transparent, fast-release formulations of nonsteroidal analgesics |
| PCT/EP1996/001021 WO1996029053A1 (en) | 1995-03-21 | 1996-03-09 | Transparent rapid-release preparations of non-steroid analgesics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2213719A1 CA2213719A1 (en) | 1996-09-26 |
| CA2213719C true CA2213719C (en) | 2005-01-11 |
Family
ID=7757016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002213719A Expired - Fee Related CA2213719C (en) | 1995-03-21 | 1996-03-09 | Transparent rapid-release preparation of non-steroid analgesics |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US6063821A (en) |
| EP (1) | EP0817612B1 (en) |
| JP (1) | JPH11502209A (en) |
| KR (1) | KR19980703160A (en) |
| AT (1) | ATE196078T1 (en) |
| AU (1) | AU5105396A (en) |
| BR (1) | BR9607867A (en) |
| CA (1) | CA2213719C (en) |
| CZ (1) | CZ286011B6 (en) |
| DE (2) | DE19509805A1 (en) |
| DK (1) | DK0817612T3 (en) |
| EA (1) | EA000434B1 (en) |
| ES (1) | ES2151150T3 (en) |
| GR (1) | GR3034441T3 (en) |
| HU (1) | HU221614B (en) |
| IL (1) | IL117531A (en) |
| NO (1) | NO318236B1 (en) |
| PT (1) | PT817612E (en) |
| TW (1) | TW416850B (en) |
| WO (1) | WO1996029053A1 (en) |
| ZA (1) | ZA962241B (en) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19602206A1 (en) * | 1996-01-23 | 1997-07-24 | Basf Ag | Preparations of nonsteroidal analgesics |
| HUP0000279A3 (en) | 1996-11-15 | 2002-07-29 | Merck Patent Gmbh | Method for producing shaped and unshaped polyol masses |
| EP1001748B1 (en) * | 1997-07-25 | 2006-04-19 | Alpex Pharma S.A. | A process for the preparation of a granulate suitable to the preparation of rapidly disintegrable mouth-soluble tablets |
| US7364752B1 (en) | 1999-11-12 | 2008-04-29 | Abbott Laboratories | Solid dispersion pharamaceutical formulations |
| JP5767429B2 (en) * | 1999-11-12 | 2015-08-19 | アッヴィ・インコーポレイテッド | Crystallization inhibitors in solid dispersants |
| ES2170645B1 (en) * | 2000-03-23 | 2003-10-01 | Alcala Farma S L Lab | SOLID PHARMACEUTICAL FORM OF ORAL ADMINISTRATION OF A WATER SOLUBLE METAMIZOL SALT, PROCEDURE FOR OBTAINING AND FORM OF PRESENTATION OF THE PHARMACEUTICAL FORM. |
| DE10026698A1 (en) * | 2000-05-30 | 2001-12-06 | Basf Ag | Self-emulsifying active ingredient formulation and use of this formulation |
| DE10031044A1 (en) * | 2000-06-26 | 2002-01-03 | Bayer Ag | Endoparasiticidal agents for voluntary oral ingestion by animals |
| US7883721B2 (en) | 2001-01-30 | 2011-02-08 | Smithkline Beecham Limited | Pharmaceutical formulation |
| US7842308B2 (en) | 2001-01-30 | 2010-11-30 | Smithkline Beecham Limited | Pharmaceutical formulation |
| GB0102342D0 (en) | 2001-01-30 | 2001-03-14 | Smithkline Beecham Plc | Pharmaceutical formulation |
| US20050175687A1 (en) * | 2001-01-30 | 2005-08-11 | Mcallister Stephen M. | Pharmaceutical formulations |
| DE60329188D1 (en) | 2002-08-12 | 2009-10-22 | Bend Res Inc | DRUG PREPARATIONS CONSISTING OF MEDICINAL PRODUCTS IN HALF-ORIENTED FORM AND POLYMERS |
| TW200526274A (en) | 2003-07-21 | 2005-08-16 | Smithkline Beecham Plc | Pharmaceutical formulations |
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
| US8377952B2 (en) * | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
| GB0403098D0 (en) | 2004-02-12 | 2004-03-17 | Euro Celtique Sa | Extrusion |
| TW200539903A (en) * | 2004-03-12 | 2005-12-16 | Smithkline Beecham Plc | Pharmaceutical formulations |
| CN101257800B (en) * | 2005-07-18 | 2012-07-18 | 好利用医疗公司 | Medicaments containing famotidine and ibuprofen |
| GB2447898B (en) * | 2007-03-24 | 2011-08-17 | Reckitt Benckiser Healthcare | A tablet having improved stability with at least two actives |
| EP2219624A2 (en) | 2007-11-08 | 2010-08-25 | Glaxo Group Limited | Pharmaceutical formulations |
| CA2727630A1 (en) * | 2008-06-13 | 2009-12-17 | Glaxo Group Limited | Pharmaceutical formulations |
| JP5499703B2 (en) * | 2009-12-28 | 2014-05-21 | ライオン株式会社 | Formulation containing ibuprofen |
| CN102892815B (en) * | 2010-03-26 | 2016-05-18 | 陶氏环球技术有限责任公司 | The film of melt extrusion |
| BR112012018818A2 (en) * | 2010-03-26 | 2016-04-12 | Dow Global Technologies Llc | process for producing a cast extruded film and cast extruded film |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3612212A1 (en) * | 1986-04-11 | 1987-10-15 | Basf Ag | METHOD FOR PRODUCING SOLID PHARMACEUTICAL FORMS |
| DE3830355A1 (en) * | 1988-09-07 | 1990-03-15 | Basf Ag | METHOD FOR PRODUCING PHARMACEUTICAL TABLETS |
| DK0607467T3 (en) * | 1992-12-01 | 1999-12-13 | Spirig Ag | Medicines containing S (+) - ibuprofen |
| GB9302259D0 (en) * | 1993-02-05 | 1993-03-24 | Cerestar Holding Bv | Starch based material |
| DE19509807A1 (en) * | 1995-03-21 | 1996-09-26 | Basf Ag | Process for the preparation of active substance preparations in the form of a solid solution of the active substance in a polymer matrix, and active substance preparations produced using this method |
| DE4418837A1 (en) * | 1994-05-30 | 1995-12-07 | Bayer Ag | Thermal granulation process |
-
1995
- 1995-03-21 DE DE19509805A patent/DE19509805A1/en not_active Withdrawn
-
1996
- 1996-03-09 EP EP96907414A patent/EP0817612B1/en not_active Expired - Lifetime
- 1996-03-09 PT PT96907414T patent/PT817612E/en unknown
- 1996-03-09 DK DK96907414T patent/DK0817612T3/en active
- 1996-03-09 AT AT96907414T patent/ATE196078T1/en not_active IP Right Cessation
- 1996-03-09 WO PCT/EP1996/001021 patent/WO1996029053A1/en not_active Application Discontinuation
- 1996-03-09 US US08/913,509 patent/US6063821A/en not_active Expired - Lifetime
- 1996-03-09 ES ES96907414T patent/ES2151150T3/en not_active Expired - Lifetime
- 1996-03-09 CZ CZ972802A patent/CZ286011B6/en not_active IP Right Cessation
- 1996-03-09 DE DE59605848T patent/DE59605848D1/en not_active Expired - Fee Related
- 1996-03-09 JP JP8528036A patent/JPH11502209A/en not_active Ceased
- 1996-03-09 HU HU9801152A patent/HU221614B/en not_active IP Right Cessation
- 1996-03-09 EA EA199700247A patent/EA000434B1/en not_active IP Right Cessation
- 1996-03-09 CA CA002213719A patent/CA2213719C/en not_active Expired - Fee Related
- 1996-03-09 KR KR1019970706563A patent/KR19980703160A/en not_active Application Discontinuation
- 1996-03-09 AU AU51053/96A patent/AU5105396A/en not_active Abandoned
- 1996-03-09 BR BR9607867A patent/BR9607867A/en not_active IP Right Cessation
- 1996-03-18 IL IL11753196A patent/IL117531A/en active IP Right Grant
- 1996-03-19 TW TW085103233A patent/TW416850B/en not_active IP Right Cessation
- 1996-03-20 ZA ZA9602241A patent/ZA962241B/en unknown
-
1997
- 1997-09-19 NO NO19974338A patent/NO318236B1/en unknown
-
2000
- 2000-09-20 GR GR20000402133T patent/GR3034441T3/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PT817612E (en) | 2001-03-30 |
| JPH11502209A (en) | 1999-02-23 |
| HUP9801152A3 (en) | 2000-06-28 |
| BR9607867A (en) | 1998-06-30 |
| EP0817612A1 (en) | 1998-01-14 |
| CA2213719A1 (en) | 1996-09-26 |
| IL117531A (en) | 2000-01-31 |
| CZ286011B6 (en) | 1999-12-15 |
| NO974338D0 (en) | 1997-09-19 |
| EA000434B1 (en) | 1999-08-26 |
| GR3034441T3 (en) | 2000-12-29 |
| TW416850B (en) | 2001-01-01 |
| MX9706652A (en) | 1997-11-29 |
| EP0817612B1 (en) | 2000-09-06 |
| DE59605848D1 (en) | 2000-10-12 |
| DE19509805A1 (en) | 1996-09-26 |
| AU5105396A (en) | 1996-10-08 |
| ATE196078T1 (en) | 2000-09-15 |
| EA199700247A1 (en) | 1998-02-26 |
| DK0817612T3 (en) | 2000-11-20 |
| CZ280297A3 (en) | 1998-03-18 |
| ES2151150T3 (en) | 2000-12-16 |
| US6063821A (en) | 2000-05-16 |
| WO1996029053A1 (en) | 1996-09-26 |
| NO318236B1 (en) | 2005-02-21 |
| HU221614B (en) | 2002-11-28 |
| NO974338L (en) | 1997-09-19 |
| ZA962241B (en) | 1997-09-22 |
| HUP9801152A2 (en) | 1998-08-28 |
| KR19980703160A (en) | 1998-10-15 |
| IL117531A0 (en) | 1996-07-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |