WO2009036712A2 - Dosage form containing tramadol with controlled 24-hour release and a process for manufacturing the same - Google Patents
Dosage form containing tramadol with controlled 24-hour release and a process for manufacturing the same Download PDFInfo
- Publication number
- WO2009036712A2 WO2009036712A2 PCT/CZ2008/000112 CZ2008000112W WO2009036712A2 WO 2009036712 A2 WO2009036712 A2 WO 2009036712A2 CZ 2008000112 W CZ2008000112 W CZ 2008000112W WO 2009036712 A2 WO2009036712 A2 WO 2009036712A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dosage form
- active ingredient
- weight
- hydrophobic polymer
- tramadol
- Prior art date
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
Definitions
- the invention deals with a dosage form containing tramadol and a process for manufacturing the same, wherein balanced release from the multiple dosage form is controlled by a hydrophobic polymer membrane for 24 hours.
- Tramadol is a synthetic opioid, the analgesic effects of which are caused by the agonistic influence on opioid receptors in the CNS. It is used for treatment of moderate to severe pain. Tramadol is easily soluble (> 100 mg/ml at 25 °C), more than 90 % is absorbed after oral administration; its bioavailability is ca. 68 %.
- One of the problems related to tramadol administration is its relatively short half-life, which requires repeated administration. However, the initial fast release of the active ingredient after administration can result in undesirable side effects, the patient thus possibly being not treated even despite receiving the administration. Therefore there has arisen a need for a formulation with controlled release which ensures release of tramadol for a longer time.
- EP patent 0 642 788 describes matrix tablets with retarded release of tramadol, containing a cellulose ether or ester with a viscosity of 3,000 to 150,000 mPas as the matrix-forming polymer.
- EP patent 0 699 436 describes a tramadol formulation suitable for treatment of moderate pain for 12 hours and more, wherein the release-controlling matrix contains C 8 -C 50 substituted or unsubstituted hydrocarbons (fatty acids, fatty alcohols, glyceryl esters of fatty acids, mineral or vegetable oils, waxes, etc.) or a hydrophilic substance with melting temperature 35 - 140 0 C, or a matrix coated with water-insoluble meltable waxes, polymethacrylates or insoluble celluloses.
- EP patent 0 654 263 describes a method of preparation of particles with controlled release containing analgesics, based on mechanical processing of the drug and a meltable hydrophobic or hydrophilic carrier with melting temperature 35 to 150 0 C. Particles with regulated release are obtained through breaking of these agglomerates.
- EP patent 0 624 366 describes a matrix with controlled release which is suitable for dosing every 12 hours, wherein tramadol is incorporated in a matrix containing 1 to 80 % of alkyl cellulose.
- Patent application WO 03/080031 presents a tramadol formulation, in which the matrix- forming polymer is xanthan gum.
- EP patent 1 190 712 describes a unit dosage form, containing tramadol particles coated with an ethyl acrylate-methyl methacrylate co-polymer which requires an isolating layer consisting of water-soluble cellulose derivatives in order to reach a stable release rate.
- the necessary presence of the isolating layer extends the time of preparation of the dosage form.
- it is suitable to use a minimum amount of excipients and as short time of dosage form preparation as possible.
- the essence of the invention is a formulation, containing tramadol or its pharmacologically acceptable salts, in the form of microparticles, wherein release of the active ingredient for 24 hours is controlled by a membrane of a hydrophobic polymer, which contains 30 to 95 wt % of the active ingredient and 5 to 25 wt % of the hydrophobic polymer.
- microparticles in the formulation according to the invention are to be understood as particles having a size of 0.1 to 2 mm, which can be either round-shaped - the pellets, or of an irregular shape - the granules.
- the active ingredient layer can be the microparticle itself; in such case the active ingredient is incorporated into the particle in the preparation process. If the microparticles are pellets, this is done before the spheronization process; if they are granules, the process of incorporation of the active ingredient occurs in the course of granulation in a high-revolution granulator or a fluidized-bed granulator.
- Another solution according to the invention can involve application of the active ingredient layer onto neutral microparticles.
- the microparticles are constituted predominantly by a filler, such as microcrystalline cellulose or sucrose.
- These microparticles are coated with a layer which contains the active ingredient and which is followed by a coat of the hydrophobic polymer.
- neutral pellets can be used, which are coated subsequently.
- the hydrophobic polymer which is particularly advantageous is polyvinyl acetate, stabilized with povidone and sodium laurylsulfate (Kollicoat SR 30 D).
- the dosage form according to the invention can contain 30 to 85 wt % of tramadol and 10 to wt 50 % of a filler selected from e.g. microcrystalline cellulose, lactose or sugar alcohols such as mannitol or sorbitol.
- the formulation can further contain 3 to 10 % of a binder, which can be starch, but also cellulose derivatives such as hydroxypropyl cellulose, or, optionally, gelatine can be used.
- release is controlled by a hydrophobic polymer, preferably on the basis of polyvinyl acetate, which is used in an amount of 5 to 25 wt %.
- the particular amount of the polymer should be chosen depending on the specific composition, i.e. the amounts and arrangements of the other substances. Its 24-hour efficacy is important. It has become apparent that such efficacy is achieved with a composition which yields the following rate of the active ingredient release in the standard basked method testing at 150 rpm and pH 6.8:
- This parameter can control the required amount of the hydrophobic coating in the product according to the invention.
- composition according to EP 1 190 712 has given a different release rate.
- the arrangement according to this invention has the advantage that it can be manufactured in a simplified technology without any isolation layer between the active ingredient and the rate- controlling polymer. Another advantage includes the possibility of using a high content of the active ingredient, which then results in a smaller, easier-to-swallow, dosage form.
- the microparticle before the coating according to the invention can contain 70 to 100 % of tramadol.
- the essence of the invention also includes a manufacturing process, which can consist in coating the tramadol microparticles or grains of granulate with a film of the hydrophobic polymer.
- Tramadol microparticles of optimum granulometry are manufactured by wet granulation or pelletization (extrusion and spheronization).
- the hydrophobic polymer is applied onto tramadol-containing particles in a fluidized bed granulator.
- the final dosage forms are capsules or tablets.
- the hydrophobic polymer forms a continuous film and the specific polymer type ensures that gradual release of tramadol is secured for 24 hours and does not need any isolation film in order to achieve the stable releasing rate.
- microparticles with a size of 0.1 to 2 mm, containing 70 to 100 wt % of tramadol, preferably in the form of hydrochloride, on which a film is applied, made of the hydrophobic polymer, preferably polyvinyl acetate in an amount of 5 to 25 wt %.
- the microparticles further contain a filler, preferably microcrystalline cellulose in an amount of 10 to 50 wt %, and a binder, preferably starch, polyvinyl pyrrolidone, in an amount of 3 to 20 wt %.
- the coated particles can be filled into capsules or compressed into tablets.
- Another procedure involves coating of a neutral particle with a tramadol-containing layer in a fluidized bed granulator.
- the composition of the active coating layer is 60 to 95 % of tramadol, preferably in the form of hydrochloride, and 5 to 40 % of an antiadherent.
- a layer of the release-controlling hydrophobic polymer is applied, preferably of polyvinyl acetate, in an amount of 5 to 25 wt %.
- the product according to the invention achieves the same range of release as the marketed product Zydol, for which the 24-hour efficacy is unambiguously demonstrated.
- the marketed product is produced by the matrix method by means of melting of the active ingredient into hydrogenated vegetable oil.
- Dissolution profile is a very important parameter in the dosage form with controlled release.
- the dissolution profiles of such produced capsules is in a good compliance with already registered and administered product Zydol XL 400mg of Grunenthal Ltd., the composition of which corresponds to EP 0 642 788 Bl.
- the dissolution profile was measured by means of a standard procedure (900 ml, phosphate buffer f pH 6.8, 150 rpm, baskets, UV determination).
Abstract
A dosage form containing tramadol or its pharmacologically acceptable salts, wherein releasing of the active ingredient for 24 hours is controlled by a hydrophobic polymer membrane, which contains 30 to 95% by weight of the active ingredient in the form of microparticles and 5 to 25 % by weight of a hydrophobic polymer, and a process for manufacturing the same.
Description
Dosage form containing tramadol with controlled 24-hour release and a process for manufacturing the same
Technical Field
The invention deals with a dosage form containing tramadol and a process for manufacturing the same, wherein balanced release from the multiple dosage form is controlled by a hydrophobic polymer membrane for 24 hours.
Background Art
Tramadol is a synthetic opioid, the analgesic effects of which are caused by the agonistic influence on opioid receptors in the CNS. It is used for treatment of moderate to severe pain. Tramadol is easily soluble (> 100 mg/ml at 25 °C), more than 90 % is absorbed after oral administration; its bioavailability is ca. 68 %. One of the problems related to tramadol administration is its relatively short half-life, which requires repeated administration. However, the initial fast release of the active ingredient after administration can result in undesirable side effects, the patient thus possibly being not treated even despite receiving the administration. Therefore there has arisen a need for a formulation with controlled release which ensures release of tramadol for a longer time. However, in the case of highly soluble substances preparation of formulations with controlled release is problematic as a considerable portion of the drug is released immediately at the beginning and the effect of controlled release is thus decreased or totally eliminated. An appropriate way of retardation should be therefore selected in order to ensure even release for 12 hours, or preferably 24 hours. There are a few patents describing controlled release formulations of tramadol or other opioids.
EP patent 0 642 788 describes matrix tablets with retarded release of tramadol, containing a cellulose ether or ester with a viscosity of 3,000 to 150,000 mPas as the matrix-forming polymer. EP patent 0 699 436 describes a tramadol formulation suitable for treatment of moderate pain for 12 hours and more, wherein the release-controlling matrix contains C8-C50 substituted or unsubstituted hydrocarbons (fatty acids, fatty alcohols, glyceryl esters of fatty acids, mineral or vegetable oils, waxes, etc.) or a hydrophilic substance with melting temperature 35 - 140
0C, or a matrix coated with water-insoluble meltable waxes, polymethacrylates or insoluble celluloses.
EP patent 0 654 263 describes a method of preparation of particles with controlled release containing analgesics, based on mechanical processing of the drug and a meltable hydrophobic or hydrophilic carrier with melting temperature 35 to 150 0C. Particles with regulated release are obtained through breaking of these agglomerates.
EP patent 0 624 366 describes a matrix with controlled release which is suitable for dosing every 12 hours, wherein tramadol is incorporated in a matrix containing 1 to 80 % of alkyl cellulose. Patent application WO 03/080031 presents a tramadol formulation, in which the matrix- forming polymer is xanthan gum.
EP patent 1 190 712 describes a unit dosage form, containing tramadol particles coated with an ethyl acrylate-methyl methacrylate co-polymer which requires an isolating layer consisting of water-soluble cellulose derivatives in order to reach a stable release rate. The necessary presence of the isolating layer extends the time of preparation of the dosage form. However, in economical terms, it is suitable to use a minimum amount of excipients and as short time of dosage form preparation as possible.
Disclosure of Invention The essence of the invention is a formulation, containing tramadol or its pharmacologically acceptable salts, in the form of microparticles, wherein release of the active ingredient for 24 hours is controlled by a membrane of a hydrophobic polymer, which contains 30 to 95 wt % of the active ingredient and 5 to 25 wt % of the hydrophobic polymer.
The microparticles in the formulation according to the invention are to be understood as particles having a size of 0.1 to 2 mm, which can be either round-shaped - the pellets, or of an irregular shape - the granules.
It is advantageous to use such hydrophobic coating which does not require application of any other coating between the active ingredient layer and the retardant coating layer.
The active ingredient layer can be the microparticle itself; in such case the active ingredient is incorporated into the particle in the preparation process. If the microparticles are pellets, this is
done before the spheronization process; if they are granules, the process of incorporation of the active ingredient occurs in the course of granulation in a high-revolution granulator or a fluidized-bed granulator.
Another solution according to the invention can involve application of the active ingredient layer onto neutral microparticles. In such case the microparticles are constituted predominantly by a filler, such as microcrystalline cellulose or sucrose. These microparticles are coated with a layer which contains the active ingredient and which is followed by a coat of the hydrophobic polymer. Advantageously, in such procedure commercially available neutral pellets can be used, which are coated subsequently.
The hydrophobic polymer which is particularly advantageous is polyvinyl acetate, stabilized with povidone and sodium laurylsulfate (Kollicoat SR 30 D).
The dosage form according to the invention can contain 30 to 85 wt % of tramadol and 10 to wt 50 % of a filler selected from e.g. microcrystalline cellulose, lactose or sugar alcohols such as mannitol or sorbitol. The formulation can further contain 3 to 10 % of a binder, which can be starch, but also cellulose derivatives such as hydroxypropyl cellulose, or, optionally, gelatine can be used.
In the composition according to the invention, release is controlled by a hydrophobic polymer, preferably on the basis of polyvinyl acetate, which is used in an amount of 5 to 25 wt %.
The particular amount of the polymer should be chosen depending on the specific composition, i.e. the amounts and arrangements of the other substances. Its 24-hour efficacy is important. It has become apparent that such efficacy is achieved with a composition which yields the following rate of the active ingredient release in the standard basked method testing at 150 rpm and pH 6.8:
This parameter can control the required amount of the hydrophobic coating in the product according to the invention.
In this respect it is interesting that the composition according to EP 1 190 712 has given a different release rate.
The arrangement according to this invention has the advantage that it can be manufactured in a simplified technology without any isolation layer between the active ingredient and the rate- controlling polymer. Another advantage includes the possibility of using a high content of the active ingredient, which then results in a smaller, easier-to-swallow, dosage form. The microparticle before the coating according to the invention can contain 70 to 100 % of tramadol.
The essence of the invention also includes a manufacturing process, which can consist in coating the tramadol microparticles or grains of granulate with a film of the hydrophobic polymer. Tramadol microparticles of optimum granulometry are manufactured by wet granulation or pelletization (extrusion and spheronization). The hydrophobic polymer is applied onto tramadol-containing particles in a fluidized bed granulator. The final dosage forms are capsules or tablets. The hydrophobic polymer forms a continuous film and the specific polymer type ensures that gradual release of tramadol is secured for 24 hours and does not need any isolation film in order to achieve the stable releasing rate.
For obtaining such a dosage form it is preferable to prepare microparticles with a size of 0.1 to 2 mm, containing 70 to 100 wt % of tramadol, preferably in the form of hydrochloride, on which a film is applied, made of the hydrophobic polymer, preferably polyvinyl acetate in an amount of 5 to 25 wt %. Out if the other excipients, the microparticles further contain a filler, preferably microcrystalline cellulose in an amount of 10 to 50 wt %, and a binder, preferably starch, polyvinyl pyrrolidone, in an amount of 3 to 20 wt %. The coated particles can be filled into capsules or compressed into tablets.
Another procedure involves coating of a neutral particle with a tramadol-containing layer in a fluidized bed granulator. In such case the composition of the active coating layer is 60 to 95 %
of tramadol, preferably in the form of hydrochloride, and 5 to 40 % of an antiadherent. Subsequently, a layer of the release-controlling hydrophobic polymer is applied, preferably of polyvinyl acetate, in an amount of 5 to 25 wt %.
The above-mentioned manufacturing process of the dosage form and selection of excipients according to the invention allow for preparation of a solid retarded dosage form, the release of which is controlled by the membrane for 24 hours, and which does not necessitate use of any isolation coating achieving a stable release rate.
Contrary to a product prepared by a similar manner, i.e. by preparing a reservoir, according to EP 1 190 712, the product according to the invention achieves the same range of release as the marketed product Zydol, for which the 24-hour efficacy is unambiguously demonstrated. However, the marketed product is produced by the matrix method by means of melting of the active ingredient into hydrogenated vegetable oil.
The invention is illustrated in more detail in the following examples.
Examples
Example 1
Tramadol once daily 400 mg capsules
Description of the manufacturing procedure:
1. Homogenization of the active ingredient, microcrystalline cellulose and starch
2. Wet granulation with purified water
3. Extrusion and spheronization
4. Coating of the microparticles with a suspension of povidone- and sodium laurylsulfate- stabilized polyvinyl acetate
5. Filling in hard gelatine capsules
Dissolution profile is a very important parameter in the dosage form with controlled release. The dissolution profiles of such produced capsules is in a good compliance with already registered and administered product Zydol XL 400mg of Grunenthal Ltd., the composition of which corresponds to EP 0 642 788 Bl. The dissolution profile was measured by means of a standard procedure (900 ml, phosphate buffer f pH 6.8, 150 rpm, baskets, UV determination).
Dissolution of Tramadol 400 mg capsules once daily in time values comparable with Zydol XL 400mg is presented in the following table:
Example 2
Tramadol OD 300 mg capsules
Description of the manufacturing process:
1. Homogenization of the active ingredient, microcrystalline cellulose and starch
2. Wet granulation with purified water
3. Extrusion and spheronization
4. Coating of the microparticles with a suspension of povidone- and sodium laurylsulfate- stabilized polyvinyl acetate
5. Filling in hard gelatine capsules
Dissolution of Tramadol once daily 300 mg capsules in time values comparable with currently marketed product Zydol XL 300, which is intended for once-daily administration, is presented in the following table:
Example 3
Tramadol OD 200 mg capsules
Description of the manufacturing process:
1. Homogenization of the active ingredient, microcrystalline cellulose and starch
2. Wet granulation with purified water
3. Extrusion and spheronization
4. Coating of the microparticles with a suspension of povidone- and sodium laurylsulfate-stabilized polyvinyl acetate
5. Filling in hard gelatine capsules
Dissolution of Tamadol once daily 200 mg capsules in time values comparable with Zydol XL 200 is presented in the following table:
Example 4
Tramadol OD 150 mg capsules
Description of the manufacturing procedure:
1. Homogenization of the active ingredient, microcrystalline cellulose and starch
2. Wet granulation with purified water
3. Extrusion and spheronization
4. Coating of the microparticles with a suspension of povidone- and sodium laurylsulfate-stabilized polyvinyl acetate
5. Filling in hard gelatine capsules
Dissolution of Tramadol once daily 150 mg capsules in time values comparable with Zydol XL 150 is presented in the following table:
Claims
1. A dosage form containing tramadol or its pharmacologically acceptable salts in the form of microparticles, wherein release of the active ingredient for 24 hours is controlled by a membrane of a hydrophobic polymer, characterized in that it contains
30 to 95% by weight of the active ingredient and 5 to 25 % by weight of the hydrophobic polymer.
2. The dosage form according to claim 1, characterized in that the membrane of the hydrophobic polymer is coated directly onto the layer containing the active ingredient, without any isolation coating between said layers.
3. The dosage form according to claim 1 or 2, characterized in that the layer containing the active ingredient is constituted by the microparticle itself.
4. The dosage form according to claim 1 or 2, characterized in that the layer containing the active ingredient is coated onto the microparticle itself which does not contain the active ingredient.
5. The dosage form according to any one of the preceding claims, characterized in that the hydrophobic polymer is polyvinyl acetate.
6. The dosage form according to any one of the preceding claims, characterized in that it contains 30 to 85 % by weight of tramadol and 10 to 50 % by weight of a filler such as microcrystalline cellulose, and/or 3 to 20 % by weight of a binder such as starch, and/or 5 to 25 % by weight of a hydrophobic polymer, particularly polyvinyl acetate.
7. The dosage form according to any one of the preceding claims, characterized in that it contains of 50 to 500 mg of the active ingredient tramadol hydrochloride and 30 mg to 200 mg of polyvinyl acetate.
8. A process for manufacturing the dosage form according to any one of the preceding claims, characterized in that micro-particles produced by one of the following two methods: a. wet granulation, b. pelletization, are coated at least once by one of the following two methods: a. in a fluidized bed granulator or b. in a stirred granulator, and the resulting mixture is filled into hard gelatine capsules or compressed into tablets.
9. The process according to claim 8, characterized in that a mixture containing 30 to 95 % of the active ingredient is subjected to extrusion and spheronization resulting in a pellet, which is subsequently coated in a fluidized-bed or stirred granulator with 5 to 25 % of a hydrophobic polymer containing polyvinyl acetate, the percentages by weight being based on the final dosage form.
10. The process according to claim 8, characterized in that a mixture containing 30 to 95 % of the active ingredient is subjected to wet granulation in a high-revolution or fluidized-bed granulator, and in the same equipment 5 to 25 % of hydrophobic polymer containing polyvinyl acetate is coated, the percentages by weight being based on the final dosage form.
11. The process according to claim 8, characterized in that a mixture containing 30 to 95 % of the active ingredient is applied onto a neutral pellet in a fluidized-bed granulator, and in the same equipment 5 to 25 % of hydrophobic polymer containing polyvinyl acetate is subsequently applied, the percentages by weight being based on the final dosage form..
12. The process according to any one of claims 8 to 10, characterized in that the microparticles, i.e. pellets or granules, contain 70 to 100 % by weight of the active ingredient before the coating.
13. The process according to any one of claims 8 to 12, characterized in that the particular type and amount of the hydrophobic polymer is so selected that the membrane controls release for 24 hours, i.e. gives the respective dissolution tests of the coated microparticles, the following values being achieved:
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CZ20070658A CZ300468B6 (en) | 2007-09-20 | 2007-09-20 | Tramadol-containing, 24 hours controlled release medicamentous formulation and process for preparing thereof |
CZPV2007-658 | 2007-09-20 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2009036712A2 true WO2009036712A2 (en) | 2009-03-26 |
WO2009036712A3 WO2009036712A3 (en) | 2009-05-07 |
Family
ID=40351686
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CZ2008/000112 WO2009036712A2 (en) | 2007-09-20 | 2008-09-22 | Dosage form containing tramadol with controlled 24-hour release and a process for manufacturing the same |
Country Status (2)
Country | Link |
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CZ (1) | CZ300468B6 (en) |
WO (1) | WO2009036712A2 (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19630035A1 (en) * | 1996-07-25 | 1998-01-29 | Asta Medica Ag | Tramadol multiple unit formulations |
WO2001015667A1 (en) * | 1999-08-31 | 2001-03-08 | Grünenthal GmbH | Oral dosage forms |
EP1190712A1 (en) * | 2000-09-22 | 2002-03-27 | SMB Technology | Oral once daily tramadol beads composition |
WO2002066026A2 (en) * | 2001-02-21 | 2002-08-29 | Grünenthal GmbH | Tramadol-based medicament |
US20070104788A1 (en) * | 2005-11-10 | 2007-05-10 | Seamus Mulligan | Once-daily administration of central nervous system drugs |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3845770A (en) * | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
GB9404544D0 (en) * | 1994-03-09 | 1994-04-20 | Euro Celtique Sa | Controlled release formulation |
NZ260408A (en) * | 1993-05-10 | 1996-05-28 | Euro Celtique Sa | Controlled release preparation comprising tramadol |
US6156342A (en) * | 1998-05-26 | 2000-12-05 | Andex Pharmaceuticals, Inc. | Controlled release oral dosage form |
-
2007
- 2007-09-20 CZ CZ20070658A patent/CZ300468B6/en not_active IP Right Cessation
-
2008
- 2008-09-22 WO PCT/CZ2008/000112 patent/WO2009036712A2/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19630035A1 (en) * | 1996-07-25 | 1998-01-29 | Asta Medica Ag | Tramadol multiple unit formulations |
US6436438B1 (en) * | 1996-07-25 | 2002-08-20 | Asto-Medica Ag | Tramadol multiple unit formulations |
WO2001015667A1 (en) * | 1999-08-31 | 2001-03-08 | Grünenthal GmbH | Oral dosage forms |
EP1190712A1 (en) * | 2000-09-22 | 2002-03-27 | SMB Technology | Oral once daily tramadol beads composition |
WO2002066026A2 (en) * | 2001-02-21 | 2002-08-29 | Grünenthal GmbH | Tramadol-based medicament |
US20070104788A1 (en) * | 2005-11-10 | 2007-05-10 | Seamus Mulligan | Once-daily administration of central nervous system drugs |
Also Published As
Publication number | Publication date |
---|---|
WO2009036712A3 (en) | 2009-05-07 |
CZ2007658A3 (en) | 2009-04-01 |
CZ300468B6 (en) | 2009-05-27 |
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