WO2009047800A2 - Oral controlled release composition of carvedilol - Google Patents
Oral controlled release composition of carvedilol Download PDFInfo
- Publication number
- WO2009047800A2 WO2009047800A2 PCT/IN2008/000652 IN2008000652W WO2009047800A2 WO 2009047800 A2 WO2009047800 A2 WO 2009047800A2 IN 2008000652 W IN2008000652 W IN 2008000652W WO 2009047800 A2 WO2009047800 A2 WO 2009047800A2
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- WO
- WIPO (PCT)
- Prior art keywords
- controlled release
- pharmaceutical composition
- pharmaceutically acceptable
- carvedilol
- oral controlled
- Prior art date
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Classifications
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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
- A61K9/48—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
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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 present invention relates to an oral controlled release pharmaceutical composition
- an oral controlled release pharmaceutical composition comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof.
- U.S. Pat. No. 4,503,067 describes a compound, which is known as carvedilol.
- This compound is a novel multiple action drug useful in the treatment of mild to moderate hypertension.
- Carvedilol is known to be both a competitive non-selective ⁇ -adrenoceptor antagonist and a vasodilator.
- the vasodilatory actions of carvedilol result primarily from ⁇ i- adrenoceptor blockade, whereas the ⁇ -adrenoceptor blocking activity of the drug prevents reflex tachycardia when used in the treatment of hypertension.
- These multiple actions of carvedilol are responsible for the antihypertensive efficacy of the drug.
- carvedilol as a consequence of its antioxidant action in attenuating oxygen free radical-initiated lipid peroxidation, is useful in organ protection, in particular, cardioprotection. Additionally, carvedilol is useful in the treatment of congestive heart failure.
- a controlled release profile from a drug dosage form is desirable in clinical use to reduce side effects and improve patient compliance.
- the technology used to formulate sustained release dosage forms is well documented.
- the entrapment of a drug in a polymer-based matrix is a common approach to formulate sustained release tablets with a desirable release profiles.
- depot drug formulations for controlled release of pharmaceutical drugs may be prepared using alginates alone (see U.S. Pat. No. 5,132,295), using combinations of alginates and polyacrylates (see U.S. Pat. No. 5,230,901) and using combinations of alginates and a pH independent gelling agent, such as, for example, hydroxypropyl methylcellulose (see U.S. Pat. No. 4,792,452). It is also known that the use of alginates alone for this purpose often presents difficulties in tabletting, film coating and storage.
- a sustained release dosage form useful in providing once-a-day medication consists of the admixture of hydroxypropyl methylcellulose (viscosity of 80 to 120 cps in a 2% aqueous solution) and ethyl celluose with etodolac (see U.S. Pat. No. 4,966,768).
- Matrix drug delivery system has been described in U. S. Patent No. 6,150,410.
- This patent discloses extended release pharmaceutical compositions of acidic pharmacological agents that have reduced dependence of the release rate upon pH and gastric residence time.
- the extended release compositions comprise a combination of water-swellable, hydrophilic polymer and acid soluble polymer, which is swellable above pH 5. These compositions provide an enhanced rate of release of the acidic pharmacological agent in the stomach where the pH of the gastric juices is low and diminished release rate at neutral or slightly alkaline pH of the intestines.
- U. S. Patent Nos. 5,695,781 and 6,083,532 disclose a three component, release rate controlling matrix composition that includes a pH dependent gelling polymer such as an alginate component, an enteric polymer and a pH independent gelling polymer.
- U. S. Patent No. 6,251,430 describes the use of ethyl cellulose or Eudragit RS or RL in combination with hydroxypropyl methylcellulose and sodium alginate to provide for a controlled release of the drug.
- each unit includes at least one core; a first coating layer surrounding a portion of outer surface of core, the coating layer including carvedilol; a second coating layer surrounding a portion of the outer surface of first coating layer, the coating layer including one or more sustained release polymers and one or more enteric polymers.
- the multiple unit system may optionally contain a seal coat between inert core and carvedilol layer, or between carvedilol layer and rate controlling polymer layer. The units are finally compressed into tablet or filled into capsule/sachet.
- WO 2006044202 describes embodiments of a pharmaceutical formulation comprising an enteric material.
- the embodiments release at least a portion of an active ingredient upon contacting gastric fluid.
- the remaining portion of the formulation releases active ingredient upon contacting intestinal fluid.
- Certain embodiments of the pharmaceutical composition comprise at least one active ingredient in a core and a leaky enteric coating, such as an enteric coating comprising a gastric fluid-channeling agent.
- Other embodiments of the pharmaceutical composition comprise at least one active ingredient substantially homogeneously admixed with at least one enteric material, such as an enteric material comprising a gastric fluid channeling agent.
- Disclosed embodiments of the pharmaceutical composition may comprise a single active ingredient, or may comprise plural active ingredients.
- the object of the invention is to provide oral controlled release pharmaceutical compositions of carvedilol or a pharmaceutically acceptable salt(s) thereof.
- an oral controlled release pharmaceutical composition comprising a) a core comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient(s) thereof; b) a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
- the present invention provides an oral controlled release pharmaceutical composition
- a) a core comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient(s) thereof; b) a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
- Carvedilol or pharmaceutically acceptable salts thereof can be used in the present invention, the preferred salt being carvedilol phosphate.
- Carvedilol or a pharmaceutically acceptable salt thereof used in the present invention may be in crystalline or amorphous or anhydrous or hydrate form thereof. These forms include but are not limited to carvedilol phosphate hemihydrate (Form I) or Form A or Form B or anhydrous form or amorphous form.
- controlled release it is meant as any formulation that achieves slow release of drug over an extended period of time. It is taken to encompass sustained release, prolonged release, timed release, modified release, retarded release and extended release.
- the formulations of the present invention allow for once-a-day dosing containing 10, 20, 40, or 80 mg of carvedilol phosphate.
- core comprises active ingredient, carvedilol or a pharmaceutically acceptable salt thereof and also includes an inert substance with or without other pharmaceutical excipients.
- Inert substances which do not interfere with the biological activity of the active ingredient, include but not limited to beads, such as sugar beads, particles, spheres, granules etc.
- the active ingredient may be present in the core or layered over an inert substance.
- the active ingredient present in the core may range from about 60 to 100 % by total weight of the active ingredient in the dosage form.
- Functional coating comprises pH dependent polymers selected from the group but not limited to cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate (PVAP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate, hydroxypropyl methylcellulose succinate, cellulose acetate succinate, cellulose acetate hexahydrophthalate, cellulose propionate phthalate, cellulose acetate maleate, cellulose acetate butyrate, cellulose acetate propionate, copolymer of methylmethacrylic acid and methyl methacrylate, copolymer of methyl acrylate, methylmethacrylate and methacrylic acid, copolymer of methylvinyl ether and maleic anhydride (Gantrez ES series), ethyl methyacrylate-methylmethacrylate- chlorotrimethylammonium ethyl acrylate
- Functional coating also comprises water-soluble pore-forming agent selected from the group but not limited to salts such as sodium chloride and potassium chloride; sugars, such as lactose, sucrose, sorbitol, and mannitol; hydroxylated compounds, including polyvinyl alcohols and glycols, such as polyethylene glycol and propylene glycol; cellulose derived materials, such as hydroxypropyl cellulose, hydroxypropyl methycellulose, polyvinyl pyrrolidone, or mixtures thereof.
- salts such as sodium chloride and potassium chloride
- sugars such as lactose, sucrose, sorbitol, and mannitol
- hydroxylated compounds including polyvinyl alcohols and glycols, such as polyethylene glycol and propylene glycol
- cellulose derived materials such as hydroxypropyl cellulose, hydroxypropyl methycellulose, polyvinyl pyrrolidone, or mixtures thereof.
- compositions used in the oral controlled release formulations of carvedilol include those known to a person ordinarily skilled in the art such as diluents, binders, and lubricants.
- Diluents may include but not limited to lactose, microcrystalline cellulose, dibasic calcium phosphate, mannitol, cellulose and the like.
- Binders may include but not limited to starches, alginates, gums, celluloses, vinyl polymers, sugars and the like.
- Lubricants may include but not limited to stearates such as magnesium stearate, talc, colloidal silicon dioxide and the like.
- Oral controlled release pharmaceutical composition of carvedilol or a pharmaceutically acceptable salt thereof of the present invention may further comprise an immediate release portion of carvedilol or a pharmaceutically acceptable salt(s) thereof coated over the functional coating.
- Immediate release portion over functional coating comprises about 0 to 40% of carvedilol or a pharmaceutically acceptable salt thereof by total weight of the active present in the dosage form.
- Immediate release portion of the active may be present in the dosage form as separate pellets together with controlled release pellets filled into hard gelatin capsules or compressed into a bi-layered dosage form.
- Oral controlled release pharmaceutical compositions of carvedilol or a pharmaceutically acceptable salt thereof of the present invention may be prepared by processes like direct compression, wet granulation and dry granulation methods.
- Preferably oral controlled release pharmaceutical composition of the present invention is prepared by the process comprising: providing a core having an inert substance layered with carvedilol or a pharmaceutically acceptable salt(s) thereof and coating the core with a functional coating comprising one or more pH dependent polymer(s) and a water soluble pore forming agent. Further, this may be optionally coated with an immediate release coating comprising carvedilol or a pharmaceutically acceptable salt thereof.
- the binder is dispersed in a suitable solvent and the active is added to get a clear solution. Load the inert substance with the solution of active to get spherical drug loaded particles of uniform size. Coat the drug loaded particles by spraying the solution containing pH dependent polymer and water-soluble pore forming agent. These pellets may be further optionally coated with an immediate release portion of the active and/or a film coating over the immediate release portion. These are further filled into hard gelatin capsules.
Abstract
An oral controlled release pharmaceutical composition comprising a carvedilol or a pharmaceutically acceptable salt(s) thereof. The oral controlled release pharmaceutical composition comprises a core comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient thereof; and a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
Description
ORAL CONTROLLED RELEASE COMPOSITION OF CARVEDILOL
FIELD OF THE INVENTION
The present invention relates to an oral controlled release pharmaceutical composition comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof.
BACKGROUND OF THE INVENTION
U.S. Pat. No. 4,503,067 describes a compound, which is known as carvedilol. This compound is a novel multiple action drug useful in the treatment of mild to moderate hypertension. Carvedilol is known to be both a competitive non-selective β-adrenoceptor antagonist and a vasodilator. The vasodilatory actions of carvedilol result primarily from αi- adrenoceptor blockade, whereas the β-adrenoceptor blocking activity of the drug prevents reflex tachycardia when used in the treatment of hypertension. These multiple actions of carvedilol are responsible for the antihypertensive efficacy of the drug. Also, carvedilol, as a consequence of its antioxidant action in attenuating oxygen free radical-initiated lipid peroxidation, is useful in organ protection, in particular, cardioprotection. Additionally, carvedilol is useful in the treatment of congestive heart failure.
A controlled release profile from a drug dosage form is desirable in clinical use to reduce side effects and improve patient compliance. The technology used to formulate sustained release dosage forms is well documented. The entrapment of a drug in a polymer-based matrix is a common approach to formulate sustained release tablets with a desirable release profiles.
It has been reported that depot drug formulations for controlled release of pharmaceutical drugs may be prepared using alginates alone (see U.S. Pat. No. 5,132,295), using combinations of alginates and polyacrylates (see U.S. Pat. No. 5,230,901) and using combinations of alginates and a pH independent gelling agent, such as, for example, hydroxypropyl methylcellulose (see U.S. Pat. No. 4,792,452). It is also known that the use of
alginates alone for this purpose often presents difficulties in tabletting, film coating and storage.
It also has been reported that a sustained release dosage form useful in providing once-a-day medication consists of the admixture of hydroxypropyl methylcellulose (viscosity of 80 to 120 cps in a 2% aqueous solution) and ethyl celluose with etodolac (see U.S. Pat. No. 4,966,768).
Matrix drug delivery system has been described in U. S. Patent No. 6,150,410. This patent discloses extended release pharmaceutical compositions of acidic pharmacological agents that have reduced dependence of the release rate upon pH and gastric residence time. The extended release compositions comprise a combination of water-swellable, hydrophilic polymer and acid soluble polymer, which is swellable above pH 5. These compositions provide an enhanced rate of release of the acidic pharmacological agent in the stomach where the pH of the gastric juices is low and diminished release rate at neutral or slightly alkaline pH of the intestines.
Further, U. S. Patent Nos. 5,695,781 and 6,083,532 disclose a three component, release rate controlling matrix composition that includes a pH dependent gelling polymer such as an alginate component, an enteric polymer and a pH independent gelling polymer.
Additionally, U. S. Patent No. 6,251,430 describes the use of ethyl cellulose or Eudragit RS or RL in combination with hydroxypropyl methylcellulose and sodium alginate to provide for a controlled release of the drug.
PCT patent application, WO 2004056336 describes an oral controlled release multiple unit system, each unit includes at least one core; a first coating layer surrounding a portion of outer surface of core, the coating layer including carvedilol; a second coating layer surrounding a portion of the outer surface of first coating layer, the coating layer including
one or more sustained release polymers and one or more enteric polymers. The multiple unit system may optionally contain a seal coat between inert core and carvedilol layer, or between carvedilol layer and rate controlling polymer layer. The units are finally compressed into tablet or filled into capsule/sachet.
PCT patent application, WO 2006044202 describes embodiments of a pharmaceutical formulation comprising an enteric material. The embodiments release at least a portion of an active ingredient upon contacting gastric fluid. The remaining portion of the formulation releases active ingredient upon contacting intestinal fluid. Certain embodiments of the pharmaceutical composition comprise at least one active ingredient in a core and a leaky enteric coating, such as an enteric coating comprising a gastric fluid-channeling agent. Other embodiments of the pharmaceutical composition comprise at least one active ingredient substantially homogeneously admixed with at least one enteric material, such as an enteric material comprising a gastric fluid channeling agent. Disclosed embodiments of the pharmaceutical composition may comprise a single active ingredient, or may comprise plural active ingredients.
Despite many efforts, there still remains a need for improved controlled release pharmaceutical compositions for oral administration, from which a wide range of drugs can be released, irrespective of pH and gastric residence time.
OBJECT OF THE INVENTION
The object of the invention is to provide oral controlled release pharmaceutical compositions of carvedilol or a pharmaceutically acceptable salt(s) thereof.
SUMMARY OF THE INVENTION
According to one aspect of the present invention there is provided an oral controlled release pharmaceutical composition comprising a) a core comprising a therapeutically effective
amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient(s) thereof; b) a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides an oral controlled release pharmaceutical composition comprising a) a core comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient(s) thereof; b) a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
Carvedilol or pharmaceutically acceptable salts thereof can be used in the present invention, the preferred salt being carvedilol phosphate. Carvedilol or a pharmaceutically acceptable salt thereof used in the present invention may be in crystalline or amorphous or anhydrous or hydrate form thereof. These forms include but are not limited to carvedilol phosphate hemihydrate (Form I) or Form A or Form B or anhydrous form or amorphous form.
By controlled release it is meant as any formulation that achieves slow release of drug over an extended period of time. It is taken to encompass sustained release, prolonged release, timed release, modified release, retarded release and extended release. The formulations of the present invention allow for once-a-day dosing containing 10, 20, 40, or 80 mg of carvedilol phosphate.
According to the instant invention, core comprises active ingredient, carvedilol or a pharmaceutically acceptable salt thereof and also includes an inert substance with or without other pharmaceutical excipients. Inert substances, which do not interfere with the biological activity of the active ingredient, include but not limited to beads, such as sugar beads,
particles, spheres, granules etc. The active ingredient may be present in the core or layered over an inert substance. The active ingredient present in the core may range from about 60 to 100 % by total weight of the active ingredient in the dosage form.
Functional coating comprises pH dependent polymers selected from the group but not limited to cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate (PVAP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate, hydroxypropyl methylcellulose succinate, cellulose acetate succinate, cellulose acetate hexahydrophthalate, cellulose propionate phthalate, cellulose acetate maleate, cellulose acetate butyrate, cellulose acetate propionate, copolymer of methylmethacrylic acid and methyl methacrylate, copolymer of methyl acrylate, methylmethacrylate and methacrylic acid, copolymer of methylvinyl ether and maleic anhydride (Gantrez ES series), ethyl methyacrylate-methylmethacrylate- chlorotrimethylammonium ethyl acrylate copolymer, polyvinyl acetate phthalate, natural resins such as zein, shellac and copal collophorium and combinations thereof.
Functional coating also comprises water-soluble pore-forming agent selected from the group but not limited to salts such as sodium chloride and potassium chloride; sugars, such as lactose, sucrose, sorbitol, and mannitol; hydroxylated compounds, including polyvinyl alcohols and glycols, such as polyethylene glycol and propylene glycol; cellulose derived materials, such as hydroxypropyl cellulose, hydroxypropyl methycellulose, polyvinyl pyrrolidone, or mixtures thereof.
Pharmaceutically acceptable excipients used in the oral controlled release formulations of carvedilol include those known to a person ordinarily skilled in the art such as diluents, binders, and lubricants. Diluents may include but not limited to lactose, microcrystalline cellulose, dibasic calcium phosphate, mannitol, cellulose and the like. Binders may include but not limited to starches, alginates, gums, celluloses, vinyl polymers, sugars and the like.
Lubricants may include but not limited to stearates such as magnesium stearate, talc, colloidal silicon dioxide and the like.
Oral controlled release pharmaceutical composition of carvedilol or a pharmaceutically acceptable salt thereof of the present invention may further comprise an immediate release portion of carvedilol or a pharmaceutically acceptable salt(s) thereof coated over the functional coating. Immediate release portion over functional coating comprises about 0 to 40% of carvedilol or a pharmaceutically acceptable salt thereof by total weight of the active present in the dosage form.
Immediate release portion of the active may be present in the dosage form as separate pellets together with controlled release pellets filled into hard gelatin capsules or compressed into a bi-layered dosage form.
Oral controlled release pharmaceutical compositions of carvedilol or a pharmaceutically acceptable salt thereof of the present invention may be prepared by processes like direct compression, wet granulation and dry granulation methods.
Preferably oral controlled release pharmaceutical composition of the present invention is prepared by the process comprising: providing a core having an inert substance layered with carvedilol or a pharmaceutically acceptable salt(s) thereof and coating the core with a functional coating comprising one or more pH dependent polymer(s) and a water soluble pore forming agent. Further, this may be optionally coated with an immediate release coating comprising carvedilol or a pharmaceutically acceptable salt thereof.
The binder is dispersed in a suitable solvent and the active is added to get a clear solution. Load the inert substance with the solution of active to get spherical drug loaded particles of uniform size. Coat the drug loaded particles by spraying the solution containing pH dependent polymer and water-soluble pore forming agent. These pellets may be further
optionally coated with an immediate release portion of the active and/or a film coating over the immediate release portion. These are further filled into hard gelatin capsules.
The following examples are illustrative of the present invention, and the examples should not be considered as limiting the scope of this invention in any way, as these examples and other equivalents thereof will become apparent to those versed in the art, in the light of the present disclosure, and the accompanying claims. EXAMPLES Examples 1:
1. Disperse HPMC in small quantity of methanol. To it add dichloromethane to dissolve it completely under stirring.
2. Add remaining methanol to the above solution under stirring and dissolve Carvedilol Phosphate to get clear solution.
3. Load the weighed quantity of sugar spheres in Fluidized Bed Processor.
4. Adjust the spray rate and air pressure and spray the solution of Carvedilol Phosphate of step - 2 on the sugar spheres to get spherical drug loaded particles of uniform size.
5. Disperse HPMC & HPMCP in methanol by stirring. Add dichloromethane to dissolve the polymer.
6. Add triethyl citrate to above solution and stir to get clear solution.
7. Coat the drug-loaded pellets by spraying the solution under proper fluidization and at temperature to the target build.
8. These pelletes are then are then filled into pharmaceutically acceptable hard gelatin capsules.
Example 2:
Manufacturing Procedure: Same as examples 1
Example 3:
Manufacturing Procedure: Same as examples 1
DISSOLUTION
The formulations exemplified above were studied for dissolution release using USP I apparatus, 100 rpm and using 900 ml 0.1N hydrochloric acid for 2 hours followed by pH 6.8 phosphate buffer. Results of the dissolution profile of Example 1 are summarized in Table I.
Claims
1. An oral controlled release pharmaceutical composition comprising: a) a core comprising a therapeutically effective amount of carvedilol or a pharmaceutically acceptable salt(s) thereof and/or other pharmaceutically acceptable excipient thereof; b) a functional coating comprising one or more pH dependent polymer(s), water soluble pore forming agent and/or other pharmaceutically acceptable excipient(s) thereof.
2. An oral controlled release pharmaceutical composition of claim 1, wherein the pH dependent polymer is selected from the group comprising cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate trimellitate, hydroxypropyl methylcellulose succinate, cellulose acetate succinate, cellulose acetate hexahydrophthalate, cellulose propionate phthalate, cellulose acetate maleate, cellulose acetate butyrate, cellulose acetate propionate, copolymer of methylmethacrylic acid and methyl methacrylate, copolymer of methyl acrylate, methylmethacrylate and methacrylic acid, copolymer of methylvinyl ether and maleic anhydride, ethyl methyacrylate- methylmethacrylate- chlorotrimethylammonium ethyl acrylate copolymer, polyvinyl acetate phthalate, natural resins such as zein, shellac and copal collophorium and combinations thereof.
3. An oral controlled release pharmaceutical composition of claim 1, wherein the water- soluble pore-forming agent is selected from the group comprising salts such as sodium chloride and potassium chloride; sugars, such as lactose, sucrose, sorbitol, and mannitol; hydroxylated compounds, including polyvinyl alcohols and glycols, such as polyethylene glycol and propylene glycol; cellulose derived materials, such as hydroxypropyl cellulose, hydroxypropyl methycellulose, polyvinyl pyrrolidone, or mixtures thereof.
4. An oral controlled release pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipients comprise diluents, binders, and lubricants.
5. An oral controlled release pharmaceutical composition of claim 4, wherein the diluent comprises lactose, microcrystalline cellulose, dibasic calcium phosphate, mannitol, cellulose and mixtures thereof.
6. An oral controlled release pharmaceutical composition of claim 4, wherein the binder comprises starches, alginates, gums, celluloses, vinyl polymers, sugars and mixtures thereof.
7. An oral controlled release pharmaceutical composition of claim 4, wherein the lubricant comprises magnesium stearate, talc, colloidal silicon dioxide and mixtures thereof.
8. An oral controlled release pharmaceutical composition of claim 1, wherein carvedilol or pharmaceutically acceptable salt thereof may be in crystalline or amorphous or anhydrous or hydrate form thereof.
9. An oral controlled release pharmaceutical composition of claim 1, wherein carvedilol or pharmaceutically acceptable salt thereof is carvedilol phosphate hemihydrate (Form I) or
Form A or Form B thereof.
10. An oral controlled release pharmaceutical composition of claim 1, further comprises an immediate release portion comprising carvedilol or a pharmaceutically acceptable salt thereof coated over the functional coating.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1385KO2007 | 2007-10-09 | ||
| IN1385/KOL/2007 | 2007-10-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2009047800A2 true WO2009047800A2 (en) | 2009-04-16 |
| WO2009047800A3 WO2009047800A3 (en) | 2009-08-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2008/000652 WO2009047800A2 (en) | 2007-10-09 | 2008-10-08 | Oral controlled release composition of carvedilol |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2009047800A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011119477A2 (en) * | 2010-03-22 | 2011-09-29 | Amneal Pharmaceuticals, LLC | Pharmaceutical compositions of carvedilol salts and process for preparation thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040019096A1 (en) * | 2001-10-23 | 2004-01-29 | Vlassios Andronis | Novel formulations of carvedilol |
| WO2004056336A2 (en) * | 2002-12-20 | 2004-07-08 | Ranbaxy Laboratories Limited | Controlled release, multiple unit drug delivery systems |
| US20050175695A1 (en) * | 2003-11-25 | 2005-08-11 | Catherine Castan | Carvedilol free base, salts, anhydrous forms or solvates thereof, corresponding pharmaceutical compositions, controlled release formulations, and treatment or delivery methods |
| WO2006044202A2 (en) * | 2004-10-19 | 2006-04-27 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University | Enteric coated compositions that release active ingredient(s) in gastric fluid and intestinal fluid |
| WO2007023325A2 (en) * | 2005-08-26 | 2007-03-01 | Egis Gyógyszergyár Nylvánosan Müködo Részvénytársaság | Controlled release pharmaceutical composition containing carvedilol |
| WO2008070072A2 (en) * | 2006-12-01 | 2008-06-12 | Mutual Pharmaceutical Company, Inc. | Carvedilol forms, compositions, and methods of preparation thereof |
| WO2008083130A2 (en) * | 2006-12-26 | 2008-07-10 | Dr. Reddy's Laboratories Limited | Amorphous and crystalline form a of carvedilol phosphate |
-
2008
- 2008-10-08 WO PCT/IN2008/000652 patent/WO2009047800A2/en active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040019096A1 (en) * | 2001-10-23 | 2004-01-29 | Vlassios Andronis | Novel formulations of carvedilol |
| WO2004056336A2 (en) * | 2002-12-20 | 2004-07-08 | Ranbaxy Laboratories Limited | Controlled release, multiple unit drug delivery systems |
| US20050175695A1 (en) * | 2003-11-25 | 2005-08-11 | Catherine Castan | Carvedilol free base, salts, anhydrous forms or solvates thereof, corresponding pharmaceutical compositions, controlled release formulations, and treatment or delivery methods |
| WO2006044202A2 (en) * | 2004-10-19 | 2006-04-27 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University | Enteric coated compositions that release active ingredient(s) in gastric fluid and intestinal fluid |
| WO2007023325A2 (en) * | 2005-08-26 | 2007-03-01 | Egis Gyógyszergyár Nylvánosan Müködo Részvénytársaság | Controlled release pharmaceutical composition containing carvedilol |
| WO2008070072A2 (en) * | 2006-12-01 | 2008-06-12 | Mutual Pharmaceutical Company, Inc. | Carvedilol forms, compositions, and methods of preparation thereof |
| WO2008083130A2 (en) * | 2006-12-26 | 2008-07-10 | Dr. Reddy's Laboratories Limited | Amorphous and crystalline form a of carvedilol phosphate |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011119477A2 (en) * | 2010-03-22 | 2011-09-29 | Amneal Pharmaceuticals, LLC | Pharmaceutical compositions of carvedilol salts and process for preparation thereof |
| WO2011119477A3 (en) * | 2010-03-22 | 2012-02-23 | Amneal Pharmaceuticals, LLC | Pharmaceutical compositions of carvedilol salts and process for preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009047800A3 (en) | 2009-08-13 |
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