CN1285738A - Novel oral dosage form for carvedilol - Google Patents

Novel oral dosage form for carvedilol Download PDF

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Publication number
CN1285738A
CN1285738A CN98813082A CN98813082A CN1285738A CN 1285738 A CN1285738 A CN 1285738A CN 98813082 A CN98813082 A CN 98813082A CN 98813082 A CN98813082 A CN 98813082A CN 1285738 A CN1285738 A CN 1285738A
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Prior art keywords
carvedilol
preparation
coating
label
controlled release
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C·K·沃
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Boehringer Mannheim Pharmaceuticals Corp- Smithkline Bechman Corp Ltd Partner
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Boehringer Mannheim Pharmaceuticals Corp- Smithkline Bechman Corp Ltd Partner
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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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—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
    • A61K9/5015—Organic compounds, e.g. fats, sugars

Abstract

The present invention discloses a matrix formulation containing carvedilol.

Description

The new peroral dosage form of carvedilol
Invention field
The present invention relates to contain the novel formulation and the purposes in treating and/or preventing some disease thereof of carvedilol or its officinal salt.
Background of invention
United States Patent (USP) 4,503,067 has described the chemical compound that is called as carvedilol.This chemical compound is a kind of new multiple active medicine that has, and can be used for treating the weak hypertension to moderate.Known carvedilol is emulative non-selective beta-adrenoceptor antagonists and vasodilation simultaneously.When being used for the treatment of hypertension, the vasodilative effect of carvedilol mainly causes that by blocking-up α 1-adrenoceptor the receptor, blocking-up activity of medicine then can stop reflex tachycardia.This multiple activity of carvedilol is that medicine has the reason that resisting hypertension is renderd a service.In addition, because its anti-oxidant action in the lipid peroxidation that weakens the oxygen-derived free radicals initiation, carvedilol also can be used for Organoprotective, particularly Cardioprotective.In addition, carvedilol also can be used for treating congestive heart failure.
Used carvedilol formulations is conventional swallow tablet at present, takes every day twice.Said preparation is a kind of dosage form that discharges immediately; That is to say that the characteristics of said preparation are, when carvedilol left stomach, it was the form of solution or fine grain suspension, i.e. the carvedilol form that can be absorbed rapidly.
Have now found that the controlled release and the slow releasing preparation that contain carvedilol can be administered once every day.These preparations can prolong the acting duration of carvedilol, thereby improve bioavailability of medicament.
Summary of the invention the invention provides controlled release or the slow releasing preparation that contains carvedilol or its officinal salt.Detailed Description Of The Invention
The invention provides the controlled release or the slow releasing preparation of the oral dosage form that contains carvedilol or its officinal salt, carvedilol be formula I (1-(and carbazole-4-base oxygen base-3-[[2-(neighbour-methoxyl group phenoxy group) ethyl] amino]-the 2-propanol):
Figure 9881308200041
The present invention also provides the matrix formulations that contains carvedilol of oral dosage form and the enteric coating preparation that contains carvedilol of oral dosage form.
Carvedilol can be easily according to United States Patent (USP) 4,503, the description preparation in 067.Can be referring to the full text of described patent, its disclosed full content all is incorporated herein by reference.
According to preparation of the present invention, carvedilol can be the form of free alkali or its officinal salt.Preferred carvedilol is the form of free alkali.
Controlled release is meant and can reaches any preparation that slowly discharges medicine in long-time.In controlled release preparation of the present invention, a part of carvedilol in the preparation can be used as starting dose and discharges, and remaining then discharges in the mode of continuity.An example of controlled release system is a matrix formulations.
Slow release is meant one or more immediately the discharge units of utilization from be incorporated into an individually dosed form, repeats, discharges off and on any preparation of carvedilol.The example of slow-released system comprises and acts on sheet and capsule repeatedly, and reaches the ECT that regularly discharges by the carrier coating.
The example that is suitable for mixing the controlled release preparation of carvedilol is recorded in:
The slow releasing pharmaceutical treatment, chemical technology, comment number 177 (Sustained ReleaseMedications, Chemical Technology, Review No.177), J.C.Johnson compiles, Noyes Data Corporation (1980); With
The control administration, ultimate principle and application (Controlled Drug Delivery, Fundamentals and Applications), the 2nd edition, J.R.Robinson, V.H.L.Lee compiles, Mercel Dekkes Inc., New York (1987).
The example that is suitable for mixing the slow releasing preparation of carvedilol is recorded in:
Remington ' s pharmacy (Remington ' s Pharmaceutical Sciences), 16 editions, A.Osol compiles, Mack Publishing Company (1980).
The example that is suitable for mixing other controlled release preparation of carvedilol is recorded in United States Patent (USP) 4,839,177 (mandates on June 13rd, 1989) and United States Patent (USP) 5,422,123 (mandate on June 6 nineteen ninety-five).The substrate controlled release preparation write up of carvedilol is in United States Patent (USP) 4,389,393 (mandates on June 21 nineteen eighty-three) and United States Patent (USP) 4,968,508 (mandate on November 6 nineteen ninety).
In addition, the controlled release preparation that contains carvedilol can also be the form of the pilule of non-tabletting, and it has the sustained release coating of enteric coating or permeable gastro-intestinal Fluid.These controlled release preparations can according to, for example United States Patent (USP) 4,524, the description of 060 (mandate on June 18th, 1985) and United States Patent (USP) 4,983,401 (mandate on January 8th, 1991) preparation.Other controlled release preparation is recorded in United States Patent (USP) 4,880,830 (mandates on November 4th, 1989) and United States Patent (USP) 5,068,112 (mandate on November 26th, 1991).
The preferred manner of formulation of controlled release preparation is that the release of carvedilol is mainly finished in the process by the harmonization of the stomach small intestinal; The preferred manner of formulation of controlled release preparation is, avoids carvedilol to discharge under one's belt and allows it mainly discharge by small intestinal the time.
The preferred manner of formulation of described preparation is that carvedilol mainly discharged at postdigestive 1.5-3 hour.
Small intestinal is meant duodenum, ileum or jejunum.
Preparation of the present invention can be administered once every day.
The preferred formulation of carvedilol is tablet or Caplet or the substrate tablet that regularly discharges or their combining form of enteric coated tablet or Caplet (caplet), wax or polymer coating.The oral administration route of preferred preparation of the present invention.
According to the present invention, controlled release preparation can be a matrix formulations.Said preparation can comprise the substrate label that contains carvedilol in a large number, and described substrate label has different drug release rates.Preferred preparation comprises the phase of release immediately and the slow release phase of carvedilol.The phase substrate label of slow release can be a coating or with the sustained-release materials coating not.When the substrate label was used the sustained-release materials coating, the content of sustained-release materials was preferably the 2-30% (w/w) of substrate label.More preferably the content of sustained-release materials is 5-25% (w/w).
Sustained-release materials of the present invention is the mixture of coating materials or coating materials, and this material can prevent that carvedilol from being degraded rapidly under one's belt.According to required rate of release, outer coating can discharge continuously, slowly discharge or delay discharges.Preferred sustained-release materials is an enteric coating, that is, pharmaceutical preparation is not changed and disintegrate in intestinal by stomach the time.
Substrate of the present invention is cut agent can be with three types material preparation: insoluble plastics, hydrophilic polymer or fatty compound.Plastic matrix comprises acrylic acid-methyl methacrylate, polrvinyl chloride and polyethylene.Hydrophilic polymer comprises methylcellulose, hydroxypropyl methylcellulose (HMPC) and sodium carboxymethyl cellulose.Fatty compound comprises various waxes such as Brazil wax and glyceryl tristearate.Modal preparation method is carvedilol to be mixed then with host material mixture is pressed into tablet.Under the situation of wax-matrix, carvedilol is dispersed in the fused wax gradually, then it is solidified, pelletize and be pressed into label.In containing the matrix formulations of carvedilol, starting dose (the carvedilol part that can discharge immediately in the preparation) is placed in the coating of tablet.This coating can be realized by the punching press coating or by the pot or the air suspension coating method of routine.
In one embodiment of the invention, carvedilol substrate tablet contains the mixture of HMPC and carbopol (carbopol).In another embodiment of the invention, carvedilol substrate tablet contains the mixture of HMPC, carbopol and mannitol.Following flow chart has been summarized the production method of the controlled release tablet that contains carvedilol.
According to the present invention, sieve carvedilol, mannitol and HPMC dry then with pure water pelletize, wet method.Dried granules is sieved.The endoparticle that obtains is mixed with the Carbopol 941 that sieves in advance until evenly.The magnesium stearate of sieving in advance mixed with mixture obtain press sheet mixture.With the label of tablet press Cheng Yuan, use Opadry then _It is about 3% that white solution coating to weight increases, and uses Opadry then _Clear solution coating to weight increases about 0.5%.
The present invention also provides the various combining forms of release immediately and controlled release forms.For example, can be with not sustained-release matrix label and the releasing pattern immediately of carvedilol and/or the matrix form combination of coating of coating.The substrate label can comprise the pilule of using different sustained-release materials coatings in a large number independently of one another, and all these all can make up with the form not coating or that discharge immediately of carvedilol.
The slow releasing preparation that contains carvedilol can also can be prepared by microencapsulation by the coated granule of carvedilol or the granule slow dissolved polymers coating with all thickness is prepared.In the preparation that adopts microencapsulation, use hydroaropic substance as the coating material around the microcapsule.Hydroaropic substance can be selected from various natural and synthetic polymer, comprises lac, wax, starch, Cellacefate or cellulose butyrate, polyvinylpyrrolidone and polrvinyl chloride.After the coating material dissolving, all carvedilols in the microcapsule all can be dissolved immediately and be absorbed.Therefore, can be by the thickness of adjusting coating and the release that rate of dissolution is controlled carvedilol.By in the scope of 3-30% gross weight, changing the amount of coating material, thickness is changed between less than 1 micromole to 200 micromole.If only use a few different thickness (be generally three or four kind), carvedilol will discharge with the different scheduled times and produce slow release effect, that is, and and effect repeatedly.If adopt a series of different thickness, then can obtain the blood levels of more uniform carvedilol.Coated granules can directly be pressed into tablet, or places capsule.
Carvedilol in controlled release or the slow releasing preparation form can be used for treating hypertension, angina pectoris and congestive heart failure.Preparation of the present invention also can be used for Organoprotective, for example, is used for Cardioprotective.
The invention provides the method for treatment hypertension, angina pectoris and congestive heart failure, this method comprises, uses the controlled release that contains carvedilol or its officinal salt or the slow releasing preparation of effective dose to the patient of the described treatment of needs.
The present invention also provides the controlled release that contains carvedilol or its officinal salt or slow releasing preparation to be used for the treatment of purposes in the medicine of hypertension, angina pectoris and congestive heart failure in production.
The present invention also is provided for treating the pharmaceutical composition of hypertension, angina pectoris and congestive heart failure, and said composition contains controlled release or the slow releasing preparation that comprises carvedilol or its officinal salt, preferred substrate preparation.
When using carvedilol according to the present invention, expection does not have unacceptable toxicology effect.
Following examples are to be used for illustrating of the present invention, and are not to want to limit the scope of the invention.Many other embodiments are conspicuous for those skilled in the art.
The embodiment production method is described and is mixed
Carvedilol, mannitol, hydroxypropyl methylcellulose and pure water that step 1. is weighed and accurately measured.
Step 2. is transferred to carvedilol, mannitol, hydroxypropyl methylcellulose in the product rotary drum of high-shear mixer.
Step 3. with impeller and chipper with low speed with composition premixing 2 minutes.Pelletize
Step 4. with pure water with the low speed pelletize until obtaining required particle appearance.
Step 5. is being used for the rustless steel container of wet grinding with the granule discharging.
Step 6. slowly joins wet granule in the rustless steel container by Quadro Comil (having screen cloth).
Transfer of granules after step 7. will be ground is to pre-heated liquid bed product rotary drum.
Step 8. is maintained at about 70 ℃ of (65 ℃-75 ℃) dried particles with the index inlet temperature, until product temperature touch the mark temperature (40-47 ℃) and drying loss (0.5-1.8%) in indication range.
Step 9. sets up Quadro Comil (speed is variable) and is connected with abradant screen cloth.
Step 10. joins dried particles in the polyethylene sack that claimed tare weight in advance by Quadro Comil (having screen cloth).Unlubricated pelletize mixes
Step 11. is sieved excessive Carbopol 941 (carbopol 971P), crosses 20 order stainless steel sifts with hand and makes its depolymerization.
The Carbopol 941 that sieves in advance (carbopol 971P) that step 12. is weighed on pan paper and accurately measured.
Step 13. is with weigh out the carvedilol endoparticle of accurate amount of the polyethylene sack of suitable labelling.
Step 14. sets up the V-blender of suitable size.
Step 15. is transferred to 1/3 carvedilol endoparticle ' in the V ' blender.
Step 16. to ' add 1/3 Carbopol 941 (carbopol 971P) in the V ' blender.
Step 17. repeating step 15 and 16 is until all endoparticles and Carbopol 941 (carbopol 971P) are joined ' in the V ' blender.
Step 18. was mixed 30 minutes or until evenly.
Step 19. taking-up sample carries out the detection in the course of processing.Lubricated pelletize mixes
Step 20. is by crossing 40 order stainless steel sifts to excessive magnesium stearate sieve (making its depolymerization) with hand.
The magnesium stearate of sieving in advance that step 21. is weighed on pan paper and accurately measured.
Step 22. joins magnesium stearate and (contains unlubricated granule) in the blender and mixed 3 minutes.Tabletting
Step 23. is transferred to press sheet mixture in the hopper of rotary tablet machine with the circular conventional tool in 7/16 " x 5/8 ".
Step 24. compacting meets the tablet of physical property index.
Step 25. is taken out sample and is detected in operating process.Coating
The circular active label of carvedilol, Opadry that step 26. is weighed respectively in the polyethylene sack and accurately measured _White and Opadry _Clear.As needs, the active label of circle can be filled the required batch size of coating pan with avette placebo cores increase-volume to reach.
Step 27. adds aequum in cleaning container suitable, that claimed tare weight pure water is to produce 12% Opadry _The solid concentration of White.
Step 28. is under vortex stirs, with Opadry _White slowly adds in the pure water.Continue to stir until there not being visible solid constituent.This solution is making use in back 24 hours.
Step 29. adds aequum in cleaning container suitable, that claimed tare weight pure water is to produce 5% Opadry _The solid concentration of Clear.
Step 30. is under vortex stirs, with Opadry _Clear slowly adds in the pure water.Continue to stir until there not being visible solid constituent.This solution is making use in back 24 hours.
Step 31. sets up Accela Coater coating pan.Setting was used for transmitting the pump of white and transparent coating solution, with about 35g/ minute speed spraying.
Step 32. is transferred to label in the coating pan.Label is preheated: inlet temperature is arranged on 55 ℃ (40 ℃-70 ℃) and regular jog coating pan.When reaching about 42 ℃ (37 ℃-45 ℃), the temperature of product begins spraying.The spraying all white coating solution of amount makes weight increase by about 3% coating with acquisition.Transparent coating solution spray then to obtain making weight increase by about 0.5% coating.
Step 33. is transferred to the tablet of coating the cylinder of double-layer polyethylene liner from coating pan.If used placebo cores with increase-volume to the coating batch size, after the coating process finishes, then need to classify/checkout procedure, from the active label of circle, to isolate avette placebo cores.
Embodiment 1
Table 1: the unit prescription of controlled release carvedilol formulations
The concentration formula composition Summary 50mg ?BC 50mg BD amount mg/ sheet 50mg BE
Carvedilol sweet mellow wine HPMC carbomer940 dolomol Opadry White (OY-S-9603) Opadry Clear (YS-1-19025A) pure water USP USP NF NF or PF.Eur. NC NC USP or PF.Eur. 50.0 152.5 37.5 7.5 2.5 7.5 1.25 is an amount of 50.0 366.25 75.0 3.75 5.0 15.0 2.5 is an amount of 50.0 360.0 75.0 10.0 5.0 15.0 2.5 is an amount of
Total sheet is heavy ?258.75 ?517.5 517.5
Embodiment 2
Table 1: the typical case of controlled release carvedilol formulations is prescription in batches
The concentration formula composition Summary 50mg ?BC 50mg BD amount kg/ criticizes 50mg ?BE
Carvedilol mannitol hydroxypropyl methylcellulose carbomer 934 P magnesium stearate Opadry White, (OY-S-9603) Opadry Clear, (YS-1-19025A) NC USP USP NF NF or PF.Eur. NC NC ?1.36 ?4.14 ?1.01 ?0.20 ?0.07 ?0.20 ?0.03 ??0.68 ??4.96 ??1.01 ??0.05 ??0.07 ??0.20 ??0.03 ?0.68 ?4.87 ?1.01 ?0.14 ?0.07 ?0.20 ?0.03
Figure 9881308200121
Embodiment 3, (discharging the pH sensitivity coating on the label immediately) label %w/w carvedilol 11.45 lactose 64.05 microcrystalline Cellulose 20.0 sodium starch glycols 4.0 magnesium stearate 0.5 total amount 100.0 tablet coatings, (applying about 6-10% of label weight) %w/w hydroxypropyl methylcellulose phthalate 90.0 glycerol triacetates 10.0 embodiment 4, (discharging the pH sensitivity coating on the label immediately)
Label is with embodiment 3 tablet coatings (applying about 6-10% of label weight) %w/w
Cellacefate 90.0
Diethyl phthalate 10.0 embodiment 5 (discharging the controlled release coat on the label immediately)
Label is with embodiment 3 tablet coatings (applying about 5-12% of label weight) %w/w
Eudragit?RS?100?????????????????86.0
Dibutyl phthalate 10.0
Talcum 4.0
FD﹠amp; No. 6 Huangs of C 0.01 embodiment 6 (the pH sensitivity coating on the controlled release label)
Label is with embodiment 3
Tablet coating is with embodiment 3 embodiment 7 (globule of the controlled release coat of sealing) piller %w/w (approximately)
Non?Pareil?Seed????30
Carvedilol 40
Gelatin 8
Lactose 20
Talcum 2 coating %w/w glyceryl monostearates 36.6 distearins 53.4 white beeswax 10.0
More than be to explanation of the present invention.But the present invention is not limited in specific embodiments as herein described, but has comprised that interior all of claims scope change form.
The various magazines that this paper quoted, patent and other publication have comprised the content of prior art, and are incorporated herein by reference according to aforementioned manner fully.

Claims (8)

1. the matrix formulations that contains the oral dosage unit form of carvedilol.
2. the preparation of claim 1 wherein contains hydrophilic polymer.
3. the preparation of claim 2, hydrophilic polymer wherein is hydroxypropyl methylcellulose (HMPC).
4. the preparation of claim 1 wherein contains the mixture of HMPC and carbopol.
5. the preparation of claim 1 wherein contains the mixture of HMPC, carbopol and mannitol.
6. the enteric coating preparation that contains carvedilol of oral dosage unit form.
7. treat the method for hypertension, angina pectoris or congestive heart failure, this method comprises the carvedilol of using the matrix formulations form.
8. treat the method for hypertension, angina pectoris or congestive heart failure, this method comprises the carvedilol of using the enteric coating dosage form.
CN98813082A 1997-11-12 1998-11-12 Novel oral dosage form for carvedilol Pending CN1285738A (en)

Applications Claiming Priority (2)

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US6545697P 1997-11-12 1997-11-12
US60/065,456 1997-11-12

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CA2309542A1 (en) 1999-05-20
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NO20002439D0 (en) 2000-05-11
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