WO2012011118A2 - Development of a fixed dose combination dosage form containing ramipril and carvedilol - Google Patents

Development of a fixed dose combination dosage form containing ramipril and carvedilol Download PDF

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Publication number
WO2012011118A2
WO2012011118A2 PCT/IN2011/000335 IN2011000335W WO2012011118A2 WO 2012011118 A2 WO2012011118 A2 WO 2012011118A2 IN 2011000335 W IN2011000335 W IN 2011000335W WO 2012011118 A2 WO2012011118 A2 WO 2012011118A2
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WO
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Prior art keywords
beta
pharmaceutical preparation
blocker
preparation according
ace inhibitor
Prior art date
Application number
PCT/IN2011/000335
Other languages
French (fr)
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WO2012011118A3 (en
Inventor
Purshotama Sagi Reddy Babu Reddy
R. Venkata Emani
Ravichandran Mahalingam
Ravi Jayapal
Bhaskara Jasti Rao
Original Assignee
Purshotama Sagi Reddy Babu Reddy
Emani R Venkata
Ravichandran Mahalingam
Ravi Jayapal
Bhaskara Jasti Rao
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Application filed by Purshotama Sagi Reddy Babu Reddy, Emani R Venkata, Ravichandran Mahalingam, Ravi Jayapal, Bhaskara Jasti Rao filed Critical Purshotama Sagi Reddy Babu Reddy
Publication of WO2012011118A2 publication Critical patent/WO2012011118A2/en
Publication of WO2012011118A3 publication Critical patent/WO2012011118A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/2072—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
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer

Definitions

  • the invention relates to the preparation of a combination product consisting of ACE inhibitor such as Ramipril, Benazapril etc., and beta-blocker compound such as Carvedilol, Propronalol etc.
  • ACE inhibitor such as Ramipril, Benazapril etc.
  • beta-blocker compound such as Carvedilol, Propronalol etc.
  • Cardiovascular diseases are the disorders of heart and blood vessels and primarily include coronary heart disease, hypertension, cerebrovascular disease, peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure.
  • CVDs are the major cause of death in developed countries and also are rapidly emerging as a main cause of death in the developing world. An estimated 17.5 million people died from CVDs till 2005, representing almost 30% of all global deaths. It is projected that almost 20 million people will die from CVDs by 2015.
  • CVDs affect many people in middle age, very often severely limiting the income and savings of the affected individuals. Lost earnings and unaffordable health care expenditures undermine the socioeconomic development of communities and nations [1,2] (also see http://www. who.int/cardiovascular_diseases/en/ and http://www.who.int/mediacentre/factsheets/fs317/en/index.htmn.
  • Ramipril an angiotensin-converting enzyme (ACE) inhibitor
  • ACE angiotensin-converting enzyme
  • It is also used following myocardial infarction in patients with clinical evidence of heart failure, prevention of myocardial infarction, stroke, cardiovascular death or need of revascularization procedures, and diabetic nephropathy with microalbuminuria.
  • ACE angiotensin-converting enzyme
  • It is a derivative of 2-aza-bicyclo [3,3,0]-octane-3-carboxylic acid, and physically available as a white crystalline solid. It is soluble in polar organic solvents and buffered aqueous solutions.
  • Carvedilol is a non-selective beta blocker/alpha-1 blocker, used in the treatment of mild to moderate congestive heart failure, and is usually used as an adjunct to conventional treatments with ACE inhibitors and diuretics. Chemically, Carvedilol is ( ⁇ )-l -(Carbazol-4-yloxy)-3-[[2-(0-methoxyphenoxy)ethyl]amino]-2-propanol. It is available as a white to off-white powder. Carvedilol is practically insoluble in water, gastric fluid (pH 1.1), and intestinal fluid (pH 7.5).
  • the current drug therapy for treating congestive heart failure and hypertension quite often include a combination of ACE inhibitor and beta blocker such as Ramipril and Carvedilol that are available as separate dosage forms. Even though ACE inhibitor and diuretic combinations are available, a combination of ACE inhibitors and Beta/Alpha blockers are not available because beta blocker such as Ramipril has been reported to interact with many commonly used excipients such as pregelatinized starch, lactose, microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, and methacrylic acid copolymers (Reference: US Patent Application #20060045911, Point # 0013) and other active ingredients like Carvedilol. Carvedilol is practically insoluble in water.
  • ACE inhibitors are prescribed for concomitant administration as Altace capsules and beta-blocker compounds such as Carvedilol are available as separate products. No combination products of these two classes of compounds are available in the market or combination information is available.
  • the invention is to prepare a combination product consisting of ACE inhibitor such as
  • Ramipril, Benazapril etc., and beta-blocker compound such as Carvedilol, Propronalol etc. This combination product will result in better compliance; reduce the frequency of administration, and overall reduction in medication costs.
  • the overarching benefit is in better efficacy outcomes in hypertensive and congestive heart failure treatments.
  • This invention relates to a pharmaceutical preparation for oral administration comprising a combination of a) an ACE inhibitor such as Ramipril, benzapril or a pharmaceutically acceptable salt thereof, and b) a non selective Beta-blocker such as Carvedilol, propranolol etc, or a pharmaceutically acceptable salt thereof, wherein
  • the beta-blocker compound is in immediate release form and
  • the combination is in a solid fixed-unit dosage form such as a capsule or a tablet.
  • Figure 2 Schematic 2. Prototype of Carvedilol tablets and Ramipril granules filled in Capsules
  • Figure 3 Schematic 3. Prototype of Ramipril granules and Carvedilol granules compressed into Tablets
  • Figure 4 Schematic 4. Prototype of Ramipril granules and Carvedilol granules compressed as multilayer Tablets
  • the present invention describes a pharmaceutical preparation for oral administration comprising a combination of an ACE inhibitor or a pharmaceutically acceptable salt thereof, and a non selective Beta-blocker or a pharmaceutically acceptable salt thereof, wherein
  • the ACE inhibitor compound is in immediate release form
  • the beta-blocker compound is in immediate release form and, 3) The combination is in a solid fixed-unit dosage form such as a capsule or a tablet.
  • the beta-blocker compound is selected from the group of Carvedilol, propranalol or a pharmaceutically acceptable salt thereof.
  • the ACE inhibitor is selected from the group of rampiril, benazapril or a pharmaceutically acceptable salt thereof.
  • the amount of the ACE inhibitor compound Ramipril or a pharmaceutically acceptable salt thereof is 2.5 to 20 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
  • the amount of the ACE inhibitor compound benazapril or a pharmaceutically acceptable salt thereof is 5-40 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
  • the amount of the ACE inhibitor compound, Ramipril or a pharmaceutically acceptable salt thereof is 2.5 to 20 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10-80 mg per dosage unit.
  • the amount of the amount of the beta-blocker compound benazapril or a pharmaceutically acceptable salt thereof is 5- 40 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10 to 80 mg per dosage unit.
  • the solid fixed-unit dosage form is a capsule or a tablet.
  • beta-blocker component is coated with a polymeric coat.
  • the pharmaceutical preparation the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components is included as granules.
  • the process for the manufacture of a pharmaceutical preparation wherein ACE inhibitor and beta-blocker components are enclosed into a capsule.
  • the figure 1 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules filled in capsules.
  • the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components are included as tablets.
  • the Figure 2 enclosed in the specification describes the prototype of Carvedilol tablets and Ramipril granules filled in capsules
  • the ACE inhibitor compounds Ramipril or benazapril is included as granules
  • the Beta-blocker Carvedilol or propranolol components are included as granules with in a tablet, wherein the ACE inhibitor and the beta-blocker components are compressed into a tablet using a tabletting machine.
  • the Figure 3 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules compressed into tablets.
  • the beta-blocker component is in a tablet layer which is joined to another tablet layer containing the ACE inhibitor component, or, optionally the beta-blocker component is in a tablet layer which is joined, indirectly via one or more layers without active components to another tablet layer containing the ACE inhibitor component.
  • the Figure 4 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules compressed as multilayer tablets.

Abstract

A pharmaceutical preparation for oral administration comprising a combination of an ACE inhibitor such as Ramipril, benzapril or a pharmaceutically acceptable salt thereof, and a non selective Beta-blocker such as Carvedilol, propranolol etc, or a pharmaceutically acceptable salt thereof, wherein the ACE inhibitor compound is in immediate release form, the beta-blocker compound is in immediate release form and, the combination is in a solid fixed-unit dosage form such as a capsule or a tablet.

Description

FIELD OF THE INVENTION:
The invention relates to the preparation of a combination product consisting of ACE inhibitor such as Ramipril, Benazapril etc., and beta-blocker compound such as Carvedilol, Propronalol etc. This combination product will result in better compliance; reduce the frequency of administration, and overall reduction in medication costs.
BACKGROUND OF THE INVENTION:
Cardiovascular diseases (CVDs) are the disorders of heart and blood vessels and primarily include coronary heart disease, hypertension, cerebrovascular disease, peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure. CVDs are the major cause of death in developed countries and also are rapidly emerging as a main cause of death in the developing world. An estimated 17.5 million people died from CVDs till 2005, representing almost 30% of all global deaths. It is projected that almost 20 million people will die from CVDs by 2015. CVDs affect many people in middle age, very often severely limiting the income and savings of the affected individuals. Lost earnings and unaffordable health care expenditures undermine the socioeconomic development of communities and nations [1,2] (also see http://www. who.int/cardiovascular_diseases/en/ and http://www.who.int/mediacentre/factsheets/fs317/en/index.htmn.
In treating these cardiovascular diseases, especially hypertension and congestive heart failure, Ramipril, an angiotensin-converting enzyme (ACE) inhibitor, is used. It is also used following myocardial infarction in patients with clinical evidence of heart failure, prevention of myocardial infarction, stroke, cardiovascular death or need of revascularization procedures, and diabetic nephropathy with microalbuminuria. It is a derivative of 2-aza-bicyclo [3,3,0]-octane-3-carboxylic acid, and physically available as a white crystalline solid. It is soluble in polar organic solvents and buffered aqueous solutions.
Carvedilol is a non-selective beta blocker/alpha-1 blocker, used in the treatment of mild to moderate congestive heart failure, and is usually used as an adjunct to conventional treatments with ACE inhibitors and diuretics. Chemically, Carvedilol is (±)-l -(Carbazol-4-yloxy)-3-[[2-(0-methoxyphenoxy)ethyl]amino]-2-propanol. It is available as a white to off-white powder. Carvedilol is practically insoluble in water, gastric fluid (pH 1.1), and intestinal fluid (pH 7.5).
Current hypertension treatment guidelines recommend a goal of <140/90 mmHg for population with uncomplicated hypertension and goals are even lower (< 130/80 mmHg) for patients with diabetes or renal disease. These recommendations are supported by long-term trials suggesting that the greater the reduction in Blood Pressure, the greater the reduction in risk of cardiovascular events. Major clinical studies have shown that most patients require two or more drugs to achieve their Blood Pressure goals. Combination therapy should be used as initial treatment for patients in whom the probability of achieving Blood Pressure control with monotherapy is low.
The current drug therapy for treating congestive heart failure and hypertension quite often include a combination of ACE inhibitor and beta blocker such as Ramipril and Carvedilol that are available as separate dosage forms. Even though ACE inhibitor and diuretic combinations are available, a combination of ACE inhibitors and Beta/Alpha blockers are not available because beta blocker such as Ramipril has been reported to interact with many commonly used excipients such as pregelatinized starch, lactose, microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, and methacrylic acid copolymers (Reference: US Patent Application #20060045911, Point # 0013) and other active ingredients like Carvedilol. Carvedilol is practically insoluble in water. Under in vivo conditions, it shows site specific absorption in stomach, and undergoes extensive first pass metabolism (25-35% oral bioavailability), and hence, the bioequivalence risk is higher. In addition, Carvedilol exhibit food effects, where food reduces its rate of absorption.
Currently ACE inhibitors are prescribed for concomitant administration as Altace capsules and beta-blocker compounds such as Carvedilol are available as separate products. No combination products of these two classes of compounds are available in the market or combination information is available.
SUMMARY OF THE INVENTION:
The invention is to prepare a combination product consisting of ACE inhibitor such as
Ramipril, Benazapril etc., and beta-blocker compound such as Carvedilol, Propronalol etc. This combination product will result in better compliance; reduce the frequency of administration, and overall reduction in medication costs. The overarching benefit is in better efficacy outcomes in hypertensive and congestive heart failure treatments.
This invention relates to a pharmaceutical preparation for oral administration comprising a combination of a) an ACE inhibitor such as Ramipril, benzapril or a pharmaceutically acceptable salt thereof, and b) a non selective Beta-blocker such as Carvedilol, propranolol etc, or a pharmaceutically acceptable salt thereof, wherein
1) the ACE inhibitor compound is in immediate release form,
2) the beta-blocker compound is in immediate release form and,
3) the combination is in a solid fixed-unit dosage form such as a capsule or a tablet.
BRIEF DESCRIPTION OF THE DRAWINGS
The following are the schematics (1 to 4) that represent combination products, where in the Carvedilol component is coated with pharmaceutical excipients such as maltodextrin, aglinic acid, sodium alginate, etc, or separated from Ramipril by an inert layer. The Ramipril component is blended with pharmaceutical excipients such as sucrose, maltodextrin etc. Both components are finally enclosed in a capsule or compressed into a tablet. The resulting formulations exhibit dissolution profiles comparable to commercially available individual products as shown in Figure 1. Figure 1 : Schematic 1. Prototype of Ramipril granules and Carvedilol granules filled in Capsules
Figure 2: Schematic 2. Prototype of Carvedilol tablets and Ramipril granules filled in Capsules
Figure 3: Schematic 3. Prototype of Ramipril granules and Carvedilol granules compressed into Tablets
Figure 4: Schematic 4. Prototype of Ramipril granules and Carvedilol granules compressed as multilayer Tablets
Figure 5: Dissolution profile of the representative combination products
DETAILED DESCRIPTION OF THE INVENTION:
The present invention describes a pharmaceutical preparation for oral administration comprising a combination of an ACE inhibitor or a pharmaceutically acceptable salt thereof, and a non selective Beta-blocker or a pharmaceutically acceptable salt thereof, wherein
1) The ACE inhibitor compound is in immediate release form,
2) The beta-blocker compound is in immediate release form and, 3) The combination is in a solid fixed-unit dosage form such as a capsule or a tablet.
According to the first aspect of the present invention the beta-blocker compound is selected from the group of Carvedilol, propranalol or a pharmaceutically acceptable salt thereof.
According to the second aspect of the present invention the ACE inhibitor is selected from the group of rampiril, benazapril or a pharmaceutically acceptable salt thereof.
According to the third aspect of the present invention the amount of the ACE inhibitor compound Ramipril or a pharmaceutically acceptable salt thereof is 2.5 to 20 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
According to the fourth aspect of the present invention the amount of the ACE inhibitor compound benazapril or a pharmaceutically acceptable salt thereof is 5-40 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
According to the fifth aspect of the present invention wherein the amount of the ACE inhibitor compound, Ramipril or a pharmaceutically acceptable salt thereof is 2.5 to 20 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10-80 mg per dosage unit.
According to the sixth aspect of the present invention the amount of the amount of the beta-blocker compound benazapril or a pharmaceutically acceptable salt thereof is 5- 40 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10 to 80 mg per dosage unit.
According to the seventh aspect of the present invention, wherein the solid fixed-unit dosage form is a capsule or a tablet.
Another aspect of the present invention is the beta-blocker component is coated with a polymeric coat. According to the eighth aspect of the present invention wherein the pharmaceutical preparation the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components is included as granules.
According to the ninth aspect of the present invention the process for the manufacture of a pharmaceutical preparation, wherein ACE inhibitor and beta-blocker components are enclosed into a capsule. The figure 1 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules filled in capsules.
According to the tenth aspect of the present invention the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components are included as tablets. The Figure 2 enclosed in the specification describes the prototype of Carvedilol tablets and Ramipril granules filled in capsules
According to the eleventh aspect of the present invention the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components are included as granules with in a tablet, wherein the ACE inhibitor and the beta-blocker components are compressed into a tablet using a tabletting machine. The Figure 3 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules compressed into tablets.
According to the twelfth aspect of the present invention the beta-blocker component is in a tablet layer which is joined to another tablet layer containing the ACE inhibitor component, or, optionally the beta-blocker component is in a tablet layer which is joined, indirectly via one or more layers without active components to another tablet layer containing the ACE inhibitor component. The Figure 4 enclosed in the specification describes the prototype of Ramipril granules and Carvedilol granules compressed as multilayer tablets.

Claims

WHAT IS CLAIMED IS:
1. A pharmaceutical preparation for oral administration comprising a combination of a) an ACE inhibitor such as Ramipril, benzapril or a pharmaceutically acceptable salt thereof, and b) a non selective Beta-blocker such as Carvedilol, propranolol etc, or a pharmaceutically acceptable salt thereof, wherein
1) The ACE inhibitor compound is in immediate release form,
2) The beta-blocker compound is in immediate release form and,
3) The combination is in a solid fixed-unit dosage form such as a capsule or a tablet.
2. A pharmaceutical preparation according to claim 1 wherein the beta-blocker compound is Carvedilol or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical preparation according to claim 1 wherein the beta-blocker compound is propranalol or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical preparation according to claim 1 wherein the ACE inhibitor is rampiril or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical preparation according to claim 1 wherein the ACE inhibitor is benazapril or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical preparation according to claims 1 to 5 wherein the amount of the ACE inhibitor compound Ramipril or a pharmaceutically acceptable salt thereof is 2.5 to 20 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
7. A pharmaceutical preparation according to claims 1 to 5 wherein the amount of the ACE inhibitor compound benazapril or a pharmaceutically acceptable salt thereof is 5-40 mg and the amount of the beta-blocker compound Carvedilol or a pharmaceutically acceptable salt thereof is 12.5 to 25 mg per dosage unit.
8. A pharmaceutical preparation according to claims 1 to 5 wherein the amount of the ACE inhibitor compound, Ramipril or a pharmaceutically acceptable salt thereof is
2.5 to 20 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10-80 mg per dosage unit.
9. A pharmaceutical preparation according to claims 1 to 5 wherein the amount of the amount of the beta-blocker compound benazapril or a pharmaceutically acceptable salt thereof is 5-40 mg and the amount of the beta-blocker compound propranolol or a pharmaceutically acceptable salt thereof is 10 to 80 mg per dosage unit.
10. A pharmaceutical preparation according to claims 6 to 9, wherein the solid fixed- unit dosage form is a capsule.
1 1. A pharmaceutical preparation according to claims 6 to 9 wherein the solid fixed- unit dosage form is a tablet.
12. A pharmaceutical preparation according to claim 10 wherein the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components is included as granules.
13. A pharmaceutical preparation according to claim 12, wherein the beta-blocker component is coated with a polymeric coat.
14. A process for the manufacture of a pharmaceutical preparation according to claims 12 and 13, wherein ACE inhibitor and beta-blocker components are enclosed into a capsule.
15 A pharmaceutical preparation according to claim 10 wherein the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components is included as tablets.
16. A process for the manufacture of a pharmaceutical preparation according to claim 15 wherein the beta-blocker components are compressed into a tablet using a tabletting machine.
17. A, pharmaceutical preparation according to claims 15 and 16, wherein the beta- blocker component is coated with a polymeric coat.
18. A process for the manufacture of a pharmaceutical preparation according to claims 15 and 17, wherein ACE inhibitor and beta-blocker components are enclosed into a capsule.
19. A pharmaceutical preparation according to claim 11 wherein the ACE inhibitor compounds Ramipril or benazapril is included as granules, and the Beta-blocker Carvedilol or propranolol components is included as granules with in a tablet.
20. A pharmaceutical preparation according to claim 19, wherein the beta-blocker component is coated with a polymeric coat.
21. A process for the manufacture of a pharmaceutical preparation according to claims 19 and 20, wherein the ACE inhibitor and the beta-blocker components are compressed into a tablet using a tabletting machine.
22. A pharmaceutical preparation according to claim 11 wherein the beta-blocker component is in a tablet layer which is joined to another tablet layer containing the ACE inhibitor component, or, optionally, wherein the beta-blocker component is in a tablet layer which is joined, indirectly via one or more layers without active components, to another tablet layer containing the ACE inhibitor component.
23. A process for the manufacture of a pharmaceutical preparation according to claim 22, wherein the ACE inhibitor and the beta-blocker components are compressed into a tablet using a tabletting machine.
24. A method of preventing or treating hypertension or congestive heart failure in humans comprising the administration of an effective amount of a pharmaceutical preparation according to claims 12 to 14 to a patient in need of such treatment.
25. A method of preventing or treating hypertension in humans comprising the administration once per day of an effective amount of a pharmaceutical preparation according to claims 15 to 18 to a patient in need of such treatment.
26. A method of preventing or treating hypertension or congestive heart failure in humans comprising the administration of an effective amount of a pharmaceutical preparation according to claims 19 to 21 to a patient in need of such treatment.
27. A method of preventing or treating hypertension in humans comprising the administration once per day of an effective amount of a pharmaceutical preparation according to claims 22 to 23 to a patient in need of such treatment.
28. A method of preparing the combination without interaction between active ACE inhibitors such as Ramipril, benazapril etc and beta-blocker compounds such as Carvedilol, propranolol, etc resulting in a combination product with degradation below the marketed products.
29. A method of preparing stable solid dosage form of ACE inhibitors such as Ramipril without interaction with the excipients resulting in a marketable product.
PCT/IN2011/000335 2010-05-13 2011-05-13 Development of a fixed dose combination dosage form containing ramipril and carvedilol WO2012011118A2 (en)

Applications Claiming Priority (2)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107970255A (en) * 2017-12-14 2018-05-01 青岛农业大学 Treat the pharmaceutical composition and its tablet and preparation method of congestive heart failure

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US20050032879A1 (en) * 2003-08-07 2005-02-10 Temple Okarter Formulations and use of a beta-blocker and an ACE-inhibitor for the treatment of cardiovascular diseases
US20090215852A1 (en) * 2005-03-21 2009-08-27 Chroma Group, Inc. Compositions and methods for ameliorating cachexia
WO2007010501A2 (en) * 2005-07-22 2007-01-25 Ranbaxy Laboratories Limited A pharmaceutical composition comprising a combination of beta blocker and an ace inhibitor
HUE046229T2 (en) * 2012-02-17 2020-02-28 Egyt Gyogyszervegyeszeti Gyar Pharmaceutical formulation having improved stability

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107970255A (en) * 2017-12-14 2018-05-01 青岛农业大学 Treat the pharmaceutical composition and its tablet and preparation method of congestive heart failure

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