WO2014102628A1 - Stable pharmaceutical composition comprising azilsartan medoxomil - Google Patents
Stable pharmaceutical composition comprising azilsartan medoxomil Download PDFInfo
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- WO2014102628A1 WO2014102628A1 PCT/IB2013/060318 IB2013060318W WO2014102628A1 WO 2014102628 A1 WO2014102628 A1 WO 2014102628A1 IB 2013060318 W IB2013060318 W IB 2013060318W WO 2014102628 A1 WO2014102628 A1 WO 2014102628A1
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- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutically acceptable
- pharmaceutical composition
- azilsartan medoxomil
- azilsartan
- stable pharmaceutical
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- 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
- A61K9/4833—Encapsulating processes; Filling of capsules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—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
- A61K9/2072—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
Definitions
- step e) compressing the granules of step c) or the blend of step d) into suitable sized tablets, or filling into suitable sized capsules.
- microcrystalline cellulose lactose, dextrose, sucrose, mannitol, sorbitol, xylitol, isomalt, erythritol, or mixtures thereof.
- the amount of diluents used in the pharmaceutical compositions of the present invention ranges from 10% w/w to 75% w/w.
- step 1 The blend of step 1 is granulated with the solution of step 2 to obtain granules.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a stable pharmaceutical composition comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from the group consisting of polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to the polymeric carrier is from about 3: 1 to about 22: 1 based on weight.
Description
STABLE PHARMACEUTICAL COMPOSITION COMPRISING AZILSARTAN
MEDOXOMIL
Field of the Invention
The present invention relates to a stable pharmaceutical composition comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from the group consisting of polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil or a pharmaceutically acceptable salt thereof to the polymeric carrier is from about 3: 1 to about 22: 1 based on weight and process for preparation thereof.
Background of the Invention
Azilsartan is an angiotensin II receptor blocker, which is indicated for the treatment of hypertension. Azilsartan medoxomil is a prodrug, which is hydro lyzed to azilsartan in the gastrointestinal tract during absorption.
U.S. Publication No. 2010/0121071 discloses that azilsartan medoxomil poses formulation concerns as azilsartan medoxomil is unstable at neutral pH. Additionally, the solubility of azilsartan medoxomil is low at an acidic pH, where it shows a better stability profile. The publication further discloses a method of stabilizing a pharmaceutical preparation comprising azilsartan medoxomil by adding a pH control agent to the pharmaceutical preparation, wherein the pH control agent has a pH of about 2 to about 5.
Azilsartan medoxomil is also known to emit an unpleasant odor, which may be due to the gradual hydrolysis of the medoxomil ester.
Summary of the Invention
The present invention provides an alternative pharmaceutical composition comprising azilsartan medoxomil along with a polymeric carrier such as polyvinyl pyrrolidone or copovidone. These pharmaceutical compositions are prepared without the use of pH control agent(s) and water or any other aqueous solvent, and are found to be stable and have a reduced odor as compared to azilsartan medoxomil. Polyvinyl pyrrolidone acts as a solublizer and a stabilizer for azilsartan medoxomil.
Detailed Description
A first aspect of the present invention provides a stable pharmaceutical composition comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from the group consisting of polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil or a pharmaceutically acceptable salt thereof to the polymeric carrier is from about 3 : 1 to about 22: 1 based on weight.
Azilsartan medoxomil or its pharmaceutically acceptable salts may be present in crystalline or amorphous forms. The pharmaceutically acceptable salts include salts with inorganic bases and organic bases. Inorganic bases may include salt with alkali metals such as sodium or potassium, or alkaline earth metals such as calcium or magnesium. Organic bases may include salts of tromethamine trimethylamine, triethylamine, tertiary butylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, and dicyclohexylamine. A particular example may be the potassium salt of azilsartan medoxomil, i.e., azilsartan kamedoxomil. The concentration of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, used in the pharmaceutical composition ranges from 15% w/w to 50% w/w by weight of the pharmaceutical composition.
The term "pharmaceutical composition", as used herein, includes tablets, capsules, pills, caplets, granules, and pellets. The pharmaceutical composition may additionally comprise one or more therapeutic agents. These pharmaceutical compositions are stable and have a reduced odor as compared to azilsartan medoxomil. Pharmaceutically acceptable excipients include disintegrants, diluents, antioxidants, and lubricants. The said excipients may be added intragranularly or extragranularly.
The term "stable", as used herein, refers to the pharmaceutical composition of the present invention, when subjected to conditions of 40°C/75% RH for a period of three months, results in less than 0.5% of desethyl azilsartan and ethyl azilsartan originating from the decomposition of azilsartan medoxomil.
The term "polymeric carrier", as used herein, refers to a carrier which is intimately mixed with azilsartan medoxomil. The polymeric carriers include polyvinyl pyrrolidone (e.g., PVP K 30), copovidone, or a mixture thereof. Copovidone is a copolymer of polyvinyl pyrrolidone and polyvinyl acetate; it is available under various trade names such as Kollidon® VA. The polymer carrier used in the pharmaceutical compositions of the
present invention ranges from 1% w/w to 10% w/w based on total weight of the composition.
According to one embodiment of this aspect, there is provided a stable
pharmaceutical composition comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and polyvinyl pyrrolidone.
According to another embodiment of this aspect, the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to polyvinyl pyrrolidone is from about 7: 1 to about 12: 1 based on weight.
A second aspect of the present invention provides a stable pharmaceutical composition consisting essentially of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from the group consisting of polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to the polymeric carrier is from about 3: 1 to about 22: 1 based on weight.
According to one embodiment of this aspect, the pharmaceutical composition does not comprise a pH control agent.
A third aspect of the present invention provides a stable pharmaceutical composition prepared by an anhydrous granulation process comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to the polymeric carrier is from about 3: 1 to about 22: 1 based on weight.
The term "anhydrous granulation", as used herein, refers to a wet granulation process carried out using anhydrous solvents without the use of water. Suitable anhydrous solvents include acetone, methyl ethyl ketone, methyl isobutyl ketone, methanol, ethanol, isopropyl alcohol, toluene, tetrahydrofuran, chloroform, methylene chloride, or mixtures thereof. A mixture of methylene chloride and isopropyl alcohol is preferred. The ratio of solvents in the mixture ranges from 15: 1 to 1 : 15, preferably from 5: 1 to about 1 :5 based on volume.
According to one embodiment of this aspect, there is a provided an anhydrous granulation process for the preparation of said pharmaceutical composition, wherein the
process comprises:
a) blending azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically acceptable excipients;
b) dissolving/dispersing a polymeric carrier in an anhydrous solvent;
c) granulating the blend of step a) with the solution/dispersion of step b);
d) optionally, blending the granules of step c) with one or more
pharmaceutically acceptable excipients; and
e) compressing the granules of step c) or the blend of step d) into suitable sized tablets, or filling into suitable sized capsules.
According to another embodiment of this aspect, there is a provided an anhydrous granulation process for the preparation of said pharmaceutical composition, wherein said process comprises:
a) blending one or more pharmaceutically acceptable excipients;
b) dissolving/dispersing azilsartan medoxomil along with a polymeric carrier in an anhydrous solvent;
c) granulating the blend of step a) with the solution/dispersion of step b);
d) optionally, blending the granules of step c) with one or more
pharmaceutically acceptable excipients; and
e) compressing the granules of step c) or the blend of step d) into suitable sized tablets, or filling into suitable sized capsules.
Azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, may be used in combination with one or more therapeutic agents. These therapeutic agents include antihypertensive agents or hypoglycemic agents.
Antihypertensive agents may be further selected from diuretics, calcium channel blockers (CCB), and ACE inhibitors.
Diuretics include chlorothalidone, chlorothiazide, hydrochlorothiazide, and methylclothiazide.
CCBs include amlodipine, felodipine, ryosidine, isradipine, lacidipine, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine,
flunarizine, prenylamine, diltiazam, fendiline, gallopamil, mibefradil, anipamil, tiapamil, and verapamil, and, in each case, a pharmaceutically acceptable salt thereof.
ACE inhibitors include alacepril, benazepril, benazeprilat, captopril, ceronapril, cilazapril, delapril, enalapril, enaprilat, fosinopril, imidapril, lisinopril, moveltopril, perindopril, quinapril, ramipril, spirapril, temocapril, and trandolapril, or, in each case, a pharmaceutically acceptable salt thereof.
Hypoglycemic agents include repaglinide, nateglinide, glimepiridum,
glibenclamidum, gliclazidum, glipizidum, glibornuridum, metformin, miglitol, acarbose, muraglitazar, pioglitazone, rosiglitazone, and tesaglitazar, or, in each case, a
pharmaceutically acceptable salt thereof.
Examples of disintegrants include sodium starch glycolate, croscarmellose, pregelatinized starch, microcrystalline cellulose, calcium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, magnesium or aluminum silicate, or mixtures thereof. The amount of disintegrants used in the pharmaceutical compositions of the present invention ranges from 1% w/w to about 50% w/w.
Examples of diluents include starch, lactose, sucrose, maltodextrin,
microcrystalline cellulose, lactose, dextrose, sucrose, mannitol, sorbitol, xylitol, isomalt, erythritol, or mixtures thereof. The amount of diluents used in the pharmaceutical compositions of the present invention ranges from 10% w/w to 75% w/w.
As used herein, the term "antioxidant" is intended to mean an agent that inhibits oxidation, and thus is used to prevent the deterioration of preparations by oxidation due to the presence of oxygen free radicals or free metals in the composition. Examples of antioxidants include ascorbic acid, butylated hydroxyl anisole, butylated hydroxyl toluene, or a mixture thereof. The amount of antioxidants used in the pharmaceutical compositions of the present invention ranges from 0.01% w/w to 2% w/w.
Examples of lubricants include magnesium stearate, calcium stearate, silicon dioxide, sodium stearyl fumarate, stearic acid, talc, or mixtures thereof. The amount of lubricant used in the pharmaceutical compositions of the present invention ranges from 0.5% w/w to 5% w/w.
The pharmaceutical composition may be further coated with a functional or nonfunctional coating. The coating composition may be comprised of pharmaceutically
acceptable excipients such as binders, plasticizers, coloring agents, and opacifiers. The total weight gain after coating may be about 1% w/w to 10% w/w of the uncoated pharmaceutical composition.
Examples of binders for coating include cellulose or cellulose derivatives such as methylcellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium; alginic acid or sodium alginate; microcrystalline cellulose; gelatin; polyvinyl pyrrolidone; copovidone; starch; pregelatinized starch; or mixtures thereof.
Examples of plasticizers for coating include propylene glycol, triethyl citrate, tributyl citrate, dibutyl sebacate, triacetin, polyethylene glycol, diethyl phthalate, acetylated monoglycerides, or mixtures thereof.
Examples of opacifiers for coating include titanium dioxide, talc, calcium carbonate, behenic acid, cetyl alcohol, or mixtures thereof.
Examples of coloring agents for coating include FDA approved colorants such as iron oxide, Lake of Tartrazine, Allura Red, Lake of Quinoline Yellow, Lake of
Erythrosine, titanium dioxide, or mixtures thereof.
Suitable solvents for the coating include ethanol, methanol, isopropyl alcohol, methylene chloride, acetone, or mixtures thereof.
The following examples illustrate the invention but are not to be construed as limiting the scope of the invention.
EXAMPLES
Example 1 :
1. Azilsartan kamedoxomil, mannitol, and micro-crystalline cellulose were blended.
2. Polyvinyl pyrrolidone was dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 was granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 were dried and blended with croscarmellose sodium.
5. The blend of step 4 was lubricated with magnesium stearate, and compressed to obtain suitable sized tablets.
Stability Testing
The compressed tablets obtained from Example 1, after being packed in HDPE bottles, were subjected to stability testing at 40°C/75% RH for three months. The samples were analyzed initially and later at three months for determining the amount of desethyl azilsartan and ethyl azilsartan generated. The method for determining desethyl azilsartan, ethyl azilsartan, and azilsartan medoxomil employed high performance liquid
chromatography (HPLC) using a Sunniest CI 8 , 5 μιη, 250 mm x 4.6 mm column, gradient mobile phase having acetate buffer pH 5.1, and a mixture of methanol and acetonitrile (organic phase) in the ratio of 55:45. The relative retention time (RRT) of desethyl azilsartan and ethyl azilsartan was 0.64 and 1.10, respectively.
The commercially marketed tablet (Edarbi® 80 mg), was also subjected to a similar stability testing protocol, and assessed for desethyl azilsartan and ethyl azilsartan. The comparative results of the stability study are shown in Table 1.
Table 1 : Assay and percentage of desethyl azilsartan and ethyl azilsartan after subjecting tablets packed in HDPE bottles to 40°C/75% RH
ND = Not Detected
The azilsartan medoxomil tablets obtained were found to be a stable v is a -vis the marketed product and had reduced odor as compared to azilsartan medoxomil.
Example 2:
Manufacturing Process:
1. Azilsartan kamedoxomil, mannitol, and microcrystallme cellulose are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 3 :
1. Azilsartan kamedoxomil, mannitol, and microcrystallme cellulose are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules. 4. The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 4:
Manufacturing Process:
1. Azilsartan kamedoxomil and mannitol are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules. 4. The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 5:
Manufacturing Process:
1. Azilsartan kamedoxomil and mannitol are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 are blended with croscarmellose sodium, microcrystalline cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 6:
1. Azilsartan kamedoxomil, microcrystallme cellulose, and mannitol are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 7:
Manufacturing Process:
Azilsartan kamedoxomil and mannitol are blended.
Polyvinyl pyrrolidone is dissolved in isopropyl alcohol to obtain a solution.
The blend of step 1 is granulated with the solution of step 2 to obtain granules.
The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
The blend of step 4 is compressed to obtain suitable sized tablets.
Example 8:
Manufacturing Process:
1. Azilsartan kamedoxomil and mannitol are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 are blended with croscarmellose sodium, microcrystalline cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Example 9:
1. Azilsartan kamedoxomil, polyvinyl pyrrolidone (PVP K-30), microcrystallme cellulose, and mannitol are blended.
2. Polyvinyl pyrrolidone is dissolved in isopropyl alcohol and methylene chloride to obtain a solution.
3. The blend of step 1 is granulated with the solution of step 2 to obtain granules.
4. The granules of step 3 are blended with croscarmellose sodium, microcrystallme cellulose, and magnesium stearate.
5. The blend of step 4 is compressed to obtain suitable sized tablets.
Claims
1. A stable pharmaceutical composition comprising azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, and a polymeric carrier selected from the group consisting of polyvinyl pyrrolidone, copovidone, or a mixture thereof, wherein the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to the polymeric carrier is from about 3: 1 to about 22: 1 based on weight.
2. The stable pharmaceutical composition according to claim 1, wherein the composition does not comprise a pH control agent.
3. The stable pharmaceutical composition according to claim 1, wherein the composition has a reduced odor as compared to azilsartan medoxomil.
4. The stable pharmaceutical composition according to claim 1, wherein the ratio of azilsartan medoxomil, or a pharmaceutically acceptable salt thereof, to polyvinyl pyrrolidone is from about 7: 1 to about 12: 1 based on weight.
5. The stable pharmaceutical composition according to claim 1, wherein the composition is prepared by an anhydrous granulation process.
6. A process for the preparation of the stable pharmaceutical composition according to claim 1, wherein the process comprises:
a) blending azilsartan medoxomil or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients;
b) dissolving/dispersing a polymeric carrier in an anhydrous solvent;
c) granulating the blend of step a) with the solution/dispersion of step b);
d) optionally, blending the granules of step c) with one or more
pharmaceutically acceptable excipients; and
e) compressing the granules of step c) or the blend of step d) into suitable sized tablets or filling into suitable sized capsules.
7. A process for the preparation of the stable pharmaceutical composition according to claim 1, wherein the process comprises:
a) blending one or more pharmaceutically acceptable excipients;
b) dissolving/dispersing azilsartan medoxomil and a polymeric carrier in an
anhydrous solvent;
c) granulating the blend of step a) with the solution/dispersion of step b); d) optionally, blending the granules of step c) with one or more
pharmaceutically acceptable excipients; and
e) compressing the granules of step c) or the blend of step d) into suitable sized tablets or filling into suitable sized capsules.
8. The process according to claim 6 or claim 7, wherein the anhydrous solvent is selected from the group consisting of acetone, methyl ethyl ketone, methyl isobutyl ketone, methanol, ethanol, isopropyl alcohol, toluene, tetrahydrofuran, chloroform, methylene chloride, or mixtures thereof.
9. The process according to claim 8, wherein the anhydrous solvent is a mixture of methylene chloride and isopropyl alcohol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN4045/DEL/2012 | 2012-12-31 | ||
| IN4045DE2012 | 2012-12-31 |
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| WO2014102628A1 true WO2014102628A1 (en) | 2014-07-03 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176663A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of Azilsartan potassium salt capsule and preparation method thereof |
| WO2018118496A1 (en) * | 2016-12-20 | 2018-06-28 | Colgate-Palmolive Company | Oral care composition |
| WO2019130277A1 (en) | 2017-12-30 | 2019-07-04 | Lupin Limited | Pharmaceutical formulations of azilsartan medoxomil |
| US20190314368A1 (en) * | 2016-07-29 | 2019-10-17 | Wuhan Ll Science And Technology Development Co., Ltd. | Oral solid preparation and use thereof |
| WO2022123592A1 (en) * | 2020-12-08 | 2022-06-16 | Alkem Laboratories Ltd | Stable pharmaceutical composition of azilsartan medoxomil or pharmaceutical acceptable salt and processes for preparing thereof |
| US11786471B2 (en) * | 2016-07-11 | 2023-10-17 | Wuhan Ll Science And Technology Development Co. Ltd. | Complex disintegrant system for oral solid preparation and oral solid preparation comprising said complex disintegrant system |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100121071A1 (en) | 2007-03-28 | 2010-05-13 | Takeda Pharmaceutical Company Limited | Solid pharmaceutical composition comprising a benzimidazole-7-carboxylate derivative and a ph control agent |
| EP2394638A1 (en) * | 2010-06-11 | 2011-12-14 | Sanovel Ilac Sanayi ve Ticaret A.S. | New Pharmaceutical Combinations |
| CN102342944A (en) * | 2011-07-14 | 2012-02-08 | 丁尧 | Medicament composition for treating hypertension |
| CN102793680A (en) * | 2011-05-23 | 2012-11-28 | 江苏恒瑞医药股份有限公司 | Azilsartan solid dispersion and preparation method and medicinal composition thereof |
-
2013
- 2013-11-21 WO PCT/IB2013/060318 patent/WO2014102628A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100121071A1 (en) | 2007-03-28 | 2010-05-13 | Takeda Pharmaceutical Company Limited | Solid pharmaceutical composition comprising a benzimidazole-7-carboxylate derivative and a ph control agent |
| EP2394638A1 (en) * | 2010-06-11 | 2011-12-14 | Sanovel Ilac Sanayi ve Ticaret A.S. | New Pharmaceutical Combinations |
| CN102793680A (en) * | 2011-05-23 | 2012-11-28 | 江苏恒瑞医药股份有限公司 | Azilsartan solid dispersion and preparation method and medicinal composition thereof |
| CN102342944A (en) * | 2011-07-14 | 2012-02-08 | 丁尧 | Medicament composition for treating hypertension |
Non-Patent Citations (2)
| Title |
|---|
| DATABASE WPI Week 201249, Derwent World Patents Index; AN 2012-C34963, XP002723081, "Pharmaceutical composition for use as e.g. capsule, to treat hypertension, comprises azilsartan medoxomil, hydrochlorothiazide and auxiliary material" * |
| DATABASE WPI Week 201316, Derwent World Patents Index; AN 2012-Q70588, XP002723082, "Solid dispersion useful as pharmaceutical composition, and in preparation of medicaments for treating hypertension, comprises azilsartan and carrier material e.g. povidone" * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11786471B2 (en) * | 2016-07-11 | 2023-10-17 | Wuhan Ll Science And Technology Development Co. Ltd. | Complex disintegrant system for oral solid preparation and oral solid preparation comprising said complex disintegrant system |
| US20190314368A1 (en) * | 2016-07-29 | 2019-10-17 | Wuhan Ll Science And Technology Development Co., Ltd. | Oral solid preparation and use thereof |
| US11013736B2 (en) * | 2016-07-29 | 2021-05-25 | Wuhan Ll Science And Technology Development Co., Ltd. | Oral solid preparation and use thereof |
| CN106176663A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of Azilsartan potassium salt capsule and preparation method thereof |
| WO2018118496A1 (en) * | 2016-12-20 | 2018-06-28 | Colgate-Palmolive Company | Oral care composition |
| US10543154B2 (en) | 2016-12-20 | 2020-01-28 | Colgate-Palmolive Company | Oral care composition |
| AU2017382566B2 (en) * | 2016-12-20 | 2020-03-12 | Colgate-Palmolive Company | Oral care composition |
| US11090243B2 (en) | 2016-12-20 | 2021-08-17 | Colgate-Palmolive Company | Oral care composition |
| WO2019130277A1 (en) | 2017-12-30 | 2019-07-04 | Lupin Limited | Pharmaceutical formulations of azilsartan medoxomil |
| WO2022123592A1 (en) * | 2020-12-08 | 2022-06-16 | Alkem Laboratories Ltd | Stable pharmaceutical composition of azilsartan medoxomil or pharmaceutical acceptable salt and processes for preparing thereof |
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