WO2007022113A2 - Solid dosage forms of valsartan and amlodipine and method of making the same - Google Patents
Solid dosage forms of valsartan and amlodipine and method of making the same Download PDFInfo
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- WO2007022113A2 WO2007022113A2 PCT/US2006/031699 US2006031699W WO2007022113A2 WO 2007022113 A2 WO2007022113 A2 WO 2007022113A2 US 2006031699 W US2006031699 W US 2006031699W WO 2007022113 A2 WO2007022113 A2 WO 2007022113A2
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- 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
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Definitions
- the present invention is directed to solid dosage formulations containing a combination of valsartan and amlodipine, as well as to methods of making such solid dosage forms and a method of treating a subject with such solid dosage forms.
- fixed-combination refers to a combination of two drugs or active ingredients presented in a single dosage unit such as a tablet or a capsule; further as used herein, “free- combination” refers to a combination of two drugs or active ingredients dosed simultaneously but as two dosage units.
- free- combination refers to a combination of two drugs or active ingredients dosed simultaneously but as two dosage units.
- the objective is to provide a patient-convenient combination dosage form of active ingredients that is bioequivalent to the corresponding free-combination of the same active ingredients.
- Development of fixed-combination dosage formulations that are bioequivalent to the free- combination is challenging due to the multiplicity of challenges arising from pharmacokinetic and pharmaceutical properties of the drugs sought to be combined.
- valsartan has an absolute oral bioavailability of only about 25% with a wide range of 10-35%.
- Valsartan also has pH dependent solubility whereby it ranges from very slightly soluble in an acidic environment to soluble in a neutral environment of the gastrointestinal tract.
- development of a patient-convenient oral dosage form of valsartan is challenging due to its low bulk density.
- Amlodipine besylate is slightly soluble in water and has an absolute bioavailability of 64-90%.
- development of a fixed-combination dosage form of valsartan and amlodipine that is bioequivalent to a free-combination thereof is challenging.
- the present invention is directed to a solid dosage form comprising a combination of valsartan and amlodipine, and pharmaceutically acceptable additives suitable for the preparation of solid dosage forms of valsartan.
- amlodipine free base is provided in the form of amlodipine besylate, and the pharmaceutically acceptable additives are selected from diluents, disintegrants, glidants, lubricants, colorants and combinations thereof.
- the solid dosage form is a monolayer tablet.
- the amount of valsartan employed in such monolayer tablets preferably ranges from about 40 mg to about 640 mg, and more preferably is 80 mg or 160 mg.
- the amount of amlodipine employed in such monolayer tablets preferably ranges from about 1.25 mg to about 20 mg, and more preferably is 2.5 mg, 5 mg or 10 mg.
- the solid dosage form is a bilayer tablet having the valsartan in one layer and the amlodipine in another layer.
- the amount of valsartan employed in such bilayer tablets preferably ranges from about 40 mg to about 640 mg, and more preferably is 320 mg.
- the amount of amlodipine employed in such bilayer tablets preferably ranges from about 1.25 mg to about 20 mg, and more preferably is 5 mg or 10 mg.
- this invention is directed to solid dosage forms of valsartan made according to the method of the second aspect.
- the present invention is directed to a method of making a solid dosage form of valsartan comprising the steps of (a) granulating valsartan and pharmaceutically acceptable additives to form a valsartan granulation; (b) blending amlodipine and pharmaceutically acceptable additives to form an amlodipine blend; and (c) compressing the valsartan granulation and the amlodipine blend together to form a bilayer solid dosage form.
- the first embodiment of the invention is directed to a solid dosage form of valsartan comprising a combination of valsartan and amlodipine, and pharmaceutically acceptable additives suitable for the preparation of solid dosage forms of valsartan.
- the solid dosage forms of the present invention can take the form of monolayer tablets (having both the valsartan and the amlodipine in one layer) or bilayer tablets (having the valsartan in one layer and the amlodipine in another layer).
- Valsartan ((S)-N-valeryl-N- ⁇ [2'-(lH-tetrazole-5-yl)-biphenyl-4-yl]- methyl ⁇ -valine) suitable for use in the present invention can be purchased from commercial sources or can be prepared according to known methods. For example, the preparation of valsartan is described in U.S. Patent No. 5,399,578, the entire disclosure of which is incorporated by reference herein. Valsartan may be used for purposes of this invention in its free form as well as in any suitable salt form.
- monolayer tablets can be formed with any amount of valsartan within the above-noted range, it is important to consider the overall objective of bioequivalence to the free-combination of valsartan and amlodipine. Accordingly, monolayer tablets preferably contain a dose of up to 160 mg of valsartan; higher doses therein do not yield complete bioequivalence when compared with a corresponding free-combination. Hence, valsartan doses higher than 160 mg are better suited for bilayer solid dosage forms of the present invention. In fact, bilayer tablets can accommodate the full range of valsartan dosage above.
- Amlodipine (3-ethyl-5-methyl-2(2-aminoethoxymethyl)-4-(2- chlrorophenyl)- 1 ,4-dihydro-6-methyl-3 ,5 -pyridinedicarboxylate benzenesulphonate) suitable for use in the present invention can be purchased from commercial sources or can be prepared according to known methods. Amlodipine may be used for purposes of this invention in its free form as well as in any suitable salt form; in a preferred embodiment of this invention, amlodipine free base is supplied to the solid dosage forms through the use of amlodipine besylate.
- Amlodipine is employed in an amount ranging from 1.25 mg to about 20 mg, preferably from about 1.875 mg to about 15 mg, more preferably from about 2.5 mg to about 10 mg, and most preferably is about 2.5 mg or about 5 mg in a monolayer tablet and about 5 mg or about 10 mg in a bilayer tablet.
- the amount of amlodipine noted above refers to the amount of free amlodipine present in a given solid dosage form.
- Pharmaceutically acceptable additives suitable for use in the present invention include, without limitation, diluents or fillers, disintegrants, glidants, lubricants, binders, colorants and combinations thereof.
- Preferred pharmaceutically acceptable additives include diluents and disintegrants.
- the amount of each additive in a solid dosage formulation may vary within ranges conventional in the art.
- Suitable diluents include, without limitation, microcrystalline cellulose (e.g., cellulose MK GR), mannitol, sucrose or other sugars or sugar derivatives, low-substituted hydroxypropyl cellulose, and combinations thereof.
- a diluent may be employed in an amount ranging from about 15% to about 70%, preferably from about 32% to about 55% by weight of the solid dosage form (prior to any optional film coating).
- a diluent is preferably employed in an amount ranging from about 15% to about 50%, more preferably in an amount of about 33% by weight of the solid dosage form.
- Suitable colorants include, without limitation, iron oxides such as yellow, white, red, and black iron oxide, and combinations thereof. When present, a colorant may be employed in an amount ranging from about 0.01% to about 0.1% by weight of the solid dosage form (prior to any optional film coating). In a preferred embodiment, monolayer tablets contain no colorant.
- the solid dosage forms of the first embodiment of the invention are monolayer or bilayer tablet dosage forms of suitable hardness (e.g., an average hardness ranging from about 30 N to about 180 N for monolayer forms and an average hardness ranging from about 250 N to about 300 N for bilayer forms). Such an average hardness is determined prior to the application of any film coating on the solid dosage forms.
- the second embodiment of the present invention is directed to a method of making a solid dosage form of valsartan comprising the steps of (a) blending valsartan, amlodipine and pharmaceutically acceptable additives to form a blended material; (b) sieving the blended material to form a sieved material; (c) blending the sieved material to form a blended/sieved material; (d) compacting the blended/sieved material to form a compacted material; (e) milling the compacted material to form a milled material; (f) blending the milled material to form blended/milled material; and (g) compressing the blended/milled material to form a monolayer solid dosage form.
- valsartan, amlodipine, and pharmaceutically acceptable additives are blended to form a blended material. Blending can be accomplished using any suitable means such as a diffusion blender or diffusion mixer.
- the blended material is sieved to form a sieved material. Sieving can be accomplished using any suitable means.
- the sieved material is blended to form a blended/sieved material. Again blending can be accomplished using any suitable means.
- the blended/sieved material is compacted to form a compacted material.
- Compacting can be accomplished using any suitable means. Typically compacting is accomplished using a roller compactor with a compaction force ranging from about 20 kN to about 60 kN, preferably about 30 kN to about 40KN. Compaction may also be carried out by slugging the blended powders into large tablets that are then size-reduced.
- a third embodiment of the present invention is directed to a monolayer solid dosage form of valsartan made according to the method of the second embodiment.
- the fourth embodiment of the present invention is directed to a method of making a solid dosage form of valsartan comprising the steps of (a) granulating valsartan and pharmaceutically acceptable additives to form a valsartan granulation; (b) blending amlodipine and pharmaceutically acceptable additives to form an amlodipine blend; and (c) compressing the valsartan granulation and the amlodipine blend together to form a bilayer solid dosage form.
- the details regarding the valsartan, amlodipine, and pharmaceutically acceptable additives, i.e., source, amount, etc., are as set forth above with regard to the first embodiment of the invention.
- valsartan is granulated with pharmaceutically acceptable additives to form a valsartan granulation.
- Valsartan granulation can be accomplished by any suitable means.
- valsartan granulation is accomplished by (al) blending valsartan and pharmaceutically acceptable additives to form a blended material; (a2) sieving the blended material to form a sieved material; (a3) blending the sieved material to form a blended/sieved material; (a4) compacting the blended/sieved material to form a compacted material; (a5) milling the compacted material to form a milled material; and (a6) blending the milled material to form the valsartan granulation.
- step (al) can be accomplished using any suitable means.
- valsartan and pharmaceutically acceptable additives are dispatched to a suitable vessel such as a diffusion blender or diffusion mixer.
- the sieving of step (a2) can be accomplished using any suitable means.
- the blending of step (a3) can be accomplished using any suitable means.
- the compacting of step (a4) can be accomplished using any suitable means. Typically compacting is accomplished using a roller compactor with a compaction force ranging from about 20 kN to about 60 kN, preferably about 35 kN. Compaction may also be carried out by slugging the blended powders into large tablets that are then size- reduced.
- the milling of step (a5) can be accomplished using any suitable means.
- step (a6) can be accomplished using any suitable means.
- the milled material is blended, often with a pharmaceutically acceptable additive such as a lubricant, in a diffusion blender.
- amlodipine is blended with pharmaceutically acceptable additives to form an amlodipine blend.
- Amlodipine blending can be accomplished by any suitable means.
- blending step (b) comprises the process of granulating amlodipine. Amlodipine granulation can be accomplished by any suitable means including wet granulation or dry granulation.
- amlodipine granulation is accomplished by (bl) blending amlodipine and pharmaceutically acceptable additives to form a blended material; (b2) sieving the blended material to form a sieved material; (b3) blending the sieved material to form a blended/sieved material; (b4) compacting the blended/sieved material to form a compacted material; (b5) milling the compacted material to form a milled material; and (b6) blending the milled material to form an amlodipine granulation.
- step (bl) can be accomplished using any suitable means.
- the sieving of step (b2) can be accomplished using any suitable means.
- the blending of step (b3) can be accomplished using any suitable means.
- the compacting of step (b4) can be accomplished using any suitable means. Typically compacting is accomplished using a roller compactor with a compaction force ranging from about 20 kN to about 50 kN, preferably about 30 kN to about 40 kN.
- the milling of step (b5) can be accomplished using any suitable means.
- the compacted material is milled through a screening mill.
- the blending of step (b6) can be accomplished using any suitable means.
- the valsartan granulation and the amlodipine blend are compressed together to form a bilayer solid dosage form. Compression can be accomplished using any suitable means. Typically compression is accomplished using a bilayer rotary tablet press. Typical compression force ranges from about 5 kN to about 35 kN.
- the method of the fourth embodiment comprises the step of (d) film coating the bilayer solid dosage form. The details regarding the film coating material, i.e., components, amounts, etc., are as described above with regard to the first embodiment of the invention. Film coating can be accomplished using any suitable means.
- a fifth embodiment of the present invention is directed to a bilayer solid dosage form of valsartan made according to the method of the fourth embodiment.
- Yet another embodiment of the invention is directed to a method of treating hypertension, congestive heart failure, angina, myocardial infarction, arteriosclerosis, diabetic nephropathy, diabetic cardiac myopathy, renal insufficiency, peripheral vascular disease, stroke, left ventricular hypertrophy, cognitive dysfunction, headache, or chronic heart failure.
- the method comprises administering a solid dosage form of valsartan as defined by the first, third or fifth embodiments of this invention to a subject in need of such treatment.
- the solid dosage form is orally administered to the subject.
- a monolayer solid dosage form of valsartan was made using the ingredients set forth in Table 1 below. Table 1.
- Ingredients A-F are placed into a diffusion blender and blended. Then, the blended material is sieved. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient G in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines subdivided batches of ingredients A-F.) Next, the blended/milled material is compressed into monolayer solid dosage forms using a rotary tablet press, and the monolayer solid dosage forms are optionally film coated.
- a monolayer solid dosage form of valsartan was made using the ingredients set forth in Table 2 below. Table 2.
- Ingredients A-F are placed into a diffusion blender and blended. Then, the blended material is sieved. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient G in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines subdivided batches of ingredients A-F.) Next, the blended/milled material is compressed into monolayer solid dosage forms using a rotary tablet press, and the monolayer solid dosage forms are optionally film coated. EXAMPLE 3 160/5 MG TABLET
- a monolayer solid dosage form of valsartan was made using the ingredients set forth in Table 3 below.
- Ingredients A-F are placed into a diffusion blender and blended. Then, the blended material is sieved. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient G in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines subdivided batches of ingredients A-F.) Next, the blended/milled material is compressed into monolayer solid dosage forms using a rotary tablet press, and the monolayer solid dosage forms are optionally film coated.
- a monolayer solid dosage form of valsartan was made using the ingredients set forth in Table 4 below. Table 4.
- Ingredients A-F are placed into a diffusion blender and blended. Then, the blended material is sieved through a screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient G in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients A-F.) Next, the blended/milled material is compressed into monolayer solid dosage forms using a rotary tablet press, and the monolayer solid dosage forms are optionally film coated.
- Ingredients A-F are placed into a diffusion blender and blended. Then, the blended material is sieved through screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient G in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients A-F.) Next, the blended/milled material is compressed into monolayer solid dosage forms using a rotary tablet press, and the monolayer solid dosage forms are optionally film coated.
- a bilayer solid dosage form of valsartan was made using the ingredients set forth in Table 6 below. Table 6.
- the valsartan is granulated by combining ingredients A-E in a diffusion blender. Then, the blended material is sieved through a screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient F in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients A- E.)
- the amlodipine besylate is granulated by combining ingredients G-K in a diffusion blender. Then, the blended material is sieved through a screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient L in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients G-K.)
- a bilayer solid dosage form of valsartan was made using the ingredients set forth in Table 7 below. Table 7.
- the valsartan is granulated by combining ingredients A-E in a diffusion blender. Then, the blended material is sieved through a screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then blended with ingredient F in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients A-
- the amlodipine besylate is granulated by combining ingredients G-K in a diffusion blender. Then, the blended material is sieved through a screen. Next, the sieved material is blended again in a diffusion blender. The blended/sieved material is then compacted using a roller compactor. The compacted material is milled through a screen and then with ingredient L in a diffusion blender. (This second blending step achieves the desired level of lubricant for the granulation and, in certain cases, combines sub-divided batches of ingredients G-K.)
- the valsartan granulation and the amlodipine granulation are compressed into bilayer solid dosage forms using a bilayer rotary tablet press, and the bilayer solid dosage forms are optionally film coated.
- the difference between the percent of valsartan dissolved from the fixed- and free-combination dosage formulations was no more than 10% at 10, 20, or 30 minutes, by which time the dissolution was nearly complete.
- the dissolution of amlodipine from the fixed-combination tablet was different from that of amlodipine in the free-combination in both pH 4.5 and 6.8 media.
- pH 6.8 phosphate solution amlodipine in the fixed- combination dosage form dissolved faster by about 30% fraction dissolved at 30 minutes, for example.
- pH 4.5 phosphate solution the dissolution of amlodipine from the fixed-combination was slower than the dissolution of amlodipine as a free-combination by about 35% fraction dissolved at 30 minutes, for example.
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
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Abstract
Description
Claims
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2006279670A AU2006279670A1 (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
US11/914,159 US20080171086A1 (en) | 2005-08-17 | 2006-08-15 | Solid Dosage Forms of Valsartan and Amlo Dipine and Method of Making the Same |
MX2008002267A MX2008002267A (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same. |
JP2008527038A JP2009504744A (en) | 2005-08-17 | 2006-08-15 | Solid dosage form of valsartan and amlodipine and process for its production |
BRPI0614790-9A BRPI0614790A2 (en) | 2005-08-17 | 2006-08-15 | solid dosage forms of valsartan and amlodipine, and method of production thereof |
CA002617367A CA2617367A1 (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
KR1020127030872A KR20120135356A (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
EP06813435A EP1917002A2 (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
NZ565020A NZ565020A (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
IL189021A IL189021A0 (en) | 2005-08-17 | 2008-01-24 | Solid dosage forms of valsartan and amlodipine and method of making the same |
TNP2008000071A TNSN08071A1 (en) | 2005-08-17 | 2008-02-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
NO20081310A NO20081310L (en) | 2005-08-17 | 2008-03-12 | Solid dosage forms for valsartan and amlodipine, and methods for preparing the same |
US12/852,542 US20100303906A1 (en) | 2005-08-17 | 2010-08-09 | Solid dosage forms of valsartan and amlodipine and method of making same |
AU2010227062A AU2010227062A1 (en) | 2005-08-17 | 2010-10-08 | Solid dosage forms of valsartan and amlodipine and method of making the same |
US13/403,638 US20120177733A1 (en) | 2005-08-17 | 2012-02-23 | Solid dosage forms of valsartan and amlodipine and method of making the same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US70908305P | 2005-08-17 | 2005-08-17 | |
US60/709,083 | 2005-08-17 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/852,542 Continuation US20100303906A1 (en) | 2005-08-17 | 2010-08-09 | Solid dosage forms of valsartan and amlodipine and method of making same |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2007022113A2 true WO2007022113A2 (en) | 2007-02-22 |
WO2007022113A3 WO2007022113A3 (en) | 2007-05-10 |
Family
ID=37758280
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2006/031699 WO2007022113A2 (en) | 2005-08-17 | 2006-08-15 | Solid dosage forms of valsartan and amlodipine and method of making the same |
Country Status (22)
Country | Link |
---|---|
US (3) | US20080171086A1 (en) |
EP (1) | EP1917002A2 (en) |
JP (2) | JP2009504744A (en) |
KR (3) | KR20120135356A (en) |
CN (1) | CN101237859A (en) |
AR (1) | AR055120A1 (en) |
AU (2) | AU2006279670A1 (en) |
BR (1) | BRPI0614790A2 (en) |
CA (1) | CA2617367A1 (en) |
EC (1) | ECSP088188A (en) |
GT (1) | GT200600371A (en) |
IL (1) | IL189021A0 (en) |
MA (1) | MA29734B1 (en) |
MX (1) | MX2008002267A (en) |
NO (1) | NO20081310L (en) |
NZ (1) | NZ565020A (en) |
PE (1) | PE20070420A1 (en) |
RU (2) | RU2008109913A (en) |
TN (1) | TNSN08071A1 (en) |
TW (1) | TW200740432A (en) |
WO (1) | WO2007022113A2 (en) |
ZA (1) | ZA200800397B (en) |
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WO2010104485A3 (en) * | 2009-03-11 | 2010-11-25 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Valsartan formulations |
WO2011001440A1 (en) * | 2009-07-03 | 2011-01-06 | Hetero Research Foundation | Pharmaceutical compositions of valsartan |
US8052999B2 (en) | 2006-11-10 | 2011-11-08 | Atacama Labs | Granules, tablets and granulation |
US8101599B2 (en) | 2002-05-17 | 2012-01-24 | Novartis Ag | Pharmaceutical composition containing anti-hypertensive agents |
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US8581134B2 (en) | 2006-11-10 | 2013-11-12 | Giovanni Politi | Method and apparatus for dry granulation |
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- 2006-08-11 GT GT200600371A patent/GT200600371A/en unknown
- 2006-08-15 MX MX2008002267A patent/MX2008002267A/en unknown
- 2006-08-15 AR ARP060103556A patent/AR055120A1/en not_active Application Discontinuation
- 2006-08-15 CN CNA2006800289354A patent/CN101237859A/en active Pending
- 2006-08-15 PE PE2006000992A patent/PE20070420A1/en not_active Application Discontinuation
- 2006-08-15 BR BRPI0614790-9A patent/BRPI0614790A2/en not_active IP Right Cessation
- 2006-08-15 CA CA002617367A patent/CA2617367A1/en not_active Abandoned
- 2006-08-15 AU AU2006279670A patent/AU2006279670A1/en not_active Abandoned
- 2006-08-15 JP JP2008527038A patent/JP2009504744A/en active Pending
- 2006-08-15 RU RU2008109913/15A patent/RU2008109913A/en unknown
- 2006-08-15 EP EP06813435A patent/EP1917002A2/en not_active Withdrawn
- 2006-08-15 WO PCT/US2006/031699 patent/WO2007022113A2/en active Application Filing
- 2006-08-15 KR KR1020127030872A patent/KR20120135356A/en active IP Right Grant
- 2006-08-15 KR KR1020087003704A patent/KR20080034159A/en not_active Application Discontinuation
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2010
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2012
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Also Published As
Publication number | Publication date |
---|---|
EP1917002A2 (en) | 2008-05-07 |
KR20120135356A (en) | 2012-12-12 |
KR20080034159A (en) | 2008-04-18 |
JP2013091660A (en) | 2013-05-16 |
MX2008002267A (en) | 2008-03-27 |
AU2006279670A1 (en) | 2007-02-22 |
WO2007022113A3 (en) | 2007-05-10 |
US20080171086A1 (en) | 2008-07-17 |
US20100303906A1 (en) | 2010-12-02 |
ZA200800397B (en) | 2009-03-25 |
JP2009504744A (en) | 2009-02-05 |
CN101237859A (en) | 2008-08-06 |
AU2010227062A1 (en) | 2010-11-04 |
MA29734B1 (en) | 2008-09-01 |
ECSP088188A (en) | 2008-03-26 |
RU2012131668A (en) | 2014-01-27 |
US20120177733A1 (en) | 2012-07-12 |
TNSN08071A1 (en) | 2009-07-14 |
GT200600371A (en) | 2007-03-21 |
IL189021A0 (en) | 2008-08-07 |
CA2617367A1 (en) | 2007-02-22 |
AR055120A1 (en) | 2007-08-08 |
NZ565020A (en) | 2011-07-29 |
KR20120078751A (en) | 2012-07-10 |
PE20070420A1 (en) | 2007-05-21 |
NO20081310L (en) | 2008-05-16 |
BRPI0614790A2 (en) | 2011-04-12 |
RU2008109913A (en) | 2009-09-27 |
TW200740432A (en) | 2007-11-01 |
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