WO2018033808A1 - Composition améliorée de ténéligliptine et de metformine et procédé pour sa préparation - Google Patents
Composition améliorée de ténéligliptine et de metformine et procédé pour sa préparation Download PDFInfo
- Publication number
- WO2018033808A1 WO2018033808A1 PCT/IB2017/053749 IB2017053749W WO2018033808A1 WO 2018033808 A1 WO2018033808 A1 WO 2018033808A1 IB 2017053749 W IB2017053749 W IB 2017053749W WO 2018033808 A1 WO2018033808 A1 WO 2018033808A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- metformin
- pharmaceutical composition
- therapeutically effective
- teneligliptin
- effective amount
- Prior art date
Links
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 title claims abstract description 115
- 229950000034 teneligliptin Drugs 0.000 title claims abstract description 101
- WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical group O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 title claims abstract description 97
- 229960003105 metformin Drugs 0.000 title claims abstract description 71
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 238000000034 method Methods 0.000 title description 22
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 13
- 239000011230 binding agent Substances 0.000 claims abstract description 12
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 11
- 229940069328 povidone Drugs 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- 239000008187 granular material Substances 0.000 claims description 37
- 239000011248 coating agent Substances 0.000 claims description 29
- 238000000576 coating method Methods 0.000 claims description 29
- 235000019441 ethanol Nutrition 0.000 claims description 26
- 239000003472 antidiabetic agent Substances 0.000 claims description 18
- 230000003178 anti-diabetic effect Effects 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 12
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 12
- 239000000725 suspension Substances 0.000 claims description 9
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 8
- 238000001033 granulometry Methods 0.000 claims description 7
- 238000013265 extended release Methods 0.000 claims description 5
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 239000002700 tablet coating Substances 0.000 claims 1
- 238000009492 tablet coating Methods 0.000 claims 1
- 239000003826 tablet Substances 0.000 abstract description 82
- 238000000338 in vitro Methods 0.000 abstract description 11
- 239000004480 active ingredient Substances 0.000 abstract description 10
- 239000000843 powder Substances 0.000 abstract description 6
- 238000007906 compression Methods 0.000 abstract description 4
- 230000006835 compression Effects 0.000 abstract description 4
- 238000005550 wet granulation Methods 0.000 abstract description 3
- 239000007935 oral tablet Substances 0.000 abstract 1
- 229940096978 oral tablet Drugs 0.000 abstract 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 46
- 229960004329 metformin hydrochloride Drugs 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 24
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 22
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 13
- 238000009472 formulation Methods 0.000 description 12
- 239000004408 titanium dioxide Substances 0.000 description 12
- 229920003081 Povidone K 30 Polymers 0.000 description 9
- 239000012530 fluid Substances 0.000 description 8
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 7
- 229950004221 besilate Drugs 0.000 description 7
- 235000013773 glyceryl triacetate Nutrition 0.000 description 7
- 239000001087 glyceryl triacetate Substances 0.000 description 7
- 238000005469 granulation Methods 0.000 description 7
- 230000003179 granulation Effects 0.000 description 7
- 229960002622 triacetin Drugs 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 description 5
- 229940098805 metformin hydrochloride 850 mg Drugs 0.000 description 5
- 230000002035 prolonged effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 4
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000000227 grinding Methods 0.000 description 4
- 229960003943 hypromellose Drugs 0.000 description 4
- 229940103788 metformin hydrochloride 1000 mg Drugs 0.000 description 4
- 229940103776 metformin hydrochloride 500 mg Drugs 0.000 description 4
- 238000001223 reverse osmosis Methods 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000012812 general test Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 229940126904 hypoglycaemic agent Drugs 0.000 description 3
- 229940123208 Biguanide Drugs 0.000 description 2
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 2
- -1 Teneligliptin compound Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 230000004116 glycogenolysis Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical group O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000003979 response to food Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
Classifications
-
- 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
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
Definitions
- the present invention relates to an improved fixed dose composition
- an improved fixed dose composition comprising the combination of two hypoglycemic active ingredients, one of the gliptin family, Teneliglipt ina and the other of the biguanide family, Metformin, for treatment by Oral route of diabetes mellitus type 2 (DM2) in humans, the process to obtain such an improved composition, and its uses.
- DM2 diabetes mellitus type 2
- the Teneligliptin compound whose IUPAC nomenclature is Methanone, [(2S, 4S) -4- [4- (3-meti 1-1-phenyl-lH-pyrazol-5-i 1) -1-piperazinyl] -2-pyrrolidinyl ] -3-thiazolidini 1, represented by formula (I), was disclosed as a product in European patent EP 1 308439 Bl and its equivalents, the holder of which is MITSUBISHI TANABE PHARMA and the priority date is 10-8-00 and 28 -12-00 (JP).
- Teneligliptin is an oral hypoglycemic agent, a dipeptidyl peptidase 4 (DPP-4) inhibitor.
- DPP-4 dipeptidyl peptidase 4
- the pharmacological action of Teneligliptin is described as follows: the glucagon-like peptide type 1 (GLP-1) is secreted by the gastrointestinal tract in response to food, promotes insulin secretion from the pancreas and, by suppression of glucagon secretion, adjust postprandial glycemia.
- GLP-1 glucagon-like peptide type 1
- DPP-4 dipeptidyl peptidase 4
- Metformin is an antihyperglycemic agent belonging to the group of biguanides, which lowers basal and postprandial glycemia. It does not stimulate insulin secretion, thus not producing hypoglycemia.
- the mechanism of action is not known exactly and it is considered that it could act: 1) decreasing hepatic glucose production by inhibition of glycogenolysis and gluconeogenesis, 2) in the muscle, increasing the sensitivity or amount of insulin receptors, improving glucose uptake and utilization and 3) decreasing the intestinal absorption of glucose.
- Metformin has been shown to produce a favorable effect on lipid metabolism, independent of its effect on blood glucose.
- Administered in therapeutic doses Metformin lowers total cholesterol, LDL cholesterol and plasma t-riglycerides.
- the usual initial dose of treatment is 500 mg or 850 mg two or three times per day administered during or after meals. Increased doses can be evaluated based on tolerance and blood glucose levels. The dose can be increased to 3000 mg per day, always divided every 8 or 12 hours.
- the object of the present invention relates to an improved formulation in the form of a coated tablet, in a unit dose, comprising two agents.
- hypoglycemic agents namely Teneliglipt ina or any of its pharmaceutically acceptable salts, and Metformin, such as Metformin hydrochloride, in a therapeutically effective amount, for the treatment of type 2 diabetes mellitus (DM2), further comprising a low content of excipients.
- Metformin such as Metformin hydrochloride
- the obtained tablets were highly friable, took very low hardness working with high compression force, and also pickled (they opened in sheets).
- the physical characteristics of Metformin hydrochloride were studied thoroughly, observing that it was usually acicular crystalline powder, which tended to form lumps and compact into the container container.
- tests were carried out, reducing the granulometry of Metformin hydrochloride by calibrating it in the Fitz Mili mill, varying the meshes and speeds. Although the compressibility improved, the hardness obtained was not optimal and the process was far from reproducible.
- the granulate was then calibrated by a 2 mm mesh, and subsequently, dried by using a fluid bed until a residual humidity between 1.5 and 2% was obtained, taken at 105 2 C. Then the dry granulate was calibrated. using a 1 mm mesh, and after adding a small aliquot of Magnesium Stearate, it was mixed for 2 minutes at 12 rpm. It was subsequently compressed with a rotary compressor, obtaining very good hardness tablets (around 20 kp), with brightness, low friability (less than 1% P / P), without presence of decape or laminate working with standard compression force. Also, the disintegration time was less than 15 minutes. The tablets obtained perfectly complied with the content uniformity test of both active ingredients.
- the usual methodology when developing a tablet formulation To vehicle one or more active ingredients it is to use one or more diluents, a binder, a disintegrant, a lubricant, and it is expected that as we increase the amount of excipients, compressibility improves. In the case object of this patent, the opposite happened, the compressibility decreased, that is why we affirm that it was an unexpected event.
- the invention relates to an improved pharmaceutical composition for oral administration, in the form of a coated tablet, for the treatment of DM2, which comprises the combination of a therapeutically effective amount of the antidiabetic Teneliglipt ina or its pharmaceutically salts. acceptable, with a therapeutically effective amount of the antidiabetic Metformin hydrochloride, with a low content of pharmaceutically acceptable excipients.
- the invention also relates to the therapeutically effective doses of Teneliglipt ina or its pharmaceutically acceptable salts, which may be in the range of 10 mg to 20 mg and the therapeutically effective doses of Metformin hydrochloride, which may be in the range of 500 to 2000 mg
- the invention relates to processes for obtaining an improved pharmaceutical composition of oral administration, in the form of a coated tablet, for the treatment of DM2, which comprises grinding Metformin, mixing, granulating, mixing again and compressing therapeutically effective amounts of the active ingredients Teneliglipt ina or its pharmaceutically acceptable salts and Metformin hydrochloride together with low content of pharmaceutically acceptable excipients and coating, the tablets obtained.
- DM2 a pharmaceutically acceptable pharmaceutically acceptable salts and Metformin hydrochloride
- Teneliglipt ina mixed with Metformin in another variant, it includes dissolved in the binder solution, and finally, in another variant, incorporates Teneligliptin from the suspension of the coating.
- the industrial lot is per 200 kg, it was kneaded in two aliquots of 100 kg each, in a Zanchetta rotator with a capacity of 300 liters.
- Titanium dioxide 9.00 0.81
- Weight of the coated tablet 1112 mg
- the industrial batch is for 200 kg, it was kneaded in two aliquots of 100 kg each, in a Zanchetta rotogranuladora of 300 liters of capacity.
- the industrial lot is for 200 kg, and was mixed in two aliquots of 100 kg each, in a Zanchetta rotogranuladora of 300 liters of capacity.
- the process for preparing a formulation of coated tablets for administration every 12 hours comprising 10 mg of Teneliglipt ina its pharmaceutically acceptable salts and 500 mg of Metformin, in which, Metformin hydrochloride will be compressed and Teneligliptin will be applied together with the covering.
- Metformin hydrochloride will be compressed and Teneligliptin will be applied together with the covering.
- the formula described below is per unit of Dosing, the industrial batch is per 100 kg, and it was kneaded in a Zanchetta rotogranuladora of 300 Liters of capacity.
- Example 5 The methodology described in Example 5 is applicable for doses of 10 mg of Teneliglipt ina its pharmaceutically acceptable salts, combined with 850 mg of Metformin, 10 mg of Teneliglipt ina combined with 1000 mg of Metformin hydrochloride (to be administered every 12 hr.) , and 20 mg of Teneliglipt ina combined with 850 mg of Metformin hydrochloride (to be administered every 24 hr).
- the industrial batch is 200 kg, Knead in two aliquots of 100 kg each,
- Example 7 The methodology applied in Example 7, is applicable for the doses of 10 mg of Teneliglipt ina or its pharmaceutically acceptable salts combined with 500 mg of Metformin, 10 mg of Teneliglipt ina combined with 1000 mg of Metformin hydrochloride, and 10 mg of Teneligliptin combined with 850 mg of Metformin hydrochloride.
- EXAMPLE 9 The methodology applied in Example 7, is applicable for the doses of 10 mg of Teneliglipt ina or its pharmaceutically acceptable salts combined with 500 mg of Metformin, 10 mg of Teneliglipt ina combined with 1000 mg of Metformin hydrochloride, and 10 mg of Teneligliptin combined with 850 mg of Metformin hydrochloride.
- Titanium dioxide 3.75 6, 25 7.00
- Friability Friabilómet ro type "ROCHE” equipment, according to USP General Tests and Assays ⁇ 1216>
- composition in the form of a coated tablet comprising Teneligliptin 10 mg and Metformin hydrochloride 500 mg, compared to coated tablets containing 10 mg of Teneligliptin and coated tablets containing 500 mg of Metformin hydrochloride.
- composition in the form of a coated tablet comprising Teneligliptin 10 mg and Metformin hydrochloride 1000 mg, compared to coated tablets containing 10 mg of Teneligliptin and coated tablets containing 1000 mg of Metformin hydrochloride.
- hydrochloride Q 70% Average: 99.3% Average: 100%
- composition in the form of a coated tablet comprising Teneligliptin 10 mg and Metformin hydrochloride 850 mg, compared to coated tablets containing 10 mg of Teneligliptin and coated tablets containing 850 mg of Metformin hydrochloride.
- composition in the form of a coated tablet comprising Teneligliptin 20 mg and Metformin hydrochloride 850 mg, compared to coated tablets containing 20 mg of Teneligliptin and coated tablets containing 850 mg of Metformin hydrochloride.
- composition in the form of a coated tablet comprising Teneligliptin 10 mg in the coating and Metformin hydrochloride 500 mg, in the core compared to coated tablets containing 10 mg of Teneligliptin and coated tablets containing 500 mg of Metformin hydrochloride.
- composition in the form of a coated tablet comprising Teneligliptin 20 mg added dissolved in the binder solution and Metformin hydrochloride 850 mg, granulated in a similar manner to the previous examples, compared with coated tablets containing 20 mg of Teneligliptin and coated tablets containing 850 mg of Metformin hydrochloride .
- composition in the form of a coated tablet comprising Teneligliptin 20 mg in the coating and Metformin hydrochloride 500 mg, in the core prolonged deliberation compared to coated tablets containing 20 mg of Teneligliptin and coated tablets containing 500 mg of Metformin hydrochloride extended release.
- Parameters Example 1 Teneligliptin 20 mg Metformin
- composition in the form of a coated tablet comprising Teneligliptin 20 mg in the coating and Metformin hydrochloride 1000 mg, in the core prolonged deliberation compared to coated tablets containing 20 mg of Teneligliptin and coated tablets containing 1000 mg of Metformin hydrochloride extended release.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR112019002909-5A BR112019002909A2 (pt) | 2016-08-17 | 2017-06-23 | composição melhorada de teneligliptina e metformina, e processo para preparação da mesma |
CONC2019/0001110A CO2019001110A2 (es) | 2016-08-17 | 2019-02-05 | Composición mejorada de teneligliptina y metformina y proceso para prepararla |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MXMX/A/2016/010682 | 2016-08-17 | ||
MX2016010682A MX2016010682A (es) | 2016-08-17 | 2016-08-17 | Composicion mejorada de teneligliptina y metformina y proceso para prepararla. |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018033808A1 true WO2018033808A1 (fr) | 2018-02-22 |
Family
ID=61196457
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2017/053749 WO2018033808A1 (fr) | 2016-08-17 | 2017-06-23 | Composition améliorée de ténéligliptine et de metformine et procédé pour sa préparation |
Country Status (9)
Country | Link |
---|---|
AR (1) | AR109253A1 (fr) |
BR (1) | BR112019002909A2 (fr) |
CL (1) | CL2019000273A1 (fr) |
CO (1) | CO2019001110A2 (fr) |
DO (1) | DOP2019000035A (fr) |
EC (2) | ECSP19010066A (fr) |
MX (1) | MX2016010682A (fr) |
PE (1) | PE20190402A1 (fr) |
WO (1) | WO2018033808A1 (fr) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014080383A1 (fr) * | 2012-11-26 | 2014-05-30 | Ranbaxy Laboratories Limited | Composition pharmaceutique d'inhibiteurs de la dipeptidyl-peptidase-iv (dpp-iv) en association avec d'autres antidiabétiques |
WO2015132679A1 (fr) * | 2014-03-05 | 2015-09-11 | Glenmark Pharmaceuticals Ltd | Compositions de ténéligliptine |
-
2016
- 2016-08-17 MX MX2016010682A patent/MX2016010682A/es unknown
-
2017
- 2017-06-23 WO PCT/IB2017/053749 patent/WO2018033808A1/fr active Application Filing
- 2017-06-23 PE PE2019000305A patent/PE20190402A1/es unknown
- 2017-06-23 BR BR112019002909-5A patent/BR112019002909A2/pt active Search and Examination
- 2017-07-04 AR ARP170101849A patent/AR109253A1/es unknown
-
2019
- 2019-02-01 CL CL2019000273A patent/CL2019000273A1/es unknown
- 2019-02-05 CO CONC2019/0001110A patent/CO2019001110A2/es unknown
- 2019-02-12 EC ECSENADI201910066A patent/ECSP19010066A/es unknown
- 2019-02-18 DO DO2019000035A patent/DOP2019000035A/es unknown
- 2019-06-25 EC ECSENADI201944926A patent/ECSP19044926A/es unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014080383A1 (fr) * | 2012-11-26 | 2014-05-30 | Ranbaxy Laboratories Limited | Composition pharmaceutique d'inhibiteurs de la dipeptidyl-peptidase-iv (dpp-iv) en association avec d'autres antidiabétiques |
WO2015132679A1 (fr) * | 2014-03-05 | 2015-09-11 | Glenmark Pharmaceuticals Ltd | Compositions de ténéligliptine |
Also Published As
Publication number | Publication date |
---|---|
ECSP19010066A (es) | 2019-11-30 |
BR112019002909A2 (pt) | 2019-05-21 |
CL2019000273A1 (es) | 2019-06-28 |
MX2016010682A (es) | 2018-02-16 |
PE20190402A1 (es) | 2019-03-13 |
DOP2019000035A (es) | 2019-06-30 |
AR109253A1 (es) | 2018-11-14 |
ECSP19044926A (es) | 2019-07-31 |
CO2019001110A2 (es) | 2019-04-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110548026B (zh) | 含有葡萄糖激酶激活剂和k-atp通道阻断剂的药物组合及其制备方法和用途 | |
ES2452019T3 (es) | Comprimido bicapa que comprende telmisartán y amlodipino | |
ES2617522T3 (es) | Procedimiento de granulación en seco para fabricar composiciones de comprimidos de metformina y composiciones de los mismos | |
TW202015722A (zh) | 包含glp-1促效劑與n-(8-(2-羥基苯甲醯基)胺基)辛酸之鹽的固體組成物 | |
KR20160000762A (ko) | 에제티미브 및 로수바스타틴을 포함하는 경구용 복합제제 및 그 제조방법 | |
EP2508172A1 (fr) | Formulations stables et uniformes d'entecavir et procédé de préparation correspondant | |
US20170231969A1 (en) | Pharmaceutical Compositions of Edoxaban | |
WO2021176096A1 (fr) | Composition pharmaceutique comprenant un inhibiteur du sglt2 | |
WO2018033808A1 (fr) | Composition améliorée de ténéligliptine et de metformine et procédé pour sa préparation | |
WO2019162800A1 (fr) | Composition pharmaceutique comprenant de la remogliflozine et un agent antidiabétique | |
EP2065035B1 (fr) | Formules pharmaceutiques contenant de l'irbesartan | |
EP4161525A1 (fr) | Procédé de préparation d'un comprimé pelliculé comprenant de la linagliptine et de la metformine | |
JP7355846B2 (ja) | 固形製剤 | |
WO2018122385A1 (fr) | Compositions pharmaceutiques de chlorhydrate de metformine et de chlorhydrate de pioglitazone | |
KR20120134545A (ko) | 안정성 및 함량 균일성이 개선된 속방성 약학 조성물의 제조방법 | |
PT2468256E (pt) | Combinações de vildagliptina e glimepirida | |
EP4162929A1 (fr) | Formulation composite comprenant de la sitagliptine et de la dapagliflozine, et son procédé de préparation | |
JP2011527316A (ja) | 直接打錠によるアリスキレン錠剤 | |
WO2022119541A1 (fr) | Formulation de comprimé pelliculé comprenant de la dapagliflozine et du chlorhydrate de metformine | |
WO2022119540A2 (fr) | Procédé pour formulations de dapagliflozine et de chlorhydrate de metformine | |
WO2022173406A1 (fr) | Procédé pour formulations de linagliptine ou d'un sel pharmaceutiquement acceptable de celle-ci | |
EP4212150A1 (fr) | Composition de comprimé bicouche comprenant de la dapagliflozine amorphe et de la metformine | |
WO2022119543A1 (fr) | Procédé de préparation de comprimés comprenant de la dapagliflozine amorphe et du chlorhydrate de metformine | |
JP2022151564A (ja) | 薬効成分としてビルダグリプチンおよびメトホルミンを含む錠剤 | |
WO2013100876A1 (fr) | Formulations de rispéridone |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
DPE1 | Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17841153 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112019002909 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112019002909 Country of ref document: BR Kind code of ref document: A2 Effective date: 20190212 |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 17841153 Country of ref document: EP Kind code of ref document: A1 |