TR202010729A1 - A tablet comprising apixaban - Google Patents
A tablet comprising apixabanInfo
- Publication number
- TR202010729A1 TR202010729A1 TR2020/10729A TR202010729A TR202010729A1 TR 202010729 A1 TR202010729 A1 TR 202010729A1 TR 2020/10729 A TR2020/10729 A TR 2020/10729A TR 202010729 A TR202010729 A TR 202010729A TR 202010729 A1 TR202010729 A1 TR 202010729A1
- Authority
- TR
- Turkey
- Prior art keywords
- sodium
- feature
- tablet according
- apixaban
- weight
- Prior art date
Links
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 229960003886 apixaban Drugs 0.000 title claims abstract description 53
- 239000002904 solvent Substances 0.000 claims abstract description 18
- 239000011230 binding agent Substances 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims description 47
- 238000009472 formulation Methods 0.000 claims description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
- -1 polyethylene Polymers 0.000 claims description 13
- 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 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 229940032147 starch Drugs 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 8
- 235000010443 alginic acid Nutrition 0.000 claims description 8
- 229920000615 alginic acid Polymers 0.000 claims description 8
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 8
- 239000000194 fatty acid Substances 0.000 claims description 8
- 229930195729 fatty acid Natural products 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 8
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 7
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 7
- 238000005469 granulation Methods 0.000 claims description 7
- 230000003179 granulation Effects 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 239000000314 lubricant Substances 0.000 claims description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 6
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 5
- 239000007884 disintegrant Substances 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- 229920002907 Guar gum Polymers 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 239000005913 Maltodextrin Substances 0.000 claims description 4
- 229920002774 Maltodextrin Polymers 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 4
- 229960000913 crospovidone Drugs 0.000 claims description 4
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 4
- 229960000878 docusate sodium Drugs 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229940014259 gelatin Drugs 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 235000010417 guar gum Nutrition 0.000 claims description 4
- 239000000665 guar gum Substances 0.000 claims description 4
- 229960002154 guar gum Drugs 0.000 claims description 4
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 4
- 229940035034 maltodextrin Drugs 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 229960000502 poloxamer Drugs 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 150000004804 polysaccharides Chemical class 0.000 claims description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims 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 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 229960001375 lactose Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000003825 pressing Methods 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 239000007916 tablet composition Substances 0.000 claims description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 229920002261 Corn starch Polymers 0.000 claims description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 2
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- 240000008042 Zea mays Species 0.000 claims description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 2
- 229940072056 alginate Drugs 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- 229940087168 alpha tocopherol Drugs 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 2
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 235000001465 calcium Nutrition 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 2
- 235000005822 corn Nutrition 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- 229940099112 cornstarch Drugs 0.000 claims description 2
- 229940096516 dextrates Drugs 0.000 claims description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 2
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 2
- RRPFCKLVOUENJB-UHFFFAOYSA-L disodium;2-aminoacetic acid;carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O.NCC(O)=O RRPFCKLVOUENJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000002270 dispersing agent Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 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 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- 239000000832 lactitol Substances 0.000 claims description 2
- 235000010448 lactitol Nutrition 0.000 claims description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 2
- 229960003451 lactitol Drugs 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 2
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- 229920001206 natural gum Polymers 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 229960000292 pectin Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229960003975 potassium Drugs 0.000 claims description 2
- 235000007686 potassium Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 229960002668 sodium chloride Drugs 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 229960000984 tocofersolan Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000001993 wax Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- 239000002076 α-tocopherol Substances 0.000 claims description 2
- 235000004835 α-tocopherol Nutrition 0.000 claims description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 1
- 229930091371 Fructose Natural products 0.000 claims 1
- 239000005715 Fructose Substances 0.000 claims 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims 1
- 239000008121 dextrose Substances 0.000 claims 1
- 229960001021 lactose monohydrate Drugs 0.000 claims 1
- 229960001855 mannitol Drugs 0.000 claims 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims 1
- 229920003109 sodium starch glycolate Polymers 0.000 claims 1
- 239000008109 sodium starch glycolate Substances 0.000 claims 1
- 229940079832 sodium starch glycolate Drugs 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 239000000811 xylitol Substances 0.000 claims 1
- 235000010447 xylitol Nutrition 0.000 claims 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims 1
- 229960002675 xylitol Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 12
- 239000002245 particle Substances 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 7
- 108010074860 Factor Xa Proteins 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000001 effect on platelet aggregation Effects 0.000 description 1
- 229940047562 eliquis Drugs 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000012395 formulation development Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007561 laser diffraction method Methods 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000009491 slugging Methods 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 208000004043 venous thromboembolism Diseases 0.000 description 1
Classifications
-
- 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
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Mevcut buluş; apiksaban ve en az bir bağlayıcı içeren bir tablet ile ilgili olup, burada apiksaban ve en az bir bağlayıcı, bir çözücü içinde çözünmektedir. Mevcut buluş ayrıca, basit, hızlı, uygun maliyetli, zaman tasarrufu sağlayan ve endüstriyel olarak uygun bir prosesle de ilgilidir.The present invention; It relates to a tablet comprising apixaban and at least one binder, wherein apixaban and at least one binder are dissolved in a solvent. The present invention also relates to a simple, fast, cost-effective, time-saving and industrially suitable process.
Description
TARFNAME APIKSABAN IÇEREN BIR TABLET Bulusun Alani Mevcut bulus; apiksaban ve en az bir baglayici içeren bir tablet ile ilgili olup, burada apiksaban ve en az bir baglayici, bir çözücü içinde çözünmektedir. Mevcut bulus ayrica, basit, hizli, uygun maliyetli, zaman tasarrufu saglayan ve endüstriyel olarak uygun bir prosesle de ilgilidir. Teknigin Bilinen Durumu Apiksaban, serbest ve pihtiya baglanan faktör Xa'nin yüksek oranda seçici, oral biyoyararlanim gösteren ve reversibl direkt inhibitörüdür. Faktör Xa, protrombinin, fibrin pihti olusumundan sorumlu koagülasyon kaskadindaki son enzim olan trombine dönüsümünü katalize eder. Apiksaban, trombosit agregasyonu üzerinde direkt etkiye sahip olmasa da, faktör Xa'yi inhibe ederek trombin ile indüklenen pihti olusumunu dolayi yoldan azaltmaktadir. tetrahidro-1H-pirazolo[3,4-c]piridin-S-karboksamiddir ve kimyasal yapisi Formül 1'de gösterilmektedir. Formül l Apiksaban molekülü, 6,967,208 numarali ABD patentinde açiklanmaktadir. Eliquis ticari adi altinda satilan apiksaban, venöz tromboembolik olaylarin tedavisinde kullanilan bir antikoagülandir. Oral yoldan uygulanir. Direkt faktör Xa inhibitörüdür ve apiksaban, suda yetersiz çözünür (24 °C'de 0.028 mg/mL) ve nispeten düsük oral biyoyararlanim (tek bir 10 mg dozu için yaklasik %50) sergiler. Önceki teknikte, apiksaban içeren oral farmasötik dozaj formlarinin açiklandigi birçok patent bulunmaktadir. Yeterince çözünmeyen apiksaban etkin maddesi içeren farmasötik kompozisyonlar teknikte bilinmektedir. Özellikle, belirli bir partikül boyutuna sahip apiksaban içeren farmasötik A1 dokümaninda d(0.9) partikül boyutu yaklasik 20 pm olan apiksaban kullanilarak hazirlanan kompozisyonlar tarif edilmektedir. apiksaban kullanilarak dissolüsyon hizi iyilestirilmis bir kompozisyon ve partikül boyutu dagiliminin kontrol edilmesiyle suda çözünmeyen bir ilaç olarak apiksabanin dissolüsyon hizinin iyilestirilmesine yönelik bir yöntem açiklanmaktadir. Apiksabanin düsük çözünürlügü nedeniyle önceki teknikte apiksabanin birçok partikül boyutu ile yapilan çalismalar bulunmaktadir. Bununla birlikte, partikül boyutunun düsürülerek dissolüsyon hizinin iyilestirilmesine yönelik yukarida tarif edilen yöntemlerde iri vivo ilaç dagiliminin partikül boyutu varyasyonuna bagli olmasi sorunu vardir. Teknikte hala, kullanilabilecek apiksaban partikül boyutundan opsiyonel olarak ve tercihen bagimsiz bir özellik olarak, daha iyi dissolüsyon hizi ve iyi içerik tekdüzeligi sergileyen iyilestirilmis bir apiksaban tabletine ihtiyaç vardir. Mevcut bulusta, apiksaban ve en az bir baglayici, bir çözücü içinde çözünmektedir. Dolayisiyla bu formülasyon, yukaridaki problemlerin üstesinden gelmektedir. Bu sekilde, apiksabanin fiziksel ve kimyasal parametrelerinden bagimsiz olarak daha da yüksek kalitede formülasyonlar garanti edilebilmektedir. Bulusun Ayrintili Açiklamasi Mevcut bulusun ana amaci, önceki teknikteki problemleri ortadan kaldirmak ve ilgili önceki teknige ek avantajlar getirmektir. Mevcut bulusun daha açik ana amaci, apiksabanin fiziksel ve kimyasal parametrelerinden bagimsiz olarak istenen dissolüsyon profiline ve istenen stabiliteye sahip apiksaban içeren bir tablet sunulmasidir. Mevcut bulusun bir baska amaci, daha iyi içerik tekdüzeligine sahip bir tablet sunulmasidir. Mevcut bulusun bir diger amaci, apiksaban içeren bir tablete yönelik bir proses sunulmasidir. Söz konusu proses basit, hizli, uygun maliyetli, zaman tasarrufu saglayan ve endüstriyel olarak uygun bir yöntemdir. Bu tarifnamede kullanildigi sekliyle "apiksaban" terimi, serbest baz formunda veya farmasötik açidan kabul edilebilir tuz, kristalin polimorf, solvat, hidrat veya ester formunda veya amorf bir formda veya bunlarin karisimlari formunda apiksaban anlamina gelmektedir. Düsük suda çözünürlük, formülasyon gelistirme sirasinda karsilasilan baslica problemdir. Apiksaban, suda yetersiz çözünür (24 °C`de 0.028 mg/mL) ve nispeten düsük oral biyoyararlanim (tek bir 10 mg dozu için yaklasik %50) sergiler. Farmasötik olarak kabul edilebilir bir dozda suda çözünürlügü düsük etkin maddeler için oral bir dozaj fomunun sunulmasi arzu edilmektedir. Mevcut bulusu bir uygulamasina göre, apiksaban içeren bir tablet olup, burada apiksaban ve en az bir baglayici çözücü içinde çözünmektedir. Mevcut bulusun bir uygulamasina göre, apiksabanin düsük çözünürlük problemi, apiksabanin su haricinde bir çözücü içerisinde çözülmesi ile asilmistir. Böylece apiksabanin partikül boyutundan bagimsiz olarak iyi çözünürlük elde edilmistir. Ayni zamanda, en az bir baglayici ayni çözücü içinde çözülmektedir. Prosesin sonraki asamalarinda, çözücü uzaklastirildiktan sonra en az bir baglayici ve apiksaban matrisi elde edilmektedir. Bu matris amorf yapidadir. Bu proses sayesinde, apiksabanin baslangiç formundan bagimsiz olarak istenen dissolüsyon profili ve stabilite elde edilmektedir. Bir uygulamada, en az bir baglayicinin apiksabana agirlik orani 1: 1 ile 5: 1 arasinda, tercihen 1: 1 ile 3: 1 arasindadir. Bu oranin, istenen dissolüsyon profilinin elde edilmesi için önemli bir faktör oldugu gözlenmistir. Apiksaban ve en az bir baglayici bu oranlarda kullanildiginda, yas granülasyon ile gelismis içerik tekdüzeligine sahip bir formülasyonun sunulmasi da daha kolaydir. Mevcut bulusun bir uygulamasina göre apiksabanin miktari, toplam formülasyonun agirliginca %05 ile %100 arasindadir. Tercihen, toplam formülasyonda agirlikça %10 ile Uygun baglayicilar; polivinilpirrolidon, sodyum karboksimetil selüloz, krospovidon, polietilen glikol, polivinil alkol, prejelatinize nisasta, glukoz, dogal zamklar, sukroz, sodyum aljinat, hidroksipropil metil selüloz, hidroksipropil selüloz, karboksimetil selüloz, metil selüloz, jelatin, karrageenan, guar zamki, karbomer, polimetakrilatlar, metakrilat polimerleri, jelatin, aljinat, aljinik asit, ksantan zamki, hyalüronik asit, pektin, polisakkaritler, karbomer, poloksamer, poliakrilamit, polioksietilen-alkil eter, polidekstroz, polietilen oksit veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir uygulamasina göre baglayicilarin miktari, toplam formülasyonun agirliginca %05 ile %100 arasindadir. Tercihen, toplam formülasyonda agirlikça %1.0 ile Mevcut bulusun bir uygulamasina göre baglayici, polivinilpirolidondur. Uygun çözücü; diklorometan, izopropil alkol, etanol, metanol, asetonitril, dimetil sülfoksit, dimetilformamid, etil asetat, aseton veya karisimlari içeren gruptan seçilmektedir. Tercihen çözücü diklorometandir. Mevcut bulusun bir uygulamasina göre, tablet, bundan baska, dolgu maddeleri, dagiticilar, yüzey aktif maddeleri, Iubrikanlar/glidantlar, kaplama maddeleri veya bunlarin karisimlarini içeren gruptan seçilen en az bir farmasötik olarak kabul edilebilir eksipiyan içermektedir. Uygun dolgu maddeleri; mikrokristalin selüloz, Iaktoz, manitol, spreyle kurutulmus manitol, kalsiyum tuzlari, polisakkaritler, dikalsiyum fosfat, sodyum klorür, dekstratlar, Iaktitol, maltodekstrin, sukroz-maltodekstrin karisimi, trehaloz, sodyum karbonat, sodyum bikarbonat, kalsiyum karbonat veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir uygulamasina göre dolgu maddelerinin miktari, toplam formülasyonun agirliginca %500 ile %950 arasindadir. Tercihen, toplam formülasyonda agirlikça %650 ile Mevcut bulusun bir uygulamasina göre dolgu maddesi, mikrokristalin selüloz veya Iaktoz veya bunlarin karisimlaridir. Uygun dagiticilar; kroskarmeloz sodyum, nisasta, krospovidon, düsük substitüye hidroksipropil selüloz, sodyum karboksimetil selüloz, kalsiyum karboksimetil selüloz, karboksimetil selüloz, dokusat sodyum, guar zamki, düsük sübstitüye hidroksipropil selüloz, poliakrilin potasyum, sodyum aljinat, misir nisastasi, sodyum nisasta glikolat, aljinik asit, alginatlar, iyon degistirici reçineler, magnezyum alüminyum silika, sodyum dodesil sülfat, poloksamer, sodyum glisin karbonat veya bunlarin karisimlarini içeren bir gruptan seçilmektedir. Mevcut bulusun bir uygulamasina göre dagiticilarin miktari, toplam formülasyonun agirliginca %20 ile %250 arasindadir. Tercihen, toplam formülasyonda agirlikça %30 ile Mevcut bulusun bir uygulamasina göre dagitici, kroskarmelloz sodyum veya nisasta veya bunlarin karisimlaridir. Uygun yüzey aktif maddeler; sodyum Iauril sülfat, sodyum dokusat, gliseril monooleat, polietilen alkil eter, polyoksietilen sorbitan yag asidi esterleri, sorbik asit, sorbitan yag asidi esteri, polyoksietilen stearatlar, polietilen glikol, sodyum benzoat, dokusat sodyum, alfa tokoferol, askorbil palmitat, sitrik asit, polietoksillenmis yag asidi esterleri, polioksietilen hidrojene kastor yagiveya bunlarin karisimlari içeren gruptan seçilmektedir. Mevcut bulusun bir uygulamasina göre yüzey aktif maddelerin miktari, toplam formülasyonun agirliginca %0.5 ile %80 arasindadir. Tercihen, toplam formülasyonda agirlikça %1.0 ile Mevcut bulusun bir uygulamasina göre yüzey aktif madde, sodyum Iauril sülfattir. Uygun Iubrikanlar/glidantlar, magnezyum stearat, talk, kolloidal silikon dioksit, misir, kalsiyum stearat, çinko stearat, mumlar, borik asit, hidrojenlenmis bitkisel yag, sodyum klorat, magnezyum lauril sülfat, sodyum oleat, sodyum asetat, sodyum benzoat, stearik asit, yag asidi, fumarik asit, gliseril palmito sülfat, sodyum stearil fumarat, veya bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bir uygulamasina göre Iubrikanlar/glidantlarin miktari, toplam formülasyonun agirliginca %005 ile %40 arasindadir. Tercihen, toplam formülasyonda agirlikça %0.1 ile Mevcut bulusun bir uygulamasina göre Iubrikan/glidant, magnezyum stearattir. Bu tarifnamede kullanildigi sekliyle, "partikül boyutu dagilimi", lazer difraksiyon yöntemi (yani malvern analizi) gibi geleneksel olarak kabul edilmis herhangi bir yöntemle test edilen kümülatif hacim boyutu dagilimi anlamina gelir. D (0.9) terimi, partiküllerin hacimce %90'dan daha ince oldugu boyut anlamina gelir. MeVCUt bulusun bir uygulamasina göre tablet, 90 pm'den büyük d (0.9) partikül boyutuna sahip apiksaban içermektedir. Mevcut bulusun bir uygulamasina göre tablet, d(0.9) 90 pm ile 99 um arasinda partikül boyutuna sahip apiksaban içermektedir. Mevcut bulusun bir uygulamasina göre tablet, toplam formülasyonda asagidaki miktarlari içermektedir; o Agirlikça %0.5 - 10.0 apiksaban o çözücü o Agirlikça %0.5-10.0 polivinilpirolidon o Agirlikça %10 - 20.0 nisasta, o Agirlikça %300 - 45.0 mikrokristalin selüloz o Agirlikça %0.5 - 8.0 sodyum lauril sülfat o agirlikça %1.0 - 5.0 kroskarmelloz sodyum o Agirlikça %005 - 4.0 magnezyum stearat. Mevcut bulusun tableti, direkt baski, yas veya kuru granülasyon, isiyla eritmeli granülasyon, isiyla eritmeli ekstrüzyon, akiskan yatakli granülasyon, ekstrüzyoni'küre haline getirme, çift baski (slugging), spreyle kurutma ve çözücü buharlastirma gibi teknikte iyi bilinen standart teknikler ve üretim prosesleri kullanilarak hazirlanabilir. Mevcut bulusun bir uygulamasina göre tablet, islak granülasyon metodu kullanilarak elde edilebilir ve bu nedenle basit ve düsük maliyetli bir üretim metodu kullanilmistir. Apiksabanin hedeflenen düsük dozu nedeniyle nihai ürünün içerik tekdüzeliginin önemli bir ürün özelligi haline geldigi farkedilmistir. Içerik tekdüzeligi, tabletlerin kalite kontrolü için farmasötik bir analiz parametresidir. Mevcut bulusta açiklanan yöntemler sayesinde, düsük dozda apiksaban içeren tablet, istenen bir içerik tekdüzeligine sahip olarak gelistirilmistir. Örnek 1: Apiksaban içeren tablet formülasyonu Apiksaban 0.5 - 10.0 Çözücü y.m. Polivinilpirolidon 0.5 - 10.0 Nisasta 1.0 - 20.0 Laktoz 30.0 - 40.0 Mikrokristalin selüloz 30.0 - 45.0 Magnezyum stearat 0.05 - 4.0 TOPLAM 100 y.m.: yeterli miktarda Örnek 2: Apiksaban içeren tablet formülasyonu Apiksaban 1.667 Çözücü y.m. Polivinilpirolidon 3 Nisasta 15 Laktoz 35 Mikrokristalin selüloz 38.333 Sodyum laurii sülfat 3 Kroskarmelloz sodyum 3 Magnezyum stearat 1 TOPLAM 100y.m.: yeterli miktarda Örnek 1 veya 2 için proses; a) Apiksabanin bir çözücüde çözdürülmesi, b) Çözücüye polivinilpirolidon eklenmesi ve polivinilpirolidonun çözdürülmesi ve ardindan granülasyon çözeltisinin eklenmesi, c) Nisasta, Iaktoz ve mikrokristalin selülozun karistirilmasi ve karisimin sivi yatakli granülatör-kurutucuya yüklenmesi, d) Ardindan karisimin spreyli granülasyon kullanilarak apiksaban içeren granülasyon çözeltisi ile kaplanmasi, e) Sodyum laurii sülfat ve kroskarmelloz sodyum eklenmesi ve karistirilmasi, f) Magnezyum stearat eklenmesi ve ardindan karistirilmasi, 9) Tablet olusturmak üzere basilmasi, h) Tabletlerin kaplama maddeleri ile kaplanmasi. TR DESCRIPTION A TABLET CONTAINING APIKSABAN Field of the Invention The present invention; It relates to a tablet comprising apixaban and at least one binder, wherein the apixaban and at least one binder are dissolved in a solvent. The present invention also relates to a simple, rapid, cost-effective, time-saving and industrially suitable process. State of the Art Apixaban is a highly selective, oral bioavailable and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin into thrombin, the final enzyme in the coagulation cascade responsible for fibrin clot formation. Although apixaban does not have a direct effect on platelet aggregation, it indirectly reduces thrombin-induced clot formation by inhibiting factor Xa. It is tetrahydro-1H-pyrazolo[3,4-c]pyridine-S-carboxamide and its chemical structure is shown in Formula 1. Formula 1 Apixaban molecule is disclosed in US patent number 6,967,208. Apixaban, sold under the trade name Eliquis, is an anticoagulant used in the treatment of venous thromboembolic events. It is administered orally. A direct inhibitor of factor There are many patents in the prior art describing oral pharmaceutical dosage forms containing apixaban. Pharmaceutical compositions containing the insufficiently soluble active ingredient apixaban are known in the art. In particular, pharmaceutical document A1 containing apixaban with a specific particle size d(0.9) describes compositions prepared using apixaban with a particle size of approximately 20 pm. A method for improving the dissolution rate of apixaban as a water-insoluble drug by controlling the composition and particle size distribution with improved dissolution rate using apixaban is disclosed. Due to the low solubility of apixaban, prior art studies have been conducted with many particle sizes of apixaban. However, the methods described above for improving dissolution rate by reducing particle size suffer from the problem that large in vivo drug distribution depends on particle size variation. There is still a need in the art for an improved apixaban tablet that exhibits better dissolution rate and good content uniformity, a feature optionally and preferably independent of the apixaban particle size that can be used. In the present invention, apixaban and at least one binder are dissolved in a solvent. Therefore, this formulation overcomes the above problems. In this way, even higher quality formulations can be guaranteed, regardless of the physical and chemical parameters of apixaban. Detailed Description of the Invention The main purpose of the present invention is to eliminate the problems in the prior art and to bring additional advantages to the relevant prior art. The clearer main object of the present invention is to provide a tablet containing apixaban having the desired dissolution profile and desired stability, independent of the physical and chemical parameters of apixaban. Another object of the present invention is to provide a tablet with better content uniformity. Another object of the present invention is to provide a process for a tablet containing apixaban. The process in question is simple, fast, cost-effective, time-saving and industrially suitable. The term "apixaban" as used herein means apixaban in its free base form, or in the form of a pharmaceutically acceptable salt, crystalline polymorph, solvate, hydrate or ester, or in an amorphous form, or mixtures thereof. Low water solubility is the main problem encountered during formulation development. Apixaban is poorly soluble in water (0.028 mg/mL at 24 °C) and exhibits relatively low oral bioavailability (approximately 50% for a single 10 mg dose). It is desirable to provide an oral dosage form for poorly water-soluble active substances at a pharmaceutically acceptable dose. According to one embodiment of the present invention, it is a tablet containing apixaban, wherein the apixaban and at least one binder are dissolved in the solvent. According to an embodiment of the present invention, the low solubility problem of apixaban is overcome by dissolving apixaban in a solvent other than water. Thus, good resolution was achieved regardless of the particle size of apixaban. At the same time, at least one binder is dissolved in the same solvent. In the later stages of the process, after the solvent is removed, at least one binder and apixaban matrix is obtained. This matrix has an amorphous structure. Thanks to this process, the desired dissolution profile and stability is achieved regardless of the initial form of apixaban. In one embodiment, the weight ratio of at least one binder to apixaban is between 1:1 and 5:1, preferably between 1:1 and 3:1. It has been observed that this ratio is an important factor for obtaining the desired dissolution profile. When apixaban and at least one binder are used in these proportions, it is also easier to deliver a formulation with improved content uniformity through wet granulation. According to one embodiment of the present invention, the amount of apixaban is between 05% and 100% by weight of the total formulation. Preferably, 10% by weight of the total formulation. Suitable binders; polyvinylpyrrolidone, sodium carboxymethyl cellulose, crospovidone, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, glucose, natural gums, sucrose, sodium alginate, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, gelatin, carrageenan, guar gum, carbomer, poly methacrylates , methacrylate polymers are selected from the group consisting of gelatin, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide, or mixtures thereof. According to one embodiment of the present invention, the amount of binders is between 05% and 100% by weight of the total formulation. Preferably, the binder according to one embodiment of the present invention is polyvinylpyrrolidone at 1.0% by weight in the total formulation. Suitable solvent; is selected from the group consisting of dichloromethane, isopropyl alcohol, ethanol, methanol, acetonitrile, dimethyl sulfoxide, dimethylformamide, ethyl acetate, acetone or mixtures thereof. Preferably the solvent is dichloromethane. According to one embodiment of the present invention, the tablet further comprises at least one pharmaceutically acceptable excipient selected from the group consisting of fillers, dispersants, surfactants, lubricants/glidants, coating agents, or mixtures thereof. Suitable fillers; is selected from the group consisting of microcrystalline cellulose, lactose, mannitol, spray dried mannitol, calcium salts, polysaccharides, dicalcium phosphate, sodium chloride, dextrates, lactitol, maltodextrin, sucrose-maltodextrin mixture, trehalose, sodium carbonate, sodium bicarbonate, calcium carbonate or mixtures thereof. According to one embodiment of the present invention, the amount of fillers is between 500% and 950% by weight of the total formulation. Preferably, the filler according to one embodiment of the present invention is microcrystalline cellulose or lactose, or mixtures thereof, with 650% by weight in the total formulation. Suitable distributors; croscarmellose sodium, starch, crospovidone, low substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, docusate sodium, guar gum, low substituted hydroxypropyl cellulose, polyacryline potassium, sodium alginate, corn starch, sodium starch ta glycolate, alginic acid, alginates, ion exchange resins, magnesium aluminum silica, sodium dodecyl sulfate, poloxamer, sodium glycine carbonate, or mixtures thereof. According to one embodiment of the present invention, the amount of disintegrants is between 20% and 250% by weight of the total formulation. Preferably, the disintegrant according to one embodiment of the present invention is croscarmellose sodium or starch, or mixtures thereof, with 30% by weight in the total formulation. Suitable surfactants; sodium lauryl sulfate, sodium docusate, glyceryl monooleate, polyethylene alkyl ether, polyoxyethylene sorbitan fatty acid esters, sorbic acid, sorbitan fatty acid ester, polyoxyethylene stearates, polyethylene glycol, sodium benzoate, docusate sodium, alpha tocopherol, ascorbyl palmitate, citric acid, polyethoxylated fatty acid esters, polyoxyethylene hydrogenated castor oil, or mixtures thereof. According to one embodiment of the present invention, the amount of surfactants is between 0.5% and 80% by weight of the total formulation. Preferably, at 1.0% by weight in the total formulation, the surfactant according to one embodiment of the present invention is sodium lauryl sulfate. Suitable lubricants/glidants are magnesium stearate, talc, colloidal silicon dioxide, corn, calcium stearate, zinc stearate, waxes, boric acid, hydrogenated vegetable oil, sodium chlorate, magnesium lauryl sulfate, sodium oleate, sodium acetate, sodium benzoate, stearic acid, fatty acid, fumaric acid, glyceryl palmito sulfate, sodium stearyl fumarate, or mixtures thereof. According to one embodiment of the present invention, the amount of lubricants/glidants is between 005% and 40% by weight of the total formulation. Preferably, at 0.1% by weight in the total formulation, the lubricant/glidant according to one embodiment of the present invention is magnesium stearate. As used herein, "particle size distribution" means the cumulative volume size distribution tested by any conventionally accepted method, such as the laser diffraction method (i.e., malvern analysis). The term D (0.9) refers to the size at which the particles are less than 90% finer by volume. According to one embodiment of the present invention, the tablet contains apixaban with a particle size d (0.9) greater than 90 pm. According to one embodiment of the present invention, the tablet contains apixaban with a particle size d(0.9) between 90 pm and 99 pm. According to one embodiment of the present invention, the tablet contains the following amounts in the total formulation; o 0.5 - 10.0% by weight apixaban o solvent o 0.5 - 10.0% by weight polyvinylpyrrolidone o 10 - 20.0% by weight starch, o 300 - 45.0% by weight microcrystalline cellulose o 0.5 - 8.0% by weight sodium lauryl sulfate o 1.0 - 5.0% by weight scarmellose sodium o 005 - 4.0% magnesium stearate by weight. The tablet of the present invention is manufactured using standard techniques and manufacturing processes well known in the art, such as direct compression, wet or dry granulation, heat melt granulation, heat melt extrusion, fluidized bed granulation, extrusion spheroidization, double pressing (slugging), spray drying and solvent evaporation. It can be prepared using . According to one embodiment of the present invention, the tablet can be obtained using the wet granulation method and therefore a simple and low-cost production method is used. It has been noticed that due to the targeted low dose of apixaban, content uniformity of the final product has become an important product feature. Content uniformity is a pharmaceutical analysis parameter for quality control of tablets. By means of the methods disclosed in the present invention, a tablet containing low dose apixaban has been developed with a desired content uniformity. Example 1: Tablet formulation containing Apixaban Apixaban 0.5 - 10.0 Solvent y.m. Polyvinylpyrrolidone 0.5 - 10.0 Starch 1.0 - 20.0 Lactose 30.0 - 40.0 Microcrystalline cellulose 30.0 - 45.0 Magnesium stearate 0.05 - 4.0 TOTAL 100 y.m.: sufficient amount Example 2: Tablet formulation containing Apixaban Apixaban 1.667 Solvent y. m. Polyvinylpyrrolidone 3 Starch 15 Lactose 35 Microcrystalline cellulose 38.333 Sodium laurii sulfate 3 Croscarmellose sodium 3 Magnesium stearate 1 TOTAL 100y.m.: sufficient quantity Process for Example 1 or 2; a) Dissolving apixaban in a solvent, b) Adding polyvinylpyrrolidone to the solvent and dissolving the polyvinylpyrrolidone and then adding the granulation solution, c) Mixing the starch, lactose and microcrystalline cellulose and loading the mixture into the fluid bed granulator-dryer, d) Then mixing the mixture with the granulation solution containing apixaban using spray granulation. si e) Adding sodium laurii sulfate and croscarmellose sodium and mixing, f) Adding magnesium stearate and then mixing, 9) Pressing to form tablets, h) Coating the tablets with coating materials. TR
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2020/10729A TR202010729A1 (en) | 2020-07-07 | 2020-07-07 | A tablet comprising apixaban |
| EP21838041.8A EP4178577A4 (en) | 2020-07-07 | 2021-05-07 | A tablet comprising apixaban |
| PCT/TR2021/050445 WO2022010437A1 (en) | 2020-07-07 | 2021-05-07 | A tablet comprising apixaban |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2020/10729A TR202010729A1 (en) | 2020-07-07 | 2020-07-07 | A tablet comprising apixaban |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR202010729A1 true TR202010729A1 (en) | 2022-01-21 |
Family
ID=79552638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2020/10729A TR202010729A1 (en) | 2020-07-07 | 2020-07-07 | A tablet comprising apixaban |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP4178577A4 (en) |
| TR (1) | TR202010729A1 (en) |
| WO (1) | WO2022010437A1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105982870B (en) * | 2015-02-03 | 2020-05-01 | 山东新时代药业有限公司 | Apixaban tablet |
| CN108472261B (en) * | 2016-01-12 | 2021-12-03 | 广东东阳光药业有限公司 | Apixaban solid composition and preparation method thereof |
| TR201717703A2 (en) * | 2017-11-10 | 2019-05-21 | Ali Raif Ilac Sanayi Ve Ticaret Anonim Sirketi | APIXABAN FORMULATIONS |
| CN108553441B (en) * | 2018-06-08 | 2019-11-08 | 北京阳光诺和药物研究有限公司 | A kind of Apixaban tablet and preparation method thereof |
-
2020
- 2020-07-07 TR TR2020/10729A patent/TR202010729A1/en unknown
-
2021
- 2021-05-07 EP EP21838041.8A patent/EP4178577A4/en active Pending
- 2021-05-07 WO PCT/TR2021/050445 patent/WO2022010437A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP4178577A1 (en) | 2023-05-17 |
| WO2022010437A1 (en) | 2022-01-13 |
| EP4178577A4 (en) | 2024-04-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI389691B (en) | Solid pharmaceutical dosage forms which can be administered orally and have rapid release of active ingredient | |
| JP5524220B2 (en) | Pharmaceutical formulation 514 | |
| ES2300845T5 (en) | Process for the manufacture of a solid pharmaceutical composition for oral administration with 5-chloro-N ({(5-2-oxo-3- [4- (3-oxo-4-morpholinyl) -phenyl] -1,3-oxazolidin -5-yl} -methyl) -2-thiophenecarboxamide | |
| WO2009034541A9 (en) | Controlled release pharmaceutical dosage forms of trimetazidine | |
| CN101951889A (en) | Imatinib compositions | |
| CA3060366A1 (en) | Pharmaceutical composition for oral administration comprising enzalutamide | |
| KR20230155504A (en) | (4S)-24-Chloro-4-ethyl-73-fluoro-35-methoxy-32,5-dioxo-14-(trifluoromethyl)-32H-6-aza-3(4,1) Pharmaceutical dosage forms comprising -pyridina-1(1)-[1,2,3]triazola-2(1,2),7(1)-dibenzenaheptaphan-74-carboxamide | |
| JP2017510625A (en) | Pharmaceutical composition | |
| KR20160005022A (en) | Sovaprevir Tablets | |
| KR100783286B1 (en) | Solid pharmaceutical composition containing S-clopidogrel free base | |
| PT2029110E (en) | Process for preparing spray dried formulations of tmc125 | |
| US10583087B2 (en) | Pharmaceutical composition for oral administration | |
| EP2435029B1 (en) | Pharmaceutical composition comprising tamsulosin | |
| TR202010729A1 (en) | A tablet comprising apixaban | |
| KR102707060B1 (en) | Stability and bioavailability enhanced solid dispersion formulations of Olaparib | |
| TR2021002085A2 (en) | A film coated tablet of apixaban | |
| EP2303233A1 (en) | Solid oral dosage form containing anti-platelet agent clopidogrel and method for the preparation thereof | |
| BRPI0621739A2 (en) | stable formulation consisting of wetting sensitive drugs and their manufacturing procedure | |
| AU2019245827B2 (en) | Pharmaceutical composition comprising brexpiprazole | |
| WO2015199115A1 (en) | Pharmaceutical composition for oral administration | |
| WO2022150030A2 (en) | A film coated tablet of apixaban | |
| WO2005053639A2 (en) | Controlled release multiparticulates formed with dissolution enhancers | |
| JP2013151475A (en) | Stabilized substance containing candesartan cilexetil and method for producing the same | |
| WO2022199896A1 (en) | Pharmaceutical composition comprising rivaroxaban and method of preparation thereof | |
| EA045652B1 (en) | METHODS FOR PREPARATION OF A PHARMACEUTICAL COMPOSITION CONTAINING BREXPIPRAZOLE AND APPLICATION OF THE SPECIFIED METHODS IN OBTAINING A PHARMACEUTICAL COMPOSITION CONTAINING BREXPIPRAZOLE |