EP1776102A1 - Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ci - Google Patents
Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ciInfo
- Publication number
- EP1776102A1 EP1776102A1 EP05797983A EP05797983A EP1776102A1 EP 1776102 A1 EP1776102 A1 EP 1776102A1 EP 05797983 A EP05797983 A EP 05797983A EP 05797983 A EP05797983 A EP 05797983A EP 1776102 A1 EP1776102 A1 EP 1776102A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- nateglinide
- premix
- granulation
- starch
- isopropyl alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical group C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 title claims abstract description 79
- 229960000698 nateglinide Drugs 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title abstract description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 114
- 239000000203 mixture Substances 0.000 claims description 53
- 238000005469 granulation Methods 0.000 claims description 31
- 230000003179 granulation Effects 0.000 claims description 31
- 239000000945 filler Substances 0.000 claims description 30
- 229920002472 Starch Polymers 0.000 claims description 22
- 239000008107 starch Substances 0.000 claims description 22
- 229940032147 starch Drugs 0.000 claims description 22
- 235000019698 starch Nutrition 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 19
- 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 18
- 229930195725 Mannitol Natural products 0.000 claims description 18
- 239000000594 mannitol Substances 0.000 claims description 18
- 235000010355 mannitol Nutrition 0.000 claims description 18
- 238000010298 pulverizing process Methods 0.000 claims description 18
- 239000011230 binding agent Substances 0.000 claims description 17
- 239000007884 disintegrant Substances 0.000 claims description 17
- 239000004094 surface-active agent Substances 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 11
- 230000001050 lubricating effect Effects 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 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 9
- 229930006000 Sucrose Natural products 0.000 claims description 9
- 229960001855 mannitol Drugs 0.000 claims description 9
- 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 8
- 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 8
- 239000008101 lactose Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229960001375 lactose Drugs 0.000 claims description 7
- 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 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- 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 description 6
- 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 description 6
- 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 description 6
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 239000005720 sucrose Substances 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 5
- 239000003086 colorant Substances 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000008103 glucose Substances 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 208000030159 metabolic disease Diseases 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 5
- 239000008109 sodium starch glycolate Substances 0.000 claims description 5
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 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 3
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 claims description 3
- 244000215068 Acacia senegal Species 0.000 claims description 3
- 229920001817 Agar Polymers 0.000 claims description 3
- 239000005995 Aluminium silicate Substances 0.000 claims description 3
- 241000416162 Astragalus gummifer Species 0.000 claims description 3
- 229920002261 Corn starch Polymers 0.000 claims description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 229930091371 Fructose Natural products 0.000 claims description 3
- 239000005715 Fructose Substances 0.000 claims description 3
- 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 description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 229920000084 Gum arabic Polymers 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 239000004373 Pullulan Substances 0.000 claims description 3
- 229920001218 Pullulan Polymers 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 229920001615 Tragacanth Polymers 0.000 claims description 3
- 235000010489 acacia gum Nutrition 0.000 claims description 3
- 239000000205 acacia gum Substances 0.000 claims description 3
- 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 3
- 239000008272 agar Substances 0.000 claims description 3
- 229940023476 agar Drugs 0.000 claims description 3
- 235000010419 agar Nutrition 0.000 claims description 3
- 235000012211 aluminium silicate Nutrition 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 229940078495 calcium phosphate dibasic Drugs 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 239000007765 cera alba Substances 0.000 claims description 3
- 239000007766 cera flava Substances 0.000 claims description 3
- 239000008120 corn starch Substances 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- 229940096516 dextrates Drugs 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 239000008121 dextrose Substances 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 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 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000832 lactitol Substances 0.000 claims description 3
- 229960003451 lactitol Drugs 0.000 claims description 3
- 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 3
- 235000010448 lactitol Nutrition 0.000 claims description 3
- 239000004200 microcrystalline wax Substances 0.000 claims description 3
- 235000019808 microcrystalline wax Nutrition 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 3
- 229940068968 polysorbate 80 Drugs 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 3
- 229960004063 propylene glycol Drugs 0.000 claims description 3
- 235000013772 propylene glycol Nutrition 0.000 claims description 3
- 235000019423 pullulan Nutrition 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 235000010965 sucrose esters of fatty acids Nutrition 0.000 claims description 3
- 239000001959 sucrose esters of fatty acids Substances 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- 235000012222 talc Nutrition 0.000 claims description 3
- 235000010487 tragacanth Nutrition 0.000 claims description 3
- 239000000196 tragacanth Substances 0.000 claims description 3
- 229940116362 tragacanth Drugs 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- 238000004040 coloring Methods 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 229960002737 fructose Drugs 0.000 claims description 2
- 229960001031 glucose Drugs 0.000 claims description 2
- 229960000829 kaolin Drugs 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 description 20
- 239000008187 granular material Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 4
- 229960000913 crospovidone Drugs 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229940110862 starlix Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- -1 flller(s) Substances 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- RLYOPPJABLAKCZ-UHFFFAOYSA-N 2-butoxycarbonylbenzenecarboperoxoic acid Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OO RLYOPPJABLAKCZ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000008199 coating composition Substances 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000003618 dip coating Methods 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 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
- A61K9/2013—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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- the present invention relates to preparations of stable pharmaceutical compositions comprising nateglinide Form B, and processes for their preparation.
- Nateglinide is an amino acid derivative that lowers blood glucose levels by stimulating insulin secretion from the pancreas. It is widely indicated as monotherapy to lower blood glucose in patients with Type 2 diabetes. It is also indicated for use in combination with metformin.
- Presently nateglinide oral tablets are available in 60 mg or 120 mg strengths and are marketed by Novartis under the trade name STARLIX®.
- Nateglinide is disclosed in Japanese Patent Application Laid Open No. 63-54321 (equivalent to EP-A-196222 and US 4,816,484) and in J. Med. Chem. 32, 1436.
- the Japanese application describes how the compound may be crystallized from aqueous methanol to yield crystals having a melting point of 129°C to 130°C. These crystals are in a crystalline form known as "B-type" crystals.
- the known B-type crystals suffer from problems of instability, especially when subjected to pulverization. The instability results in conversion of the B-type crystals into other forms.
- US 5,463,116 discloses a method of producing a crystalline form of nateglinide having improved stability (H Type) to pulverization, and is thus said to be more suitable for use in dosage forms than those of the B-type.
- compositions of nateglinide, or a pharmaceutically acceptable salt thereof which are capable of being granulated without the need for pulverization after the granulation step.
- the process of granulation as described in this patent is carried out in the presence of water, i.e., aqueous granulation.
- nateglinide form B when prepared by dry granulation or direct compression show low dissolution profiles, in addition to the known processing issues such as poor flow, poor compressibility, etc.
- nateglinide Form B converts to other polymorphic forms.
- compositions comprising nateglinide Form B, when prepared by granulation with isopropyl alcohol, are stable even after pulverization, i.e., there is no conversion of Form B to any other polymorphic form even when stored at accelerated aging conditions of temperature. Moreover these preparations showed a dissolution profile comparable with STARLIX®.
- a process for preparing a stable pharmaceutical composition of nateglinide Form B includes a step of granulating with isopropyl alcohol.
- Embodiments of the process may include one or more of the following features.
- the process may further include blending nateglinide with one or more of filler, surfactant and disintegrant to form a blend; granulating the blend with a solution of binder in isopropyl alcohol to form a granulation; and drying, pulverizing; lubricating, and compressed the granulation into tablets.
- the process also may further include mixing the nateglinide with one or more of filler, surfactant, disintegrant and binder to form a blend; granulating the blend with isopropyl alcohol to form a granulation; and drying, pulverizing, lubricating and compressing the granulation into tablets.
- the nateglinide Form B may include a premix of nateglinide Form B with premix filler(s).
- the premix filler may include one or more of mannitol, starch, lactose, mannitol, microcrystalline cellulose, starch or a combination thereof.
- the premix filler may include a mixture of starch and mannitol.
- the ratio of nateglinide, mannitol and starch in the premix may be about 2:1:1.
- the process may further include blending the nateglinide premix with filler, surfactant and disintegrant to form a blend; granulating the blend with a solution of binder in isopropyl alcohol to form a granulation; and drying, pulverizing, lubricating, and compressing the granulation into tablets.
- the process instead may further include blending the nateglinide premix with filler, surfactant, disintegrant and binder to form a blend; granulating the blend with isopropyl alcohol to form a granulation; and drying, pulverizing, lubricating, and compressing the granulation into tablets.
- the composition may further include one or more pharmaceutically acceptable excipients including filler, binder, disintegrant, surfactant, lubricant, coloring and flavoring agent.
- the filler may be one or more of corn starch, lactose, mannitol, white sugar, sucrose, sugar compressible, sugar confectioners, glucose, sorbitol, calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, sorbitol, starch, starch pregelatinized, sucrose, and mixtures thereof.
- the binder may be one or more of polyvinylpyrrolidone, methyl cellulose, hydroxypropyl cellulose, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, and mixtures thereof.
- the disintegrant may be one or more of crospovidone, sodium starch glycolate, croscarmellose sodium, starch and mixtures thereof.
- the surfactant may be one or more of sodium lauryl sulphate, poloxamer, Polysorbate 80 and mixtures thereof.
- the lubricant maybe one or more of magnesium stearate, stearic acid, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acids, microcrystalline wax, yellow beeswax, white beeswax and mixtures thereof.
- a medicament for the prevention, delay of progression or treatment of metabolic disorders, type 2 diabetes mellitus or a disease or condition associated with diabetes mellitus includes nateglinide Form B and the medicament is formed by a process that includes a step of granulation with isopropyl alcohol.
- the medicament may include any one or more of the features described above.
- a medicament for the prevention, delay of progression or treatment of metabolic disorders, type 2 diabetes mellitus or a disease or condition associated with diabetes mellitus includes a premix of nateglinide form B with fillers and the medicament is formed by a process comprising a step of granulation with isopropyl alcohol.
- the medicament may include any one or more of the features described above.
- a premix of nateglinide Form B, one or more fillers, and isopropyl alcohol may include one or more of the following features or those described above.
- the premix may be incorporated into a medicament.
- the medicament may contain a pharmaceutically acceptable residual amount of isopropyl alcohol being present at an amount that is less than 50 mg and/or 5,000 ppm.
- Figure 1 is an XRD profile of nateglinide Form B.
- Figure 2 is an XRD profile of a nateglinide premix.
- Figures 3 and 4 are XRD profiles of nateglinide tablet of Examples 1 and 2.
- Figures 5 and 6 are XRD of the placebo tablet for Example 1 and 2, respectively.
- a process for preparing stable pharmaceutical compositions that comprise nateglinide Form B, the process comprising a step of granulation with isopropyl alcohol.
- nateglinide tablets may be prepared by blending nateglinide with other excipients such as flller(s), surfactant(s), and disintegrant(s); granulating the blend with a solution of binder(s) in isopropyl alcohol; drying the granules; pulverizing; lubricating; and compressing the lubricated granules.
- excipients such as flller(s), surfactant(s), and disintegrant(s
- nateglinide tablets may be prepared by blending nateglinide with other excipients such as filler(s), surfactant(s), disintegrant(s) and binder(s); granulating the blend with isopropyl alcohol; drying the granules; pulverizing; lubricating; and compressing the lubricated granules.
- excipients such as filler(s), surfactant(s), disintegrant(s) and binder(s).
- nateglinide tablets may be prepared by blending nateglinide with other excipients such as fillers and disintegrant; mixing the blend with a solution of surfactant in a half quantity of the isopropyl alcohol; granulating the mixture with a solution of binder in the remaining quantity of isopropyl alcohol; drying the granules; pulverizing; lubricating; and compressing the lubricated granules.
- excipients such as fillers and disintegrant
- Nateglinide may be mixed as such with other excipients to make the blend, or used as a premix that can be prepared with filler(s) and then this premix is mixed with other excipients to prepare a blend, which is granulated with isopropyl alcohol and compressed to form tablet.
- the present invention provides a process for preparing stable pharmaceutical compositions that include a premix of nateglinide Form B with fillers, wherein the process includes a step of granulation with isopropyl alcohol.
- the fillers may be selected from lactose, mannitol, microcrystalline cellulose, starch and the likes thereof.
- a premix of nateglinide can be made with mannitol and starch wherein these three components can be used in ratio of, for example, 2:1:1.
- the present invention provides a process of preparation of stable pharmaceutical composition
- a process of preparation of stable pharmaceutical composition comprising a premix of nateglinide Form B with mannitol and starch in the ratio of 2 : 1 : 1 , wherein the process comprises a step of granulation with isopropyl alcohol.
- nateglinide can be used alone or in combination with other antidiabetic agents.
- the present invention also provides a process for preparing stable pharmaceutical compositions of nateglinide Form B or a premix of nateglinide Form B in combination with mannitol and starch, wherein the composition is used for the preparation of a medicament for the prevention, delay of progression or treatment of metabolic disorders, in particular of type 2 diabetes mellitus or a disease or condition associated with diabetes mellitus and the process comprises a step of granulation with isopropyl alcohol.
- compositions as described herein may include other pharmaceutically acceptable excipients in addition to nateglinide or its premix.
- 'nateglinide' as used herein includes nateglinide in a free or pharmaceutically acceptable salt form such as an acid addition salt, for example, as a sodium salt or as a maleate.
- the composition comprises the B type crystal modification of nateglinide.
- Nateglinide or a pharmaceutically acceptable salt thereof may also be used in the form of a hydrate or include other solvents used for crystallization.
- Nateglinide may be present either substantially in the form of one optically pure enantiomer or as a mixture, racemic or otherwise, of enantiomers.
- Nateglinide may be present in an amount of about 5% to about 70% (w/w), and most preferably about 15% to about 40% (w/w), based on the total weight of the pharmaceutical composition.
- Premix' refers to a combination of nateglinide form B with fillers, particularly mannitol and starch in the ratio of 2: 1 : 1.
- compositions refers to ingredients of the composition, but excludes the active drug substance.
- examples of other pharmaceutically acceptable excipients as used herein include fillers, binders, disintegrants, lubricants, surfactants, glidants, colors and the like.
- the fillers can be selected from one or more of corn starch, lactose, white sugar, sucrose, sugar compressible, sugar confectioners, glucose, sorbitol, calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, mannitol, sorbitol, starch, starch pregelatinized, sucrose, and the like.
- lactose, microcrystalline cellulose or mannitol can be used.
- binders include one or more of methyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, and the like.
- disintegrants include one or more of starch, croscarmellose sodium, crospovidone, sodium starch glycolate and the like.
- lubricants and glidants include one or more of colloidal anhydrous silica, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acids, microcrystalline wax, yellow beeswax, white beeswax and the like.
- surfactants include one or more of sodium lauryl sulphate, poloxamer,
- Polysorbate 80 and the like.
- the coloring agents of the present invention may be selected from any FDA approved colors for oral use.
- the premix can be prepared by simple physical mixing at controlled temperature and pressure wither with or without the presence of organic solvents.
- the stable pharmaceutical composition can be prepared by wet granulation and may be in the form of tablet or capsule. After granulation pulverization can be carried out in conventional milling instruments such as an air jet mill, multi mill, ball mill or by any other method of particle attrition.
- the tablets prepared by the present invention may be coated with one or more additional layers comprising film forming agents and/or pharmaceutically acceptable excipients.
- the coating layers over the tablet may be applied as a solution/dispersion of coating ingredients using any conventional technique known in the art such as spray coating in a conventional coating pan or fluidized bed processor, dip coating, and the like.
- solvents used for preparing a solution/dispersion of the coating ingredients include methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, water and the like and mixtures thereof.
- film forming agents examples include ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropyl methyl phthalate, cellulose acetate, cellulose acetate trimelliatate, cellulose acetate phthalate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit ® RL and RS; and the like and mixture thereof.
- commercially available coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry® may also be used for coating.
- the following examples are illustrative of the invention, and are not to be construed as limiting the invention.
- Concentration may be adjusted to maintain constant tablet weight based on the quantity of premix.
- Nateglinide premix, lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide and sodium starch glycolate are mixed in a high shear blender to give a uniform dry mixture.
- Sodium lauryl sulphate is dispersed in about 50% of the total quantity of isopropyl alcohol and is added slowly to the dry mixture of Step 1 under fast mixing in a rapid mixer granulator (RMG).
- RMG rapid mixer granulator
- Polyvinylpyrrolidone is dissolved in the remaining quantity of isopropyl alcohol till a clear solution is formed, and this solution is added slowly to the mixture of Step 2 and the bulk is then granulated.
- the wet granules are dried in a fluid bed drier, passed through a screen and then subjected to a pulverization step to mill the retentions.
- the extragranular colloidal silicon dioxide, microcrystalline cellulose, lactose nionohydrate and crospovidone are mixed, passed through a screen and blended with the granules of step 4.
- the magnesium stearate is passed through a screen, blended with the blend of step
- Nateglinide premix, lactose monohydrate, colloidal silicon dioxide, microcrystalline cellulose and sodium starch glycolate are mixed in a high shear blender to give a uniform dry mixture.
- Step 2 Sodium lauryl sulphate is dissolved in about 50% of the isopropyl alcohol and is added slowly to the dry mixture of Step 1 under fast mixing in a rapid mixer granulator (RMG).
- RMG rapid mixer granulator
- Polyvinylpyrrolidone is dissolved in the remaining quantity of the isopropyl alcohol till a clear solution is formed, and this solution is added slowly to the premixture of Step 2 and the bulk is then granulated.
- the wet granules are dried in a fluid bed drier, passed through a screen and then subjected to a pulverization step.
- step 5 The extragranular colloidal silicon dioxide, mannitol and crospovidone are mixed, passed through a screen and blended with the granules of step 4.
- the magnesium stearate is passed through a screen, blended with the blend of step 5 and the total mixture is compressed into tablets.
- Table 1 clearly indicates that pharmaceutical compositions of present invention show a comparable dissolution profile to that of STARLIX.
- Figure 1 shows the XRD profile of Nateglinide Form B which indicates characteristic peaks at 2 ⁇ 3.8, 4.9, 5.1, 6.1, 6.5, 14.0, 17.8, 18.9 and 20.2.
- Figure 2 shows the XRD profile of nateglinide premix.
- Figures 3 and 4 show the XRD profiles of the nateglinide tablet prepared as per the details given in Example 1 and 2.
- Figures 5 and 6 show the XRD of the placebo tablet for Examples 1 and 2, respectively. From the above given XRD data it is clear that pharmaceutical compositions of nateglinide when granulated with isopropyl alcohol remain stable, and there is no conversion of Form B to other forms on granulation.
- any single feature or any combination of optional features of the inventive variations described herein may be specifically excluded from the claimed invention and be so described as a negative limitation.
- the resulting dosage form made from either the premix process or other processes disclosed herein will contain residual amounts of isopropyl alcohol present within pharmaceutically acceptable limits (e.g., FDA, ICH guidelines) as measured by conventional analytical means (e.g., LCMS and/or gas chromatography).
- FDA limits for isopropyl alcohol, a class 3 solvent are a permitted daily exposure of 50 mg or 5,000 ppm.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L'invention concerne des préparations de compositions pharmaceutiques stables de natéglinide et des procédés de préparation de celles-ci. Les procédés de préparation de la compostion pharmaceutique stable de la forme B du natéglinide comprennent une étape consistant en une granulation avec de l'alcool isopropylique.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1397DE2004 | 2004-07-28 | ||
PCT/IB2005/002245 WO2006013444A1 (fr) | 2004-07-28 | 2005-07-28 | Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ci |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1776102A1 true EP1776102A1 (fr) | 2007-04-25 |
Family
ID=35502667
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05797983A Withdrawn EP1776102A1 (fr) | 2004-07-28 | 2005-07-28 | Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ci |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP1776102A1 (fr) |
WO (1) | WO2006013444A1 (fr) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1923053A1 (fr) | 2006-09-27 | 2008-05-21 | Novartis AG | Composition pharmaceutique comprenant de la nilotinib ou son sel |
GB2475701B (en) * | 2009-11-26 | 2011-10-19 | Michael Hilary Burke | A process for the preparation of an orally administered anthelmintic unit dose tablet |
CN106265575A (zh) * | 2016-10-20 | 2017-01-04 | 安阳天助药业有限责任公司 | 药物片剂压片用防潮预混剂及制造方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT965339E (pt) * | 1996-11-15 | 2006-06-30 | Ajinomoto Kk | Composicao de nateglinida em comprimidos |
WO2005016315A1 (fr) * | 2003-08-14 | 2005-02-24 | Ranbaxy Laboratories Limited | Compositions pharmaceutiques de nateglinide |
US20070219250A1 (en) * | 2003-11-28 | 2007-09-20 | Romi Singh | Pharmaceutical Compositions of Nateglinide |
-
2005
- 2005-07-28 WO PCT/IB2005/002245 patent/WO2006013444A1/fr active Application Filing
- 2005-07-28 EP EP05797983A patent/EP1776102A1/fr not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO2006013444A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2006013444A1 (fr) | 2006-02-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2009292615B2 (en) | Granulates, process for preparing them and pharmaceutical products containing them | |
RU2485947C2 (ru) | Фармацевтические композиции энтакапона, леводопы и карбидопы с улучшенной биодоступностью | |
TWI564008B (zh) | 難溶性藥物之溶解性改善製劑 | |
WO2005079751A2 (fr) | Compositions pharmaceutiques orales de candesartan cilexetil | |
US20180207128A1 (en) | Immunosuppressant formulation | |
WO2005084648A1 (fr) | Compositions pharmaceutiques comprenant du candesartan cilexetil | |
US20070219250A1 (en) | Pharmaceutical Compositions of Nateglinide | |
US20230157947A1 (en) | Oral pharmaceutical composition comprising carbamate compound and preparation method therefor | |
WO2012172461A1 (fr) | Compositions pharmaceutiques de febuxostat | |
EP2050436A1 (fr) | Composition pharmaceutique qui comporte de la dutastéride | |
EP1776102A1 (fr) | Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ci | |
WO2016175230A1 (fr) | Composition pharmaceutique pour administration par voie orale | |
JP2023036924A (ja) | レナリドミドを含む医薬組成物 | |
WO2019116386A1 (fr) | Compositions pharmaceutiques orales d'aprémilast amorphe et ses procédés de préparation | |
EP2190417A2 (fr) | Compositions pharmaceutiques comprenant un sensibilisateur à l insuline et un secrétagogue d insuline | |
WO2005020979A1 (fr) | Procede de preparation de compositions pharmaceutiques a base de nateglinide | |
JP7206872B2 (ja) | アジルサルタン及びアムロジピンを含有する医薬組成物及びその製造方法 | |
WO2022153330A1 (fr) | Compositions pharmaceutiques comprenant de l'acalabrutinib | |
WO2017037645A1 (fr) | Formulations pharmaceutiques stables de tériflunomide | |
WO2005092319A1 (fr) | Compositions pharmaceutiques a desintegration rapide, comprenant du nateglinide et un delitant | |
WO2005016315A1 (fr) | Compositions pharmaceutiques de nateglinide | |
EP1526842A1 (fr) | Procede de preparation de formulations orales de modafinil | |
WO2005117840A1 (fr) | Compositions pharmaceutiques stables comprenant des granules pulverises de nateglinide de forme b | |
US11331283B2 (en) | Pharmaceutical compositions comprising cinacalcet hydrochloride and one or more binders | |
WO2024084496A1 (fr) | Compositions pharmaceutiques comprenant du maléate d'acalabrutinib |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20070228 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
|
R17P | Request for examination filed (corrected) |
Effective date: 20070228 |
|
DAX | Request for extension of the european patent (deleted) | ||
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20090203 |