CN115177595A - Oxagolide sodium tablet and preparation method thereof - Google Patents
Oxagolide sodium tablet and preparation method thereof Download PDFInfo
- Publication number
- CN115177595A CN115177595A CN202210788466.7A CN202210788466A CN115177595A CN 115177595 A CN115177595 A CN 115177595A CN 202210788466 A CN202210788466 A CN 202210788466A CN 115177595 A CN115177595 A CN 115177595A
- Authority
- CN
- China
- Prior art keywords
- sodium
- tablet
- super
- disintegrant
- tabletting
- 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.)
- Pending
Links
- 239000011734 sodium Substances 0.000 title claims abstract description 107
- 229910052708 sodium Inorganic materials 0.000 title claims abstract description 105
- 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 title claims abstract description 97
- 238000002360 preparation method Methods 0.000 title description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 239000007884 disintegrant Substances 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 22
- 239000011248 coating agent Substances 0.000 claims abstract description 18
- 238000000576 coating method Methods 0.000 claims abstract description 18
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920002472 Starch Polymers 0.000 claims abstract description 12
- 239000008107 starch Substances 0.000 claims abstract description 12
- 235000019698 starch Nutrition 0.000 claims abstract description 12
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 9
- 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 abstract description 9
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 9
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 8
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 8
- 229960000913 crospovidone Drugs 0.000 claims abstract description 6
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 6
- 229940032147 starch Drugs 0.000 claims abstract 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- 239000000463 material Substances 0.000 claims description 22
- 239000000314 lubricant Substances 0.000 claims description 16
- 238000010521 absorption reaction Methods 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 229920000881 Modified starch Polymers 0.000 claims description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 239000000853 adhesive Substances 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 230000001070 adhesive effect Effects 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 7
- 229940069328 povidone Drugs 0.000 claims description 7
- 229920003081 Povidone K 30 Polymers 0.000 claims description 6
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 4
- 239000008116 calcium stearate Substances 0.000 claims description 4
- 235000013539 calcium stearate Nutrition 0.000 claims description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 4
- 239000002994 raw material 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
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 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 3
- 239000011230 binding agent Substances 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 229940014259 gelatin Drugs 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 239000008101 lactose Substances 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
- 239000001863 hydroxypropyl cellulose Substances 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
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 2
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims 2
- 238000004090 dissolution Methods 0.000 abstract description 32
- 239000008187 granular material Substances 0.000 abstract description 14
- 229940124531 pharmaceutical excipient Drugs 0.000 abstract description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract description 4
- 239000001569 carbon dioxide Substances 0.000 abstract description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 abstract description 3
- 210000004211 gastric acid Anatomy 0.000 abstract description 3
- 210000002784 stomach Anatomy 0.000 abstract description 3
- 206010067484 Adverse reaction Diseases 0.000 abstract description 2
- 230000006838 adverse reaction Effects 0.000 abstract description 2
- 230000010100 anticoagulation Effects 0.000 abstract description 2
- 206010016766 flatulence Diseases 0.000 abstract description 2
- 230000004927 fusion Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 81
- 239000012535 impurity Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 238000007908 dry granulation Methods 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 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 description 11
- 229930195725 Mannitol Natural products 0.000 description 11
- 239000000594 mannitol Substances 0.000 description 11
- 235000010355 mannitol Nutrition 0.000 description 11
- JAPHQRWPEGVNBT-UTUOFQBUSA-N loracarbef Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CC[C@@H]32)C([O-])=O)=O)[NH3+])=CC=CC=C1 JAPHQRWPEGVNBT-UTUOFQBUSA-N 0.000 description 10
- 229960001977 loracarbef Drugs 0.000 description 10
- 238000001000 micrograph Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 150000003951 lactams Chemical group 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000007873 sieving Methods 0.000 description 6
- 238000007922 dissolution test Methods 0.000 description 5
- 229960003088 loratadine Drugs 0.000 description 5
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 238000005550 wet granulation Methods 0.000 description 5
- 238000000635 electron micrograph Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- -1 oxadiargyl sodium Chemical compound 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 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 description 3
- 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 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- HEAUOKZIVMZVQL-VWLOTQADSA-N Elagolix Chemical compound COC1=CC=CC(C=2C(N(C[C@H](NCCCC(O)=O)C=3C=CC=CC=3)C(=O)N(CC=3C(=CC=CC=3F)C(F)(F)F)C=2C)=O)=C1F HEAUOKZIVMZVQL-VWLOTQADSA-N 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229950004823 elagolix Drugs 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 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 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 231100001126 band 3 compound Toxicity 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229950005770 hyprolose Drugs 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000008201 pharmaceutical excipient composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910021487 silica fume Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- DQYGXRQUFSRDCH-UQIIZPHYSA-M sodium;4-[[(1r)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]amino]butanoate Chemical compound [Na+].COC1=CC=CC(C=2C(N(C[C@H](NCCCC([O-])=O)C=3C=CC=CC=3)C(=O)N(CC=3C(=CC=CC=3F)C(F)(F)F)C=2C)=O)=C1F DQYGXRQUFSRDCH-UQIIZPHYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
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
- A61K9/205—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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an oxa-rogue sodium tablet which takes oxa-rogue sodium as a medicine or an active ingredient and a pharmaceutical excipient containing a super disintegrantMixing the compositions, granulating, tabletting and/or coating to obtain tablets suitable for oral administration; the super disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low-substituted hydroxypropyl cellulose. The selected super-disintegrant not only has super-strong disintegration and anticoagulation, but also can overcome the phenomena of fusion, sticking and the like of granules containing the oxagoril sodium caused by high-speed tabletting; the super disintegrant has no carbonate ion, and can not be orally taken
When the carbonate meets gastric acid, a large amount of carbon dioxide is instantaneously generated to bring side effects or adverse reactions such as flatulence and the like; the oxagolide sodium tablet is hardly influenced by the acidity in the stomach, and the dissolution curve is stable.
Description
Technical Field
The invention belongs to the field of pharmacy, and mainly relates to an oxa-lagog natrium tablet and a preparation method thereof.
Background
Oxagolide sodium (Elagolix, CAS number: 832720-36-2) is a gonadotropin releasing hormone (GnRH) antagonist developed by Albvie corporation, and is mainly used for clinically relieving symptoms of uterine myoma, endometriosis and the like of adult women.
In the development of oral tablets of oxalagril sodium, albervol company found that there were at least two problems (CN 11169892A, CN 111246850A): 1. when the loracarbef sodium is orally applied in a solid dosage form, gel formation is prone to happen, particularly when the solid preparation does not contain proper anti-gelling agents, the gel formation is prone to happen, the formed gel limits the dissolution of the loracarbef sodium, and finally, the bioavailability of the loracarbef sodium among patients and in the patients can be greatly changed; 2. oxalagrol sodium may degrade to form compounds with lactam structures. The pharmaceutical composition of the sodium oxagolide + sodium carbonate can reduce the gel formation of the sodium oxagolide and/or reduce the generation of lactam degradation products, so as to maintain the safety and efficacy of the product.
Aiming at the 'two problems' in CN 1116988992A and CN111246850A and a solution thereof, the Aibervis company develops an oxalago natrium tablet:
(150mg、200mg)。
the inventors have determined that by looking up the physicochemical properties of loracarbef sodium and its Biopharmaceutical Classification System (BCS) and listing them in table 1: (1) The oxagolide sodium is low-melting-point amorphous powder, and is easy to melt and stick when heated (50-60 ℃); (2) the oxalagogrel sodium is a BCS III medicament: high solubility, low permeability, i.e. the solubility of oxa-degril sodium is high and independent of the pH of the physiological medium in the gastrointestinal tract, but its absorption is limited (low permeability or low absorption of the drug). Therefore, in the pharmaceutical field, the pharmaceutical excipients which may interfere with the absorption of the low-permeability or low-absorption drug of oxadegril sodium, such as polyols (mannitol, sorbitol, polyethylene glycol) and surfactants, should be avoided as much as possible as the formulation components; (3) In pharmacy, the bioavailability of low-absorption medicines in a human body is often highly variable.
Table 1: physicochemical Properties and Biopharmaceutical Classification System (BCS) of Oxagolide sodium
The inventor inquires through
The bioavailability and the coefficient of variation of oxagoril sodium in the specification are shown in table 2. The inventors further determined based on table 2: oxa-rogine sodium is a low permeability or low absorption drug and has a large variability in bioavailability (20-30%). Thus, in oxa-rogatide sodiumIn the prescription composition of the tablet, the addition of pharmaceutical excipients which interfere with the absorption of the oxadegril sodium, such as polyols (mannitol, sorbitol, polyethylene glycol), surfactants and the like, should be avoided as much as possible.
Table 2: is administered orally
Is of high bioavailability
| Biopharmaceutical parameters | Oxagoli sodium (Elagolix) |
| Bioavailability of the active ingredient | 30％～50％ |
| Coefficient of Variation (CV) | 20％～30％ |
The inventor inquires through
The compositions of the prescription listed in the specification are subjected to reverse quantitative analysis, and the mass fractions of the compositions of the prescription are listed in Table 3.
Table 3:
prescription composition, mass fraction and prescription analysis thereof
| Prescription composition | Mass fraction (%) | Prescription analysis |
| Oxagolide sodium salt | 35 | Medicine (active ingredient) |
| Sodium carbonate | 17 | Alkaline auxiliary material, disintegrant and anticoagulant |
| Mannitol | 34 | Excipient |
| Pregelatinized |
10 | Excipient and disintegrant |
| Povidone | 3 | Adhesive agent |
| Magnesium stearate | 1 | Lubricant agent |
The inventors can determine based on table 3: (1) In
In the prescription composition, the key auxiliary material is sodium carbonate which can overcome the defect of oxa-roglyme sodium in CN 1116988992A and CN111246850A"at least two problems" of "the pharmaceutical composition, but in the pharmaceutical composition, sodium carbonate is not only used to overcome" at least two problems "of" oxa-goril sodium; (2) In the pharmacy, mannitol is often used as an excipient for dry granulation and tabletting, but mannitol is a pharmaceutically accepted interference; (3) In pharmacy, mannitol possibly influences the absorption of low-permeability medicines, and is commonly recognized in the industry, and if mannitol is required to be used in the prescription composition, the dosage is controlled to be the minimum dosage; (4) Pharmaceutically, povidone is commonly used as a binder, with povidone K30 being the most commonly used type. (5) Magnesium stearate is a commonly used hydrophobic lubricant in pharmacy; if the mass fraction of magnesium stearate in the prescription composition is too large (> 1%), the hardness of the tablet and the dissolution of the drug may be affected; (6) From, to
The characteristics of various auxiliary materials selected in the prescription composition can be presumed, and the product is prepared by dry granulation and tabletting.
Disclosure of Invention
In pharmacy and the prescription composition of tablets, besides medicaments or active ingredients, the pharmaceutical composition generally also comprises other functional pharmaceutical excipients: disintegrants, excipients (diluents, fillers), binders, lubricants, and the like.
The disintegrant is a pharmaceutical excipient which rapidly disintegrates in an aqueous medium, thereby rapidly dissolving the drug. In the pharmacy, except for the slow-release tablets or the tablets with certain special purposes, the components of the tablet prescription are provided with a certain mass fraction (2-10%) of disintegrant.
Disintegrating agents are generally classified into general disintegrating agents and super disintegrating agents according to the strength of the disintegrating ability. Common disintegrating agents mainly include dry starch, sugar powder, effervescent disintegrating agent (sodium carbonate, sodium bicarbonate, or citric acid, tartaric acid), etc.; the common super disintegrant is mainly croscarmellose sodium (CCMC-Na), sodium carboxymethyl starch (CMS-Na), crospovidone (PVPP), low substituted hydroxypropyl cellulose (L-HPC), etc.
The main mechanism of action of the disintegrant is: (1) Capillary action, namely when the tablet meets an aqueous medium, the disintegrant enables water to rapidly enter the inside of the tablet through capillary action, so that the whole tablet is broken up; (2) The disintegrating agent has water absorption expansibility, so that the binding force of the tablet is damaged and the tablet is disintegrated; (3) The tablet has gas generating effect, if sodium carbonate, sodium bicarbonate and/or citric acid, tartaric acid and other auxiliary materials are added into the tablet prescription, when the tablet meets gastric acid and/or water, carbon dioxide is generated, so that the volume of the tablet is expanded and the tablet is disintegrated.
Excipients are pharmaceutical excipients that form the basic skeleton of a tablet. Common excipients include starch, microcrystalline cellulose, lactose, mannitol, inorganic salts, and the like.
The adhesive is a pharmaceutical excipient which is prepared by bonding raw and auxiliary material powder into granules so as to facilitate tabletting. The adhesive can be liquid (wetting agent), and commonly used is water, ethanol-water and the like; or solid powder, which often also has the functions of excipient and/or disintegrant, such as hypromellose, hyprolose, povidone, gelatin, sodium alginate, etc.
The lubricant is a pharmaceutical excipient for improving the flowability of the prescription composition. The commonly used lubricant comprises magnesium stearate, calcium stearate, talcum powder, micro silica gel, sodium dodecyl sulfate, hydrogenated vegetable oil, etc.
The invention aims to solve the two problems of CN 1116988992A and CN111246850A, and is different from the problems
The prescription measures of (1): (1) By using super disintegrant instead of
The effervescent disintegrant in the prescription composition overcomes at least two problems existing in the oxalagril sodium in CN 1116988992A and CN 111246850A; (2) Replacement with non-polyol excipients
The excipient mannitol in the prescription composition can remove the possibly influenced absorption of the loragol sodium to the maximum extentCollecting auxiliary materials; and/or (3) replacement of talc powder by hydrophilic lubricant
The hydrophobic lubricant magnesium stearate in the prescription composition overcomes the defects caused by excessive magnesium stearate.
The purpose of the invention is realized by the following technical scheme:
the tablets are tablets suitable for oral administration, which are prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant and then granulating, tabletting and/or coating.
The mass ratio of the oxalagril sodium to the super-disintegrant is 35-35, preferably 35-35.
In the oxa-rogue sodium tablet, the mass fraction of the oxa-rogue sodium is 35%.
The pharmaceutical excipient composition of the present invention refers to a powder which is used in the production of a drug or the formulation of a prescription, has been reasonably evaluated in terms of safety, and contains no biological activity in a pharmaceutical preparation, in addition to a drug or an active ingredient.
The pharmaceutical adjuvant composition comprises super disintegrant, excipient, adhesive, lubricant, etc. The pharmaceutical adjuvant composition does not contain excipients which are possibly influencing the absorption of the oxadiargyl sodium in the gastrointestinal tract, such as mannitol, sorbitol, polyethylene glycol, surfactants and the like, and does not contain lubricants which are possibly influencing the tabletting of the oxadiargyl sodium, such as magnesium stearate, calcium stearate, hydrogenated vegetable oil and the like.
The super disintegrant is selected from one or more of croscarmellose sodium (CCMC-Na), sodium carboxymethyl starch (CMS-Na), crospovidone (PVPP) and low-substituted hydroxypropyl cellulose (L-HPC), preferably one or more of croscarmellose sodium, sodium carboxymethyl starch or crospovidone having the same cation as that of sodium oxarogrel, and more preferably croscarmellose sodium. The super disintegrant with the same cation as the oxalaggrin sodium is selected, so that the stability of the oxalaggrin sodium is facilitated.
The mass fraction of the super disintegrant is 1-20%, preferably 10-20%, more preferably 12-18%.
The excipient is selected from one or more of microcrystalline cellulose, starch, lactose, inorganic salt and the like, and is preferably one or the combination of microcrystalline cellulose and starch.
The mass fraction of the excipient is 25-40%.
The adhesive is selected from one or more of water, ethanol water, pregelatinized starch, povidone, hydroxypropyl cellulose, gelatin, sodium alginate, powdered sugar and the like, preferably one or more of pregelatinized starch, povidone and hydroxypropyl methylcellulose, more preferably one or a combination of two of pregelatinized starch and povidone K30, and when the adhesive is the combination of pregelatinized starch and povidone K30, the mass ratio of the pregelatinized starch to the povidone K30 is 10-10.
The mass fraction of the adhesive is 10-25%.
The lubricant is selected from one or more of talcum powder, superfine silica gel powder, magnesium stearate, calcium stearate and the like, preferably the talcum powder and the superfine silica gel powder, and more preferably the talcum powder.
The mass fraction of the lubricant is 1-3%.
As a more specific technical scheme of the oxa-goril sodium tablet, the oxa-goril sodium tablet is prepared by mixing oxa-goril sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super disintegrant, and then granulating and tabletting the mixture to prepare the tablet suitable for oral administration; the mass fraction of the raw and auxiliary materials is as follows, and the total amount of the raw and auxiliary materials is 100%:
as another more specific technical scheme of the oxa-gol sodium tablet, the invention provides the oxa-gol sodium tablet which is a coated tablet suitable for oral administration and prepared by mixing oxa-gol sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating, tabletting and coating; the mass fraction of the raw and auxiliary materials is as follows, and the total mass of the raw and auxiliary materials is 100%:
the coating material is selected from
Premixing common coating powder, specifically selected from
85F630048-CN，
85F640105-CN; the mass fraction of the coating material is 2-3%. The oxagoril sodium coated tablet is prepared by adopting common coating equipment to carry out conventional operation.
Another object of the present invention is to provide a method for preparing the oxalagrol sodium tablet, which comprises: crushing the raw material drug of the oxagoril sodium, sieving the crushed raw material drug with a 80-mesh sieve, and sieving the medicinal auxiliary material with the 80-mesh sieve; weighing raw and auxiliary materials according to the prescription, mixing, granulating and tabletting to obtain the oxa-gol natrium tablet.
The granulation is dry granulation or wet granulation.
As a further preferable technical scheme of the preparation method of the present invention, the tablets further comprise a coating, and the tablets are coated with the oxagoril sodium, which is suitable for oral administration.
And with
In contrast, the present inventionThe oxagoid sodium tablet can at least obtain the following beneficial effects:
(1) Besides the super-strong disintegration and anticoagulation effects, the selected super-disintegrant can overcome the phenomena of fusion, sticking and the like of granules containing the oxagoli sodium caused by high-speed tabletting, so that the continuous and smooth production of tablets is facilitated, and the uniformity and the attractiveness of the content of the tablets can be increased.
(2) The selected super disintegrating agent has no carbonate ions, and oral administration can not occur
When the carbonate meets gastric acid, a large amount of carbon dioxide is instantaneously generated to bring side effects or adverse reactions such as flatulence and the like.
(3) When the patient takes the medicine before or after meals, the acidity in stomach is different
Contains sodium carbonate with a mass fraction of about 17 percent
The different rates of disintegration, thus causing the different dissolution rates of oxalagogrel, and the variability of the curative effect of the patients or among the patients; the oxalagogelix sodium tablet is hardly influenced by the acidity in the stomach, and the dissolution curve is stable.
(4) The formula of the oxalagrol sodium tablet of the invention does not contain
The highest amount of mannitol (mass fraction: 37%, table 3) in the formulation composition, so as to avoid as much as possible interfering with formulation factors of BCS class III, sodium oxalagonate absorbed in the intestinal tract.
(5) The invention is to
The hydrophobic lubricant magnesium stearate in the prescription composition is replaced by the hydrophilic lubricant talcum powder, so that the problem of hardness in the granulating process can be avoidedLoose particles and difficult tabletting caused by excessive magnesium stearate or uneven mixing.
(6) The preparation method of the oxalago sodium tablet is simple in steps and high in yield.
Drawings
FIG. 1 is an electron micrograph of granules obtained by dry granulation in example 1.
Fig. 2 is a microscopic view of the granules obtained by dry granulation in example 1.
Fig. 3 is a micrograph of the oxarogatide sodium tablet of example 1 after standing for 1 hour in 0.1mol hydrochloric acid.
Fig. 4 is a dissolution profile of the oxalagogelix sodium tablets of example 1 at various phs.
Fig. 5 is an electron micrograph of granules prepared by wet granulation in example 2.
Fig. 6 is a microscopic image of the granules obtained by wet granulation in example 2.
Fig. 7 is a micrograph of the oxarogatide sodium tablet of example 2 left to stand in 0.1mol hydrochloric acid for 1 hour.
Fig. 8 is a dissolution profile of the oxalagonidine sodium tablets of example 2 at various phs.
Fig. 9 is a dissolution profile of the oxalagrol sodium tablet of example 3.
Fig. 10 is a dissolution profile of the oxalagrol sodium tablet of example 4.
Fig. 11 is a dissolution profile of the oxalagrol sodium tablet of example 5.
Fig. 12 is a dissolution profile of the oxalagrol sodium tablet of example 6.
Detailed Description
In order to make the technical solution of the present invention more clearly understood, the technical solution of the present invention is further described in detail with reference to specific examples, but the examples of the present invention are not to be construed as limiting the scope of the present invention.
Tablet manufacturing equipment: the device comprises a grinder, a mixer, a dry-method granulator, a swing-type granulator, an air-blast drying box, a rotary tablet press and a high-efficiency coating machine.
Example 1
Prescription:
the lorago sodium tablet of the embodiment is prepared by a dry granulation method, and the steps are as follows:
step (1), pretreatment: crushing the sodium oxalagogride, and sieving the crushed sodium oxalagogride with a 80-mesh sieve; sieving the auxiliary materials with a 80-mesh sieve;
step (2), weighing: weighing raw and auxiliary materials according to the prescription amount;
step (3), granulating: putting the oxalagogrel sodium, the croscarmellose sodium, the microcrystalline cellulose, the pregelatinized starch and the povidone K30 into a mixer, mixing, performing dry granulation by using a dry granulator according to the process shown in Table 4, observing particles by using a scanning electron microscope (model: flexSEM-1000-II), wherein an electron microscope picture of the particles is shown in figure 1, and observing the particles by using a microscope (model: XSP-200X), and a micrographic picture of the particles is shown in figure 2;
table 4: dry granulation process parameters
| Granulating process | Granulation parameters |
| Speed of filling | 6.00HZ |
| Speed of sheet pressing | 10.00HZ |
| Speed of granulation | 20.00HZ |
| Mesh aperture | 14 mesh |
Step (4), total mixing: mixing the granules prepared in the step (3) with talcum powder;
step (5), tabletting: adding the totally mixed materials into a rotary tablet machine, adjusting the loading (450 mg) and tabletting (8-10 kg of hardness) to obtain the oxagoril tablet.
The oxalagrol sodium tablet of this example was left to stand in 0.1mol hydrochloric acid for 1 hour, and the micrograph is shown in fig. 3.
Dissolution test method: according to the technical guideline for dissolution test of common oral solid preparation and determination method of dissolution rate and release rate (0931 of the four-part general rule of 2020 edition of Chinese pharmacopoeia), hydrochloric acid solution with pH of 1.2, citrate buffer solution with pH of 4.5, phosphate buffer solution with pH of 6.8 and purified water are respectively used as dissolution media, the volume of the dissolution media is 900ml, the rotating speed is 50rpm, samples are respectively taken at 5, 10, 15, 20, 25, 30 and 45min, the absorbance (n = 6) is determined at the wavelength of ultraviolet 274nm, the dissolution curve is shown in figure 4, and it can be seen that the dissolution of the sodium loratadine in the sodium loratadine tablet is hardly influenced by pH, and the dissolution curve (pH of 1.2, 4.5, 6.8 and purified water) is stable.
The influence factor test results are shown in table 5, and it can be seen from table 5 that the amount of the oxalagrilamide impurities is not increased.
Table 5: experimental results of influencing factors
| Conditions of | Theeragolide lactam% | Maximum unknown impurity% | Total |
| Day | |||
| 0 | 0.01 | 0.03 | 0.04 |
| 60 ℃ for 10 days | 0.01 | 0.03 | 0.04 |
| 4500LX + -500LX for 10 days | 0.01 | 0.03 | 0.04 |
| 45 ℃ and 75% RH for 10 days | 0.01 | 0.03 | 0.05 |
Example 2
Prescription:
the lorago sodium tablet of the embodiment is prepared by a wet granulation method, and the steps are as follows:
step (1), pretreatment: crushing the sodium oxalagogride, and sieving the crushed sodium oxalagogride with a 80-mesh sieve; sieving the auxiliary materials with a 80-mesh sieve;
step (2), weighing: weighing raw and auxiliary materials according to the prescription amount;
step (3), slurry preparation: dissolving polyvidone K30 in purified water, and stirring to obtain a pulp solution with polyvidone K30 concentration of 5% (w/w);
step (4), granulating: putting the oxagoril sodium, the croscarmellose sodium, the microcrystalline cellulose and the pregelatinized starch into a mixer, and adding the prepared slurry to prepare a soft material; then placing the soft material in a swing type granulator, granulating (with 14 mesh sieve), drying (< 50 ℃), grading to obtain dry granules, observing the granules by using a scanning electron microscope (model: flexSEM-1000-II), wherein the particle electron microscope picture is shown in figure 5, and observing the granules by using a microscope (model: XSP-200X), and the particle micrograph is shown in figure 6;
step (5), tabletting: and (4) mixing the dry granules prepared in the step (4) with talcum powder, and tabletting (the hardness is 8-10 kg) to obtain the oxa-goril sodium tablet.
The oxalagrol sodium tablet of this example was left to stand in 0.1mol hydrochloric acid for 1 hour and the micrograph is shown in fig. 7.
By observing micrographs of granules (electron micrographs and micrographs) and tablets obtained by dry granulation in example 1 and kept standing in 0.1mol of hydrochloric acid for 1 hour, and micrographs of granules (electron micrographs and micrographs) and tablets obtained by wet granulation in example 2 and kept standing in 0.1mol of hydrochloric acid for 1 hour, there was no difference in sensitivity between them.
The dissolution rate of the loratadine sodium tablet of this example was measured (n = 6) by referring to the dissolution rate measurement method of example 1, and the dissolution curve is shown in fig. 8, and it can be seen that the dissolution rate of loratadine sodium in the loratadine sodium tablet is hardly affected by pH.
The results of the influence factor test are shown in table 6, and it is known that the impurity content of the oxagolide is not increased.
Table 6: experimental results of influence factors
| Condition | Theeragolide lactam% | Maximum unknown impurity% | Total |
| Day | |||
| 0 | 0.01 | 0.03 | 0.04 |
| 60 ℃ for 10 days | 0.01 | 0.03 | 0.04 |
| 4500LX + -500LX for 10 days | 0.01 | 0.03 | 0.04 |
| 45 ℃ and 75% RH for 10 days | 0.01 | 0.03 | 0.05 |
Example 3
Prescription:
the lorago sodium tablet of this example was prepared by dry granulation, which was the same as example 1.
The dissolution of the oxalagrine tablet of this example was measured (n = 6) by the dissolution test method of example 1, and the dissolution curve is shown in fig. 9, and it can be seen that the dissolution of the oxalagrine in the oxalagrine tablet is hardly affected by pH.
The results of the influence factor test are shown in table 7, and it is understood that the impurity content of the oxagolide is not increased.
Table 7: experimental results of influencing factors
| Condition | Oxagolide lactam% | Maximum unknown impurity% | Total |
| Day | |||
| 0 | 0.01 | 0.03 | 0.04 |
| 60 ℃ for 10 days | 0.01 | 0.03 | 0.04 |
| 4500LX + -500LX for 10 days | 0.01 | 0.03 | 0.04 |
| 45 ℃ and 75% RH for 10 days | 0.01 | 0.03 | 0.05 |
Example 4
Prescription:
referring to example 1, an oxaregamide tablet was prepared by a dry granulation method, and the oxaregamide tablet was coated:
preparing a coating solution: taking prescription amount
85F630048-CN, adding purified water to prepare 10% suspension, and continuously stirring;
coating: and (3) putting the oxagoril tablets into a high-efficiency coating pot, and performing conventional coating operation until the coating solution is used up to obtain the oxagoril coated tablets.
The dissolution of the oxalagril sodium-coated tablet of this example was measured (n = 6) by the dissolution test method of example 1, and the dissolution curve is shown in fig. 10, and it can be seen that the dissolution of oxalagril sodium in the oxalagril sodium-coated tablet is hardly affected by pH.
The influence factor test results are shown in table 8, and it can be seen that the amount of the oleanolic amide impurities is not increased.
Table 8: experimental results of influencing factors
Example 5
Prescription:
referring to example 4, an oxalaggrin sodium tablet was prepared by dry granulation, and the oxalaggrin sodium tablet was coated to prepare an oxalaggrin sodium coated tablet.
Referring to the dissolution test method of example 1, the dissolution rate (n = 6) of the loracarbef tablet of this example was measured, and the dissolution curve is shown in fig. 11, and it can be seen that the dissolution of loracarbef sodium in the loracarbef coated tablet was hardly affected by pH.
The results of the influence factor test are shown in table 9, and it is understood that the impurity content of the oxagolide is not increased.
Table 9: experimental results of influence factors
| Condition | Theeragolide lactam% | Maximum unknown impurity% | Total |
| Day | |||
| 0 | 0.01 | 0.03 | 0.04 |
| 60 ℃ for 10 days | 0.01 | 0.03 | 0.04 |
| 4500LX + -500LX for 10 days | 0.01 | 0.03 | 0.04 |
| 45 ℃ and 75% RH for 10 days | 0.02 | 0.03 | 0.05 |
Example 6
Prescription:
referring to example 4, an oxaregamide tablet was prepared by dry granulation, and the oxaregamide tablet was coated to obtain an oxaregamide-coated tablet.
The dissolution rate (n = 6) of the tablets coated with loracarbef of this example was measured by the dissolution rate measurement method of example 1, and the dissolution curve is shown in fig. 12, and it can be seen that the dissolution rate of loracarbef in the tablets coated with loracarbef was hardly affected by pH.
The influence factor test results are shown in table 10, and it is known that the amount of the oleanolic amide impurities is not increased.
Table 10: experimental results of influencing factors
| Condition | Oxagolide lactam% | Maximum unknown impurity% | Total |
| Day | |||
| 0 | 0.01 | 0.03 | 0.04 |
| 60 ℃ for 10 days | 0.01 | 0.03 | 0.04 |
| 4500LX + -500LX for 10 days | 0.01 | 0.03 | 0.04 |
| 45 ℃ and 75% RH for 10 days | 0.02 | 0.03 | 0.05 |
Claims (10)
1. An oxagoril tablet characterized by: the tablet is prepared by mixing the oxadegril sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing the super-disintegrant, and then granulating, tabletting and/or coating the mixture.
2. The oxarogatide tablet according to claim 1, wherein: the mass ratio of the oxalagril sodium to the super-disintegrant is 35-35, preferably 35-35.
3. The oxalagrol sodium tablet of claim 1, wherein: the pharmaceutical adjuvant composition comprises a super disintegrant, an excipient, a binder and a lubricant, but does not contain an excipient which can affect the absorption of the oxa-gol sodium in the gastrointestinal tract and does not contain a lubricant which can affect the tabletting of the oxa-gol sodium.
4. The oxarogine sodium tablet according to claim 1 or 3, characterized in that: the super disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low-substituted hydroxypropyl cellulose, and preferably one or more of croscarmellose sodium, sodium carboxymethyl starch or crospovidone.
5. The oxalagrol sodium tablet of claim 3, wherein: the excipient is selected from one or more of microcrystalline cellulose, starch, lactose and inorganic salt, preferably one or a combination of microcrystalline cellulose and starch.
6. The oxarogine sodium tablet of claim 3, wherein: the adhesive is selected from one or more of water, ethanol water, pregelatinized starch, povidone, hydroxypropyl cellulose, gelatin, sodium alginate and powdered sugar, preferably one or more of pregelatinized starch, povidone and hydroxypropyl methylcellulose, and more preferably one or a combination of two of pregelatinized starch and povidone K30.
7. The oxalagrol sodium tablet of claim 3, wherein: the lubricant is selected from one or more of talcum powder, superfine silica powder, magnesium stearate and calcium stearate, preferably the talcum powder and the superfine silica powder, and more preferably the talcum powder.
8. The oxalagrol sodium tablet of claim 1, wherein: the coating material is selected from
Premixing common coating powder.
9. The oxalagrol sodium tablet is characterized in that: the tablets are prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating and tabletting; wherein the mass fraction of the raw materials and the auxiliary materials is as follows:
10. the oxagolide sodium tablet is characterized in that: the coated tablet is prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating, tabletting and coating; wherein the mass fraction of the raw materials and the auxiliary materials is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210788466.7A CN115177595A (en) | 2022-07-06 | 2022-07-06 | Oxagolide sodium tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210788466.7A CN115177595A (en) | 2022-07-06 | 2022-07-06 | Oxagolide sodium tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115177595A true CN115177595A (en) | 2022-10-14 |
Family
ID=83518244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210788466.7A Pending CN115177595A (en) | 2022-07-06 | 2022-07-06 | Oxagolide sodium tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115177595A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459225A (en) * | 2023-04-26 | 2023-07-21 | 东莞市金美济药业有限公司 | Alagox sodium tablet and preparation process thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1623593A (en) * | 2003-12-05 | 2005-06-08 | 北京博尔达生物技术开发有限公司 | Solid instant preparation extracted from ginkgo leaf and its preparing process |
| CN109568278A (en) * | 2017-09-28 | 2019-04-05 | 北京万全德众医药生物技术有限公司 | Mo Fanse forest tract agent and preparation method thereof |
| WO2021180862A1 (en) * | 2020-03-12 | 2021-09-16 | Synthon B.V. | Pharmaceutical compositions comprising elagolix sodium |
| CN113876728A (en) * | 2021-11-17 | 2022-01-04 | 南京唯创远医药科技有限公司 | Oxagolide freeze-dried tablet and preparation method thereof |
-
2022
- 2022-07-06 CN CN202210788466.7A patent/CN115177595A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1623593A (en) * | 2003-12-05 | 2005-06-08 | 北京博尔达生物技术开发有限公司 | Solid instant preparation extracted from ginkgo leaf and its preparing process |
| CN109568278A (en) * | 2017-09-28 | 2019-04-05 | 北京万全德众医药生物技术有限公司 | Mo Fanse forest tract agent and preparation method thereof |
| WO2021180862A1 (en) * | 2020-03-12 | 2021-09-16 | Synthon B.V. | Pharmaceutical compositions comprising elagolix sodium |
| CN113876728A (en) * | 2021-11-17 | 2022-01-04 | 南京唯创远医药科技有限公司 | Oxagolide freeze-dried tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 侯秀英等: "《新编现代实用药剂学》", 30 July 2015, 西安交通大学出版社, pages: 99 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459225A (en) * | 2023-04-26 | 2023-07-21 | 东莞市金美济药业有限公司 | Alagox sodium tablet and preparation process thereof |
| CN116459225B (en) * | 2023-04-26 | 2023-11-10 | 东莞市金美济药业有限公司 | Alagox sodium tablet and preparation process thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201815384A (en) | Tablets comprising 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde | |
| US8597666B2 (en) | Compressed solid dosage form manufacturing process well-suited for use with drugs of low aqueous solubility and compressed solid dosage forms made thereby | |
| CN104546747A (en) | Pharmaceutical composition containing safinamide mesylate and preparation method of pharmaceutical composition | |
| US20060240101A1 (en) | Orally disintegrating pharmaceutical tablet formulations of olanzapine | |
| CN104398481A (en) | Bilastine orally disintegrating tablet and preparing method thereof | |
| CN109793715B (en) | Apixaban oral solid preparation and preparation method thereof | |
| US20100034885A1 (en) | Formulations containing glimepiride and/or its salts | |
| CN115177595A (en) | Oxagolide sodium tablet and preparation method thereof | |
| CN106880611A (en) | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing | |
| US20160271126A1 (en) | Pharmaceutical composition | |
| AU2013347264B2 (en) | Dispersible tablet | |
| AU2004324858B2 (en) | Compressed solid dosage form manufacturing process well-suited for use with drugs of low aqueous solubility and compressed solid dosage forms made thereby | |
| WO2021107967A1 (en) | Pharmaceutical compositions of lurasidone | |
| CN110354093A (en) | A kind of mosapride citrate pharmaceutical composition | |
| CN111214442B (en) | Apixaban co-micropowder | |
| WO2022042646A1 (en) | Lurasidone hydrochloride composition and preparation method therefor | |
| US20150283083A1 (en) | Dispersible Tablet | |
| EP2098223A1 (en) | Compressed solid dosage form | |
| TW202345810A (en) | Solid extended-release composition comprising bradykinin b2-receptor antagonists | |
| JP2024531701A (en) | Bempedoic acid pharmaceutical composition | |
| CN111374954A (en) | Amlodipine besylate dispersible tablets and preparation method thereof | |
| CN116782888A (en) | Pharmaceutical composition | |
| CN113768889A (en) | Cilostazol-containing pharmaceutical composition and preparation method thereof | |
| CN108066347A (en) | Orally disintegrating tablet medicament composition comprising Tamsulosin and dutasteride | |
| KR20070112043A (en) | Orally disintegrating tablets for treating dysuria |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |