KR20010105771A - A tablet composition containing ibuprofen - Google Patents
A tablet composition containing ibuprofen Download PDFInfo
- Publication number
- KR20010105771A KR20010105771A KR1020000026677A KR20000026677A KR20010105771A KR 20010105771 A KR20010105771 A KR 20010105771A KR 1020000026677 A KR1020000026677 A KR 1020000026677A KR 20000026677 A KR20000026677 A KR 20000026677A KR 20010105771 A KR20010105771 A KR 20010105771A
- Authority
- KR
- South Korea
- Prior art keywords
- ibuprofen
- water
- tablet composition
- soluble
- organic compound
- Prior art date
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims description 47
- 229960001680 ibuprofen Drugs 0.000 title claims description 46
- 239000007916 tablet composition Substances 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000000463 material Substances 0.000 claims abstract description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 239000004475 Arginine Substances 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 9
- 239000007884 disintegrant Substances 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 229920003169 water-soluble polymer Polymers 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 6
- 229940069328 povidone Drugs 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 5
- 229960003194 meglumine Drugs 0.000 claims description 5
- 239000002861 polymer material Substances 0.000 claims description 5
- IKXCHOUDIPZROZ-LXGUWJNJSA-N (2r,3r,4r,5s)-6-(ethylamino)hexane-1,2,3,4,5-pentol Chemical compound CCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO IKXCHOUDIPZROZ-LXGUWJNJSA-N 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920000084 Gum arabic Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 241000978776 Senegalia senegal Species 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000000205 acacia gum Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 2
- 229920001112 grafted polyolefin Polymers 0.000 abstract 3
- 238000002844 melting Methods 0.000 abstract 3
- 230000008018 melting Effects 0.000 abstract 3
- 229920000098 polyolefin Polymers 0.000 abstract 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 abstract 1
- 150000008064 anhydrides Chemical class 0.000 abstract 1
- 229920002678 cellulose Polymers 0.000 abstract 1
- 239000001913 cellulose Substances 0.000 abstract 1
- 150000001991 dicarboxylic acids Chemical class 0.000 abstract 1
- 239000000428 dust Substances 0.000 abstract 1
- 239000000835 fiber Substances 0.000 abstract 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 abstract 1
- 239000011976 maleic acid Substances 0.000 abstract 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 abstract 1
- 239000004745 nonwoven fabric Substances 0.000 abstract 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 229920002785 Croscarmellose sodium Polymers 0.000 description 11
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 11
- 229960001681 croscarmellose sodium Drugs 0.000 description 11
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 10
- 239000008108 microcrystalline cellulose Substances 0.000 description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 9
- 239000000454 talc Substances 0.000 description 9
- 229910052623 talc Inorganic materials 0.000 description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 8
- 229940082170 ibuprofen 200 mg Drugs 0.000 description 6
- 150000007514 bases Chemical class 0.000 description 4
- 238000007922 dissolution test Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940098416 ibuprofen 400 mg Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 229910052806 inorganic carbonate Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 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
- 208000006820 Arthralgia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N Chloride-Acetic acid Natural products CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 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 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- OJJVRJWONUKKMI-UHFFFAOYSA-N O=[Si]=O.CCCCCCCCCCCCCCCCCC(O)=O Chemical compound O=[Si]=O.CCCCCCCCCCCCCCCCCC(O)=O OJJVRJWONUKKMI-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- -1 amine salt Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
본 발명은 이부프로펜을 수용성 염기성 화합물을 혼합하여 직타하여 경구제형화시키거나, 수용성 고분자물질의 용액과 먼저 혼합하여 흡착시키는 습식공정으로 제제화함으로써 용출성이 향상된 이부프로펜 정제 조성물에 관한 것이다.The present invention relates to an ibuprofen tablet composition having improved elution by formulating ibuprofen by oral formulation by mixing a water-soluble basic compound or by direct wetting or adsorbing by mixing with a solution of a water-soluble polymer first.
2-(4-이소부틸페닐)프로피온산인 이부프로펜은 비스테로이드성, 진통성, 항염증성 및 항발열성을 지닌 잘 알려진 약제이다. 본 약제는 만성 관절류마티스, 관절통 및 관절염, 신경통 및 신경염, 상기도염, 월경곤란증, 홍반, 소염과 진통, 만성 기관지염, 하열, 강직성 적수염, 수술후 통증, 근육통, 쇠통 및 감기를 포함하는 열병 및 유행성 감기 증상에 통상적으로 일일량 600㎎을 3회에 나누어 복용한다. 소아의 경우, 5∼7세 200㎎, 8∼10세 300㎎~400㎎, 11∼15세 400㎎∼600㎎을 일일량으로 해서 2∼3회에 걸쳐 복용한다.Ibuprofen, a 2- (4-isobutylphenyl) propionic acid, is a well known drug with nonsteroidal, analgesic, anti-inflammatory and antipyretic properties. The drug is a fever and pandemic, including chronic arthritis, arthralgia and arthritis, neuralgia and neuritis, upper respiratory tract, dysmenorrhea, erythema, anti-inflammatory and analgesic, chronic bronchitis, fever, ankylosing erythritis, postoperative pain, myalgia, iron pain and cold Usually 600mg daily dose divided into three doses for cold symptoms. In children, 200 mg for 5-7 years old, 300 mg to 400 mg for 8-10 years old, and 400 mg to 600 mg for 11-15 years old are taken two to three times.
이부프로펜은 이러한 유용한 약리 효과를 가지지만 약물자체의 난용성으로 용출이 저조하므로 제제화에 많은 어려움이 있다. 그 예로, 대한민국 특허공개번호 제 99-87084호(99. 12. 15)에 이부프로펜이 산성 물질인 점을 고려하여 알카리성물질인 무기탄산염 또는 중탄산염등을 가해 신속히 붕괴되어 용출을 나타내는 제제화 방법이 개시되어 있다. 그러나, 이러한 탄산염을 함유하는 제제는 이부프로펜의 산성기와 반응하여 제제화 공정중 이산화탄소와 물이 발생되어 제제화가 어렵고, 또한 이로 인해 제제화 후에도 인습성, 부착성 등을 증가시키는 문제점을 가지고 있다.Ibuprofen has such a useful pharmacological effect, but there is a lot of difficulty in formulating because of poor dissolution due to poor solubility of the drug itself. For example, in consideration of the fact that ibuprofen is an acidic substance, Korean Patent Publication No. 99-87084 (99. 12. 15) discloses a formulation method which rapidly disintegrates by adding an inorganic carbonate or bicarbonate, which is an alkaline substance, to dissolve. have. However, such a carbonate-containing formulation reacts with an acidic group of ibuprofen to generate carbon dioxide and water during the formulation process, making it difficult to formulate, and thus, has a problem of increasing humidity and adhesion after formulation.
본 발명은 상기와 같은 사실에 의거한 것으로서, 본 발명자들은 이러한 기존 제제화의 단점을 극복하고 동시에 용출율을 향상시킬 수 있는 이부프로펜 경구제형의 제조공정을 연구하던중, 이부프로펜을 수용성 염기성 화합물과 혼합하여 직타하여 경구제형화시키거나, 수용성 고분자물질의 용액과 먼저 혼합하여 흡착시키는 습식공정으로 제제화하는 경우 인습성등의 문제점없이 지속적이며 높은 용출율을 유지시키는 것을 발견하게 되어 본 발명을 완성하게 되었다.The present invention is based on the above facts, while the present inventors have studied the manufacturing process of ibuprofen oral formulation which can overcome the disadvantages of the existing formulation and at the same time improve the dissolution rate, by mixing ibuprofen with a water-soluble basic compound When formulated by oral formulation, or when formulated in a wet process of admixing with a solution of a water-soluble polymer first to adsorb, it has been found to maintain a continuous and high dissolution rate without problems such as humidity and to complete the present invention.
본 발명의 정제 조성물은 이부프로펜, 수용성 염기성 유기 화합물, 선택적으로 수용성 고분자 물질, 붕해제, 기타 약제학적 첨가제로 구성될 수 있다.The tablet composition of the present invention may consist of ibuprofen, a water soluble basic organic compound, optionally a water soluble high molecular material, a disintegrant, and other pharmaceutical additives.
이부프로펜은 광학적 이성체를 포함하는 모든 이부프로펜이 사용 가능하다. 이부프로펜의 입도는 크게 영향을 주지 않으나 주로 5 내지 100㎛, 바람직하게는 10 내지 50㎛이다. 또한, 통상적으로 이부프로펜은 제제중에서 20 내지 80%, 바람직하게는 40 내지 70%가 포함될 수 있다.Ibuprofen can be used with all ibuprofen including optical isomers. The particle size of ibuprofen does not significantly affect, but is mainly 5 to 100 µm, preferably 10 to 50 µm. In general, ibuprofen may also comprise 20 to 80%, preferably 40 to 70% in the formulation.
이부프로펜 제제에 첨가될 수 있는 수용성 염기성 유기 화합물은 이부프로펜의 용출율도 지속적으로 유지시키고 향상시키는데 필수적인 성분으로 무기탄산염의 단점을 보완할 수 있는 수용성 염기성 유기화합물은 모두 가능하다. 예를 들면, 아르기닌, 리신 히스티딘과 같은 수용성 염기성 아미노산이나, 메글루민, 에글루민, 그리고 유기성 아민염과 같은 염기성 화합물등을 들수 있다. 이 성분은 통상적으로 이부프로펜 1 에 대해 중량비로 0.1 내지 1.5, 바람직하게는 0.25 내지 1 포함될 수 있다.The water-soluble basic organic compound that can be added to the ibuprofen preparation is an essential ingredient for continuously maintaining and improving the dissolution rate of ibuprofen, and any water-soluble basic organic compound that can compensate for the disadvantages of the inorganic carbonate is possible. For example, water-soluble basic amino acids, such as arginine and lysine histidine, and basic compounds, such as meglumine, eglumine, and an organic amine salt, etc. are mentioned. This component may typically comprise 0.1 to 1.5, preferably 0.25 to 1, by weight relative to ibuprofen 1.
선택적으로 사용될 수 있는 수용성 고분자 물질은 난용성인 이부프로펜에 흡착하여 용출률을 증가시킬 수 있는 것이면 어느것이나 가능하다. 예를 들면, 폴리비닐피롤리돈(포비돈), 폴리에틸렌글리콜류, 히드록시프로필셀룰로오스, 히드록시프로필메틸셀룰로오스, 아라비아 검류, 젤라틴, 히드록시에틸셀룰로오스, 폴록사머, 카르복시비닐 폴리머등이 사용될 수 있다. 이 성분은 통상적으로 이부프로펜 1에 대해 중량비로 0.001 내지 0.5, 바람직하게는 0.01 내지 0.2가 포함될 수 있다.The water-soluble polymer material which can be optionally used can be any so long as it can adsorb to poorly soluble ibuprofen to increase the dissolution rate. For example, polyvinylpyrrolidone (povidone), polyethylene glycols, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gum arabic, gelatin, hydroxyethyl cellulose, poloxamer, carboxyvinyl polymer and the like can be used. This component may typically comprise 0.001 to 0.5, preferably 0.01 to 0.2, by weight relative to ibuprofen 1.
그리고, 첨가될 수 있는 붕해제로는 약제학적으로 일반적으로 사용되는 붕해제는 모두 사용될 수 있다. 예를 들면, 나트륨전분글리콜레이트, 저치환원히드록시프로필셀룰로오스, 알긴산, 가교결합된 폴리비닐피롤리돈, 마그네슘 알루미늄 실리케이트 및 크로스카멜로오스나트륨등을 들 수 있다. 바람직한 붕해제는 하나 이상의 크로스카멜로오스나트륨을 사용할 수 있다.In addition, as a disintegrant which may be added, all disintegrants which are generally used pharmaceutically may be used. For example, sodium starch glycolate, low-substituted hydroxypropyl cellulose, alginic acid, crosslinked polyvinylpyrrolidone, magnesium aluminum silicate, croscarmellose sodium, and the like. Preferred disintegrants may use one or more croscarmellose sodium.
이 성분은 통상적으로 이부프로펜 1에 대해 중량비로 0.01 내지 0.5, 바람직하게는 0.01 내지 0.3 포함될 수 있다.This component may typically be included in a weight ratio of 0.01 to 0.5, preferably 0.01 to 0.3, relative to ibuprofen 1.
기타 첨가될 수 있는 약제학제 첨가제로는 불활성희석제, 활택제 등이 사용될 수 있다. 불활성희석제로는 미결정셀룰로오스, 유당, 만니톨, 전분, 인산수소 칼슘, 황산칼슘등이 사용 가능하며, 활택제 성분으로는 스테아린산, 스테아린산 마그네슘, 스테아린산 아연, 탈크, 규산마그네슘, 규산알루미늄마그네슘, 메타규산알루미늄마그네슘, 경질무수규산, 수소화 식물성유등이 사용 가능하다.Inert diluents, lubricants and the like may be used as pharmaceutical additives that may be added. As an inert diluent, microcrystalline cellulose, lactose, mannitol, starch, calcium hydrogen phosphate, calcium sulfate, etc. can be used.Gluents include stearic acid, magnesium stearate, zinc stearate, talc, magnesium silicate, aluminum silicate silica, aluminum metasilicate. Magnesium, light anhydrous silicic acid and hydrogenated vegetable oils can be used.
이들 성분은 통상적으로 이부프로펜 1에 대하여 중량비로 0.01 내지 0.5, 바람직하게는 0.01 내지 0.3 포함될 수 있다.These components may typically be included from 0.01 to 0.5, preferably 0.01 to 0.3, by weight relative to ibuprofen 1.
따라서, 바람직한 이부프로펜 정제로 (a) 이부프로펜 1에 대해 중량비로 (b) 수용성 염기성 유기화합물 0.1 내지 1.5, (c) 선택적으로 수용성고분자 물질 0.001 내지 0.5, (d) 기타 약제학적 첨가제 0.001 내지 0.5를 포함한다. 또한, 바람직하게는 이부프로펜 1에 대해 중량비로 수용성 염기성 유기화합물 0.25 내지 1, 선택적으로 수용성 고분자물질 0.01 내지 0.2, 기타 약제학적 첨가제 0.01 내지 0.3을 포함한다.Thus, a preferred ibuprofen tablet comprises (a) 0.1 to 1.5 water soluble basic organic compounds (b) optionally from 0.001 to 0.5 water soluble polymer material, and (d) 0.001 to 0.5 other pharmaceutical additives in a weight ratio relative to ibuprofen 1 do. In addition, it preferably comprises from 0.25 to 1 of water-soluble basic organic compounds, optionally from 0.01 to 0.2 of water-soluble polymers, and from 0.01 to 0.3 of other pharmaceutical additives by weight relative to ibuprofen 1.
본 발명의 이부프로펜 제제는 다음과 같은 방법으로 제조된다.The ibuprofen formulation of the present invention is prepared by the following method.
이부프로펜과 수용성 염기성 유기화합물을 잘 혼합한 후 붕해제 및 기타약제학적 첨가제를 섞어 직타하여 제조한다. 또는, 이부프로펜에 대하여 수용성 고분자 물질을 물 또는 에탄올, 이소프로필알콜등 유기용매에 녹여 이부프로펜과 연합, 건조한다. 여기에 수용성 염기성 유기화합물과 붕해제 및 기타약제학적 첨가제를 혼합하는 습식공정을 거친 후 타정하여 제조한다.It is prepared by mixing ibuprofen and a water-soluble basic organic compound well and then directly mixing a disintegrant and other pharmaceutical additives. Alternatively, with respect to ibuprofen, a water-soluble high molecular substance is dissolved in water or an organic solvent such as ethanol or isopropyl alcohol, and then combined with ibuprofen and dried. It is prepared by tableting after a wet process of mixing a water-soluble basic organic compound with a disintegrant and other pharmaceutical additives.
이하, 본 발명의 구체적인 구성과 작용을 실시예와 비교예를 통하여 구체적으로 설명하면 다음과 같으며, 본 발명이 이에 한정되는 것은 아니다.Hereinafter, the specific configuration and operation of the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.
실시예 1.Example 1.
이부프로펜에 대하여 수용성 고분자 물질인 포비돈을 물, 이소프로필알콜에 녹여 이부프로펜과 연합, 건조한다. 여기에, 수용성 염기성 유기화합물인 아르기닌과 나머지 성분인 붕해제 및 기타약제학적 첨가제를 혼합하여 타정하여 제조한다.About ibuprofen Povidone, a water-soluble polymer, is dissolved in water and isopropyl alcohol, and then combined with ibuprofen and dried. Herein, arginine, which is a water-soluble basic organic compound, and a disintegrating agent and other pharmaceutical additives, which are the remaining components, are mixed and prepared.
실시예 2.Example 2.
상기 실시예 1의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 1, followed by tableting.
실시예3.Example 3.
상기 실시예 1의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 1, followed by tableting.
실시예 4.Example 4.
이부프로펜 및 수용성 염기성 유기화합물 그리고, 붕해제 및 기타 약제학적 첨가제를 섞어 직타하여 제품을 얻는다.Ibuprofen and a water-soluble basic organic compound and a disintegrant and other pharmaceutical additives are mixed and fired to obtain a product.
실시예5.Example 5.
상기 실시예 1의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 1, followed by tableting.
실시예6.Example 6.
상기 실시예 1의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 1, followed by tableting.
실시예7.Example 7.
상기 실시예 1의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 1, followed by tableting.
비교예 1.Comparative Example 1.
상기 실시예 4의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 4, followed by tableting.
비교예 2.Comparative Example 2.
상기 실시예 4의 제조방법과 동일하게 제조한 후 타정하여 제조한다.It is prepared in the same manner as in Preparation Example 4, followed by tableting.
실험예. 비교 용출 시험Experimental Example Comparative dissolution test
실시예 1 및 실시예 4에서 제조된 검체와 비교예 1 및 비교예 2의 검체를 약전 일반시험법중 용출시험법 제 2 법(패들법)에 따라 시험하고 10, 15, 30, 60분후 용출액을 취하여 용출된 양을 아래 분석법에 따라 시험하였다.The samples prepared in Examples 1 and 4 and the samples of Comparative Examples 1 and 2 were tested according to the Dissolution Test Method 2 (Paddle Method) of the Pharmacopoeia General Test Method, and the eluate after 10, 15, 30, and 60 minutes. The amount eluted was tested according to the assay below.
용출실험장치 : Erweka DT 80Dissolution Test Equipment: Erweka DT 80
용출액 : 물 900mlEluent: 900 ml of water
용출액의 온도 : 37±0.5℃Eluent temperature: 37 ± 0.5 ℃
회전속도 : 50 rpmRotational Speed: 50 rpm
분석법 : 액체크로마토그라피법Assay: Liquid Chromatography
칼 럼 : Cosmosil C18(150㎜×4.6㎜)Column: Cosmosil C 18 (150㎜ × 4.6㎜)
이동상 : 아세토니트릴 : 1% 염화 초산 (pH3.0) (65 : 35)Mobile phase: Acetonitrile: 1% chloride acetic acid (pH 3.0) (65: 35)
유 속 : 1.2 ㎖/minFlow rate: 1.2 ml / min
검출기 : UV 254㎚Detector: UV 254 nm
주입량 : 20㎕Injection amount: 20µl
하기 표 1에 나타낸 결과로부터 알 수 있는 바와 같이, 수용성 고분자 물질과 수용성 염기성 유기 화합물의 첨가에 의한 본 발명에 따르는 실시예 1 제제는 비교예 1에 비해 용출을 현저히 증가시켜 난용성 이부프로펜의 용해성 증가를 확인할 수 있었고, 기존의 공지문헌보다 제조공정이 용이하므로 당해 기술 분야에서 명백한 진보성을 제공한다.As can be seen from the results shown in Table 1, the formulation of Example 1 according to the present invention by the addition of a water-soluble high molecular substance and a water-soluble basic organic compound significantly increased dissolution compared to Comparative Example 1, thereby increasing the solubility of poorly soluble ibuprofen. It could be confirmed, and since the manufacturing process is easier than the existing known literature provides a clear advance in the art.
이상 설명하고 실시예를 통하여 알 수 있는 바와 같이, 본 발명의 정제 조성물은 이부프로펜을 수용성 염기성 화합물을 혼합하여 직타하여 경구제형화시키거나, 수용성 고분자물질의 용액과 먼저 혼합하여 흡착시키는 습식공정으로 제제화함으로써 용출성이 향상된 이부프로펜 정제 조성물에 관한 것으로, 제제화시 인습성등의 문제점이 없으며, 지속적이며 높은 용출율을 유지할 수 있는 효과가 있다.As described above and as can be seen through the examples, the tablet composition of the present invention is formulated by oral formulation of ibuprofen by mixing a water-soluble basic compound with orthogonal or by first mixing with a solution of a water-soluble polymer to adsorb it. The present invention relates to an ibuprofen tablet composition having improved dissolution properties, and does not have a problem such as humidity during formulation, and has an effect of maintaining a continuous and high dissolution rate.
Claims (6)
Priority Applications (1)
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KR10-2000-0026677A KR100523242B1 (en) | 2000-05-18 | 2000-05-18 | A tablet composition containing ibuprofen |
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KR10-2000-0026677A KR100523242B1 (en) | 2000-05-18 | 2000-05-18 | A tablet composition containing ibuprofen |
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KR20010105771A true KR20010105771A (en) | 2001-11-29 |
KR100523242B1 KR100523242B1 (en) | 2005-10-24 |
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KR10-2000-0026677A KR100523242B1 (en) | 2000-05-18 | 2000-05-18 | A tablet composition containing ibuprofen |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20040106915A (en) * | 2003-06-05 | 2004-12-20 | 한국유나이티드제약 주식회사 | Formulation and manufacturing process solubilized ibuprofen soft capsules |
CN107198676A (en) * | 2017-06-23 | 2017-09-26 | 江苏神龙药业股份有限公司 | A kind of ibuprofen injection for intravenously administrable |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5028625A (en) * | 1989-06-20 | 1991-07-02 | American Home Products Corporation | Acid addition salt of ibuprofen and meglumine |
EP0424028B1 (en) * | 1989-10-17 | 1995-09-27 | Merck & Co. Inc. | S(+)-ibuprofen-L-amino acid and S(+)-ibuprofen-D-amino acid as onset hastened enhanced analgesics |
IT1264856B1 (en) * | 1993-06-21 | 1996-10-17 | Zambon Spa | PHARMACEUTICAL COMPOSITION WITH ANALGESIC ACTIVITY |
DE4444051A1 (en) * | 1994-12-10 | 1996-06-13 | Rhone Poulenc Rorer Gmbh | Pharmaceutical, oral preparation |
GB9603699D0 (en) * | 1996-02-21 | 1996-04-17 | Boots Co Plc | Therapeutic composition |
IT1301966B1 (en) * | 1998-07-30 | 2000-07-20 | Zambon Spa | PHARMACEUTICAL COMPOSITIONS WITH ANALGESIC ACTIVITY |
US6551617B1 (en) * | 2000-04-20 | 2003-04-22 | Bristol-Myers Squibb Company | Taste masking coating composition |
-
2000
- 2000-05-18 KR KR10-2000-0026677A patent/KR100523242B1/en active IP Right Grant
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20040106915A (en) * | 2003-06-05 | 2004-12-20 | 한국유나이티드제약 주식회사 | Formulation and manufacturing process solubilized ibuprofen soft capsules |
CN107198676A (en) * | 2017-06-23 | 2017-09-26 | 江苏神龙药业股份有限公司 | A kind of ibuprofen injection for intravenously administrable |
Also Published As
Publication number | Publication date |
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KR100523242B1 (en) | 2005-10-24 |
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