WO2007069874A1 - Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same - Google Patents
Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same Download PDFInfo
- Publication number
- WO2007069874A1 WO2007069874A1 PCT/KR2006/005526 KR2006005526W WO2007069874A1 WO 2007069874 A1 WO2007069874 A1 WO 2007069874A1 KR 2006005526 W KR2006005526 W KR 2006005526W WO 2007069874 A1 WO2007069874 A1 WO 2007069874A1
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- WO
- WIPO (PCT)
- Prior art keywords
- tablet
- solid dispersion
- fused solid
- pharmaceutically acceptable
- oral administration
- Prior art date
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- 239000007962 solid dispersion Substances 0.000 title claims abstract description 65
- 239000004480 active ingredient Substances 0.000 title claims abstract description 48
- 238000002844 melting Methods 0.000 title claims abstract description 19
- 230000008018 melting Effects 0.000 title claims abstract description 18
- 230000002745 absorbent Effects 0.000 claims abstract description 19
- 239000002250 absorbent Substances 0.000 claims abstract description 19
- 238000013270 controlled release Methods 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 25
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 9
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 claims description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 8
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 8
- 229960001680 ibuprofen Drugs 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
- 235000019698 starch Nutrition 0.000 claims description 8
- 150000005846 sugar alcohols Chemical class 0.000 claims description 8
- 229920003169 water-soluble polymer Polymers 0.000 claims description 8
- 229960003428 dexibuprofen Drugs 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 7
- 235000012239 silicon dioxide Nutrition 0.000 claims description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 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 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000000811 xylitol Substances 0.000 claims description 4
- 235000010447 xylitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 4
- 229960002675 xylitol Drugs 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 239000008119 colloidal silica Substances 0.000 claims description 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920000858 Cyclodextrin Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920000161 Locust bean gum Polymers 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 2
- 229940009868 aluminum magnesium silicate Drugs 0.000 claims description 2
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000440 bentonite Substances 0.000 claims description 2
- 229910000278 bentonite Inorganic materials 0.000 claims description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 229940049654 glyceryl behenate Drugs 0.000 claims description 2
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 2
- 229940046813 glyceryl palmitostearate Drugs 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 2
- 229960001545 hydrotalcite Drugs 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 235000010420 locust bean gum Nutrition 0.000 claims description 2
- 239000000711 locust bean gum Substances 0.000 claims description 2
- 229940057948 magnesium stearate Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 2
- 239000011118 polyvinyl acetate Substances 0.000 claims description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 2
- 229960004029 silicic acid Drugs 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- -1 sucrose fatty acid ester Chemical class 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 93
- 238000007922 dissolution test Methods 0.000 description 27
- 238000000338 in vitro Methods 0.000 description 20
- 229940079593 drug Drugs 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 238000007906 compression Methods 0.000 description 13
- 238000004090 dissolution Methods 0.000 description 13
- 230000006835 compression Effects 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 8
- 239000012530 fluid Substances 0.000 description 7
- 230000002496 gastric effect Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000011978 dissolution method Methods 0.000 description 6
- 239000012085 test solution Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 239000007970 homogeneous dispersion Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000005422 blasting Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- HFGHRUCCKVYFKL-UHFFFAOYSA-N 4-ethoxy-2-piperazin-1-yl-7-pyridin-4-yl-5h-pyrimido[5,4-b]indole Chemical compound C1=C2NC=3C(OCC)=NC(N4CCNCC4)=NC=3C2=CC=C1C1=CC=NC=C1 HFGHRUCCKVYFKL-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940102098 revolution Drugs 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940033134 talc Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to a compress tabletting fused solid dispersion comprising an active ingredient having a low melting point, and a tablet for oral administration comprising same.
- Non steroidal anti-inflammatory drugs such as ibuprofen or dexibuprofen (S(+)-ibuprofen) having low melting points, tend to melt by the heat generated during a compress tabletting process, causing the problems of capping and sticking, particularly when the drug content is high.
- a relatively high amount of excipient needs to be used but, in this case, the dosage unit must be increased to achieve an effective plasma concentration of the active ingredient. Accordingly, there have been reported numerous methods for effectively compressing such a low-melting active ingredient into a tablet.
- WO 92/020334 and DE 3,922,441 disclose a pharmaceutical composition comprising an ibuprofen or dexibuprofen salt
- WO 93/004676 discloses a pharmaceutical composition comprising ibuprofen agglomerates using a suspension comprising ibuprofen or a salt thereof, starch, surfactant, water and a solvent.
- WO 95/001781 discloses a method for preparing a bilayer tablet consisting of a rapid release layer and a controlled release layer, wherein the rapid release layer comprises ibuprofen, corn starch, cross-linked polyvinylpyrrolidone, carboxymethyl starch, magnesium stearate, while the controlled release layer comprises ibuprofen, mannitol, hydroxypropylmethyl cellulose, talc, magnesium stearate and colloidal silica.
- the above methods are not to fully satisfactory in solving the problems of capping and sticking that occur during a compression tabletting process.
- a fused solid dispersion comprising an active ingredient having a melting point of 80 ° C or below and a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 mVg.
- a controlled release tablet for oral administration comprising the fused solid dispersion.
- a multilayer tablet for oral administration consisting of a rapid release layer and a controlled release layer containing the fused solid dispersion.
- a process for preparing a tablet for oral administration comprising: (a) heating to melt an active ingredient having a melting point of
- step (b) cooling, drying and pulverizing the fused solid dispersion obtained in step (a) to obtain granules;
- step (c) adding a release-controlling agent or a pharmaceutically acceptable excipient to the granules obtained in step (b) and compressing the resulting mixture into a tablet.
- Fig. 1 the in vitro dissolution profiles of the rapid release tablets prepared in Examples 6 to 10 of the present invention
- Fig. 2 the in vitro dissolution profiles of the controlled release tablet prepared in Example 11 of the present invention as well as those of the bilayer tablets consisting of a rapid release layer and a controlled release layer prepared in Examples 12 and 13 of the present invention;
- Fig. 3 the variation in the in vitro dissolution profile of the tablet prepared in Example 12 of the present invention as function of the rate of the paddle rotation;
- Fig. 4 the in vitro dissolution profiles of the bilayer tablets consisting of a rapid release layer and a controlled release layer prepared in Examples 14 to 16 of the present invention
- Fig. 5 the variation in the in vitro dissolution profile of the tablet prepared in Example 16 of the present invention as function of the rate of the paddle rotation.
- the inventive tablet for oral administration comprises a controlled release tablet comprising a fused solid dispersion containing an active ingredient and a release-controlling agent, a rapid release tablet comprising the fused solid dispersion and a pharmaceutically acceptable excipient, and a multilayer tablet for oral administration having a controlled release layer formed using ingredients for the controlled release tablet and a rapid release layer, using ingredients for the rapid release tablet.
- the fused solid dispersion of the present invention comprises an active ingredient having a melting point of 80 °C or below and one or more pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 mVg.
- the fused solid dispersion may further comprise a tabletting aid selected from the group consisting of a sugar alcohol, a water soluble polymer, an oily base and a mixture thereof.
- the weight ratio of the active ingredient : the pharmaceutically acceptable absorbent : the tabletting aid preferably ranges from 1 : 0.01 ⁇ 3 : 1 ⁇ 2.
- the active ingredient used in the fused solid dispersion has a melting point of 80 °C or below, preferably 50 to 80 ° C, and representative examples of the active ingredient include ibuprofen (melting point : 75 ⁇ 77 “ C), dexibuprofen (melting point : 50 ⁇ 54 " C) or a mixture thereof which are non steroidal anti-inflammatory drugs useful in the treatment of a rheumatoid arthritis
- the pharmaceutically acceptable absorbent used in the fused solid dispersion may be any of those conventionally used in the pharmaceutical field, and representative examples of the absorbent include light anhydrous silicic acid, hydrotalcite, aluminum magnesium silicate, aluminum hydroxide, aluminum silicate, magnesium aluminum methasilicate, bentonite, lactose, dextrin, starch, microcrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, polyethylene glycol, finely- divided cross-linked polyvinylpyrrolidone or a mixture thereof.
- a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 mVg, preferably, 100 to 300 mVg, more preferably, 150 to 250 mVg is used.
- the range of the specific surface area of pharmaceutically acceptable absorbent is less than the lower limit, the capping and sticking problems still occur.
- the weight ratio of the active ingredient and the absorbent may range from 1 :0.01 ⁇ 3, preferably, from 1 :0.1 ⁇ 2.
- the absorbent may be added after heating to melt the active ingredient.
- the inventive fused solid dispersion may further comprise a tabletting aid selected from the group consisting of a sugar alcohol, a water soluble polymer, an oily base and a mixture thereof.
- the weight ratio of the active ingredient : the tabletting aid preferably ranges
- sugar alcohol used in the present invention include xylitol, sorbitol, mannitol and a mixture thereof
- water soluble polymer include hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide, polyvinyl alcohol and a mixture thereof
- oily base include sucrose fatty acid ester, glyceryl behenate, glyceryl palmitostearate, glyceryl monooleate, glyceryl monostearate and a mixture thereof.
- the fused solid dispersion according to the present invention may be prepared using any conventional mixer, preferably a universal mixer or a heat-melt extruder.
- a universal mixer or a heat-melt extruder The method of preparing the fused solid dispersion with a universal mixer or the heat-melt extruder is described in detail as follows:
- the dispersion After shutting down the heater, the dispersion is stirred at room temperature, and the resulting agglomerate is collected and dried by cold blasting to obtain a fused solid dispersion comprising the active ingredient.
- the fused solid dispersion thus obtained is ground with a high-speed grinder and the resulting granules are filtered through No. 14 mesh (1410 ⁇ m) to 20 mesh (850 ⁇ m), preferably 20 mesh (850 ⁇ m) to obtain a fused solid dispersion.
- the active ingredient and the pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 mVg are homogeneously mixed, and the mixture placed in a loading hopper is heated to melt in the hot compression screw chamber, followed of extruding the melt.
- the obtained agglomerate is homogeneously mixed with kneader- mixer, and the mixtures are filtered through a screen to obtain a fused solid dispersion having a uniform size.
- a fused solid dispersion having a uniform size distribution can be obtained.
- a fused solid dispersion having a uniform size distribution can be manufactured by a less time-consuming single process which is conducted by carrying out the inputting, melting and screening of the active ingredients in sequence.
- Various types of tablets such as controlled release tablet, rapid release tablet and multilayer tablet can be prepared by optionally adding a pharmaceutically acceptable excipient to the fused solid dispersion and compressing into a tablet without the use of a cooler.
- the compressed tablet preferably has a hardness in the range from 4 to 16 kp, preferably 8 to 12 kp.
- a controlled release tablet comprises the above-mentioned fused solid dispersion and a release-controlling agent and may further comprises a pharmaceutically acceptable excipient.
- the weight ratio of the fused solid dispersion : the release-controlling agent : the pharmaceutically acceptable excipient ranges from 1 :0.01 ⁇ 3:0 ⁇ 3, and preferably, from l :0.05 ⁇ 2:0.01 ⁇ 2.
- the release-controlling agent for maintaining uniform release rate for a long period of time can be selected from the group consisting of polyethylene oxide having a molecular weight ranging from 10,000 to 9,000,000, hydroxypropylmethyl cellulose having a molecular weight ranging from 1,000 to 4,000,000, hydroxypropyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, xanthan gum, guar gum, locust bean gum, carboxymethyl cellulose and its derivative, methyl cellulose and its derivative, and povidone-polyvinylacetate copolymer having a molecular weight ranging from 2,000 to 2,000,000.
- the weight ratio of the fused solid dispersion : release-controlling agent may range from 1 : 0.01 ⁇ 3, and preferably, from 1 : 0.05 ⁇ 2.
- the controlled release tablet may further comprise a pharmaceutically acceptable excipient.
- the pharmaceutically acceptable excipient used in the present invention may be used any conventional one used in the pharmaceutical field, and representative examples of the pharmaceutically acceptable excipient include a cross-linked polyvinylpyrrolidone, a cross-linked sodium carboxymethyl cellulose, carboxymethyl starch, calcium methacrylate- divinylbenzene copolymer, polyvinyl alcohol, lactose, microcrystalline cellulose and cellulose derivative, starch and its derivative, cyclodextrin and dextrin derivative, pregelatinized starch and its derivative, colloidal silica, magnesium stearate, glyceryl monostearate, sodium stearyl fumarate, talc, and hydrogenated caster oil.
- a cross-linked polyvinylpyrrolidone a cross-linked sodium carboxymethyl cellulose, carboxymethyl starch, calcium methacrylate- divinylbenzene copolymer, polyvinyl alcohol, lactose, microcrystalline cellulose and cellulose derivative, starch and its derivative
- the weight ratio of the fused solid dispersion : the pharmaceutically acceptable excipient may range from 1 : 0 ⁇ 3, and preferably, from 1 : 0.01-2.
- a rapid release tablet comprises the above- mentioned fused solid dispersion, and the above-mentioned pharmaceutically acceptable excipient used in the controlled release tablet.
- the weight ratio of the fused solid dispersion : the pharmaceutically acceptable excipient may range from 1 : 0.05 ⁇ 3, and preferably, from 1 : 0.1-2.
- a multilayer tablet in accordance with the present invention may be prepared by forming a controlled release layer with ingredients of the controlled release tablet and by forming a rapid release layer with ingredients of the rapid release tablet to manipulate the release of the active ingredient.
- the bilayer tablet consisting of the rapid release tablet and the controlled release layer can be prepared by subjecting the ingredient for the rapid release layer to a first tablet compression step, depositing the ingredients for the controlled release layer thereon, and subjecting the resulting mixture to a second tablet compression step.
- the tablet compression process of the controlled release layer does not always have to be carried out after tabletting the rapid release layer.
- the tablet compression of the controlled release layer can be carried out first, and then the granules of the rapid release layer are added thereto, followed of tablet compression.
- the rapid release layer and the controlled release layer can be sequentially or reversely filled, which is compressed into a tablet in one step.
- the multilayer tablet of the present invention can be also prepared as a trilayer tablet consisting of rapid release and controlled release layers.
- the tablet consisting of the rapid release layer and the controlled release layer comprising the same active ingredient according to the present invention is subjected to in vitro release tests in accordance with the paddle method at 100 rpm (Korea pharmacopoeia 8 th ed.
- the span of the release time of the active ingredient of the controlled release layer or the controlled release tablet can be prolonged by controlling the type and amount of excipient used in the controlled release layer.
- the active ingredient of the rapid release layer in the multilayer tablet is released, preferably in amounts corresponding to 1 to 30% within 1 hour, 30 to 70% within 6 hours, 60 to 90% within 12 hours, 80% or more within 24 hours after initiating the test.
- the rapidly-released active ingredient allows the plasma drug concentration to promptly reach the effective treating level while the slowly- released active ingredient can maintain the effective plasma drug concentration during the intended time.
- the pharmaceutically useful tablet according to the present invention is easily prepared without being hindered by such problems as capping and sticking during the course of compression tabletting, which can be effectively implemented in a large- scale manufacturing process.
- Example 1 30O g of dexibuprofen was added to a universal mixer (VERSATILE
- MIXER 250DM-rrs
- DALTON DALTON
- 60 g of light anhydrous silicic acid having a specific surface area of 200 ⁇ 25 mVg was slowly added thereto, and the mixture was stirred for 45 minutes to obtain a homogeneous dispersion ⁇ see Table 1).
- the resulting dispersion was cooled to the room temperature while stirring to obtain a solid dexibuprofen dispersion agglomeration.
- the resulting agglomeration was cooled to the room temperature by cold blasting (30 0 C) for about 2 hours, and the resulting product was then ground with a high-speed grinder.
- the resulting granules were filtered through No. 20 mesh (850 ⁇ m) to obtain a fused solid dispersion.
- a fused solid dispersion was prepared by repeating the procedure of Example 1 except for using 110 g of light anhydrous silicic acid having a specific surface area of 200 ⁇ 25 nn'/g.
- a fused solid dispersion was prepared by repeating the procedure of Example 1 except for using 110 g of light anhydrous silicic acid having a specific surface area of 300 ⁇ 25 ⁇ f/g.
- Example 4 A fused solid dispersion was prepared by repeating the procedure of Example 1 except that 300 g of dexibuprofen and 50 g of xylitol were added to the Universal mixer preheated to 95 °C and melted. 60 g of light anhydrous silicic acid having a specific surface area of 200 ⁇ 25 mVg was slowly added thereto and the mixture was stirred for 45 minutes to obtain a homogeneous dispersion.
- a fused solid dispersion was prepared by repeating the procedure of Example 4 except for using 20 g of hydroxypropylmethyl cellulose instead of 50 g of xylitol.
- Example 2 205 mg of the fused solid dispersion obtained in Example 3 (amount of dexibuprofen : 150 mg per tablet), 10 mg of lactose, 49.7 mg of microcrystalline cellulose, 3.8 mg of cross-linked sodium carboxymethyl cellulose, and 5.1 mg of light anhydrous silicic acid as a pharmaceutically acceptable excipient were mixed together for 60 minutes and 11.4 mg of talc as a lubricant was added thereto. The resulting mixture was stirred for 5 minutes and compressed to a hardness of about 8 to 12 kp to obtain a rectangular rapid release tablet.
- Fused solid dispersions were prepared by repeating the procedure of Example 6 using the component listed in Table 2.
- Test Example 1 In vitro dissolution test of rapid release tablet
- the rapid release tablets prepared in Examples 6 to 10 were each subjected to an in vitro dissolution test based on Korea Food and Drug Administration (KFDA) and Release Guidelines on the drug for oral administration, and the release pattern was analyzed under the following conditions.
- KFDA Korean Food and Drug Administration
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇ 0.5 ° C
- Dissolution method The dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 50 rpm
- inventive rapid release tablet comprising the inventive fused solid dispersion as an active ingredient provides rapid therapeutical effects.
- a controlled release tablet was prepared by repeating the procedure of Example 6 except that the fused solid dispersion, the release-controlling agent, and the lubricant listed in Table 4 were used.
- Test Example 2 In vitro dissolution test of controlled release tablet
- Example 11 The controlled release tablet prepared in Example 11 was subjected to in vitro dissolution test under the following conditions, and the results are shown in Table 5 and Fig. 2.
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇ 0.5 °C
- Dissolution method the dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 100 rpm
- Example 11 slowly released the active ingredient of the controlled release portion over a period of 12 hours.
- Test Example 3 In vitro dissolution test of bilayer tablet (1) In vitro dissolution tests were conducted using the bilayer tablets prepared in Examples 12 and 13 under the following condition, and the results are shown in Table 7 and Fig. 2.
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇ 0.5 ° C
- Dissolution method The dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 100 rpm
- each of the bilayer tablets prepared in Examples 12 and 13 showed that all the active ingredient of the rapid release portion was released, regardless of the amount of the active ingredient, and thereafter, the active ingredient of the controlled release portion was slowly released over a period of 12 hours.
- Test Example 4 In vitro dissolution test of bilayer tablet (1) as function of the rotation number An in vitro dissolution test was conducted using the bilayer tablet prepared in Example 12 under the following conditions, and the results are shown in Table 8 and Fig. 3.
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇ 0.5 ° C
- Dissolution method The dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 50, 100 and 150 rpm
- the tablet rapidly released the drug during the initial 1 hour to provide prompt therapeutical effects, regardless of the rotation speed, and thereafter the tablet displayed a steady release pattern of the drug, suitable for maintaining continuous therapeutical effects.
- Examples 14 to 16 Preparation of bilayer tablet (2) The components of the controlled release listed in Table 9 were subjected to a first tablet compression step to a hardness of about 2 to 3 kp, and then, the rapid release layer was deposited thereon, and the resulting material was subjected to a second tablet compression step to a hardness of about 8 to 12 kp to obtain bilayer tablets.
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇ 0.5 °C
- Dissolution method The dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 100 rpm
- Test Example 6 In vitro dissolution test of bilayer tablet (2) as function of the rotation number
- Test solution The disintegrating-test 2nd method described in Korea pharmacopoeia, pH 6.8 artificial gastric fluid, 900 mL, 37 ⁇
- Dissolution method The dissolution test method described in Korea pharmacopoeia (the paddle method), rotation speed: 50, 100 and 150 rpm
- the tablet rapidly released the drug in the initial 1 hour to provide fast therapeutical effects, followed by a steady release pattern of the drugs suitable for continuously maintaining the therapeutical effect.
- the active ingredient of the rapid release portion was rapidly released within the initial 1 hour to attain an effective blood concentration thereof, exerting fast therapeutical effects.
- the active ingredient of the controlled release portion was slowly released over a period of 12 to 24 hours, thereby maintaining an effective concentration of the drug in the blood at a constant level during the intended time.
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Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/097,299 US20080292702A1 (en) | 2005-12-16 | 2006-12-18 | Solid Dispersion Comprising An Active Ingredient Having A Low Melting Point And Tablet For Oral Administration Comprising Same |
BRPI0619868A BRPI0619868A8 (en) | 2005-12-16 | 2006-12-18 | SOLID DISPERSION COMPRISING AN ACTIVE INGREDIENT HAVING A LOW COMPRESSED MELTING POINT FOR ORAL ADMINISTRATION COMPRISING THE SAME |
ES06824193T ES2429097T3 (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active substance of low melting point and tablet for oral administration comprising it |
AU2006325658A AU2006325658B2 (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
NZ569813A NZ569813A (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and an absorbent, and a tablet for oral administration comprising same |
JP2008545503A JP2009519326A (en) | 2005-12-16 | 2006-12-18 | Molten solid dispersion containing an active ingredient having a low melting point, and tablet for oral administration containing the same |
CA2633266A CA2633266C (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
CN2006800474904A CN101330904B (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
EP06824193.4A EP1968542B1 (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
IL191804A IL191804A0 (en) | 2005-12-16 | 2008-05-29 | Solid dispersion containing an active ingredient and tablets for oral administration containing the same |
NO20083151A NO339674B1 (en) | 2005-12-16 | 2008-07-15 | Process for the preparation of a tablet for oral administration of ibuprofen, dexibuprofen (S (+) - ibuprofen) or a mixture thereof |
HK09105603.9A HK1126671A1 (en) | 2005-12-16 | 2009-06-23 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20050124386 | 2005-12-16 | ||
KR10-2005-0124386 | 2005-12-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007069874A1 true WO2007069874A1 (en) | 2007-06-21 |
Family
ID=38163142
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2006/005526 WO2007069874A1 (en) | 2005-12-16 | 2006-12-18 | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same |
Country Status (15)
Country | Link |
---|---|
US (1) | US20080292702A1 (en) |
EP (1) | EP1968542B1 (en) |
JP (1) | JP2009519326A (en) |
CN (1) | CN101330904B (en) |
AU (1) | AU2006325658B2 (en) |
BR (1) | BRPI0619868A8 (en) |
CA (1) | CA2633266C (en) |
ES (1) | ES2429097T3 (en) |
HK (1) | HK1126671A1 (en) |
IL (1) | IL191804A0 (en) |
NO (1) | NO339674B1 (en) |
NZ (1) | NZ569813A (en) |
RU (1) | RU2403013C2 (en) |
WO (1) | WO2007069874A1 (en) |
ZA (1) | ZA200806138B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101005391B1 (en) * | 2008-07-22 | 2010-12-30 | 한국콜마 주식회사 | Controlled releasing syrup containing dexibuprofen and its manufacturing method |
CN102144982A (en) * | 2011-03-30 | 2011-08-10 | 江苏神龙药业有限公司 | Minodronate tablets and preparation method thereof |
KR101067224B1 (en) * | 2008-07-22 | 2011-09-22 | 한국콜마 주식회사 | Controlled releasing syrup containing ibuprofen and its manufacturing method |
WO2013154511A1 (en) * | 2012-04-13 | 2013-10-17 | Mahmut Bilgic | Film tablet formulations comprising dexibuprofen |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
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US7700652B2 (en) | 2003-09-11 | 2010-04-20 | Xenoport, Inc. | Treating urinary incontinence using prodrugs of GABA analogs |
CN101961306B (en) * | 2009-07-24 | 2011-11-09 | 北京化工大学 | Preparation method of low melting point drug solid dispersion |
CN102406940B (en) * | 2011-11-01 | 2013-07-03 | 温州大学 | Application of nanoscale flaky carboxymethyl starch sodium in solid dispersion |
UY36046A (en) | 2014-03-26 | 2015-10-30 | Millennium Pharm Inc | PHARMACEUTICAL FORMULATIONS, PREPARATION PROCESSES AND METHODS OF USE |
JP6647902B2 (en) * | 2015-10-30 | 2020-02-14 | 株式会社ファンケル | Sustained release granules |
CN106265522A (en) * | 2016-08-30 | 2017-01-04 | 铜陵翔宇商贸有限公司 | Ibuprofen PVP co-precipitation thing and preparation method thereof |
JP7109255B2 (en) * | 2017-05-23 | 2022-07-29 | ライオン株式会社 | Method for producing pulverized material and method for producing tablet |
JP7147262B2 (en) * | 2017-05-23 | 2022-10-05 | 大正製薬株式会社 | solid formulation |
CN110621305A (en) * | 2017-07-24 | 2019-12-27 | 爱科思华制药研发有限责任公司 | High drug loading pharmaceutical composition |
RU2685294C1 (en) * | 2018-05-10 | 2019-04-17 | Общество с ограниченной ответственностью "ДИНОН" (ООО "ДИНОН") | Absorbing compound, method for preparation thereof (versions) and method of removing carbon dioxide from gas mixtures |
CN112263567B (en) * | 2020-10-19 | 2022-05-03 | 南京易亨制药有限公司 | Ibuprofen sustained-release capsule and preparation method thereof |
CN117363320B (en) * | 2023-12-07 | 2024-02-13 | 黑龙江省鑫博鑫交通科技有限公司 | Snow-melting agent for highway and preparation method thereof |
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WO2001041733A2 (en) * | 1999-12-09 | 2001-06-14 | The Boots Company Plc | Compressed tablet composition comprising a nsaid |
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JPS56120616A (en) * | 1980-02-27 | 1981-09-22 | Kaken Pharmaceut Co Ltd | Ibuprofen-containing granule, its preparation, and internal medicine comprising it |
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DE19509807A1 (en) * | 1995-03-21 | 1996-09-26 | Basf Ag | Process for the preparation of active substance preparations in the form of a solid solution of the active substance in a polymer matrix, and active substance preparations produced using this method |
IE80467B1 (en) * | 1995-07-03 | 1998-07-29 | Elan Corp Plc | Controlled release formulations for poorly soluble drugs |
US6391338B1 (en) * | 1995-09-07 | 2002-05-21 | Biovail Technologies Ltd. | System for rendering substantially non-dissoluble bio-affecting agents bio-available |
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GB0113839D0 (en) * | 2001-06-07 | 2001-08-01 | Boots Co Plc | Therapeutic agents |
-
2006
- 2006-12-18 WO PCT/KR2006/005526 patent/WO2007069874A1/en active Application Filing
- 2006-12-18 BR BRPI0619868A patent/BRPI0619868A8/en not_active IP Right Cessation
- 2006-12-18 ZA ZA200806138A patent/ZA200806138B/en unknown
- 2006-12-18 CA CA2633266A patent/CA2633266C/en not_active Expired - Fee Related
- 2006-12-18 JP JP2008545503A patent/JP2009519326A/en active Pending
- 2006-12-18 AU AU2006325658A patent/AU2006325658B2/en not_active Ceased
- 2006-12-18 CN CN2006800474904A patent/CN101330904B/en not_active Expired - Fee Related
- 2006-12-18 RU RU2008129041/15A patent/RU2403013C2/en not_active IP Right Cessation
- 2006-12-18 NZ NZ569813A patent/NZ569813A/en not_active IP Right Cessation
- 2006-12-18 US US12/097,299 patent/US20080292702A1/en not_active Abandoned
- 2006-12-18 ES ES06824193T patent/ES2429097T3/en active Active
- 2006-12-18 EP EP06824193.4A patent/EP1968542B1/en not_active Not-in-force
-
2008
- 2008-05-29 IL IL191804A patent/IL191804A0/en unknown
- 2008-07-15 NO NO20083151A patent/NO339674B1/en not_active IP Right Cessation
-
2009
- 2009-06-23 HK HK09105603.9A patent/HK1126671A1/en not_active IP Right Cessation
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US4867987A (en) * | 1986-06-25 | 1989-09-19 | Mepha Ag | Pharmaceutical product for the sustained release of ibuprofen |
US4806359A (en) * | 1987-04-22 | 1989-02-21 | Mcneilab, Inc. | Iburprofen sustained release matrix and process |
WO2001041733A2 (en) * | 1999-12-09 | 2001-06-14 | The Boots Company Plc | Compressed tablet composition comprising a nsaid |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101005391B1 (en) * | 2008-07-22 | 2010-12-30 | 한국콜마 주식회사 | Controlled releasing syrup containing dexibuprofen and its manufacturing method |
KR101067224B1 (en) * | 2008-07-22 | 2011-09-22 | 한국콜마 주식회사 | Controlled releasing syrup containing ibuprofen and its manufacturing method |
CN102144982A (en) * | 2011-03-30 | 2011-08-10 | 江苏神龙药业有限公司 | Minodronate tablets and preparation method thereof |
CN102144982B (en) * | 2011-03-30 | 2012-12-12 | 江苏神龙药业有限公司 | Minodronate tablets and preparation method thereof |
WO2013154511A1 (en) * | 2012-04-13 | 2013-10-17 | Mahmut Bilgic | Film tablet formulations comprising dexibuprofen |
Also Published As
Publication number | Publication date |
---|---|
AU2006325658A1 (en) | 2007-06-21 |
CN101330904B (en) | 2012-04-18 |
ES2429097T3 (en) | 2013-11-13 |
JP2009519326A (en) | 2009-05-14 |
HK1126671A1 (en) | 2009-09-11 |
CN101330904A (en) | 2008-12-24 |
EP1968542A4 (en) | 2010-06-02 |
AU2006325658B2 (en) | 2010-04-08 |
CA2633266C (en) | 2011-08-02 |
RU2008129041A (en) | 2010-01-27 |
RU2403013C2 (en) | 2010-11-10 |
EP1968542A1 (en) | 2008-09-17 |
IL191804A0 (en) | 2008-12-29 |
ZA200806138B (en) | 2009-11-25 |
EP1968542B1 (en) | 2013-08-14 |
US20080292702A1 (en) | 2008-11-27 |
BRPI0619868A8 (en) | 2016-06-07 |
NZ569813A (en) | 2011-07-29 |
BRPI0619868A2 (en) | 2011-10-25 |
CA2633266A1 (en) | 2007-06-21 |
NO20083151L (en) | 2008-09-05 |
NO339674B1 (en) | 2017-01-23 |
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