WO1994010994A1 - Compositions effervescentes de sel d'ibuprofene - Google Patents
Compositions effervescentes de sel d'ibuprofene Download PDFInfo
- Publication number
- WO1994010994A1 WO1994010994A1 PCT/EP1993/003207 EP9303207W WO9410994A1 WO 1994010994 A1 WO1994010994 A1 WO 1994010994A1 EP 9303207 W EP9303207 W EP 9303207W WO 9410994 A1 WO9410994 A1 WO 9410994A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- isobutylphenyl
- propionic acid
- pharmaceutically acceptable
- microns
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 94
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical class CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000002253 acid Substances 0.000 claims abstract description 35
- 239000013078 crystal Substances 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 239000000843 powder Substances 0.000 claims abstract description 19
- 239000007916 tablet composition Substances 0.000 claims abstract description 19
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 239000004141 Sodium laurylsulphate Substances 0.000 claims abstract description 10
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 8
- 239000000314 lubricant Substances 0.000 claims abstract description 6
- 239000002831 pharmacologic agent Substances 0.000 claims abstract description 6
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 4
- 239000004615 ingredient Substances 0.000 claims description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 8
- PTTPUWGBPLLBKW-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound [Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 PTTPUWGBPLLBKW-UHFFFAOYSA-M 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 239000003434 antitussive agent Substances 0.000 claims description 3
- 229940124584 antitussives Drugs 0.000 claims description 3
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 3
- 239000000850 decongestant Substances 0.000 claims description 3
- 239000003172 expectorant agent Substances 0.000 claims description 3
- 230000003419 expectorant effect Effects 0.000 claims description 3
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 2
- 206010037660 Pyrexia Diseases 0.000 claims description 2
- 230000001387 anti-histamine Effects 0.000 claims description 2
- 229960004126 codeine Drugs 0.000 claims description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 229960003908 pseudoephedrine Drugs 0.000 claims description 2
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims description 2
- 229960001680 ibuprofen Drugs 0.000 abstract description 15
- 206010011224 Cough Diseases 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 30
- VTGPMVCGAVZLQI-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate;dihydrate Chemical compound O.O.[Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 VTGPMVCGAVZLQI-UHFFFAOYSA-M 0.000 description 23
- 239000007787 solid Substances 0.000 description 9
- -1 alkali metal salts Chemical class 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 7
- 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 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960004543 anhydrous citric acid Drugs 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 150000005323 carbonate salts Chemical class 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000002516 radical scavenger Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000007911 effervescent powder Substances 0.000 description 2
- 239000007938 effervescent tablet Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 description 1
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- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- PTUSXMWNCXRKAX-UHFFFAOYSA-N 2-(1h-inden-1-yl)acetic acid Chemical class C1=CC=C2C(CC(=O)O)C=CC2=C1 PTUSXMWNCXRKAX-UHFFFAOYSA-N 0.000 description 1
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- JTOUASWUIMAMAD-UHFFFAOYSA-N 7-[2-hydroxy-3-[4-(3-phenylsulfanylpropyl)piperazin-1-yl]propyl]-1,3-dimethylpurine-2,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CC(O)CN(CC1)CCN1CCCSC1=CC=CC=C1 JTOUASWUIMAMAD-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
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- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- 229960002698 oxatomide Drugs 0.000 description 1
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- CNDQSXOVEQXJOE-UHFFFAOYSA-N oxyphenbutazone hydrate Chemical compound O.O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 CNDQSXOVEQXJOE-UHFFFAOYSA-N 0.000 description 1
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- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
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- IZRPKIZLIFYYKR-UHFFFAOYSA-N phenyltoloxamine Chemical compound CN(C)CCOC1=CC=CC=C1CC1=CC=CC=C1 IZRPKIZLIFYYKR-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
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- 229960000851 pirprofen Drugs 0.000 description 1
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- UZXRQGSKGNYWCP-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzenesulfonate hydrate Chemical compound O.[K+].COc1cc(ccc1O)S([O-])(=O)=O UZXRQGSKGNYWCP-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
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- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- CYMJPJKHCSDSRG-UHFFFAOYSA-N pyrazolidine-3,4-dione Chemical class O=C1CNNC1=O CYMJPJKHCSDSRG-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 235000019613 sensory perceptions of taste Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229950003911 setastine Drugs 0.000 description 1
- VBSPHZOBAOWFCL-UHFFFAOYSA-N setastine Chemical compound C=1C=CC=CC=1C(C=1C=CC(Cl)=CC=1)(C)OCCN1CCCCCC1 VBSPHZOBAOWFCL-UHFFFAOYSA-N 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000035923 taste sensation Effects 0.000 description 1
- 229950004607 tazifylline Drugs 0.000 description 1
- 229950005829 temelastine Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 229950010257 terpin Drugs 0.000 description 1
- RBNWAMSGVWEHFP-WAAGHKOSSA-N terpin Chemical compound CC(C)(O)[C@H]1CC[C@@](C)(O)CC1 RBNWAMSGVWEHFP-WAAGHKOSSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- GUHPRPJDBZHYCJ-UHFFFAOYSA-N tiaprofenic acid Chemical compound S1C(C(C(O)=O)C)=CC=C1C(=O)C1=CC=CC=C1 GUHPRPJDBZHYCJ-UHFFFAOYSA-N 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 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
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
Definitions
- compositions for oral administration comprising water soluble pharmaceutically acceptable salts of 2-(4- isobutylphenyDpropionic acid and stereoisomers thereof.
- the compositions of the invention effervesce when added to water to form an aqueous solution of the pharmaceutically acceptable salt of 2- (4- isobutylphenyDpropionic acid.
- Racemic 2- (4-isobutylphenyl)propionic acid which is also known as ibuprofen, is a well known medicament with anti-inflammatory, antipyretic and analgesic activities.
- Known uses of 2-(4-isobutylphenyl)propionic acid include the treatment of pain and inflammation in musculoskeletal disorders such as rheumatic disease, and the treatment of pain in a variety of other disorders, for example headache, neuralgia and dys enorrhoea.
- 2- (4-Isobutylphenyl)propionic acid contains a single chiral centre at an asymmetrically substituted carbon atom, and therefore exists in two enantiomeric forms: S(+)2- (4-isobutylphenyl)propionic acid (dexibuprofen) and R(-)2-(4-isobutylphenyDpropionic acid. It will be understood that the term 2- (4- isobutylphenyDpropionic acid as used herein includes either enantiomer separately or any mixture thereof including a racemic mixture.
- Aqueous solutions of 2- ( -isobutylphenyDpropionic acid salts are convenient in use and are advantageous for those patients, often children and the elderly, who have difficulty in swallowing tablets or capsules.
- 2 - (4-IsobutylphenyDpropionic acid particularly when present in its free acid form or in an aqueous suspension has an unpleasant taste with a burning sensation in the throat. Therefore, it is an object of the present invention to produce a powder or tablet composition containing a 2- (4-isobutylphenyl)propionic acid salt which effervesces when added to water to produce a clear solution, and which has no unpleasant taste sensation and to provide a simplified method of producing the same.
- 2-(4-IsobutylphenyDpropionic acid salts may be produced by reaction between 2- (4-isobutylphenyl) - propionic acid and the corresponding base followed by crystallisation of the required salt.
- 2- (4-isobutylphenyl) - propionic acid For example reacting sodium hydroxide with 2- (4-isobutylphenyl) - propionic acid produces sodium 2- (4-isobutylphenyl) - propionate.
- the resulting sodium salt is typically a flaky coarse crystalline solid material, which is milled to produce a finer powder having a crystal size typically less than 100 microns.
- a fine powder was considered necessary for use in simple effervescent compositions as it was believed that a fine powder gave a faster dissolution rate than a material having a larger crystal size which it was thought could not be used directly in simple effervescent compositions.
- Such fine powders are known to be formulated into effervescent tablet compositions, for example in compositions described in the applicant's European Patent Application 0228164.
- a disadvantage of using a fine powder in the production of ibuprofen tablets is that once granulated and dried, a fine powder has a tendency to produce a sticky non flowing mass which will not flow freely into tablet dies and can obstruct the dies.
- an ibuprofen salt which is a fine powder ( ⁇ 100 microns) is a difficult material to handle particularly when tabletting.
- Others have also sought to produce satisfactory effervescent compositions of ibuprofen or a salt thereof.
- European Patent Application 0351353 (Aesculapuis Pharma) and documents on the public file thereof teach that effervescent compositions comprising particular ranges of ingredients of ibuprofen or its sodium salt, sodium bicarbonate and citric acid should be mixed in a particular manner, not being admixed in a single phase. There is no teaching in this document of use of a particular crystal size of ibuprofen or its sodium salt.
- European Patent Application 0369228 discloses a granulated composition requiring various proportions of a water soluble ibuprofen salt, excipient, stabiliser, sodium or potassium carbonate and an acid component.
- This composition comprises many expensive ingredients for example stabilisers such as water soluble polymers.
- stabilisers such as water soluble polymers.
- European Patent Application 0203768 discloses effervescent compositions comprising a pre-blended mixture of a granulated therapeutic agent having a particle size of between 100 and 600 microns and a component of a first effervescent system having a similar particle size, the pre-blend being mixed with a second effervescent system.
- the use of two effervescent systems and the pre-blending of the therapeutic agent results in compositions which are expensive and complicated to prepare.
- the therapeutic agents disclosed include non-steroidal anti-inflammatory drugs such as acetaminophen, aspirin and ibuprofen.
- compositions described in this document do not provide satisfactory effervescent formulations, when ibuprofen is used as the therapeutic agent.
- compositions of the present invention also have the advantage of using inexpensive and readily available ingredients which can simply be blended together in intimate admixture in a single step to form powder or tablet compositions, without requiring complicated processing steps.
- Aqueous solutions formed by the compositions of the present invention contain negligible amounts of 2-(4- isobutylphenyl)propionic acid as its free acid.
- 2-(4- isobutylphenyl)propionic acid as its free acid.
- the unpleasant taste of 2-(4- isobutylphenyDpropionic acid is largely absent from aqueous solutions formed by the compositions of the present invention.
- the present invention provides a pharmaceutical powder or tablet composition
- a pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid as either enantiomer separately or any mixture thereof, in intimate admixture with a pharmaceutically acceptable couple comprising at least one acid component and at least one carbonate component, the couple producing carbon dioxide in the presence of water; in which 95% or more of the 2-(4- isobutylphenyl) -propionic acid salt has a crystal size, as defined hereinafter, from 180 microns to 800 microns; and further in which the carbonate component of the couple is present in an amount from two to six times by weight the amount of acid component of the couple, such that the pH of an aqueous solution formed from 1 g of the composition in 100 ml of purified water is greater than 5.0.
- 2- (4-Isobutylphenyl)propionic acid may form salts with organic or inorganic bases in a conventional manner.
- Particularly suitable salts of 2-(4- isobutylphenyl)propionic acid include, for example, alkali metal salts (such as sodium and potassium salts) , alkaline earth metal salts (such as magnesium and calcium salts), aluminium and ammonium salts, salts with suitable organic bases such as alkylamines, N-methyl-D- glucamine and salts with amino acids such as arginine and lysine. It will be readily understood that these salts may also exist as racemates, separate enantiomers or mixtures thereof.
- 2- (4-isobutylphenyl) - propionic acid salt is defined herein as either enantiomer separately or any mixture thereof including a racemic mixture, of all pharmaceutically acceptable salts of 2-(4-isobutylphenyl)propionic acid that are soluble in water.
- a preferred salt is sodium 2-(4- isobutylphenyDpropionate, more preferably S(-) sodium 2- (4-isobutylphenyDpropionate.
- 2-(4-Isobutylphenyl)propionic acid and its salts may exist in more than one crystal form and references to them herein include each crystal form and mixtures thereof.
- 2-(4-Isobutylphenyl)propionic acid and its salts may also exist in the form of solvates, for example hydrates such as the dihydrate, and references to them herein include each solvate and mixtures thereof.
- the composition of the present invention comprises from about 1% to about 99% (w/w) of the 2- (4-isobutylphenyl)propionic acid salt, more preferably from about 5% to about 30% (w/w) , most preferably from about 5% to about 10% (w/w) .
- ' (w/w) ' signifies that the percentages referred to are the percentage weight (or mass) of the ingredient relative to the total weight (or mass) of the composition.
- Pharmaceutically acceptable effervescent couples that produce carbon dioxide in the presence of water may comprise one or more of the following pharmaceutically acceptable acids which are solid at room temperature, for example one or more of the organic acids: citric, tartaric, adipic or malic, together with one or more carbonate component which is defined herein as a pharmaceutically acceptable organic or inorganic carbonate salt which is solid at room temperature, such as one or more of any of the following: sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate.
- the effervescent couple may comprise as each component separately one or more acid and/or one or more carbonate salt, provided the separate acid and/or carbonate salt mixtures are blended to be homogeneous.
- the composition comprises one acid as the acid component and one carbonate salt as the carbonate component, more preferably one acid component and one carbonate component.
- the composition may comprise from about 40% to about 99% (w/w) couple ingredients, more preferably from about 50% to about 95% (w/w) , most preferably from about 75% to about 95% (w/w) .
- Water soluble salts of 2-(4-isobutylphenyl) - propionic acid can react with the acid component of the couple in the presence of water to precipitate 2- (4- isobutylphenyl)propionic acid. Therefore, to minimise precipitation of 2- (4-isobutylphenyl)propionic acid, the carbonate component and acid component of the couple are present in a respective ratio by weight of from about two to about six, more preferably from about three to about five, most preferably about four.
- about 95% or more of the 2- (4- isobutylphenyl)propionic acid salt has a crystal size from about 250 microns to about 600 microns, more preferably from about 300 microns to about 500 microns.
- Crystal size is defined herein to be the length of a crystal measured along its longest axis. Measurement may be made by any suitable method, for example that described in Example 1, below. The range of crystal sizes of the 2-(4-isobutylphenyl)propionic acid salt can be determined by sieve separation. The crystal sizes can then be measured by microscopic image analysis, in comparison with standards supplied by the National Physics Laboratory.
- the pH of an aqueous solution formed from the composition of the present invention at a concentration of about 1 g of the composition in about 100 ml of purified water is greater than about 5.0, more preferably from about 6.0 to about 9.0, most preferably from about 7.0 to about 8.0.
- the composition of the present invention is a tablet
- the composition comprises a pharmaceutically acceptable surface active agent preferably from a trace amount to about 10% (w/w) , more preferably from about 0.01% to about 5% (w/w), most preferably from about 0.1% to about 1% (w/w) .
- the surface active agent used in the above tablet composition may ionic or non-ionic. Such an agent is present to disperse the active ingredient within the tablet and to prevent grit forming at the surface of the tablet.
- the surface active agent may have the function of a lubricant or alternatively a separate lubricant may be added.
- the surface active agent may be a solid or liquid and one or more surface active agents can be used.
- a suitable surface active agent which also acts as lubricant, is sodium lauryl sulphate.
- a tablet composition of the present invention comprises from a trace amount to about 10% (w/w) of a separate lubricant, more preferably from about 0.01% to about 5% (w/w), most preferably from about 0.1% to about 1% (w/w).
- ingredients which may be added to a powder or tablet composition of the present invention include; intense sweeteners such as aspartame, or saccharin, flavour components for example mints such as peppermint; colorants for example brilliant blue FC1 or Cl food blue (as identified in the standard colour index book) ; and to a tablet composition, compression agents such as sorbitol or lactose which increase the hardness of the tablet.
- intense sweeteners such as aspartame, or saccharin
- flavour components for example mints such as peppermint
- colorants for example brilliant blue FC1 or Cl food blue (as identified in the standard colour index book)
- compression agents such as sorbitol or lactose which increase the hardness of the tablet.
- the type and quantity of such ingredients are selected to be readily soluble in water, and to minimise the effect on the pH of the aqueous solution formed when compositions of the invention are added to water.
- these optional ingredients separately comprise from a trace amount to about 20% w/w of the composition, more preferably from
- a further optional component in the compositions of the present invention is a water scavenging agent to absorb any water remaining after the granulation step and prevent premature effervescence of the composition.
- a water scavenging agent may be sodium or potassium carbonate especially if already present in the composition as the carbonate component, in which case no additional water scavenging agent need be added.
- Effervescent compositions of the present invention may optionally comprise other pharmacologically active ingredients and/or enhancing agents compatible with the 2-(4-isobutylphenyl)propionic acid salt.
- the 2-(4-isobutylphenyl)propionic acid salt may be combined with one or more additional pharmacologically active ingredient or ingredients commonly used in cough or cold remedies, selected from; an antihistamine; caffeine and/or another xanthine derivative; a cough suppressant; a decongestant; an expectorant; a muscle relaxant; a further non-steroidal anti-inflammatory drug (hereinafter known as NSAID) other than 2-(4-isobutylphenyl)propionic acid or its salts; and combinations thereof.
- NSAID non-steroidal anti-inflammatory drug
- Suitable antihistamines which are preferably non-sedating include acrivastine, astemizole, azatadine, azelastine, bromodiphenhydramine, brompheniramine, carbinoxamine, cetirizine, chloropheniramine, cyproheptadine , dexbromopheniramine, dexchlorpheniramine, diphenhydramine, ebastine, ketoifen, lodoxamide, loratidine, levelcubastine, equitazine, oxatomide, phenindamine, phenyltoloxamine, pyridamine, setastine, tazifylline, warmthlastine, terfenadine, tripelennamine or tripolidine.
- Suitable cough suppressants include caramiphen, codeine or dextromethorphan.
- Suitable decongestants include pseudeoephedrine, phenylpropanolamine and phenylephrine.
- Suitable expectorants include guaifensin, potassium citrate, potassium guaiacolsulphonate, potassium sulphate and terpin hydrate.
- NSAIDs can be classified chemically as derivatives of arylcarboxylic acids, including salicylic and anthranilic acid derivatives; arylalkanoic acids, including arylacetic, arylpropionic, heteroarylacetic, indoleacetic and indenacetic acids; and enolic acids, including pyrazolidinediones and oxicams .
- NSAID when used herein includes, but is not restricted to, the following compounds and pharmaceutically acceptable salts thereof.
- Arylcarboxylic acids salicylic acid, acetylsalicylic acid, diflunisal, chlorine magnesium trisalicylate, salicylate, benorylate, flufenamic acid, mefenamic acid, meclofenamic acid, niflumic acid;
- Arylalkanoic acids diclofenac, fenclofenac, alcofenac, fentaizac, flurbiprofen, ketoprofen, naproxen, fenorprofen, fenburfen, suprofen, indiprofen, tiaprofen acid, benoxaprofen, pirprofen tolmetin, zomepirac, clopinac, indomethacin, sulindac;
- Enolic acids phenylbutazone, oxyphenbutazone, azapropazone, feprazone, piroxicam, isoxicam, sudoxicam.
- compositions according to the present invention may be packaged in any conventional means to protect them from moisture, such as aluminium sachets for powder compositions, or aluminium foil strips for tablet compositions. Tablet compositions may be coated with conventional film or sugar coatings.
- the present invention further comprises a method of making the powder or tablet .
- compositions described herein comprising blending in a single step a water soluble pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid, as either enantiomer or any mixture thereof, having a crystal size from 180 microns to 800 microns with a pharmaceutically acceptable couple comprising at least one acid component and at least one carbonate component to produce a uniform intimately mixed composition; followed by the optional step of adding after the blending step any optional ingredients; followed by the further optional step of compressing the composition in a tablet die to produce tablets.
- the 2-(4- isobutylphenyl)propionic acid salt and/or the two components of the couple may be pregranulated by any convenient method such as wetting. Initial contact between the two components of the couple may produce some slight effervescence in the mixture, which is useful in the production of tablets as it can improve the compressibility of the resultant composition.
- the blended composition thus produced can be optionally granulated (for example by a method such as fluidised bed granulation) to produce a more even particle size, reduce agglomeration and make tabletting the composition easier if tablets are being produced.
- a further aspect of the invention comprises use of the compositions disclosed herein in the treatment of pain and fever, the compositions comprising a therapeutically effective amount of a water soluble pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid, as either enantiomer separately or any mixture thereof.
- compositions of the invention are generally prepared in unit dosage form.
- the unit dosage of the 2- (4-isobutylphenyl)propionic acid salt is from about 50 mg to about 2000 mg.
- the amount of the 2-(4-isobutylphenyl)propionic acid salt is calculated to provide doses equivalent by weight to doses of, for example, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg (preferably 200 mg or 400 mg) of racemic 2- (4-isobutylphenyl)propionic acid.
- the quantity of the 2- (4-isobutylphenyl)propionic acid salt in each dose may be substantially reduced to have equivalent effect to the above mentioned doses of the racemic acid.
- ibuprofen (900 kg) [produced by any convenient method], and flakes of B.P. grade sodium hydroxide (185.5 kg) were dissolved in industrial methylated spirit 600 B.P. (3,078 kg) to give coarse flaky crystals of sodium ibuprofen dihydrate (854 kg) .
- the coarse sodium ibuprofen dihydrate crystals were separated from the reaction mixture, dried and used without further purification as an ingredient in the following composition.
- the crystal shape of sodium ibuprofen was determined by microscopic image analysis to be flat, planar flakes, crystal size being measured in the plane which appears in the microscopic screen, with the crystals lying flat and 95% of the crystals were found to have a size in the range of 180 microns to 630 microns.
- Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
- the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
- the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
- the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- Example 2 Total These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
- the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- Pseudoephedrine hydr ⁇ chloride Anhydrous citric acid Sodium bicarbonate Sodium lauryl sulphate
- Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
- the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- the ibuprofen salt was present at a level equivalent to 100 mg (128 mg) , 200 mg (256 mg) and 400 mg (512 mg) of ibuprofen (mass of salt in parentheses) .
- Example 7
- Example 7 The S(-)sodium ibuprofen dihydrate was produced in a similar manner to that described in Example 1 from pharmaceutical grade S(+) -ibuprofen and had a similar crystal size to the racemic sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
- Each tablet of Example 7 comprised 256 mg of S(-)sodium ibuprofen dihydrate (equivalent to 200 mg of S(+) -ibuprofen) .
- the sodium lauryl sulphate ingredient was omitted from each of Examples 1 to 7 respectively, and granules were prepared as described in Example 1 prior to the tablet compression step, to give respective effervescent powder compositions Examples 8 to 14.
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Abstract
Composition pharmaceutique sous forme de poudre entrant en effervescence lorsqu'elle est ajoutée à de l'eau pour former une solution aqueuse transparente à administration orale. La composition renferme: un sel pharmaceutiquement acceptable soluble dans l'eau d'un acide 2-(4-isobutylphenyl)propionique, en tant que l'un des deux énantiomères, séparément ou sous forme de mélange, en combinaison intime avec un couple pharmaceutiquement acceptable comprenant au moins un composant acide et un composant carbonate, ce couple produisant du dioxyde de carbone en présence d'eau; dans cette composition, une proportion de l'ibuprofène égale à 95 % ou plus présente une dimension des cristaux comprise entre 180 et 800 microns et son composant carbonate est présent sous une quantité comprise entre deux et six fois la quantité du composant acide, de telle sorte que le pH de la solution aqueuse élaborée avec 1 gramme de la composition de 100 ml est supérieure à 5,0. L'invention porte sur une telle composition de comprimés renfermant en outre un agent tensioactif pharmaceutiquement acceptable, tel que du sulphate de lauryle de sodium et, facultativement, un lubrifiant. Cette composition effervescente peut en outre contenir des ingrédients pharmacologiquement actifs employés couramment pour soigner les rhumes et les refroidissements.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU54660/94A AU5466094A (en) | 1992-11-16 | 1993-11-16 | Ibuprofen salt effervescent compositions |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB929224021A GB9224021D0 (en) | 1992-11-16 | 1992-11-16 | Effervescent compositions |
GB9224021.7 | 1992-11-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994010994A1 true WO1994010994A1 (fr) | 1994-05-26 |
Family
ID=10725176
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1993/003207 WO1994010994A1 (fr) | 1992-11-16 | 1993-11-16 | Compositions effervescentes de sel d'ibuprofene |
Country Status (4)
Country | Link |
---|---|
AU (1) | AU5466094A (fr) |
GB (1) | GB9224021D0 (fr) |
WO (1) | WO1994010994A1 (fr) |
ZA (1) | ZA938539B (fr) |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995034284A1 (fr) * | 1994-06-15 | 1995-12-21 | Gerhard Gergely | Preparation pharmaceutique comportant un principe actif hydrophobe et un systeme effervescent, et procede de fabrication de ladite preparation |
EP0748628A3 (fr) * | 1995-06-13 | 1997-04-23 | American Home Prod | Compositions orales contenant de l'S(+)-étodolac |
EP0753296A3 (fr) * | 1995-06-13 | 1997-04-23 | American Home Prod | Compositions orales, contenant de l'S(+)-ibuprofène |
EP0769294A1 (fr) * | 1995-10-17 | 1997-04-23 | RECKITT & COLMAN PRODUCTS LIMITED | Solutions aqueuses masquant le goût contenant du menthol |
WO1999049843A1 (fr) * | 1998-03-31 | 1999-10-07 | Asta Medica Aktiengesellschaft | Formulations solides et a decomposition rapide contenant de la cetirizine |
US6284271B1 (en) | 1997-07-01 | 2001-09-04 | Astrazeneca Ab | Multiple unit effervescent dosage form |
WO2002083105A3 (fr) * | 2001-04-10 | 2003-04-10 | Zagros Pharma Inc | Composition pour une meilleure absorption d'anti-inflammatoires non steroidiens |
WO2004066978A1 (fr) * | 2003-01-23 | 2004-08-12 | The Procter & Gamble Company | Compositions pharmaceutiques en poudre |
WO2004069132A3 (fr) * | 2003-02-06 | 2004-10-28 | Gebro Pharma Gmbh | Preparations pharmaceutiques et leur procede de production |
JP2006505558A (ja) * | 2002-10-14 | 2006-02-16 | エフ.ホフマン−ラ ロシュ アーゲー | イブプロフェンナトリウムの剤形 |
EP1800667A1 (fr) | 2005-12-23 | 2007-06-27 | Losan Pharma GmbH | Granulate d'ibuprofen solubilisé rapidement |
EP1814512A2 (fr) * | 2004-08-31 | 2007-08-08 | Aristocon Verwaltungs-GmbH | Formes galeniques perorales pour obtenir un effet de retard apres la prise de medicament lors d'un repas |
EP2559430A1 (fr) | 2005-03-22 | 2013-02-20 | Losan Pharma GmbH | Ibuprofen solubilisé |
US20140030326A1 (en) * | 2011-05-18 | 2014-01-30 | Mahmut Bilgic | Effervescent formulations comprising dexketoprofen |
EP2965746A1 (fr) | 2014-07-10 | 2016-01-13 | Santa Farma Ilaç Sanayi A.S. | Composition pharmaceutique orale comprenant de l'ibuprofène, du dihydrate de sodium d'ibuprofène, de l'hydrochlorure de pseudoéphédrine et du maléate de chlorophéniramine |
EP2054367B1 (fr) | 2006-08-22 | 2017-03-22 | SI Group, Inc. | Procédé de préparation de sel de sodium d'ibuprofène à dimensions de particules différentes |
US10471006B2 (en) * | 2017-07-06 | 2019-11-12 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992020334A1 (fr) * | 1991-05-13 | 1992-11-26 | The Boots Company Plc | Composition pharmaceutique comprenant un sel d'ibuprofene |
-
1992
- 1992-11-16 GB GB929224021A patent/GB9224021D0/en active Pending
-
1993
- 1993-11-16 WO PCT/EP1993/003207 patent/WO1994010994A1/fr active Application Filing
- 1993-11-16 AU AU54660/94A patent/AU5466094A/en not_active Abandoned
- 1993-11-16 ZA ZA938539A patent/ZA938539B/xx unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992020334A1 (fr) * | 1991-05-13 | 1992-11-26 | The Boots Company Plc | Composition pharmaceutique comprenant un sel d'ibuprofene |
Cited By (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH686865A5 (de) * | 1994-06-15 | 1996-07-31 | Gergely Gerhard | Pharmazeutische Zubereitung mit einem hydrophoben Wirkstoff und einem Brausesystem, sowie Verfahren zur Herstellung der Zubereitung. |
US5834019A (en) * | 1994-06-15 | 1998-11-10 | Gerhard Gergely | Pharmaceutical formulation containing a hydrophobic active substance and an effervescent system |
WO1995034284A1 (fr) * | 1994-06-15 | 1995-12-21 | Gerhard Gergely | Preparation pharmaceutique comportant un principe actif hydrophobe et un systeme effervescent, et procede de fabrication de ladite preparation |
EP0748628A3 (fr) * | 1995-06-13 | 1997-04-23 | American Home Prod | Compositions orales contenant de l'S(+)-étodolac |
EP0753296A3 (fr) * | 1995-06-13 | 1997-04-23 | American Home Prod | Compositions orales, contenant de l'S(+)-ibuprofène |
EP0769294A1 (fr) * | 1995-10-17 | 1997-04-23 | RECKITT & COLMAN PRODUCTS LIMITED | Solutions aqueuses masquant le goût contenant du menthol |
US6284271B1 (en) | 1997-07-01 | 2001-09-04 | Astrazeneca Ab | Multiple unit effervescent dosage form |
WO1999049843A1 (fr) * | 1998-03-31 | 1999-10-07 | Asta Medica Aktiengesellschaft | Formulations solides et a decomposition rapide contenant de la cetirizine |
US6245353B1 (en) | 1998-03-31 | 2001-06-12 | Asta Medica Ag | Solid, rapidly disintegrating cetirizine formulations |
WO2002083105A3 (fr) * | 2001-04-10 | 2003-04-10 | Zagros Pharma Inc | Composition pour une meilleure absorption d'anti-inflammatoires non steroidiens |
JP2006505558A (ja) * | 2002-10-14 | 2006-02-16 | エフ.ホフマン−ラ ロシュ アーゲー | イブプロフェンナトリウムの剤形 |
WO2004066978A1 (fr) * | 2003-01-23 | 2004-08-12 | The Procter & Gamble Company | Compositions pharmaceutiques en poudre |
WO2004069132A3 (fr) * | 2003-02-06 | 2004-10-28 | Gebro Pharma Gmbh | Preparations pharmaceutiques et leur procede de production |
EP1814512A2 (fr) * | 2004-08-31 | 2007-08-08 | Aristocon Verwaltungs-GmbH | Formes galeniques perorales pour obtenir un effet de retard apres la prise de medicament lors d'un repas |
US9205054B2 (en) | 2005-03-22 | 2015-12-08 | Losan Pharma Gmbh | Solubilized ibuprofen |
EP2559430A1 (fr) | 2005-03-22 | 2013-02-20 | Losan Pharma GmbH | Ibuprofen solubilisé |
EP1800667A1 (fr) | 2005-12-23 | 2007-06-27 | Losan Pharma GmbH | Granulate d'ibuprofen solubilisé rapidement |
EP2054367B1 (fr) | 2006-08-22 | 2017-03-22 | SI Group, Inc. | Procédé de préparation de sel de sodium d'ibuprofène à dimensions de particules différentes |
US20140030326A1 (en) * | 2011-05-18 | 2014-01-30 | Mahmut Bilgic | Effervescent formulations comprising dexketoprofen |
US9717692B2 (en) * | 2011-05-18 | 2017-08-01 | Mahmut Bilgic | Effervescent formulations comprising dexketoprofen |
EP2965746A1 (fr) | 2014-07-10 | 2016-01-13 | Santa Farma Ilaç Sanayi A.S. | Composition pharmaceutique orale comprenant de l'ibuprofène, du dihydrate de sodium d'ibuprofène, de l'hydrochlorure de pseudoéphédrine et du maléate de chlorophéniramine |
WO2016007105A1 (fr) | 2014-07-10 | 2016-01-14 | Santa Farma Ilaç Sanayi A. Ş. | Composition pharmaceutique orale comprenant de l'ibuprofène, de l'ibuprofène sodique dihydraté, du chlorhydrate de pseudoéphédrine et du maléate de chlorphéniramine |
US10471006B2 (en) * | 2017-07-06 | 2019-11-12 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
US11026886B2 (en) | 2017-07-06 | 2021-06-08 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
US11642312B2 (en) | 2017-07-06 | 2023-05-09 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
US20230226000A1 (en) * | 2017-07-06 | 2023-07-20 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
US12011504B2 (en) * | 2017-07-06 | 2024-06-18 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
US20240293309A1 (en) * | 2017-07-06 | 2024-09-05 | Marenda Pharmaceuticals Llc | Blend compositions for oral administration as a rapidly dissolving powder and/or suspension |
Also Published As
Publication number | Publication date |
---|---|
AU5466094A (en) | 1994-06-08 |
ZA938539B (en) | 1994-05-23 |
GB9224021D0 (en) | 1993-01-06 |
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