IL44646A - Pharmaceutical tablet comporising penicillins or cephalosporins - Google Patents
Pharmaceutical tablet comporising penicillins or cephalosporinsInfo
- Publication number
- IL44646A IL44646A IL44646A IL4464674A IL44646A IL 44646 A IL44646 A IL 44646A IL 44646 A IL44646 A IL 44646A IL 4464674 A IL4464674 A IL 4464674A IL 44646 A IL44646 A IL 44646A
- Authority
- IL
- Israel
- Prior art keywords
- tablet
- penicillin
- magnesium carbonate
- heavy magnesium
- penicillins
- Prior art date
Links
- 229930182555 Penicillin Natural products 0.000 title claims description 41
- 229930186147 Cephalosporin Natural products 0.000 title claims description 15
- 229940124587 cephalosporin Drugs 0.000 title claims description 15
- 150000001780 cephalosporins Chemical class 0.000 title claims description 15
- 150000002960 penicillins Chemical class 0.000 title claims description 14
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 40
- 239000001095 magnesium carbonate Substances 0.000 claims description 38
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 38
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 28
- 229940049954 penicillin Drugs 0.000 claims description 26
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 24
- -1 alkaline earth metal salt Chemical class 0.000 claims description 13
- 238000007907 direct compression Methods 0.000 claims description 13
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000004615 ingredient Substances 0.000 claims description 10
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 8
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 claims description 7
- 229960000723 ampicillin Drugs 0.000 claims description 7
- 239000011575 calcium Substances 0.000 claims description 7
- 229910052791 calcium Inorganic materials 0.000 claims description 7
- 238000007906 compression Methods 0.000 claims description 7
- 230000006835 compression Effects 0.000 claims description 7
- 229960004273 floxacillin Drugs 0.000 claims description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229960003022 amoxicillin Drugs 0.000 claims description 5
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 5
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 5
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 5
- NONJJLVGHLVQQM-JHXYUMNGSA-N phenethicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C)OC1=CC=CC=C1 NONJJLVGHLVQQM-JHXYUMNGSA-N 0.000 claims description 5
- 229960004894 pheneticillin Drugs 0.000 claims description 5
- 229960003326 cloxacillin Drugs 0.000 claims description 4
- LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 claims description 4
- 229960001585 dicloxacillin Drugs 0.000 claims description 3
- YFAGHNZHGGCZAX-JKIFEVAISA-N dicloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl YFAGHNZHGGCZAX-JKIFEVAISA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 claims description 2
- 229960002588 cefradine Drugs 0.000 claims description 2
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 claims description 2
- 229960004244 cyclacillin Drugs 0.000 claims description 2
- HGBLNBBNRORJKI-WCABBAIRSA-N cyclacillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C1(N)CCCCC1 HGBLNBBNRORJKI-WCABBAIRSA-N 0.000 claims description 2
- 229960002457 epicillin Drugs 0.000 claims description 2
- RPBAFSBGYDKNRG-NJBDSQKTSA-N epicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CCC=CC1 RPBAFSBGYDKNRG-NJBDSQKTSA-N 0.000 claims description 2
- 229960003884 hetacillin Drugs 0.000 claims description 2
- DXVUYOAEDJXBPY-NFFDBFGFSA-N hetacillin Chemical compound C1([C@@H]2C(=O)N(C(N2)(C)C)[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 DXVUYOAEDJXBPY-NFFDBFGFSA-N 0.000 claims description 2
- 229960003806 metampicillin Drugs 0.000 claims description 2
- FZECHKJQHUVANE-MCYUEQNJSA-N metampicillin Chemical compound C1([C@@H](N=C)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 FZECHKJQHUVANE-MCYUEQNJSA-N 0.000 claims description 2
- 229960003342 pivampicillin Drugs 0.000 claims description 2
- ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 claims description 2
- 229960002780 talampicillin Drugs 0.000 claims description 2
- SOROUYSPFADXSN-SUWVAFIASA-N talampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OC2C3=CC=CC=C3C(=O)O2)(C)C)=CC=CC=C1 SOROUYSPFADXSN-SUWVAFIASA-N 0.000 claims description 2
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 3
- 150000001340 alkali metals Chemical class 0.000 claims 3
- ODFHGIPNGIAMDK-NJBDSQKTSA-N azidocillin Chemical compound C1([C@@H](N=[N+]=[N-])C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 ODFHGIPNGIAMDK-NJBDSQKTSA-N 0.000 claims 1
- 229960004328 azidocillin Drugs 0.000 claims 1
- 229960003669 carbenicillin Drugs 0.000 claims 1
- 229940106164 cephalexin Drugs 0.000 claims 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims 1
- SCLZRKVZRBKZCR-SLINCCQESA-M cloxacillin sodium Chemical compound [Na+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl SCLZRKVZRBKZCR-SLINCCQESA-M 0.000 claims 1
- 229960004659 ticarcillin Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 24
- 238000009472 formulation Methods 0.000 description 14
- 238000004090 dissolution Methods 0.000 description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- 239000000945 filler Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- 229920003110 Primojel Polymers 0.000 description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 7
- 239000004141 Sodium laurylsulphate Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 5
- 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 5
- 239000011777 magnesium Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000001509 sodium citrate Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 229920003072 Plasdone™ povidone Polymers 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000019589 hardness Nutrition 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 229960001019 oxacillin Drugs 0.000 description 2
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 241000220479 Acacia Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000350158 Prioria balsamifera Species 0.000 description 1
- JAPODEFAFYXINK-UHFFFAOYSA-K S(=O)(=O)(OCCCCCCCCCCCC)[O-].[Na+].C([O-])([O-])=O.[Mg+2] Chemical compound S(=O)(=O)(OCCCCCCCCCCCC)[O-].[Na+].C([O-])([O-])=O.[Mg+2] JAPODEFAFYXINK-UHFFFAOYSA-K 0.000 description 1
- 241000212342 Sium Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 159000000013 aluminium salts Chemical class 0.000 description 1
- 229910000329 aluminium sulfate Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 229960002543 carfecillin Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- UOVKYUCEFPSRIJ-UHFFFAOYSA-D hexamagnesium;tetracarbonate;dihydroxide;pentahydrate Chemical compound O.O.O.O.O.[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O UOVKYUCEFPSRIJ-UHFFFAOYSA-D 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 235000011160 magnesium carbonates Nutrition 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000025 natural resin Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—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
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- General Health & Medical Sciences (AREA)
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- Oncology (AREA)
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Description
D'i'^'S'JB ηι"?»3ΐοη nwn mnpn m' ao Novel pharmaceutical tablets comprising penicillins or cephalosporins BEECEAM GROUP LIMITED C, 42798 This invention relates to pharmaceut cal tablets. More specifically, this invention relates to pharmaceutical tablets containing high proportions of heavy magnesium carbonate. Such novel tablets may be prepared by direct compression.
The dissolution rate of water soluble, sparingly acid soluble medicaments may be increased at low pH by the addition of an agent capable of increasing the pH of the medium. For example, attempts to formulate benzyl enicil lin in tablets containing calcium carbonate have been made in the hone that the partial neutralisation of stomach acids brought about by action of the calcium carbonate would increase the dissolution rate of benzyl-penicillin. Unfortunately, it has not been possible to form a tablet with various other penicillins such as the isoxazolyl-penicillins together with substantial quantities of calcium carbonate without either (a) using a wet granulation process which may result in possible stability problems; (b) including considerable quantities of tab letting aids or (c) reducing the proportion of the penicillin to an unacceptable amount.
We have n∞ found that if heavy mannesium carbonate BP is used as exci ient, then hard tablets of a penicillin or other medicament may be produced that contain a high proportion of penicillin and further, such tablets disperse in stomach acids in a short period. It has also been discovered that these tablets may be prepared by direct compression without the need for inclusion of large amounts of tablettin! aids. This is particularly surprising in view of the comments by Jaffe and Foss, [J. Amer. Pharm. Assoc., Sci. fid., XLVIII, 26 (1959)] that "Those substances containing the carbonate radical show a poor tendency to form tablets upon direct compression". 44646/2 Direct compression which consists essentially of only mixing and compaction stages offers great economies in terms of time, labour, space, equipment and power when compared to the usual methods of tabletting such as wet granulatio or double compression. Magnesium carbonate appears to be unique in that it is a pH modifying agent that is suitable for inclusion in tablets formed by direc compression. Conventional pH modifiers such as sodium citrate, sodium acetate, sodium carbonate, potassium carbonate, calcium citrate or calcium carbonate are not directly compressible.
The discovery that heavy magnesium carbonat BP is a directly compressible buffer, allows for the simplified manufacture of medicament tablets which benefit from the presence of an acidity reducing or disintegration enhancing substance.
Heavy magnesium carbonate is also known as Magnesii Subcarbonas Ponderosus and is a hydrated basic magnesium carbonate of varying composition corresponding approximately to the formula 3MgC03, Mg(OH)2, H20.
Magnesium carbonate per se (i.e. MgCO^] is not sufficiently compressible for use as sole buffer in the compositions of this invention and light magnesium carbonate BP [i.e. 3MgC03, Mg (OH) 21 3H20] hasr.disadvantageous flow characteristics which prevent it from being used as sole buffer in compositions of this invention.
Accordingly the present i invention provides a pharmaceutical tablet which comprises 10-70% of heavy magnesium carbonate, 44646/2 All percentages used herein are on a weight/weight basis.
When used herein the term "penicillin or cephalosporin" means a semi-synthetic penicillin or cephalosporin which is suitable for oral administration.
Suitable conventional tabletting ingredients for use in the tablets of this invention include lubricants, preservatives, dyes, flavours, fillers, binders, solid organic acids and other conventional agents. In mos applications, fillers and binders are no necessary to form acceptable tablets.
Preservatives and dyes are generally present only in very small quantities, for example, usually less tha 1% in total. The quantities of binders, fillers, flavours and the like, depend upon the nature of the medicament, for example, high potency medicaments frequently require the presence of more fillers and the like than do low potency medicaments. Typical fillers include calcium phosphate, sodium sulphate, starch, silica, lactose, dextrose and the like. Typical binders include natural and synthetic resins such as polyvinylpyrollidone, starches and gums such as acacia and tragacanth.
Most suitably, the penicillin or cephalosporin (which may be in th form of a salt or ester) , is sparingly soluble by which it is meant that it is less than 3% soluble in aqueous hydrochloric acid at pH 1.3 at 37°C.
Preferably, such taHets contain 40-60% of a sparingly soluble penicillin or cephalosporin or a salt of ester thereof, 30-60% of heavy magnesium carbonate and 2-10% of conventional tabletting agents. 44646/2 However, if two or more penicillins or cephalosporins are used in the same tablet, it is frequently advantageous to use higher total quantities of antibiotics and lower total quantities of other materials. For example, especially suitable tablets of this sort comprises 60-85% of penicillin or cephalosporin, 10-20% of heavy magnesium carbonate acid and 2-15% of conventional tabletting agents.
One group of useful penicillins suitable for inclusion in the tablets of the invention are the isoxazolyl penicillins and their salts, for example, cloxacillin, flucloxacillin , dicloxacillin and their alkali and alkaline earth metal salts. Tablets containing carbenicillin esters and ticarcillin esters also benefit from the inclusion of heavy magnesium carbonate.
Heavy magnesium carbonate may be advantageously used when an isoxazolyl or other sparingly soluble penicillin is combined in a tablet with another more soluble penicillin.
Suitable penicillins for inclusion in the tablets of this invention include those of the formulae I and II) : (I) 44646/2 wherein R. is a hydrogen, floorine or chlorine atom, R« is a ■ : 1 . ' . · '■ ' £ phenyl or thienyl group and R- is a hydrocarboyl group such as r * phenyl, tola/1 or indanyl; and their alkali and alkaline earth metal salts.
Such compositions may be present together with other penicillins such as ampicillin or amoxycillin or their pivaloyloxymethyl or phthalyl esters.
Other penicillins and cephalosporins which may be included in the tablets of this invention include phenethicillin, propacillin, azldocillin, hetacillin (a form of ampicillin) , metampicillin (a form of ampicillin), cyclacillin, epicillin, pivampicillin, talampicillin, cephalexihnand cephradine.
If desired, the heavy magnesium carbonate may be replaced by a mixture of heavy magnesium carbonate plus other carbonate in which mixture the heavy magnesium carbonate comprises at least half the ingredients present. Suitable other carbonates include CaCO^, NajGO-j, NaHCO^, MgCO^ and the like. Hie preferred other carbonate to be present is CaCO . This preference exists because the presence of Ca 2+ ions counteracts the light laxative properties of the Mg 2+ ions in the, composition. However, there should be at least 8% of heavy magnesium carbonate present in the tablet.
Thus, another aspect of this invention of great usefulness comprises a tablet containing 30-85% of a penicillin or cephalosporin, 10-70% of heavy magnesium carbonate, 2-35% of calcium carbonate and 0-40% of conventional tabletting agents; the weight of heavy magnesium carbonate present in the tablet being The medicament may be microencapsulated or dispersed in a filler prior to inclusion in the tablet.
In some instances, fillers may be added in addition to the heavy magnesium carbonate. Suitable fillers for such tablets include 3tarch, cellulose, urea (as in Belgian patent specification No. 817515) , glycine, calcium phosphate, sodium sulphate and the like. Glycine, urea and calcium carbonate are particularly useful fillers to be used if it is intended to use more than 10% of fillers in addition to the heavy magnesium carbonate.
The tablets of the present invention nay be prepared by blending together, ingredients in conventional manner and compressing the resulting mixture in a tablet press.
Conventional single or multiple punch presses may be used and generally at conventional pressures.
In one of its broadest process aspect, this invention provides a process for the preparation of a pharmaceutical tablet which comprises 10-35% of heavy magnesium carbonate, 5-85% of penicillin or cephalosporin and 0-40% of conventional tablet ingredients and which process comprises the direc 'compression of a mixture of the blended tablet ingredients.
It will be appreciated that the benefits resulting from the use of a direct compression process are very great in tern>3 of saving on labour, time and equipment so that the process of this invention is of considerable commercial usefulness.
Within the scope of this invention is included the preparation of any of the aforesaid tablets by conventional means and particularly by means of direct compression.
The following Examples Illustrate the Invention :- EXAMPLE 1 Sodium CloxacHHn Microencapsulated with 1% Plasdone K29/33 ["Plasdone" (a Registered Trade Hark) 1s comprised of polyvlnyl-py roll done], showed adequate compresslonal characteristics when mixed with 1/2% aerosll (as flow aid), 1 1/2% magnesium stearnte (as lubricant), 4% primojel (as dlslntegrant) and 15% avicel (as compression aid) but the resulting tablets containing 250 mgs. sodium cloxacllUn failed to dissolve at a satisfactory rate at pH * 1.3 [See Table].
However, using heavy magnesium carbonate, the following formulation :- % Sodium CloxacilUn Microcapsules Heavy Magnesium Carbonate Sodium Lauryl Sulphate 1.7 Magnesium Stearate 0.7 Primojel 4.0 was directly compressed at 1200 kg/cm to give tablets of short dissolution time [See Table] and good hardness qualities [14 on Erweka Scale].
Dissolution Rates of 250 mg. Tablets of Example 1 at pH = Ί.3 and 37°C Uhen Measured by a Flask and Stirrer Method at 60 r.p.m.
EXAMPLE 2 Phenethicniin microencapsulated with 1% Plasdone K29/33 was formed into tablets by direct compression at 820 kg/cm . The formulation used was :- % Phenethicillin Microcapsules 49 (= 250 mg. Phenethicillin) Heavy Magnesium Carbonate BP 39 Magnesium Stearate 2 Primojel 8 Sodium Lauryl Sulphate 2 - - S The time for 50% dissolution of the tablets at pH 1. , 3 an 60 r.p.m. stirring was 7 1/2 minutes. In equivalent tablets 1n which the pheneth1c1H1n and magnesium carbonate were replaced by 88% of microencapsulated phenethici llin, the dissolution time under the same conditions was 12 1/2 minutes. The direct compressibility of the two systems was the same.
EXAMPLE 3 Calcium flucloxacilUn was formulated as follows :- % Calcium Flucl oxacillin 52.2 Heavy Magnesium Carbonate 40.8 Sodium Lauryl Sulphate 1.6 Magnesium S tear ate 0.4 Primojel 5.0 This formulation was directly compressible giving hard tablets with a dissolution efficiency (as defined by K.A. Khan and C.T. Rhodes, Pharm. Acta Helv. 47, nage 5941972) of 31%, using a conventional flask and stirrer method at 60 r.p.m., pH 1.2 and 37°C.
[If other buffers e.g. sodium citrate, glycine or calcium carbonate were used In place of the heavy magnesium carbonate, the mixture was no longer directly, compressible. The following formulation was made into tablets using a double compression procedure :- % Calcium FlucloxacilUn 52.1 Sodium Citrate 10.4 Glycine 31.3 Sodium Starch Glycol ate 3.7 Sodium Lauryl Sulphate 1.9 Ma n sium S If a conventional direct compression excipient-di calcium phosphate dihydrate (unir.illed) was used, tablets could be compressed directly . but even with a conventional buffer - sodium citrate, present the · dissolution was still poor e.g. a formulation :- % Calcium FlucloxacllUn ^ 61.8 Sodium Citrate 12.3 Dicaldum Phosphate 18.6 Sodium Lauryl Sulphate 2.2 Prirnojel 4.4 Mannesium Stearate 0.7 had a dissolution efficiency of 3.9% at 100 r.p.m. ].
EXAMPLE 4 Heavy magnesium carbonate BP may be advantageously used in formulations where two penicillins, one sparingly soluble in acid one more soluble, are combined. The presence of heavy magnesium carbonate both greatly improves the tabletting properties of the formulation and increases the dissolution rate of the total penicillin. An example of such a formulation 1s :- Calcium Flucl oxacillin 32 % Amoxycillin 32 % Heavy Magnesium Carbonate 31 % Magnesium Stearate 1 Prirnojel 4 .1' 44646/2 This formulation 1s directly compressible. Any other salt of flucloxacillln, e.g. the sodium, potassium, magnesium or aluminium salt, could replace the calcium salt 1n this formulation, however, the calcium salt is easiest to compress.
EXAMPLE 5 ' In certain combination tablets, the total tablet weight may limit the amount of heavy magnesium carbonate that can be used 1n the formulation. However, In such formulations, the incorporation of 5-20% heavy magnesium carbonate will greatly Improve the tab letting properties and the disintegration/dissolution rates of the formulation.
Examples of such tablets are :- A% B P Sodium CI oxacillin 40 30 33 Ampi ci 11 i n Tri hydrate 40 42 33 Heavy Magnesium Carbonate 12 20 14 Primojel 4 5 4 Sodium Lauryl Sulphate 2 1 2 Magnesium Stearate 2 2 2 Calcium Carbonate 0 0 8 EXAMPLE 6.
The following tablets could be prepared by direct compression : A¾ B¾ Carbenicillin Phenyl Ester Sodium Salt 59 79 Microcrystalline Cellulose 0 15 Λ Heavy Magnesium Carbonate BP 35 0 Magnesium Stearate 1 1 Sodium Lauryl Sulphate 1 1 Primojel 4 Λ Although both formulations produced tablets with acceptable hardnesses, friabilities, etc., tablet Λ had a much faster dissolution rate than tablet B. Increasing the level f microcrystal line cellulose did not improve the dissolution ratr; of tablet B. '.'hen the tablets were given to hyman volunteers, the tablets containing heavy magnesium carbonate produced almost douMe the cumulative urinary nxcretion of penicillins over the first six hours than did tablet B.
The inclusion of other buffers, e.g. glycine, at sufficient concentrations to attain the same cumulative urinary excrstion of penicillins as tablet A, prevented the tablets being made by direct compression. Very friable, capped tablets were produced after a single compression.
These results clearly show the unique properties of heavy magnesium carbonate In being both a pH modifying agent, increasing the bioavailability of sparingly acid soluble drugs and of also being a directly compressible tablotting excipient.
Example 7 The following tablet was prepared by direct compression % Calcium CI oxacil in 50 (= 250 mg. CI oxacillin) Calcium Carbonate 18.5 Heavy Magnesium Carbonate 25 Magnesium Stearate 0.5 Primojel 5.0 Sodium Lauryl Sulphate 1.0 44646
Claims (17)
1. A pharmaceutical tablet which comprises 10-70$ of heavy magnesium carbonate, 30-85$ of penicillin or cephalosporin as hereinbefore defined and 0-40$ of conventional tabletting ingredients.
2. A tablet as in Claim 1 which comprises 40-60$ of a sparingly soluble penicillin or cephalosporin as hereinbefore defined, 30-60$ of heavy magnesium carbonate and 0-10$ of conventional tabletting ingredients.
3. A tablet as in Claims 1 or 2 which comprises 30-85$ of penicillin or cephalosporin, 10-68$ of heavy magnesium carbonate, 2-35$ of calcium carbonate and 0-40$ of conventional tabletting ingredients; the weight of heavy magnesium carbonate present in the tablet being at least as great as the weight of calcium carbonate present.
4. A tablet as in Claim 2 or 3 wherein the penicillin is cloxacillin, flucloxacillin, dicloxacillin or an alkali metal or alkaline earth metal salt thereof.
5. A tablet as in Claim 2 or 3 wherein the penicillin is an a ester of carbenicillin or ticarcillin or an alkali metal or alkaline earth metal salt thereof.
6. A tablet as in Claim 2 or 3 wherein the penicillin or cephalosporin is phenethicillin, propacillin, azidocillin, hetacillin, metampicillin, 44646/3 cyclacillin, epicillin, pivampicillin , talampicillin, cephalexin and cephradine.
7. A tablet as in Claim 2 or 3 in vhich tvo penicillins are present.
8. A tablet as in Claim 7 vhich comprises 60-85 of penicillin, 10-20$ of heavy magnesium carbonate, 2-10$ "of calcium carbonate and 2-15$ of conventional tabletting ingredients.
9. A tablet as. in Claims 7 or 8 vherein one of the penicillins is cloxacillin, flucloxacillin, dicloxacillin or an alkali metal or alkaline earth metal salt, thereof and the other penicillin is ampicillin, amoxycillin, arapicillin pivaloyloxymethyl ester, or a salt thereof or ampicillin phthalyl ester or a salt thereof.
10. A tablet as in Claim 9 vherein one of the penicillins is an alkaline earth metal salt of cloxacillin or flucloxacillin.
11. A tablet as in Claim 10 vherein the second penicillin is ampicillin or amoxycillin.
12. A tablet as in Claim 9 vherein one penicillin is sodium cloxacillin and the other penicillin is -ampicillin.
13. A tablet as in Claim 9 vherein one penicillin is calcium flucloxa-cillin and the other penicillin is amoxycillin. 44646
14. A process for the preparation of a tablet as in any of Claims 1-13 which process comprises the blending of the ingredients followed by compression.
15. A process as in Claim 14 which comprises direct compression.
16. A tablet as in any of Claims 1-13 and substantially as described in any of the Examples herein.
17. A tablet as in any of Claims 1-13 whenever prepared by direct compression.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2150273A GB1422176A (en) | 1973-05-05 | 1973-05-05 | Pharmaceutical tablets |
| GB5685873 | 1973-12-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL44646A0 IL44646A0 (en) | 1974-06-30 |
| IL44646A true IL44646A (en) | 1977-04-29 |
Family
ID=26255363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL44646A IL44646A (en) | 1973-05-05 | 1974-04-16 | Pharmaceutical tablet comporising penicillins or cephalosporins |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5714649B2 (en) |
| CA (1) | CA1018890A (en) |
| DE (1) | DE2421273A1 (en) |
| DK (1) | DK145712C (en) |
| FR (1) | FR2227856B1 (en) |
| GB (1) | GB1422176A (en) |
| IE (1) | IE39216B1 (en) |
| IL (1) | IL44646A (en) |
| NL (1) | NL7406023A (en) |
| SE (1) | SE402405B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH647676A5 (en) * | 1978-12-22 | 1985-02-15 | Donald E Panoz | ORAL, PROGRAM RELEASED GALENIC FORMS AND METHODS OF PREPARING THE SAME. |
| DE3239592C2 (en) * | 1982-10-26 | 1986-10-30 | Institut organičeskogo sinteza Akademii Nauk Latvijskoj SSR, Riga | Antibacterial drug |
| ES2019583B3 (en) * | 1985-10-19 | 1991-07-01 | Beecham Group Plc | COMPOSITION FOR THE TREATMENT OF INFECTIONS. |
| US6749864B2 (en) | 1986-02-13 | 2004-06-15 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| CA1327010C (en) * | 1986-02-13 | 1994-02-15 | Tadashi Makino | Stabilized solid pharmaceutical composition containing antiulcer benzimidazole compound and its production |
| US5433959A (en) * | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US4743450A (en) * | 1987-02-24 | 1988-05-10 | Warner-Lambert Company | Stabilized compositions |
| GB9613470D0 (en) | 1996-06-27 | 1996-08-28 | Ciba Geigy Ag | Small solid oral dosage form |
| IS7724A (en) * | 2005-03-02 | 2006-09-03 | Actavis Group | Composition of tablets with rapid decomposition containing heavy magnesium carbonate |
| EP1728511A1 (en) * | 2005-05-31 | 2006-12-06 | Faust Pharmaceuticals | New use of phenethicillin and salts thereof. |
| WO2011095269A2 (en) * | 2010-02-03 | 2011-08-11 | Merck Patent Gmbh | Directly compressible magnesium hydroxide carbonate |
| US20140065220A1 (en) * | 2011-03-17 | 2014-03-06 | Kyowa Chemical Industry Co., Ltd. | Binder for forming tablets |
-
1973
- 1973-05-05 GB GB2150273A patent/GB1422176A/en not_active Expired
-
1974
- 1974-04-16 IL IL44646A patent/IL44646A/en unknown
- 1974-04-17 IE IE803/74A patent/IE39216B1/en unknown
- 1974-04-26 SE SE7405687A patent/SE402405B/en unknown
- 1974-04-26 FR FR7414543A patent/FR2227856B1/fr not_active Expired
- 1974-05-02 DE DE2421273A patent/DE2421273A1/en not_active Withdrawn
- 1974-05-03 CA CA198,938A patent/CA1018890A/en not_active Expired
- 1974-05-03 NL NL7406023A patent/NL7406023A/xx not_active Application Discontinuation
- 1974-05-03 DK DK243274A patent/DK145712C/en not_active IP Right Cessation
- 1974-05-07 JP JP5066074A patent/JPS5714649B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2227856B1 (en) | 1978-02-03 |
| DK145712B (en) | 1983-02-07 |
| NL7406023A (en) | 1974-11-07 |
| SE402405B (en) | 1978-07-03 |
| GB1422176A (en) | 1976-01-21 |
| IE39216L (en) | 1974-11-05 |
| JPS5029732A (en) | 1975-03-25 |
| IL44646A0 (en) | 1974-06-30 |
| IE39216B1 (en) | 1978-08-30 |
| DK145712C (en) | 1983-07-25 |
| AU6853574A (en) | 1975-11-06 |
| FR2227856A1 (en) | 1974-11-29 |
| CA1018890A (en) | 1977-10-11 |
| JPS5714649B2 (en) | 1982-03-25 |
| DE2421273A1 (en) | 1974-11-14 |
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