EP2515862A1 - Rapidly dispersing pharmaceutical formulation with cefdinir - Google Patents
Rapidly dispersing pharmaceutical formulation with cefdinirInfo
- Publication number
- EP2515862A1 EP2515862A1 EP10807505A EP10807505A EP2515862A1 EP 2515862 A1 EP2515862 A1 EP 2515862A1 EP 10807505 A EP10807505 A EP 10807505A EP 10807505 A EP10807505 A EP 10807505A EP 2515862 A1 EP2515862 A1 EP 2515862A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formulation
- cefdinir
- sodium
- formulation according
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 title claims abstract description 50
- 229960003719 cefdinir Drugs 0.000 title claims abstract description 50
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000013543 active substance Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 77
- 238000009472 formulation Methods 0.000 claims description 67
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical group OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 235000002639 sodium chloride Nutrition 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 9
- 229960003324 clavulanic acid Drugs 0.000 claims description 9
- 235000003599 food sweetener Nutrition 0.000 claims description 9
- 230000001105 regulatory effect Effects 0.000 claims description 9
- 239000003765 sweetening agent Substances 0.000 claims description 9
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000013355 food flavoring agent Nutrition 0.000 claims description 6
- 150000004677 hydrates Chemical class 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 239000001509 sodium citrate Substances 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 229960004793 sucrose Drugs 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 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 claims description 4
- 235000015165 citric acid Nutrition 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- -1 glidants Substances 0.000 claims description 4
- 229960001031 glucose Drugs 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- 235000012222 talc Nutrition 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 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 claims description 4
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 4
- 229940038773 trisodium citrate Drugs 0.000 claims description 4
- 235000019263 trisodium citrate Nutrition 0.000 claims description 4
- 235000010493 xanthan gum Nutrition 0.000 claims description 4
- 239000000230 xanthan gum Substances 0.000 claims description 4
- 229920001285 xanthan gum Polymers 0.000 claims description 4
- 229940082509 xanthan gum Drugs 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 229960004106 citric acid Drugs 0.000 claims description 3
- 235000013681 dietary sucrose Nutrition 0.000 claims description 3
- 239000000391 magnesium silicate Substances 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 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 claims description 2
- 206010021531 Impetigo Diseases 0.000 claims description 2
- 206010024971 Lower respiratory tract infections Diseases 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- 206010033078 Otitis media Diseases 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 2
- 208000006311 Pyoderma Diseases 0.000 claims description 2
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 2
- 206010062255 Soft tissue infection Diseases 0.000 claims description 2
- 239000004376 Sucralose Substances 0.000 claims description 2
- 206010046306 Upper respiratory tract infection Diseases 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 claims description 2
- 229960005164 acesulfame Drugs 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 2
- 229940045110 chitosan Drugs 0.000 claims description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 2
- 229960002737 fructose Drugs 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 238000005469 granulation Methods 0.000 claims description 2
- 230000003179 granulation Effects 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 239000000832 lactitol Substances 0.000 claims description 2
- 235000010448 lactitol Nutrition 0.000 claims description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 2
- 229960003451 lactitol Drugs 0.000 claims description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 claims description 2
- 235000019792 magnesium silicate Nutrition 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 239000000845 maltitol Substances 0.000 claims description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 2
- 235000010449 maltitol Nutrition 0.000 claims description 2
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- 229940035034 maltodextrin Drugs 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 2
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 claims description 2
- 239000004223 monosodium glutamate Substances 0.000 claims description 2
- 235000013923 monosodium glutamate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- 235000010235 potassium benzoate Nutrition 0.000 claims description 2
- 239000004300 potassium benzoate Substances 0.000 claims description 2
- 229940103091 potassium benzoate Drugs 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 229960002816 potassium chloride Drugs 0.000 claims description 2
- 239000001508 potassium citrate Substances 0.000 claims description 2
- 229960002635 potassium citrate Drugs 0.000 claims description 2
- 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 claims description 2
- 235000011082 potassium citrates Nutrition 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 208000020029 respiratory tract infectious disease Diseases 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 201000009890 sinusitis Diseases 0.000 claims description 2
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- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
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- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 2
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 2
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- 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 claims description 2
- 229960001790 sodium citrate Drugs 0.000 claims description 2
- 235000011083 sodium citrates Nutrition 0.000 claims description 2
- 229960001462 sodium cyclamate Drugs 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
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- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
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- IPYWNMVPZOAFOQ-NABDTECSSA-N (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;trihydrate Chemical compound O.O.O.S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 IPYWNMVPZOAFOQ-NABDTECSSA-N 0.000 claims 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
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- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
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- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 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 2
- 241000894006 Bacteria Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RTXOFQZKPXMALH-PRHODGIISA-N Cefzon Chemical compound S1C(N)=NC(C(=NO)C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-PRHODGIISA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 229940031908 omnicef Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004562 water dispersible granule Substances 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
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
Definitions
- Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-2- carboxylic acid.
- the molecule which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
- Said formulations dissolve in water without requiring any physical intervention such as stirring, shaking etc. and without effervescence.
- Sweetener which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, sugar, maltose, sorbitol, saccharide, saccharine sodium, saccharose, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
- potassium clavulanate is preferably used with syloid or microcrystalline cellulose in an amount in the ratio of 1 : 1
- cefdinir or its pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal or amorphous forms can be present in an amount in the range of 2-20% by total weight of the unit dose.
- 0-50% of clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof with respect to the total weight of unit dose can be used.
- Another aspect of the present invention relates to use of pharmaceutical composition prepared according to present invention for the manufacture of a medicament for use in treatment or prophylaxis of upper respiratory tract infections such as; ear, throat, nose infections, otitis media, sinusitis, tonsillitis, pharangitis, for lower respiratory tract infections such as; pyelonephrit, cyctit, urteritis, for skin and soft tissue infections such as furoncule, pyoderma, impetigo and for gonore and lyme.
- upper respiratory tract infections such as; ear, throat, nose infections, otitis media, sinusitis, tonsillitis, pharangitis
- lower respiratory tract infections such as; pyelonephrit, cyctit, urteritis, for skin and soft tissue infections such as furoncule, pyoderma, impetigo and for gonore and lyme.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Present invention relates to water dispersible pharmaceutical dosage forms comprising cefdinir as active agent and methods for preparation thereof.
Description
RAPIDLY DISPERSING PHARMACEUTICAL FORMULATION WITH
CEFDINIR
Present invention relates to water dispersible pharmaceutical dosage forms comprising cefdinir as active agent and methods for preparation thereof
Background of the invention
Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-2- carboxylic acid. The molecule which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
ormii
Cefdinir which physically appears as a white powder has very poor solubility in common organic solvents such as methanol, ethanol, and acetonitrile and in water. Due to this property there are some problems while developing formulations comprising this molecule and in the bioavailability of the finished product.
Cefdinir do not dissolve in water and also its wettability is very low, this causes problems while developing water dispersible formulations and also for this reason sefdinir has low bioavailability.
The product sold in the market under the trade name OMNICEF® is present in capsule and suspension forms. Clinic studies show that the bioavailability of the suspension product is 120% more than the bioavailability of the product in capsule form.
Although the suspension forms have higher bioavailability, use of this dosage form especially for pediatric and geriatric patients brings about .the possibility of taking high and/or uncontrolled dose. Additionally, the fact that the suspensions have physical and chemical stability problems, they have short shelf life and high production costs and the fact that they
cause problems while transporting and use are disadvantageous for the manufacturers.
Due to the reasons stated above it is necessary to provide new dosage forms in antibiotic theraphy in order to provide effective dosing, meet patient requirements and to offer different alternatives to patients having special conditions, such as pediatric and geriatric patients. Subject of the present invention is related to cefdinir formulations that disperse in water in less than 10 minutes and that do not comprise dispersing agent or effervescent agent. This way it was aimed to develope cefdinir formulations which disperse in water and provide ease of use for the patients without using dispersing agent and acidic and basic effervescent couple which increases the cost of manufacture. Accordingly present invention relates to cefdinir formulations wherein at least 90% of the formulation dissolve in water in less than 10 minutes.
Said formulations dissolve in water without requiring any physical intervention such as stirring, shaking etc. and without effervescence.
Formulations according to present invention are preferably in sachet form. Cefdinir formulations according to present invention have
• Higher bioavailability since they are used by dissolving in water
• Higher stability since they are packed in solid form in single dose units
• Dose accuracy since they are packed in single dose units,
• Lower cost since they do not comprise effervescent couple and dispersing agent For these reasons, cefdinir formulations according to present invention provide formulating cefdinir, which is a compound that hardly disperse in water and dissolving of at least 90% of said formulation in water in less than 10 minutes.
In another aspect present invention relates to cefdinir formulations wherein at least 90% of said formulation dissolve in water in less than 10 minutes. Accordingly said formulations may comprise pharmaceutically acceptable excipients in addition to cefdinir that is used as active agent.
Said pharmaceutical excipients can be selected from a group comprising sweeteners, pH regulating agents, preserving agents, viscosity agents, glidants, lubricants and flavoring
agents.
Sweetener which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, sugar, maltose, sorbitol, saccharide, saccharine sodium, saccharose, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof. pH regulating agent which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising tribasic calcium phosphate, monosodium glutamate, potassium citrate, sodium citrate, trisodium citrate, sodium hydroxide, dibasic calcium phosphate, monobasic sodium phosphate or combinations thereof.
Preserving agent which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising ascorbic acid, citric acid, malic acid, propionic acid, sodium ascorbate, sodium benzoate or combinations thereof.
Viscosity agent which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, chitosan, colloidal silicon dioxide, gelatine, guar gum, xanthan gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hypromellose, maltodextrin, polyvinyl alcohol or combinations thereof.
Glidant which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising magnesium silicate, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate, or combinations thereof. In pharmaceutical compositions of the present invention preferably colloidal silicon dioxide is used.
Lubricant which can be used in cefdinir formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, can be selected from a group comprising calcium stearate, magnesium stearate, polytethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof. In
pharmaceutical compositions of the present invention preferably magnesium stearate can be used.
In another aspect present invention relates to pharmaceutical formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, comprising cefdinir as active agent and pH regulating agent, sweetener, viscosity agent, lubicant, glidant and preserving agent as excipients.
In another aspect present invention relates to pharmaceutical formulations, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, comprising cefdinir as active agent and combination of saccharose, citric acid, trisodium citrate, xanthan gum, flavoring agents, colloidal silicon dioxide and magnesium stearate as excipients.
Inventors have found that pharmaceutical compositions comprising said excipient combination is effective for preparing formulations wherein at least 90% of said formulation dissolves in water in less than 10 minutes.
In said pharmaceutical composition 20-800 mg of cefdinir or pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
Formulations of the invention, wherein at least 90% of the formulation dissolves in water in less than 10 minutes, may further comprise a second active agent in addition to cefdinir. Said second active agent is preferably clavulanic acid or a pharmaceutically acceptable salt thereof.
Accrodingly in pharmaceutical compositions, wherein at least 90% of the formulation dissolves in water in less than 10 minutes, 50-500 mg of clavulanic acid or pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used. Preferably sodium clavulanate and/or potassium clavulanate is used as the second active agent that is a clavulanic acid derivative
Clavulanic acid and its derivatives (for example potassium clavulanate) are very sensitive to humidity. For this reason, in formulations of the present invention potassium clavulanate can be used with a humidity absorbing agent, wherein ratio of potassium clavulanate to humidity absorbing agent is preferably in the ratio of 1 : 1.
As humidity absorbing agent one or more of agents which can be selected from the group comprising silica, colloidal silica, such as colloidal silica anhydrous, magnesium trisilicate,
powdered cellulose, magnesium oxide, calcium silicate, Syloid®, starch, talk can be used.
In pharmaceutical compositions comprising cefdinir as active agent, wherein 90% of the composition dissolves in water in less than 10 minutes, potassium clavulanate is preferably used with syloid or microcrystalline cellulose in an amount in the ratio of 1 : 1 In pharmaceutical compositions comprising cefdinir as active agent, wherein 90% of the composition dissolves in water in less than 10 minutes, cefdinir or its pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal or amorphous forms can be present in an amount in the range of 2-20% by total weight of the unit dose. In pharmaceutical composition according to present invention 0-50% of clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof with respect to the total weight of unit dose can be used.
In water dispersible cefdinir formulation, wherein at least 90% of the formulation dissolves in water in less than 10 minutes with respect to the total weight of the unit dose; 2-20% of cefdinir or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal/amorphous forms, 0-50% of potassium clavulanate, 0.1-5 % glidant, 0.1-5 % lubricant, % 10-90% sweetener, 0.5-10 pH regulating agent, 0.1-5% viscosity agent, 0.1-10 % flavouring agent can be used.
In another aspect pharmaceutical composition comprising cefdinir, wherein at least 90% of said composition dissolves in less than 10 minutes, can be in the form of water dispersible powder, granule or tablet.
In another aspect present invention relates to processes that can be used for preparation of pharmaceutical compositions comprising cefdinir wherein at least 90% of said composition dissolves in less than 10 minutes. Accordingly, process used in present invention comprises granulation of cefdinir and optionally clavulanic acid or its derivatives with conventional dry and/or wet granulation methods known in the art or mixing cefdinir and clavulanic acid derivative and other excipients with a dry blending method and optionally pressing them in tablet form or preferably packing the formed formulation in sachets.
In another aspect present invention relates to use of pharmaceutical composition prepared according to present invention for the treatment of infections caused by gram positive and gram negative bacteria.
Another aspect of the present invention relates to use of pharmaceutical composition prepared according to present invention for the manufacture of a medicament for use in treatment or prophylaxis of upper respiratory tract infections such as; ear, throat, nose infections, otitis media, sinusitis, tonsillitis, pharangitis, for lower respiratory tract infections such as; pyelonephrit, cyctit, urteritis, for skin and soft tissue infections such as furoncule, pyoderma, impetigo and for gonore and lyme.
Though not limited with these examples, water dispersible formulations according to present invention can be prepared according to the examples given below.
EXAMPLE 1: Formulation and process for preparation of water dispersible powder comprising cefdinir
Water dispersible cefdinir composition according to the present invention is produced by mixing cefdinir, sweetener, pH regulating agent and other excipients in amounts given in the example and sieving them with 1.3 mm sieve. Said composition is optionally compressed in tablet or filled in sachets.
EXAMPLE 2: Formulation and process for preparation of water dispersible granule comprising cefdinir
Water dispersible cefdinir composition according to the present invention is produced by mixing cefdinir, a combination of the mixture of potassium clavulanate:microcrystalline cellulose, sweetener, pH regulating agent and other excipients in amounts given in the example and sieving them with 1.3 mm sieve. Optionally, said composition is compressed in tablet form or filled in sachets
Claims
1. A water dispersible formulation comprising cefdinir characterized in that said compsition does not comprise disintegrant and/or effervescent couple and at least 90% of said composition disperse in water in less than 10 minutes.
2. A formulation comprising cefdinir according to claim 1 wherein said formulation is preferably in sachet form.
3. Water dispersible cefdinir formulation, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, according to claim 1 comprises pharmaceutically acceptable excipients in addition to cefdinir that is used as active agent.
4. A formulation according to claim 3 wherein said pharmaceutical excipients are selected from a group comprising sweeteners, pH regulating agents, preserving agents, viscosity agents, glidants, lubricants and flavoring agents.
5. A formulation according to claim 4 wherein sweetener is selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, sugar, maltose, sorbitol, saccharide, saccharine sodium, saccharose, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
6. A formulation according to claim 4 wherein pH regulating agent is selected from a group comprising tribasic calcium phosphate, monosodium glutamate, potassium citrate, sodium citrate, trisodium citrate, sodium hydroxide, dibasic calcium phosphate, monobasic sodium phosphate or combinations thereof.
7. A formulation according to claim 4 wherein preserving agent is selected from a group comprising ascorbic acid, citric acid, malic acid, propionic acid, sodium ascorbate, sodium benzoate or combinations thereof.
8. A formulation according to claim 4 wherein viscosity agent is selected from a group comprising carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, chitosan, colloidal silicon dioxide, gelatine, guar gum, xanthan gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hypromellose, maltodextrin, polyvinyl alcohol or combinations thereof. *
9. A formulation according to claim 4 wherein glidant is selected from a group comprising magnesium silicate, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate, or combinations thereof.
10. A formulation according to claim 9, wherein glidant is silicon dioxide.
11. A formulation according to claim 4 wherein lubricant is selected from a group comprising calcium stearate, magnesium stearate, polytethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof.
12. A formulation according to claim 11 wherein lubricant is magnesium stearate.
13. A formulation according to claim 4 wherein said formulation comprises cefdinir as active agent and combination of saccharide, citric acid, trisodium citrate, xanthan gum, flavoring agents, silicon dioxide, magnesium stearate as excipients.
14. A formulation according to claim 1 wherein 20-800 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that is used.
15. A formulation according to claim 1-14 wherein said formulation optionally comprises a second active agent in addition to cefdinir.
16. A formulation according to claim 15 wherein second active agent is clavulanic acid or its pharmaceutically acceptable derivatives thereof.
17. A formulation according to claim 16 wherein clavulanic acid is in the form of its pharmaceutically acceptable salts, preferably in the form of potassium and/or sodium salt.
18. A formulation comprising cefdinir according to any of the preceeding claims, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, according to any of the preceding claims comprises 2-20% of cefdinir, 0-50% potassium clavulanate, 0,1-5 % glidant, 0.1-5% lubricant, 10-90% sweetener, 0.5-10% pH regulating agent, 0.1-5% preservative, 0.1-5% viscosity agent and 0.1-10% flavoring agent with respect to the total weight of the unit dose.
19. A process for the preparation of pharmaceutical formulations according to any of the preceding claims, wherein at least 90% of said formulation dissolves in water in less than 10 minutes, comprises granulation of cefixime and optionally clavulanic acid or a derivative thereof or dry blending of cefdinir and optionally clavulanic acid or a derivative thereof together with other excipients and optionally compression of the obtained formulation in tablet form or filling into sachets.
20. A formulation according to any of the preceeding claims wherein said formulation is used for treatment and/or prophylaxis of of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2009/09785A TR200909785A1 (en) | 2009-12-25 | 2009-12-25 | Pharmaceutical compositions containing cefdinir as the active agent. |
| PCT/TR2010/000259 WO2011078829A1 (en) | 2009-12-25 | 2010-12-24 | Rapidly dispersing pharmaceutical formulation with cefdinir |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2515862A1 true EP2515862A1 (en) | 2012-10-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| EP10795487.7A Active EP2515850B1 (en) | 2009-12-25 | 2010-12-03 | Pharmaceutical compositions comprising cefdinir as an active agent |
| EP10807505A Withdrawn EP2515862A1 (en) | 2009-12-25 | 2010-12-24 | Rapidly dispersing pharmaceutical formulation with cefdinir |
| EP10805667.2A Active EP2515860B1 (en) | 2009-12-25 | 2010-12-24 | Improved pharmaceutical compositions comprising cefdinir |
| EP10805546A Withdrawn EP2515857A1 (en) | 2009-12-25 | 2010-12-24 | The production method for effervescent tablet with cefdinir |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
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| EP10795487.7A Active EP2515850B1 (en) | 2009-12-25 | 2010-12-03 | Pharmaceutical compositions comprising cefdinir as an active agent |
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| EP10805667.2A Active EP2515860B1 (en) | 2009-12-25 | 2010-12-24 | Improved pharmaceutical compositions comprising cefdinir |
| EP10805546A Withdrawn EP2515857A1 (en) | 2009-12-25 | 2010-12-24 | The production method for effervescent tablet with cefdinir |
Country Status (3)
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| EP (4) | EP2515850B1 (en) |
| TR (1) | TR200909785A1 (en) |
| WO (4) | WO2011078822A1 (en) |
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| TR201010859A2 (en) * | 2010-11-05 | 2012-05-21 | Bi̇lgi̇ç Mahmut | Tablet forms containing cefdinir. |
| TR201010212A2 (en) * | 2010-12-08 | 2012-06-21 | Bi̇lgi̇ç Mahmut | Solid oral dosage form containing cefdinir. |
| WO2013095313A1 (en) * | 2011-12-19 | 2013-06-27 | Mahmut Bilgic | Pharmaceutical formulations comprising cefdinir |
| CN103637992B (en) * | 2013-12-19 | 2015-04-08 | 石家庄市华新药业有限责任公司 | Cefdinir granular preparation and preparation method thereof |
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| ZA836918B (en) | 1982-09-30 | 1984-05-30 | Fujisawa Pharmaceutical Co | 7-substituted-3-vinyl-3-cephem compounds and processes for the production of the same |
| ATE216887T1 (en) * | 1996-02-29 | 2002-05-15 | Fujisawa Pharmaceutical Co | TABLETS CONTAINING BETA-LACTAM ANTIBIOTIC AND METHOD FOR THE PRODUCTION THEREOF |
| WO2004104010A1 (en) * | 2003-05-20 | 2004-12-02 | Ranbaxy Laboratories Limited | Crystalline form of cefdinir |
| US20050131079A1 (en) * | 2003-12-10 | 2005-06-16 | Pujara Chetan P. | Cefdinir oral suspension |
| WO2006106529A1 (en) * | 2005-04-05 | 2006-10-12 | Lupin Limited | A co-spray dried composition of cefepime with base and process for preparation thereof |
| CN1706389A (en) * | 2005-05-26 | 2005-12-14 | 济南平志医药科技有限公司 | Effervescent cefdinir prepn and its prepn process |
| US20070128268A1 (en) * | 2005-12-07 | 2007-06-07 | Herwig Jennewein | Pharmaceutical compositions comprising an antibiotic |
| US20090275552A1 (en) * | 2006-04-28 | 2009-11-05 | Mahesh Vithalbhai Patel | Therapy for Treating Resistant Bacterial Infections |
| US20080103124A1 (en) * | 2006-10-25 | 2008-05-01 | Astellas Pharma Inc. | Cefdinir-containing pharmaceutical composition |
| DE102007002924A1 (en) * | 2007-01-19 | 2008-07-24 | Bayer Healthcare Ag | ß-lactam-containing formulations with increased stability in aqueous solution |
| CN101352424A (en) * | 2008-09-16 | 2009-01-28 | 天津市中央药业有限公司 | Cefdinir dispersible tablet and preparation method thereof |
-
2009
- 2009-12-25 TR TR2009/09785A patent/TR200909785A1/en unknown
-
2010
- 2010-12-03 EP EP10795487.7A patent/EP2515850B1/en active Active
- 2010-12-03 WO PCT/TR2010/000242 patent/WO2011078822A1/en not_active Ceased
- 2010-12-24 EP EP10807505A patent/EP2515862A1/en not_active Withdrawn
- 2010-12-24 WO PCT/TR2010/000257 patent/WO2011078827A1/en not_active Ceased
- 2010-12-24 WO PCT/TR2010/000261 patent/WO2011078831A1/en not_active Ceased
- 2010-12-24 WO PCT/TR2010/000259 patent/WO2011078829A1/en not_active Ceased
- 2010-12-24 EP EP10805667.2A patent/EP2515860B1/en active Active
- 2010-12-24 EP EP10805546A patent/EP2515857A1/en not_active Withdrawn
Non-Patent Citations (2)
| Title |
|---|
| MARTIN M A ET AL: "INCREASE IN THE ACTIVITY OF THIRD-GENERATION CEPHALOSPORINS IN COMBINATION WITH CLAVULANIC ACID AND SULBACTAM AGAINST BACTEROIDES-FRAGILIS", MEDICAL LABORATORY SCIENCES, ACADEMIC PRESS, LONDON, GB, vol. 47, no. 3, 1 January 1990 (1990-01-01), pages 163 - 167, XP008133356, ISSN: 0308-3616 * |
| See also references of WO2011078829A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011078827A1 (en) | 2011-06-30 |
| EP2515850A1 (en) | 2012-10-31 |
| EP2515857A1 (en) | 2012-10-31 |
| EP2515860B1 (en) | 2015-07-29 |
| TR200909785A1 (en) | 2011-07-21 |
| EP2515850B1 (en) | 2016-06-29 |
| WO2011078829A1 (en) | 2011-06-30 |
| EP2515860A1 (en) | 2012-10-31 |
| WO2011078831A1 (en) | 2011-06-30 |
| WO2011078822A1 (en) | 2011-06-30 |
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