OA16372A - Reclaimer machine. - Google Patents
Reclaimer machine. Download PDFInfo
- Publication number
- OA16372A OA16372A OA1201300141 OA16372A OA 16372 A OA16372 A OA 16372A OA 1201300141 OA1201300141 OA 1201300141 OA 16372 A OA16372 A OA 16372A
- Authority
- OA
- OAPI
- Prior art keywords
- pharmaceutical composition
- deferasirox
- composition according
- inhibitor
- sodium
- Prior art date
Links
- -1 ore Substances 0.000 claims abstract description 36
- FMSOAWSKCWYLBB-VBGLAJCLSA-N Deferasirox Chemical compound C1=CC(C(=O)O)=CC=C1N(N\C(N\1)=C\2C(C=CC=C/2)=O)C/1=C\1C(=O)C=CC=C/1 FMSOAWSKCWYLBB-VBGLAJCLSA-N 0.000 claims description 99
- 229960001489 Deferasirox Drugs 0.000 claims description 99
- 239000000203 mixture Substances 0.000 claims description 50
- 239000008194 pharmaceutical composition Substances 0.000 claims description 47
- 239000002245 particle Substances 0.000 claims description 42
- 239000003826 tablet Substances 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 29
- 239000008187 granular material Substances 0.000 claims description 20
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 18
- 239000006185 dispersion Substances 0.000 claims description 18
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 18
- APSBXTVYXVQYAB-UHFFFAOYSA-M Dioctyl sodium sulfosuccinate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 16
- 229960000878 Docusate Sodium Drugs 0.000 claims description 16
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 16
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 16
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 16
- VUKAUDKDFVSVFT-UHFFFAOYSA-N 2-[6-[4,5-bis(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound COC1C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)OC1OC1C(COCC(C)O)OC(OC)C(OCC(C)O)C1OCC(C)O VUKAUDKDFVSVFT-UHFFFAOYSA-N 0.000 claims description 15
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 14
- 206010065973 Iron overload Diseases 0.000 claims description 13
- 229960004793 Sucrose Drugs 0.000 claims description 11
- 239000002002 slurry Substances 0.000 claims description 11
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-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 10
- 239000011230 binding agent Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000007919 dispersible tablet Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 claims description 8
- 239000003381 stabilizer Substances 0.000 claims description 8
- 239000005720 sucrose Substances 0.000 claims description 8
- 229960001375 Lactose Drugs 0.000 claims description 7
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 claims description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 238000003801 milling Methods 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
- XAPRFLSJBSXESP-UHFFFAOYSA-N Oxycinchophen Chemical group N=1C2=CC=CC=C2C(C(=O)O)=C(O)C=1C1=CC=CC=C1 XAPRFLSJBSXESP-UHFFFAOYSA-N 0.000 claims description 5
- 229940032147 Starch Drugs 0.000 claims description 5
- 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 5
- 239000000969 carrier Substances 0.000 claims description 5
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000194 fatty acid Substances 0.000 claims description 5
- 150000004665 fatty acids Chemical class 0.000 claims description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2R,3R,4S,5R,6S)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4S,5R,6R)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 4
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 4
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N Indometacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- SYELZBGXAIXKHU-UHFFFAOYSA-N Lauryldimethylamine oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 claims description 4
- 229920002675 Polyoxyl Polymers 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 3
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 claims description 3
- 229920000858 Cyclodextrin Polymers 0.000 claims description 3
- 229940067606 Lecithin Drugs 0.000 claims description 3
- 239000005913 Maltodextrin Substances 0.000 claims description 3
- 229920002774 Maltodextrin Polymers 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- 235000013681 dietary sucrose Nutrition 0.000 claims description 3
- 150000002334 glycols Chemical class 0.000 claims description 3
- 235000010445 lecithin Nutrition 0.000 claims description 3
- 239000000787 lecithin Substances 0.000 claims description 3
- 229940035034 maltodextrin Drugs 0.000 claims description 3
- 239000006186 oral dosage form Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- GSDSWSVVBLHKDQ-JTQLQIEISA-N (2S)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.0^{5,13}]trideca-5(13),6,8,11-tetraene-11-carboxylic acid Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17 Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 2
- ORFOPKXBNMVMKC-DWVKKRMSSA-O (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-O 0.000 claims description 2
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 claims description 2
- JYCQQPHGFMYQCF-UHFFFAOYSA-N 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCO)C=C1 JYCQQPHGFMYQCF-UHFFFAOYSA-N 0.000 claims description 2
- ZMKGDQSIRSGUDJ-IMVLJIQESA-N 33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone Chemical compound CCCC1NC(=O)C(C(O)C(C)C\C=C\C)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-IMVLJIQESA-N 0.000 claims description 2
- MBGGBVCUIVRRBF-UHFFFAOYSA-N 4-[2-(benzenesulfinyl)ethyl]-1,2-diphenylpyrazolidine-3,5-dione Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 claims description 2
- 239000005541 ACE inhibitor Substances 0.000 claims description 2
- 102000005758 Adenosylmethionine Decarboxylase Human genes 0.000 claims description 2
- 108010070753 Adenosylmethionine Decarboxylase Proteins 0.000 claims description 2
- 229940064005 Antibiotic throat preparations Drugs 0.000 claims description 2
- 229940083879 Antibiotics FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE Drugs 0.000 claims description 2
- 229940042052 Antibiotics for systemic use Drugs 0.000 claims description 2
- 229940042786 Antitubercular Antibiotics Drugs 0.000 claims description 2
- WZPBZJONDBGPKJ-VEHQQRBSSA-N Aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 claims description 2
- 229960003644 Aztreonam Drugs 0.000 claims description 2
- 210000000941 Bile Anatomy 0.000 claims description 2
- 229940112871 Bisphosphonate drugs affecting bone structure and mineralization Drugs 0.000 claims description 2
- 229960000484 Ceftazidime Drugs 0.000 claims description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N Ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 2
- 108010078777 Colistin Proteins 0.000 claims description 2
- 108010036949 Cyclosporine Proteins 0.000 claims description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N Furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
- 229960003883 Furosemide Drugs 0.000 claims description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 2
- 102400000932 Gonadoliberin-1 Human genes 0.000 claims description 2
- 108010084340 Gonadotropin-Releasing Hormone Proteins 0.000 claims description 2
- 229940093922 Gynecological Antibiotics Drugs 0.000 claims description 2
- 102100003684 HPSE Human genes 0.000 claims description 2
- 229940031574 HYDROXYMETHYL CELLULOSE Drugs 0.000 claims description 2
- 229960002182 IMIPENEM Drugs 0.000 claims description 2
- GSOSVVULSKVSLQ-JJVRHELESA-N Imipenem Chemical compound O.C1C(SCCNC=N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 GSOSVVULSKVSLQ-JJVRHELESA-N 0.000 claims description 2
- CBVCZFGXHXORBI-PXQQMZJSSA-N Indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 claims description 2
- 229960000905 Indomethacin Drugs 0.000 claims description 2
- 102000014150 Interferons Human genes 0.000 claims description 2
- 108010050904 Interferons Proteins 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- DMJNNHOOLUXYBV-PQTSNVLCSA-N Meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 claims description 2
- 210000004688 Microtubules Anatomy 0.000 claims description 2
- 102000028664 Microtubules Human genes 0.000 claims description 2
- 108091022031 Microtubules Proteins 0.000 claims description 2
- 229940066429 Octoxynol Drugs 0.000 claims description 2
- 229940056360 Penicillin G Drugs 0.000 claims description 2
- 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 2
- IVBHGBMCVLDMKU-GXNBUGAJSA-N Piperacillin Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 IVBHGBMCVLDMKU-GXNBUGAJSA-N 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 229940068965 Polysorbates Drugs 0.000 claims description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N Probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 claims description 2
- 229960000329 Ribavirin Drugs 0.000 claims description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 2
- 102000000505 Ribonucleotide Reductases Human genes 0.000 claims description 2
- 108010041388 Ribonucleotide Reductases Proteins 0.000 claims description 2
- NCDNCNXCDXHOMX-XGKFQTDJSA-N Ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims description 2
- QWAXKHKRTORLEM-UGJKXSETSA-N Saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 claims description 2
- 229960001852 Saquinavir Drugs 0.000 claims description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N Sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 2
- 102000011096 Somatostatin receptor family Human genes 0.000 claims description 2
- 108050001286 Somatostatin receptor family Proteins 0.000 claims description 2
- 229960003329 Sulfinpyrazone Drugs 0.000 claims description 2
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N Taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims description 2
- 229940024982 Topical Antifungal Antibiotics Drugs 0.000 claims description 2
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 2
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 claims description 2
- 229950002810 Valopicitabine Drugs 0.000 claims description 2
- TVRCRTJYMVTEFS-ICGCPXGVSA-N [(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] (2S)-2-amino-3-methylbutanoate Chemical compound C[C@@]1(O)[C@H](OC(=O)[C@@H](N)C(C)C)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 TVRCRTJYMVTEFS-ICGCPXGVSA-N 0.000 claims description 2
- 239000003655 absorption accelerator Substances 0.000 claims description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 2
- 239000003463 adsorbent Substances 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 150000001298 alcohols Polymers 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000001833 anti-estrogenic Effects 0.000 claims description 2
- 230000000719 anti-leukaemic Effects 0.000 claims description 2
- 230000000340 anti-metabolite Effects 0.000 claims description 2
- 239000002256 antimetabolite Substances 0.000 claims description 2
- 239000003886 aromatase inhibitor Substances 0.000 claims description 2
- 230000003115 biocidal Effects 0.000 claims description 2
- 150000004663 bisphosphonates Chemical class 0.000 claims description 2
- 239000006172 buffering agent Substances 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- 229960001265 ciclosporin Drugs 0.000 claims description 2
- 229960003405 ciprofloxacin Drugs 0.000 claims description 2
- 229960003346 colistin Drugs 0.000 claims description 2
- XDJYMJULXQKGMM-RVYUQJQSSA-N colistin A Chemical compound CC[C@@H](C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O XDJYMJULXQKGMM-RVYUQJQSSA-N 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 108010019249 cyclosporin G Proteins 0.000 claims description 2
- 239000003954 decarboxylase inhibitor Substances 0.000 claims description 2
- 229960003964 deoxycholic acid Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000000328 estrogen antagonist Substances 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 229960002518 gentamicin Drugs 0.000 claims description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims description 2
- 229960001442 gonadorelin Drugs 0.000 claims description 2
- 108010037536 heparanase Proteins 0.000 claims description 2
- 239000003906 humectant Substances 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229960001936 indinavir Drugs 0.000 claims description 2
- 229940079322 interferon Drugs 0.000 claims description 2
- 229940079866 intestinal antibiotics Drugs 0.000 claims description 2
- 150000002617 leukotrienes Chemical class 0.000 claims description 2
- 229960003376 levofloxacin Drugs 0.000 claims description 2
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims description 2
- 229940121386 matrix metalloproteinase inhibitors Drugs 0.000 claims description 2
- 229960002260 meropenem Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 claims description 2
- 229920002113 octoxynol Polymers 0.000 claims description 2
- 229940005935 ophthalmologic Antibiotics Drugs 0.000 claims description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 229960002292 piperacillin Drugs 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229960003081 probenecid Drugs 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrugs Drugs 0.000 claims description 2
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims description 2
- 229960000311 ritonavir Drugs 0.000 claims description 2
- 229960002930 sirolimus Drugs 0.000 claims description 2
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 claims description 2
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 229950006081 taribavirin Drugs 0.000 claims description 2
- 239000003277 telomerase inhibitor Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims 2
- DKOQGJHPHLTOJR-PUIFZAHNSA-N (6R,7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(6,7-dihydro-5H-cyclopenta[b]pyridin-1-ium-1-ylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@@H]1C(N2C(=C(C[N+]=3C=4CCCC=4C=CC=3)CS[C@@H]21)C([O-])=O)=O)C(=O)/C(=N/OC)C1=CSC(N)=N1 DKOQGJHPHLTOJR-PUIFZAHNSA-N 0.000 claims 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N 1,2-ethanediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims 1
- KUXGUCNZFCVULO-UHFFFAOYSA-N 2-(4-nonylphenoxy)ethanol Chemical compound CCCCCCCCCC1=CC=C(OCCO)C=C1 KUXGUCNZFCVULO-UHFFFAOYSA-N 0.000 claims 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N Amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims 1
- 229960000466 CEFPIROME Drugs 0.000 claims 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N Maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims 1
- 229960002285 Methylbenzethonium chloride Drugs 0.000 claims 1
- 108010093965 Polymyxin B Proteins 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 229960004821 amikacin Drugs 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 239000003098 androgen Substances 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- QWZLBLDNRUUYQI-UHFFFAOYSA-M benzyl-dimethyl-[2-[2-[2-methyl-4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]azanium;chloride Chemical compound [Cl-].CC1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 QWZLBLDNRUUYQI-UHFFFAOYSA-M 0.000 claims 1
- 125000002091 cationic group Chemical group 0.000 claims 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- 229920000847 nonoxynol Polymers 0.000 claims 1
- 229920000058 polyacrylate Polymers 0.000 claims 1
- 229960005266 polymyxin B Drugs 0.000 claims 1
- 229920000024 polymyxin B Polymers 0.000 claims 1
- 230000002335 preservative Effects 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 239000003245 coal Substances 0.000 abstract 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 34
- 239000003814 drug Substances 0.000 description 31
- 229940079593 drugs Drugs 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinylpyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 21
- 229960000913 Crospovidone Drugs 0.000 description 20
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 20
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 20
- 229910052742 iron Inorganic materials 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 15
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 15
- 229940016286 microcrystalline cellulose Drugs 0.000 description 15
- 239000008108 microcrystalline cellulose Substances 0.000 description 15
- WSVLPVUVIUVCRA-RJMJUYIDSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol;hydrate Chemical compound O.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 WSVLPVUVIUVCRA-RJMJUYIDSA-N 0.000 description 13
- 229960001021 Lactose Monohydrate Drugs 0.000 description 13
- GUBGYTABKSRVRQ-XLOQQCSPSA-N 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 8
- 239000008213 purified water Substances 0.000 description 8
- PVVVEHXCVQRLOC-AKSHDPDZSA-N (2R,3R,4S,5S,6R)-2-[(2S,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol;dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O.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 PVVVEHXCVQRLOC-AKSHDPDZSA-N 0.000 description 7
- 230000036912 Bioavailability Effects 0.000 description 7
- 230000035514 bioavailability Effects 0.000 description 7
- 235000010980 cellulose Nutrition 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- 239000002105 nanoparticle Substances 0.000 description 7
- 238000005507 spraying Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000005461 lubrication Methods 0.000 description 5
- 210000004369 Blood Anatomy 0.000 description 4
- 229960001681 Croscarmellose Sodium Drugs 0.000 description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004027 cells Anatomy 0.000 description 4
- 239000006184 cosolvent Substances 0.000 description 4
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000002609 media Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000006011 modification reaction Methods 0.000 description 3
- 235000019426 modified starch Nutrition 0.000 description 3
- 239000002159 nanocrystal Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 210000000056 organs Anatomy 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000001519 tissues Anatomy 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- XJKJWTWGDGIQRH-BFIDDRIFSA-N Alginic acid Chemical compound O1[C@@H](C(O)=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](C)[C@@H](O)[C@H]1O XJKJWTWGDGIQRH-BFIDDRIFSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 229940097362 Cyclodextrins Drugs 0.000 description 2
- 229940024583 Exjade Drugs 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229940014259 Gelatin Drugs 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- 206010053317 Hydrophobia Diseases 0.000 description 2
- 210000004185 Liver Anatomy 0.000 description 2
- 239000004368 Modified starch Substances 0.000 description 2
- 241000048284 Potato virus P Species 0.000 description 2
- 208000007056 Sickle Cell Anemia Diseases 0.000 description 2
- 229940005550 Sodium alginate Drugs 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N Stearic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000546 pharmaceutic aid Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- MSXHSNHNTORCAW-UHFFFAOYSA-M sodium 3,4,5,6-tetrahydroxyoxane-2-carboxylate Chemical compound [Na+].OC1OC(C([O-])=O)C(O)C(O)C1O MSXHSNHNTORCAW-UHFFFAOYSA-M 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 230000000087 stabilizing Effects 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000002525 ultrasonication Methods 0.000 description 2
- YUFLXDLVTAPPHN-UHFFFAOYSA-N 1-(4,5-dihydroimidazol-1-yl)ethanol Chemical class CC(O)N1CCN=C1 YUFLXDLVTAPPHN-UHFFFAOYSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UMZBRFQRSA-N 4-[(3R,5S,7R,12S)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CCC1(C)C1C2C2CCC(C(CCC(O)=O)C)C2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-UMZBRFQRSA-N 0.000 description 1
- YJISHJVIRFPGGN-UHFFFAOYSA-N 5-[5-[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxy-6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)O)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 YJISHJVIRFPGGN-UHFFFAOYSA-N 0.000 description 1
- WHJKCPTVEYZNOG-UHFFFAOYSA-N 6-(hydroxymethyl)-5-methoxy-2-[4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane-3,4-diol Chemical compound COCC1OC(OC)C(OC)C(OC)C1OC1C(O)C(O)C(OC)C(CO)O1 WHJKCPTVEYZNOG-UHFFFAOYSA-N 0.000 description 1
- 229940023476 Agar Drugs 0.000 description 1
- PZZYQPZGQPZBDN-UHFFFAOYSA-N Aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N Ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
- 229940093761 Bile Salts Drugs 0.000 description 1
- 210000001736 Capillaries Anatomy 0.000 description 1
- 208000005846 Cardiomyopathy Diseases 0.000 description 1
- 229940113118 Carrageenan Drugs 0.000 description 1
- HVFLCNVBZFFHBT-ZKDACBOMSA-N Cefepime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 HVFLCNVBZFFHBT-ZKDACBOMSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 description 1
- 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 description 1
- 229940096516 Dextrates Drugs 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 210000003608 Feces Anatomy 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N Fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229960001031 Glucose Drugs 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 206010019641 Hepatic cirrhosis Diseases 0.000 description 1
- 229940039371 Karaya Gum Drugs 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920003107 Methocel™ A15C Polymers 0.000 description 1
- 229920003106 Methocel™ A4C Polymers 0.000 description 1
- 229920003108 Methocel™ A4M Polymers 0.000 description 1
- SNQQPOLDUKLAAF-UHFFFAOYSA-N Nonylphenol Chemical compound CCCCCCCCCC1=CC=CC=C1O SNQQPOLDUKLAAF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N 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 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-DCSYEGIMSA-N 0.000 description 1
- 229940044519 Poloxamer 188 Drugs 0.000 description 1
- 229940069328 Povidone Drugs 0.000 description 1
- 229940100486 RICE STARCH Drugs 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000934878 Sterculia Species 0.000 description 1
- 206010043391 Thalassaemia beta Diseases 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 229960004659 Ticarcillin Drugs 0.000 description 1
- 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 description 1
- 229960000707 Tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N Tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 229940116362 Tragacanth Drugs 0.000 description 1
- 229940093612 Zein Drugs 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 229940077484 ammonium bromide Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000181 anti-adherence Effects 0.000 description 1
- 230000002280 anti-androgenic Effects 0.000 description 1
- 230000001772 anti-angiogenic Effects 0.000 description 1
- 230000000118 anti-eoplastic Effects 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000005980 beta-Thalassemia Diseases 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 201000008031 cardiomyopathy Diseases 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229960002100 cefepime Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
- 239000011362 coarse particle Substances 0.000 description 1
- 230000000536 complexating Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- 230000003111 delayed Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- FFQBWYTWHOTQFS-UHFFFAOYSA-N dioxido-bis(trioxidosilyloxy)silane Chemical compound [O-][Si]([O-])([O-])O[Si]([O-])([O-])O[Si]([O-])([O-])[O-] FFQBWYTWHOTQFS-UHFFFAOYSA-N 0.000 description 1
- KZHJGOXRZJKJNY-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Si]=O.O=[Al]O[Al]=O.O=[Al]O[Al]=O.O=[Al]O[Al]=O KZHJGOXRZJKJNY-UHFFFAOYSA-N 0.000 description 1
- PYKDHVPTPKFRPN-UHFFFAOYSA-L disodium;3-(2-carboxylatoethylamino)propanoate Chemical compound [Na+].[Na+].[O-]C(=O)CCNCCC([O-])=O PYKDHVPTPKFRPN-UHFFFAOYSA-L 0.000 description 1
- 239000002612 dispersion media Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000001804 emulsifying Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- 230000012953 feeding on blood of other organism Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004676 glycans Polymers 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000797 iron chelating agent Substances 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 239000000231 karaya gum Substances 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 238000001459 lithography Methods 0.000 description 1
- 201000004044 liver cirrhosis Diseases 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 201000003793 myelodysplastic syndrome Diseases 0.000 description 1
- 230000002107 myocardial Effects 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N n-methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000011146 organic particle Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical class CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 230000000541 pulsatile Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- STFSJTPVIIDAQX-LTRPLHCISA-M sodium;(E)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O STFSJTPVIIDAQX-LTRPLHCISA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 229940066765 systemic antihistamines Substituted ethylene diamines Drugs 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N β-Alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N β-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
Abstract
This document describes a reclaimer machine (100) for reclaiming and homogenizing materials such as ore, coal and others, stock-piled in yards. The reclaimer machine (100) comprising a bucket wheel (1) which includes a series of buckets (8) rotating a shaft (2), a conveyor belt (3) connected to the bucket wheel (1) and to a transfer chute (5), the conveyor belt (3) being supported by a mobile upper platform (4) which moves laterally to a pile on tracks attached to a mobile lower platform (7), wherein a first end of the conveyor belt (21) structure is connected to the bucket wheel (1) and another end of the conveyor belt structure (3) is connected to a counterweight' (6) which maintains the balance of the reclaimer machine (100) and supports the bucket wheel (1), upper platform (4) and lower platform (7) movements.
Description
The présent invention relates to a pharmaceutical composition comprising an iron chelating agent, and more particularly, relates to a pharmaceutical composition comprising deferasirox or a pharmaceutically acceptable sait thereof, a process for preparing such pharmaceutical composition, and its use in the treatment of chronic iron overload.
BACKGROUND AND PRIOR ART:
One of the major obstacles to the development of highly potent pharmaceutical formulations is the poor water solubility of many drugs. Approximately 40% of potentîal drugs identified by pharmaceutical companies are poorly soluble în water, which greatly hinders their clinical use. Low water solubility limits the bioavailability and absorption of these agents.
Deferasirox has the chemical name 4-[3, 5-bîs (2-hydroxyphenyl) - [1, 2, 4] triazol-l-yl] enzoic acid, and is reported to hâve the following chemical structure.
Deferasirox is an orally active iron chelator, and has been approved for the treatment of iron overload in transfusion dépendent anémias (transfusion hemosîderosis), in particular thalassemia major, thalassemia intermediate and in sickle cell disease to reduce iron-related morbidity and mortality, in patients having an âge of two years and older.
Chronic iron overload îs a resuit of regular blood transfusions used in the treatment of several conditions including β-thalassemia, sickle cell disease and myelodysplastic syndromes.
Each unit of blood contains iron and as the human body has no physiological mechanism to actively excrete excess iron, repeated blood transfusions resuit in excessive accumulation of iron.
This excess of iron deposited in body tissues can cause severe damage to organs such as liver, heart, endocrine organs. This may lead to many complications including cardiomyopathy, liver cirrhosis, diabètes mellitus and reduced life expectancy.
Deferasirox mobilizes tissue iron by forming soluble stable complexes that are then excreted in the feces. It Îs a tridentate iron chelator requiring two molécules of the drug to form a stable complex. Iron is chelated both from the réticuloendothélial cells (RE cells) as well as various parenchymal tissues. The chelated iron is cleared by the liver and excreted through the bile. It also has the ability to prevent the myocardial cell iron uptake by removing iron directly from myocardîal cells.
Deferasirox is highly water-insoluble and is highly lipid-soluble, and is also observed to possess good permeability. According to the Bio-pharmaceutics Classification System (BCS), it has been classified as a Class II drug, implying that it is a poorly soluble, and a highly permeable drug. Though deferasirox is highly water-insoluble, whatever limited solubility it has, that too exhibits a high pH-dependent solubility. Though it is practically insoluble in lower pH, even at a pH of 6.8, it still remains insoluble, untîl the buffer strength is altered to get optimal dissolution profile.
Deferasirox being practically insoluble in aqueous media exhibits a generally poor dissolution profile and hence consequently poor bioavailability.
Several strategies and formulations have been employed to overcome these limitations of solubility and poor bioavailability. Although existing strategies such as complexing drugs with cyclodextrins, conjugation to dendrimers, sait formation of îonizable drugs and the use of cosolvents have been shown to improve drug solubility, solubilization methods that can improve the absorption ofthe drug are still highly désirable.
WO 2004035026 discloses a dispersîble tablet of deferasirox wherein the active ingrédient is présent in an amount of from 5% to 40% by weight based on total weight of the tablet.
WO 2005097062 discloses a dispersîble tablet of deferasirox wherein the active ingrédient îs présent in an amount of from 42% to 65% by weight based on total weight of the tablet.
WO 2007045445 discloses a dispersîble tablet of deferasirox or a pharmaceutically acceptable sait thereof présent in an amount of from 42% to 65% by weight based on total weight of the tablet and at least one pharmaceutically acceptable excipient suitable for the préparation of dispersible tablets and to process for making said dispersible tablet.
WO 2009067557 discloses a process of preparing deferasirox formulations having sufficiently high dissolution rate and good bioavailability wherein said process comprises co- milling deferasirox with at least two pharmaceutically acceptable excipients in the absence of any solvent.
WO 2010035282 discloses oral pharmaceutical composition comprising deferasirox in the form of a dispersible tablet wherein the active ingrédient has a mean particle size less than about lOOpm and is présent in an amount greater than 66% by weight based on total weight of the tablet.
Deferasirox is commercîally available as dispersible tablet (EXJADE®) for oral administration. EXJADE is supplied as a dispersible tablet containing 125 mg, 250 mg and 500 mg of deferasirox per tablet. This tablet is dispersed in a glass of water or any other suitable drink, and this resulting suspension is then administered to the patient.
Deferasirox is administered as a once daily oral iron chelator, which is prescribed as a dispersible tablet, i.e., a tablet which needs to be dispersed in an aqueous medium prior to administration,
Deferasirox îs typicalîy administered at an initial dose of about 20 mg/kg body weight, and the dose is adjusted up to a maximum of 30 mg/kg body weight.
Further, the recommended dosage of deferasirox is on the higher side in order to hâve a clinical benefit. Due to its high dosage, the overall tablet weight and its volume including its dimension makes it inconvénient to administer, in order to provide a pharmacologically active daily dosage amount of deferasirox.
Hence, there is a need for an oral dosage form having a high drug content which would be convenient for patient administration, which would exhibit acceptable dissolution and absorption which leads to better bioavailability.
OBJECT OF THE INVENTION:
The object of the présent invention is to provide a pharmaceutical composition comprising nanosized deferasirox having improved surface area and solubility.
Another object of the présent invention îs to provide a process for preparing the pharmaceutical composition comprising nanosized deferasirox.
Yet another object of the présent invention is to provide a method for treatment of chronic iron overload which comprises administering a pharmaceutical composition comprising nanosized deferasirox.
SUMMARY OF THE INVENTION:
According to one aspect of the présent invention there îs provided a composition comprising deferasirox in the form of particles, wherein substantially the particles hâve an average particle size of less than or equal to about 2000nm.
According to another aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox and at least one excipient.
According to another aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox and a pharmaceutically acceptable carrier.
According to another aspect of the présent invention there is provided a process for preparing a pharmaceutical composition, which process comprising the steps of: homogenizing deferasirox and at least one excipient to produce a homogenized dispersion of the deferasirox in the excipient; and milling said homogenized dispersion to produce a slurry of particles having an average particle size of less than or equal to about 2000nm.
According to another aspect of the présent invention there is provided the use of a composition according to présent invention in the manufacture of a médicament for treating chronic iron overload.
According to another aspect of the présent invention there is provided a method of treating chronic iron overload comprising administering a therapeutically effective amount of a composition having deferasirox according to the présent invention to a patient in need thereof.
According to another aspect of the présent invention there is provided a method of treating chronic iron overload comprising administering a therapeutically effective amount of deferasirox according to the présent invention to a patient in need thereof.
According to one aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox or pharmaceutically acceptable sait, solvaté, dérivatives, hydrate, enantiomer, polymorph, complex, or mixtures thereof.
According to another aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox or pharmaceutically acceptable sait, solvaté, dérivatives, hydrate, enantiomer, polymorph, complex or mixtures thereof wherein the deferasirox is in the nanosize range.
According to yet another aspect of the présent invention there is provided a process for preparing a pharmaceutical composition comprising deferasirox or pharmaceutically acceptable sait, solvaté, dérivatives, hydrate, enantiomer, polymorph, complex or mixtures thereof wherein the deferasirox is in the nanosize range.
According to a further aspect of the présent invention there is provided a method of treatment of chronic iron overload using a pharmaceutical composition comprising deferasirox or pharmaceutically acceptable sait, solvaté, dérivatives, hydrate, enantiomer, polymorph, complex or mixtures thereof wherein deferasirox is în the nanosize range.
DETAILED DESCRIPTION OF THE INVENTION:
In iron chélation therapy, a chelating drug binds with free or “labile” iron in the blood and organs, which allows for removal of excess iron from the body. Thus if more of deferasirox is available for chélation, there will be better removal of excess iron from the body.
Also, where multiple transfusions are repeatedly needed and phlebotomy is not possible, the chélation therapy provides a means of controlling the iron overload. The bioavailability (the percentage of the drug absorbed compared to its initial dosage) is Iimited by însolubility.
Dissolution rate is a function of the surface area of the particles and solubility. Dissolution rate is a direct function of total surface area for a dispersed phase.
The recommended dosage of deferasirox is on the higher side, i.e., an initial dose of about 20mg/kg body weight, and this dose is adjusted up to a maximum of 30mg/kg body weight. Further, deferasirox has been classified as a Class II drug which exhibits poor solubility.
Therefore, formulating a suitable formulation of deferasirox with désirable advantages such as, easy to manufacture as well as which possess advantages such as patient compliance is a challenge.
The inventors of the présent invention hâve found that, the solubility properties of deferasirox were improved by using nanosîzed deferasirox and thus leading to better bioavailability of the drug.
Nanonization of hydrophobie or poorly water-soluble drugs generally învolves the production of drug nanocrystals through either chemical précipitation (bottom-up technology) or disintegration ( top-do wn technology). Different methods may be utilized to reduce the particle size of the hydrophobie or poorly water soluble drugs. [Huabing Chen et al., discusses the various methods to develop nanoformulations in “Nanonization strategies for poorly water-soluble drugs,” Drug Discovery Today, Volume 00, Number 00, March 2010].
The term “nanosizing” as used herein refers to the réduction of deferasirox particle size to the sub-micron range. By submicron range, this suitably means having an average particle size of less than or equal to about 2000nm.
Nanosizing leads to increase in the exposure of surface area of deferasirox particles leading to an increase in the rate of dissolution.
The présent invention thus provides a pharmaceutical composition comprising deferasirox wherein deferasirox is in the nanosize range.
The term “nanosize” as used herein refers to deferasirox particles having an average particle size of less than or equal to about 2000nm, preferably less than or equal to about lOOOnm. The average particle size may, for example, be measured using laser based particle size analyzer.
Preferably, substantially ail particles hâve a particle size of less than or equal to about 2000 nm, preferably less than or equal to about 1000 nm.
The term “particles” as used herein refers to individual particle of deferasirox, or particles of deferasirox or deferasirox granules or deferasirox compositions and/or mixtures thereof.
The average particle size of the deferasirox is preferably above l nanometre.
The term “Deferasirox” is used in broad sense to include not only “Deferasirox” per se but also their pharmaceutically acceptable salts, pharmaceutically acceptable solvatés, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable esters, pharmaceutically acceptable dérivatives, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes etc.
The nanoparticles of the présent invention can be obtained by any of the process such as but not limited to milling, précipitation and homogenization.
According to one embodiment of the présent invention, the process of milling comprises dispersing deferasirox particles in a liquid dispersion medium in which deferasirox is poorly soluble, followed by applying mechanical means in the presence of grinding media like milling pearls to reduce the particle size of deferasirox to the desired average particle size.
According to another embodiment of the présent invention, the process of précipitation involves the formation of crystalline or semi-crystalline deferasirox nanoparticles by nucléation and the growth of drug crystals. In a typical procedure, drug molécules are first dissolved in an appropriate organic solvent such as acetone, tetrahydrofuran or N-methyl-2-pyrrolidone at a super saturation concentration to allow for the nucléation of drug seeds. Drug nanocrystals are then formed by adding the organic mixture to an antisolvent like water in the presence of stabîlizers such as Tween 80, Poloxamer 188 or lecithin. The choice of solvents and stabilizers and the mixing process are key factors to control the size and stability of the drug nanocrystals.
According to one another embodiment of the présent invention, the process of homogenization in volves passing a suspension of crystalline deferasirox and stabilizers through the narrow gap of a homogenizer at high pressure (for eg- 500-2000 bar). The pressure créâtes powerful disruptive forces such as cavitation, collision and shearing, which disintegrate coarse particles to nanoparticles.
According to one more embodiment of the présent invention, the process of spray-freeze drying involves the atomîzation of an aqueous deferasiorx solution into a spray chamber filled with a cryogénie liquid (liquid nitrogen) or halocarbon réfrigérant such as chlorofluorocarbon or fluorocarbon. The water is removed by sublimation after the liquid droplets solidify.
According to a still another embodiment of the présent invention, the process of supercritical fluid technology involves controlled crystallization of deferasiorx from dispersion in supercritical fluids, carbon dioxide.
According to another embodiment of the présent invention, the process of double emulsion/solvent évaporation technique involves préparation of oil/water (o/w) émulsions with subséquent removal of the organic phase through évaporation. The émulsions are prepared by emulsifying an organic phase containing deferasirox, polymer and organic solvent in an aqueous solution containing emulsifier. The organic solvent diffuses out of the polymer phase and into the aqueous phase, and is then evaporated, forming deferasirox-loaded polymeric nanoparticles.
According to a further embodiment of the présent invention, the process of PRINT (Particle réplication in non-wetting templates) involves utilization of a low surface energy fluoropolymeric mold that enables high-resolution imprint lithography, to fabricate a variety of organic particles. PRINT can precisely manipulate particle size of deferasirox ranging from 20 nm to more than 100 pm.
According to one further embodiment of the présent invention, the process of thermal condensation involves use of capillary aérosol generator (CAG) to produce high concentration condensation submicron to micron sized aérosols from a deferasirox solution.
According to still further embodiment of the présent invention, the process of ultrasonication may be used for nano-sizing deferasirox. The process of ultrasonication involves application of ultrasound during particle synthesis or précipitation, which leads to smaller particles of deferasirox and increased size uniformity.
According to another embodiment of the présent invention, the nano-sized deferasirox may be prepared by spray drying. The process of spray drying involves supplying a feed solution at room température and pumping it through the nozzle where it is atomized by a nozzle gas. The atomized solution is then dried by preheated drying gas in a spécial chamber to remove moisture from the system, thus forming dry particles of deferasirox.
According to a preferred embodiment of the présent invention, the nanomilled deferasirox may be obtained by nanomilling of deferasirox with at least one surface stabilizer, at least one viscosity building agent and at least one polymer.
The présent invention thus provides a pharmaceutical composition comprising nanosîzed deferasirox particles, prefereably in the form of granules. The granules may comprise at least one excipient. The excipient may comprise at least one of the following, but not limited to, at least one surface stabilizers, at least one viscosity building agent and at least one polymer and optionally other pharmaceutically acceptable carriers.
Surface stabilizer, according to the présent inventions, means surfactants that are capable of stabilizing the increased surfaced charge of the nanomilled drug. Suîtable amphoteric, non-ionic, cationic or anionic surfactants may be included as surface stabilizers in the pharmaceutical composition of the présent invention.
According to the présent invention, surfactants may comprise one or more, but not limited to Polysorbates, Sodium dodecyl sulfate (sodium lauryl sulfate), Lauryl dimethyl amine oxide, Docusate sodium, Cetyl trîmethyl ammonium bromide (CTAB) Polyethoxylated alcohols, Polyoxyethylene sorbitan, Octoxynol, N, N-dimethyldodecylamineN-oxide, Hexadecyltrimethylammonium bromide, Polyoxyl 10 lauryl ether, Brij, Bile salts (sodium deoxycholate, sodium cholate), Polyoxyl castor oil, Nonylphénol ethoxylate, Cyclodextrins, Lecithin, Methylbenzethonîum chloride. Carboxylates, Sulphonates, Petroleum sulphonates, alkylbenzenesulphonates, Naphthalenesulphonates, Olefin sulphonates, Alkyl sulphates, Sulphates, Sulphated naturel oils & fats, Sulphated esters, Sulphated alkanolamides, Alkylphenols, ethoxylated & sulphated, Ethoxylated aliphatic alcohol, polyoxyethylene surfactants, carboxylic esters Polyethylene glycol esters, Anhydrosorbitol ester & ît's ethoxylated dérivatives, Glycol esters of fatty acids, Carboxylic amides, Monoalkanolamine condensâtes, Polyoxyethylene fatty acid amides, Quatemary ammonium salts, Amines with amide linkages, Polyoxyethylene alkyl & alicyclic amines, Ν,Ν,Ν,Ν tetrakis substituted ethylenediamines 2alkyl 1- hydroxyethyl 2-imidazolines, N -coco 3-aminopropionic acid/ sodium sait, N-tallow 3 ίο iminodipropionate disodium sait, N-carboxymethyl n dimethyl n-9 octadecenyl ammonium hydroxide, n-cocoamidethyl n-hydroxyethylglycine sodium sait etc.
Viscosity builders means, excipients that are capable of stabilizing the nanoparticles by increasing the viscosity of the composition and thus preventing physical interaction of nanoparticles under the operating conditions employed.
According to the présent invention, viscosity builders, may comprise one or more, but not limited to dérivatives of sugars, such as lactose, saccharose, hydrolyzed starch (maltodextrin) etc or mixtures thereof.
Polymers or polymers blends, according to the présent invention, may comprise one or more hydrophilic polymers, but not limited to cellulose dérivâtes like hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose polymers hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylene and carboxymethyl hydroxyethylcellulose; acrylics like acrylic acid, acrylamide, and maleîc anhydride polymers, acacia, gum tragacanth, locust bean gum, guar gum, or karaya gum, agar, pectin, carrageenan, gelatin, casein, zein and algînates, carboxypolymethylene, bentonîte, magnésium aluminum silicate, polysaccharides, modified starch dérivatives and copolymers..
The deferasirox composition having nanosized partîcles of the invention can be formulated into any suitable dosage form, including but not limited to liquid dispersions, gels, aérosols, oîntments, créants, controlled release formulations, lyophilized formulations, tablets, capsules, delayed release formulations, extended release formulations, pulsatile release formulations, and mixed immédiate release and controlled release formulations along with pharmaceutically acceptable carriers.
Solid oral dosage forms for administration include, but are not limited to, capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active agent îs admixed with at least one of the following carriers: (a) one or more inert excipients (or carriers) (b) fillers or extenders (c) binders (d) humectants (e) disintegrating agents (f) solution retarders (g) absorption accelerators (h) wetting agents (i) adsorbents and (j) lubricants. For capsules, tablets, and pills, the dosage forms may also comprise buffering agents.
The granules comprising nanosized deferasirox, according to the présent invention, may either be encapsulated in capsules or be compressed to form tablets or may be provided as sachets or be provided as powders for reconstitution.
The solid dosage form, according to the présent invention, may also optionally be coated. More preferably, the formulation may be seal coated and then film coated.
According to an embodiment of the présent invention, pharmaceutical composition may be film coated with but not limited to Ready colour mix Systems (such as Opadry colour mix Systems) and Kollicoat® Protect.
According to the présent invention, the seal coat comprises film forming polymeric materials, such as but not limited to, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolîdone, methylcellulose, carboxymethylcellulose, hypromellose, acacia, gelatîn to increase adhérence and cohérence of the seal coat.
In one aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox in the form of dispersible tablet, wherein deferasirox is in the nanosize range.
In another aspect of the présent invention there is provided a pharmaceutical composition comprising deferasirox in the form of dispersible tablet, wherein deferasirox îs in the nanosize range of less than or equal to about 2000nm, preferably less than or equal to about lOOOnm.
The term “dispersible tablet” as used herein refers to a tablet which normally disperses in aqueous phase, e.g. in water, with or without external agitation.
Suitable carriers may be used for formulating the various dosage forms according to the présent invention.
According to the présent invention, pharmaceutically acceptable opacifier for use in the pharmaceutical composition of the présent invention may comprise one or more, but is not limited to titanium dioxide.
According to the présent invention, pharmaceutically acceptable diluents or fillers for use în the pharmaceutical composition of the présent invention may comprise one or more, but not limited to lactose (for example, spray-dried lactose, a-lactose, β-lactose) lactose available under the trade mark Tablettose, various grades of lactose available under the trade mark Pharmatose or other commercially available forms of lactose, lactitol, saccharose, sorbitol, mannitol, dextrates, dextrins, dextrose, maltodextrin, croscarmellose sodium, microcrystalline cellulose (for example, microcrystalline cellulose available under the trade mark Avîcel), hydroxypropylcellulose, Lhydroxypropyl cellulose (low substituted), hydroxypropyl methylcellulose (HPMC), methylcellulose polymers (such as, for example, Methocel A, Methocel A4C, Methocel A15C, Methocel A4M), hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylene, carboxymethyl hydroxyethylcellulose and other cellulose dérivatives, starches or modified starches (including potato starch, com starch, maize starch and rice starch) and mixtures thereof.
According to the présent invention, glidants, anti-adherents and lubricants may also be incorporated in the pharmaceutical composition of the présent invention, which may comprise one or more, but not limited to stearic acid and pharmaceutically acceptable salts or esters thereof (for example, magnésium stéarate, calcium stéarate, sodium stearyl fumarate or other metallic stéarate), talc, waxes (for example, microcrystalline waxes) and glycerides, light minerai oil, PEG, silica acid or a dérivative or sait thereof (for example, silicates, silicon dioxide, colloïdal silicon dioxide and polymers thereof, crospovidone, magnésium aluminosilicate and/ or magnésium alumino metasilicate), sucrose ester of fatty acids, hydrogenated vegetable oils (for example, hydrogenated castor oil), or mixtures thereof.
According to the présent invention, suitable binders may also be présent in the pharmaceutical composition of the présent invention, which may comprise one or more, but not limited to polyvinyl pyrrolidone (also known as povidone), polyethylene glycol(s), acacia, alginic acid, agar, calcium carragenan, cellulose dérivatives such as ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, dextrîn, gelatin, gum arable, guar gum, tragacanth, sodium alginate, or mixtures thereof or any other suitable binder.
According to the présent invention, suitable disintegrants may also be présent in the pharmaceutical composition of the présent invention, which may comprise one or more, but not limited to hydroxylpropyl cellulose (HPC), low density HPC, carboxymethylcellulose (CMC), sodium CMC, calcium CMC, croscarmellose sodium; starches exemplified under examples of fillers and also carboxymethyl starch, hydroxylpropyl starch, modified starch; crystalline cellulose, sodium starch glycolate; alginic acid or a sait thereof, such as sodium alginate or their équivalents and mixtures thereof.
Further, the pharmaceutical composition according to the présent invention may further comprise at least one additional active ingrédient such as but not limited to leukotriene, probenecid, indomethacin, penicillin G, ritonavir, indinavir, saquinavir, furosemide, methotrexate, sulfinpyrazone, interferon, ribavirin, viramidine, valopicitabine, aromatase inhibitor, antiestrogen, anti-androgen, gonadorelin agonist, topoisomerase I inhibitor, topoisomerase II inhibitor, microtubule active agent, alkylating agent, anti-neoplastic, anti-metabolite, platin compound, anti-angiogenic compound, cyclooxygenase inhibitor, bisphosphonate, heparanase inhibitor, telomerase inhibitor, protease inhibitor, matrix metalloproteinase inhibitor, protéasome inhibitor, somatostatin receptor antagonist, anti-leukemic compound, ribonucleotide reductase inhibitor, S-adenosylmethionine decarboxylase inhibitor; ACE inhibitor, antibiotics such as gentamicin, amikacîn, tobramycin, ciprofloxacin, levofloxacin, ceftazidime, cefepime, cefpîrome, piperacillin, ticarcillin, meropenem, imipenem, polymyxîn B, colistin and aztreonam; cyclosporin A, cyclosporin G, rapamycin.
There îs also provided a process for preparing the pharmaceutical composition of the présent invention, which process comprises homogenizing deferasirox and at least one excipient to produce a homogenîzed dispersion of the deferasirox in the excipient; and milling said homogenized dispersion to produce a slurry of deferasirox particles having an average particle size of less than or equal to about 2000 nm.
According to one embodiment the pharmaceutical composition of the présent invention, may be prepared by a process which comprises (a) preparing a dispersion of deferasirox with Docusate sodium, HPMC, sodium lauryl sulphate and sucrose in purified water under stirring conditions;
(b) homogenizing the dispersion of step (a) and then nanomilling the homogenized dispersion;
(c) adsorbing the nanomilled drug by spraying the nanomilled slurry on lactose monohydrate, microcrystalline cellulose and crospovidone mixture în fluidized bed granulator; (d) drying and blending the granules obtained in step (c). The granules may be lubricated and finally compressed into tablets. The tablets obtained may be seal coated and then film coated.
The présent invention further provides a method for treating chronic iron overload which method comprises administering a therapeutically effective amount of a pharmaceutical composition according to the présent invention.
Furthcrmore. the présent invention provides pharmaceutical compositions comprising deferasirox for use in the treatment of chronic iron overload.
The following examples are for the purpose of illustration of the invention only and are not 10 intended in any way to limit the scope of the présent invention.
Example 1
Sr. No. | Ingrédients | Qty mg/tablet |
Binder Solution | ||
I. | Deferasirox | 500.00 |
2. | Docusate Sodium IP | 5.00 |
3. | Hydroxypropylmethylcellulo.se 3cps IP | 100.00 |
4. | Sodium lauryl sulphate IP | 14.00 |
5. | Sucrose IP | 150.00 |
6. | Purified water IP | q.s |
Dry Mix | ||
7. | Lactose Monohydrate(200 mesh) IP | 175.00 |
8. | Microcrystalline Cellulose IP (Avicel PH 101) | 152.00 |
9. | Crospovidone IP | 50.00 |
Lubrication | ||
10. | Crospovidone IP | 36.00 |
11. | Magnésium Stéarate IP | 6.00 |
Total | 1188.00 | |
Seal Coating | ||
12. | Hydroxypropylmethylcellulose 3cps IP | 12.00 |
13. | Isopropyl Alcohol IP | q.s |
14. | Dichloromethane BP | q.s |
Total | 1200.00 | |
Film Coating | ||
15. | Opadry AMB White OY-B-28920 INH | 25.00 |
16. | Purified Water | q.S. |
Total | 1225.00 |
Process:
1. Docusate sodium, HPMC, sodium lauryl sulphate and sucrose were solubalized in water under stirring conditions.
2. Deferasirox was dispersed in the solution obtained in step (l).
3. Above dispersion was homogenîzed and then nanomilled .
4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluidized bed granulator.
5. Granules obtained were sized and lubricated.
6. Lubricated granules were finally compressed into tablets.
7. The tablets obtained were seal coated and then film coated.
Example 2
Sr. No. | Ingrédients | Qty mg/tablet |
Binder Solution | ||
1. | Deferasirox | 500.00 |
2. | Docusate Sodium IP | 5.00 |
3. | H ydroxypropylmethyl cellulose 3cps IP | 100.00 |
4. | Sodium lauryl sulphate IP | 14.00 |
5. | Sucrose IP | 150.00 |
6. | Purified water IP | q.s |
Dry Mix | ||
7. | Lactose Monohydrate(200 mesh) IP | 175.00 |
8. | Microcrystalline Cellulose IP (Avicel PH 101) | 152.00 |
9. | Crospovidone IP | 50.00 |
Lubrication | ||
10. | Crospovidone IP | 36.00 |
11. | Magnésium Stéarate IP | 6.00 |
Total | 1188.00 | |
Seal Coating | ||
12. | Hydroxypropyl methylcellulose 3cps IP | 12.00 |
13. | Isopropyl Alcohol IP | q.s |
14. | Dichloromethane BP | q.s |
Total | 1200.00 | |
Film Coating |
15. | Kollîcoat Protect | 15.00 |
16. | Talc IP | 60.25 |
17. | Titanium dioxide IP | 3.75 |
18. | Purifîed Water IP | q.s. |
19. | Isopropyl Alcohol IP | q.s. |
Total | 1225.00 |
Process:
1. Docusate sodium, HPMC, sodium lauryl sulphate and sucrose were solubalized in water under stirring conditions;
2. Deferasirox was dispersed in the solution obtained in step (1);
3. Above dispersion was homogenized and then nanomilled. 4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluidized bed granulator;
5. Granules obtained were sized and lubricated;
6. Lubricated granules were finally compressed into tablets; and
7. The tablets obtained were seal coated and then film coated.
Example 3 | ||
Sr.No. | Ingrédients | Qty mg/tablet |
Binder Solution | ||
1. | Deferasirox | 250.00 |
2. | Docusate Sodium | 5.00 |
3. | Hydroxypropylmethyl cellulose | 15.00 |
4. | Sodium lauryl sulphate | 13.80 |
5. | Sucrose | 25.00 |
6. | Purifîed water | q.s. |
Dry Mix | ||
7. | Lactose Monohydrate (200 mesh) | 154.70 |
9. | Crospovidone | 50.00 |
Imbrication | ||
10. | Silicified Microcrystalline Cellulose | 50.00 |
11. | Crospovidone | 40.00 |
12.
13.
14.
Croscannellose Sodium
Magnésium Stéarate
Total
20.00
1.50
625.00
Process:
1. Docusate sodium, HPMC, sodium lauryl sulphate and sucrose were solubalized in water under stirring conditions;
2. Deferasirox was dispersed în the solution obtained în step (1);
3. Above dispersion was homogenized and then nanomilled;
4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluidized bed granulator;
5. Granules obtained were sized and lubricated; and
6. Lubricated granules were finally compressed into tablets.
Example 4
Sr.No. Ingrédients
Binder Solution
1. Deferasirox
2. Docusate Sodium
3. Hydroxypropylmethylcellulose
4. Sodium lauryl sulphate
5. Sucrose
Qty mg/tablet
500.00
10.00
30.00
27.6
50.00
6. Purified water
q.s
Dry Mix
7. Lactose Monohydrate (200 mesh)
309.40
9. Crospovidone
100.00
Lubrication
11. Crospovidone
80.00
12. Croscannellose Sodium
40.00
13. Magnésium Stéarate
3.00
Total
1250.00
10. Silicified Microcrystalline Cellulose
100.00
Process:
1. Docusate sodium, HPMC, sodium lauryl sulphate and sucrose were solubalized in water under stirring conditions;
2. Deferasirox was dispersed în the solution obtained în step (l);
3. Above dispersion was homogenized and then nanomilled;
4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluîdized bed granulator;
5. Granules obtained were sized and lubricated; and
6. Lubricated granules were finally compressed into tablets.
Example 5
Sr.No. Ingrédients
Binder Solution
1. Deferasirox
2. Docusate Sodium
3. Polyvinylpyrrolidone
4. Sodium lauryl sulphate
5. Sucrose
Qty mg/tablet
250.00
5.00
15.00
13.80
25.00
6. Purified water
q.s.
Dry Mix
7. Lactose Monohydrate (200 mesh)
154.70
9. Crospovidone
50.00
Lubrication
10. Silicified Microcrystalline Cellulose 50.00
11. Crospovidone
40.00
12. Croscarmellose Sodium
20.00
13. Magnésium Stéarate
1.50
Total
625.00
Process:
1. Docusate sodium, PVP, sodium lauryl sulphate and sucrose were solubalized in water under stirring conditions;
2. Deferasirox was dispersed in the solution obtained in step (l);
3. Above dispersion was homogenized and then nanomilled;
4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluidized bed granulator;
5. Granules obtained were sized and lubricated; and
6. Lubricated granules were finally compressed into tablets.
Ëxample 6
Sr.No. | Ingrédients Binder Solution | Qty mg/tablet |
L | Deferasirox | 500.00 |
2. | Docusate Sodium | 10.00 |
3. | Polyvinylpyrrolidone | 30.00 |
4. | Sodium lauryl sulphate | 27.6 |
5. | Sucrose | 50.00 |
6. | Purified water | q.s |
Dry Mix | ||
7. | Lactose Monohydrate (200 mesh) | 309.40 |
9. | Crospovidone | 100.00 |
Lubrication | ||
10. | Silicified Microcrystalline Cellulose | 100.00 |
11. | Crospovidone | 80.00 |
12. | Croscarmellose Sodium | 40.00 |
13. | Magnésium Stéarate | 3.00 |
Total | 1250.00 |
Process:
1. Docusate sodium, PVP, sodium lauryl sulphate and sucrose were solubalized in purified water under stirring conditions;
2. Deferasirox was dispersed in the solution obtained în step (1);
3. Above dispersion was homogenized and then nanomilled;
4. Nanomilled drug slurry was adsorbed by spraying on lactose monohydrate, microcrystalline cellulose and crospovidone mixture in a fluidized bed granulator;
5. Granules obtained were sized and lubricated; and
6. Lubricated granules were final ly compressed into tablets.
It will be readîly apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the présent invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limîting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and équivalents thereof as well as additional items.
It must be noted that, as used in this spécification and the appended claims, the singular forms a, an and the include plural référencés unless the context clearly dictâtes otherwise. Thus, for example, reference to a propellant includes a single propellant as well as two or more different propellants; reference to a cosolvent refers to a single cosolvent or to combinations of two or more cosolvents, and the like.
Claims (18)
- CLAIMS:1. A pharmaceutical composition comprising deferasirox in the form of particles, wherein the particles hâve an average particle size of less than or equal to about 2000 nm.
- 2. A pharmaceutical composition according to claim 1, wherein the particles hâve an average particle size of less than or equal to about 1000 nm.
- 3. A pharmaceutical composition according to claim 1 or 2, comprising at least one excipient, which is selected from the group comprising at least one surface stabilizer, viscosîty building agent and polymer.
- 4. A pharmaceutical composition according to any one of claims 3, wherein the surface stabilizer is a surfactant, which is an amphoteric, non-ionic, cationic or anionic or combinations thereof.
- 5. A pharmaceutical composition according to claim 4, wherein the surfactant comprises one or more of polysorbates; sodium dodecyl sulfate (sodium lauryl sulfate); lauryl dimethyl amine oxide; docusate sodium; cetyl trimethyl ammonium bromide (CTAB); a polyethoxylated alcohol; a polyoxyethylene sorbitan; Octoxynol; N,N-dimethyldodecylamine-N-oxide; hexadecyltrimethylammonium bromide, polyoxyl 10 lauryl ether, brij, a bile sait, such as sodium deoxycholate or sodium cholate; a polyoxyl castor oil; nonylphenol ethoxylate; a Cyclodextrin; lecithin; methylbenzethonium chloride; a carboxylate; a sulphonate; a petroleum sulphonate; an alkylbenzenesulphonates; a naphthalenesulphonate; and olefin sulphonate; a sulphate surfactant; an alkyl sulphate; a sulphated natural oil or fat; a sulphated ester; a sulphated alkanolamide; an alkylphenol, optionally ethoxylated and sulphated; an ethoxylated aliphatiç alcohol; polyoxyethylene; a carboxylic ester; a polyethylene glycol esters; an anhydrosorbitol ester or an ethoxylated dérivative therof; a glycol ester of a fatty acid; a carboxylic amide; a monoalkanolamine condensate; a polyoxyethylene fatty acid amide; a quaternary ammonium sait; an amine with amide linkages; a polyoxyethylene alkyl amine; a polyoxyethylene alicyclic amine; a N,N,N,N tetrakis substituted ethylenediamine; a 2-alkyl-l-hydroxyethyl-2-imidazoline; N-coco-3-aminopropionic acid or a sodium sait thereof; N-tallow-3-iminodipropionate disodium sait; N-carboxymethyl-n-dimethyl-n-9 octadecenyl ammonium hydroxide; n-cocoamidethyl-nhydroxyethylglycine sodium sait; or mixtures thereof.
- 6. A pharmaceutical composition according to claim 3, 4, or 5, wherein the surfactant is docusate sodium and/or sodium lauryl sulphate.
- 7. A pharmaceutical composition according any one of claims 3, wherein the viscosîty building agent is lactose; sucrose; saccharose; a hydrolyzed starch, such as maltodextrin; or a mixture thereof.
- 8. A pharmaceutical composition according any one of claims 3, wherein the polymer is hydroxypropylcellulose; hydroxym ethyl cellulose; hydroxypropyl methylcellulose; a methylcellulose polymer; hydroxyethylcellulose; sodium carboxymethylcellulose; carboxymethylene hydroxyethylcellulose and/or carboxymethyl hydroxyethylcellulose; an acrylic polymer, such as acrylic acid, acrylamide, and maleic anhydride polymers and copolymers; or a mixture thereof.
- 9. A pharmaceutical composition according to any one of the preceding claims, wherein substantially ail the particles hâve an average particle size above 1 nm.
- 10. A pharmaceutical composition comprising a composition according to any one of claims 1 to 9 and a pharmaceutically acceptable carrier, optionally the particles are adsorbed on the surface of the carrier.
- 11. A pharmaceutical composition according to claim 10, wherein the carrier comprises: one or more diluents or fïllers; one or more binders; one or more lubricauts; one or more glidants; one or more disintegrants; one or more preservatives; one or more humectants; one or more solution retarders; one or more absorption accelerators; one or more wetting agents; one or more adsorbents; one or more buffering agents; or a mixture thereof,
- 12. A pharmaceutical composition according to any one of claims 10 or 11, which is for oral administration, optionally in a solid oral dosage form.
- 13. A pharmaceutical composition according to claim 12, which is in a form of a tablet, optionally the tablet is a dispersible tablet.
- 14. A pharmaceutical composition according to any one of claims 1 to 13 for use in treating chronic iron overload.
- 15. A process for preparing a pharmaceutical composition, which process comprises the steps of:(1) homogenizing deferasirox and at least one excipient to produce a homogenized dispersion of the deferasirox; and (2) milling said homogenized dispersion to produce a slurry of deferasirox particles having an average particle size of less than or equal to about 2000 nm, optionally further comprising:(i) adsorbîng the milled slurry on a pharmaceutically acceptable carrier to form granules, which are optionally compressed to form tablets; or (ii) forming the slurring into a liquid dispersions, gels or aérosols.
- 16. A process according to any one of claim 15, wherein the excipient is as defined in any one of claims 3 to 8.
- 17. The use of a pharmaceutical composition according to any one of claims 1 to 13 in the manufacture of a médicament for treating chronic iron overload.
- 18. A pharmaceutical composition according to any one of claims 1 to 13 further comprising one or more actîve(s) selected from leukotriene, probenecid, indomethacin, penicillin G, ritonavir, indinavir, saquinavir, furosemide, methotrexate, sulfinpyrazone, interferon, ribavirin, viramidine, valopicitabine, aromatase inhibitor, antiestrogen, antî-androgen, gonadorelin agonist, topoisomerase I inhibitor, topoisomerase II inhibitor, microtubule active agent, alkylatîng agent, anti-neoplastîc, anti-metabolite, platin compound, antî-angiogenic compound, cyclooxygenase inhibitor, bisphosphonate, heparanase inhibitor, telomerase inhibitor, protease inhibitor, matrix metalloproteinase inhibitor, protéasome inhibitor, somatostatin receptor antagonîst, antileukemic compound, ribonucleotide reductase inhibitor, S-adenosylmethionine decarboxylase inhibitor; ACE inhibitor, antibiotics such as gentamicin, amikacin, tobramycîn, ciprofloxacin, levofloxacin, ceftazidime, cefepîme, cefpirome, piperacillin, tîcarcillin, meropenem, imipenem, polymyxin B, colistin and aztreonam; cyclosporin A, cyclosporin G, rapamycin or their pharmaceutically acceptable salts, solvatés, tautomers, dérivatives, enantiomers, isomers, hydrates, prodrugs or polymorphs thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61/393,063 | 2010-10-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
OA16372A true OA16372A (en) | 2015-10-07 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2011309872B2 (en) | Pharmaceutical composition comprising deferasirox | |
JP6651489B2 (en) | Process for the preparation of biologically active compounds in nanoparticulate form | |
US20200163882A1 (en) | Solid Pharmaceutical Compositions Of Androgen Receptor Antagonists | |
AU2011244783B2 (en) | Pharmaceutical compositions | |
EP2442799B2 (en) | Solid pharmaceutical composition comprising rivaroxaban | |
JP5484910B2 (en) | Revaprazan-containing solid dispersion and method for producing the same | |
US20090209541A1 (en) | Aprepitant compositions | |
US20160303102A1 (en) | Process for the production of drug formulations for oral administration | |
US20190008874A1 (en) | Abiraterone Acetate Formulation and Methods of Use | |
JP2016518398A (en) | Low dose pharmaceutical composition | |
JP2015536970A (en) | Fixed dose pharmaceutical composition comprising deferasirox and deferiprone | |
US20140044788A1 (en) | Solid Oral Formulations of a Pyridopyrimidinone | |
CA2323363C (en) | Novel compositions of eprosartan | |
US20100104634A1 (en) | Pharmaceutical compositions of entacapone | |
US20070237828A1 (en) | Ziprasidone Dosage Form | |
KR101730865B1 (en) | Pharmaceutical compositions comprising revaprazan-containing nanoparticles and processes for the preparation thereof | |
OA16372A (en) | Reclaimer machine. | |
OA16350A (en) | Pharmaceutical composition comprising deferasirox. | |
US11260055B2 (en) | Oral pharmaceutical composition of lurasidone and preparation thereof | |
WO2003028645A2 (en) | Novel compositions of carvedilol | |
MX2012012084A (en) | Pharmaceutical compositions. | |
AU2007263016A1 (en) | Oral pharmaceutical composition of a poorly water-soluble active substance |