NZ713151B2 - Sustained-release formulations of colchicine and methods of using same - Google Patents
Sustained-release formulations of colchicine and methods of using same Download PDFInfo
- Publication number
- NZ713151B2 NZ713151B2 NZ713151A NZ71315114A NZ713151B2 NZ 713151 B2 NZ713151 B2 NZ 713151B2 NZ 713151 A NZ713151 A NZ 713151A NZ 71315114 A NZ71315114 A NZ 71315114A NZ 713151 B2 NZ713151 B2 NZ 713151B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- formulation
- colchicine
- hpmc
- pharmaceutically acceptable
- release
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 72
- IAKHMKGGTNLKSZ-INIZCTEOSA-N Colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 title claims abstract description 55
- 229960001338 colchicine Drugs 0.000 title claims abstract description 26
- 230000002459 sustained Effects 0.000 title claims abstract description 12
- 238000009472 formulation Methods 0.000 claims abstract description 62
- 239000003340 retarding agent Substances 0.000 claims abstract description 13
- 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 claims abstract description 10
- 229960001021 Lactose Monohydrate Drugs 0.000 claims abstract description 10
- 208000008787 Cardiovascular Disease Diseases 0.000 claims abstract description 6
- 200000000018 inflammatory disease Diseases 0.000 claims abstract description 6
- 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 21
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 21
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 21
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 21
- 239000008187 granular material Substances 0.000 claims description 14
- 239000000546 pharmaceutic aid Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 4
- 230000000271 cardiovascular Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 208000004981 Coronary Disease Diseases 0.000 claims description 3
- 201000008739 coronary artery disease Diseases 0.000 claims description 3
- 201000005569 gout Diseases 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 229940023488 Pill Drugs 0.000 claims description 2
- 239000007894 caplet Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000007933 dermal patch Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000005469 granulation Methods 0.000 claims description 2
- 230000003179 granulation Effects 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 4
- XAPRFLSJBSXESP-UHFFFAOYSA-N Oxycinchophen Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=C(O)C=1C1=CC=CC=C1 XAPRFLSJBSXESP-UHFFFAOYSA-N 0.000 claims 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N Stearic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 4
- 239000001913 cellulose Substances 0.000 claims 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 4
- 229920002472 Starch Polymers 0.000 claims 3
- 239000011230 binding agent Substances 0.000 claims 3
- 229920002678 cellulose Polymers 0.000 claims 3
- 235000010980 cellulose Nutrition 0.000 claims 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 3
- 235000019698 starch Nutrition 0.000 claims 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims 2
- 108010010803 Gelatin Proteins 0.000 claims 2
- GUBGYTABKSRVRQ-YOLKTULGSA-N Maltose 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-YOLKTULGSA-N 0.000 claims 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 2
- 208000008494 Pericarditis Diseases 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 2
- 208000004347 Postpericardiotomy Syndrome Diseases 0.000 claims 2
- 229940032147 Starch Drugs 0.000 claims 2
- 235000021355 Stearic acid Nutrition 0.000 claims 2
- 230000001154 acute Effects 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 229920000159 gelatin Polymers 0.000 claims 2
- 239000008273 gelatin Substances 0.000 claims 2
- 235000019322 gelatine Nutrition 0.000 claims 2
- 235000011852 gelatine desserts Nutrition 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 2
- 239000008107 starch Substances 0.000 claims 2
- 239000008117 stearic acid Substances 0.000 claims 2
- 239000003826 tablet Substances 0.000 claims 2
- 239000000454 talc Substances 0.000 claims 2
- 229910052623 talc Inorganic materials 0.000 claims 2
- 235000012222 talc Nutrition 0.000 claims 2
- SQKIRAVCIRJCFS-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.C=CC1=CC=CC=C1C=C SQKIRAVCIRJCFS-UHFFFAOYSA-N 0.000 claims 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010064930 Age-related macular degeneration Diseases 0.000 claims 1
- 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 claims 1
- 229960001681 Croscarmellose Sodium Drugs 0.000 claims 1
- 229920002785 Croscarmellose sodium Polymers 0.000 claims 1
- 229960000913 Crospovidone Drugs 0.000 claims 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 claims 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 claims 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 claims 1
- 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 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N DL-leucine Chemical compound CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 1
- 206010016207 Familial mediterranean fever Diseases 0.000 claims 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N Glyceryl behenate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims 1
- 206010061256 Ischaemic stroke Diseases 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- 229960001375 Lactose Drugs 0.000 claims 1
- 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 1
- 229940037627 MAGNESIUM LAURYL SULFATE Drugs 0.000 claims 1
- 208000002780 Macular Degeneration Diseases 0.000 claims 1
- 229960002160 Maltose Drugs 0.000 claims 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 claims 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinylpyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 1
- 208000004957 Out-of-Hospital Cardiac Arrest Diseases 0.000 claims 1
- 229960000540 POLACRILIN POTASSIUM Drugs 0.000 claims 1
- 229960002965 Pravastatin Drugs 0.000 claims 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N Pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N Rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims 1
- RYMZZMVNJRMUDD-HGQWONQESA-N Simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims 1
- 229940005550 Sodium alginate Drugs 0.000 claims 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N Stearyl alcohol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 229960004793 Sucrose Drugs 0.000 claims 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N Talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 claims 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N Trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims 1
- 229940074410 Trehalose Drugs 0.000 claims 1
- QORWJWZARLRLPR-UHFFFAOYSA-H Tricalcium phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims 1
- 235000010443 alginic acid Nutrition 0.000 claims 1
- 239000000783 alginic acid Substances 0.000 claims 1
- 229920000615 alginic acid Polymers 0.000 claims 1
- 229960001126 alginic acid Drugs 0.000 claims 1
- 229960005370 atorvastatin Drugs 0.000 claims 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 1
- 239000008119 colloidal silica Substances 0.000 claims 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims 1
- 229940049654 glyceryl behenate Drugs 0.000 claims 1
- 229940075507 glyceryl monostearate Drugs 0.000 claims 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 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 claims 1
- 239000000391 magnesium silicate Substances 0.000 claims 1
- 235000019359 magnesium stearate Nutrition 0.000 claims 1
- 229940099273 magnesium trisilicate Drugs 0.000 claims 1
- 235000019793 magnesium trisilicate Nutrition 0.000 claims 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 229960001855 mannitol Drugs 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims 1
- -1 polacrilin potassium Polymers 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
- 229920003124 powdered cellulose Polymers 0.000 claims 1
- 235000019814 powdered cellulose Nutrition 0.000 claims 1
- 239000008213 purified water Substances 0.000 claims 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N rac-1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims 1
- 230000000306 recurrent Effects 0.000 claims 1
- 229960000672 rosuvastatin Drugs 0.000 claims 1
- 229960002855 simvastatin Drugs 0.000 claims 1
- 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 claims 1
- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 1
- 229920003109 sodium starch glycolate Polymers 0.000 claims 1
- 229940079832 sodium starch glycolate Drugs 0.000 claims 1
- 239000008109 sodium starch glycolate Substances 0.000 claims 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims 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 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 229960002920 sorbitol Drugs 0.000 claims 1
- 235000010356 sorbitol Nutrition 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 235000019731 tricalcium phosphate Nutrition 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 229940002157 Colcrys Drugs 0.000 description 3
- 229940084627 Colchicine 0.5 MG Drugs 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000007502 Anemia Diseases 0.000 description 1
- 210000004369 Blood Anatomy 0.000 description 1
- 210000001772 Blood Platelets Anatomy 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 231100000494 adverse effect Toxicity 0.000 description 1
- 201000004384 alopecia Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 201000008286 diarrhea Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
Abstract
Pharmaceutical compositions of colchicine for once-a-day oral administration are provided. The formulations comprise a sustained-release component and an optional immediate- release component, the compositions of which can be selectively adjusted, respectively, to release the active ingredient along a pre-determined or desired release profile. The formulation comprises a release-retarding agent comprising HMPC and lactose monohydrate. Methods of treating or preventing cardiovascular disease and/or inflammatory disease in mammalian subjects comprising the administration of the novel formulations disclosed herein is also provided. a pre-determined or desired release profile. The formulation comprises a release-retarding agent comprising HMPC and lactose monohydrate. Methods of treating or preventing cardiovascular disease and/or inflammatory disease in mammalian subjects comprising the administration of the novel formulations disclosed herein is also provided.
Description
(93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and
followed for a median of 3 years (Nidorf et al., JACC, 2013, 61 (4), 404-410). This study
showed that colchicine 0.5 mg/day administered in addition to statins and other standard
secondary prevention therapies appeared effective for the prevention of cardiovascular events in
patients with stable coronary disease.
For the treatment of gout, the recommended dose of colchcine (COLCRYS®) is 1.8
mg/day in one or multiple doses in one hour For adults with gout, treatment is initiated with a
dose of 1.2 mg at the first sign of symptoms followed by 0.6 mg one hour later. (Physician's
Desk Reference, 68th ed., (2014)).
COLCRYS® is an immediate release formulation. Adverse effects associated with the
administration of COLCRYS® include, but are not limited to, nausea, vomiting, abdominal
pain, diarrhea, hair loss, weakness, nerve irritation, severe anemia, low white blood counts, and
low platelets (Physician's Desk Reference, 68th ed., (2014)).
The instant invention addresses these and other needs by providing a modified
formulation of colchicine characterized by a sustained release of an active ingredient. This
invention additionally provides an effective, once-daily dosage form of colchicine or salts
thereof, which may improve patient compliance and also may reduce some of the side effects of
colchicine compared to the current or higher daily doses of immediate release colchicine
formulations.
BRIEF SUMARY OF THE INVENTION
[0013a] In a first aspect there is provided a sustained release formulation of colchicine,
comprising:
(a) granules comprising 0.5 mg of colchicine or a pharmaceutically acceptable salt
thereof, and a first hydroxypropyl methylcellulose (HPMC) in an amount of 0.5% to
1.5% (w/w) of the formulation;
(b) a release retarding agent admixed with the colchicine granules in an amount of 10%
to 30% w/w of the formulation, wherein the release retarding agent is equal parts
(w/w) of a second HPMC and lactose monohydrate; and
(c) at least one pharmaceutically acceptable excipient admixed with the granules;
wherein the viscosity of the second HPMC is higher than the viscosity of the first HPMC,
AH26(25575208_1):RTK
wherein the formulation is in a form of a pill, a capsule, a caplet, a suppository,
sublingual formulation, a pouch, a dermal patch, sprinkles, or in fixed combination with a
surgically insertable medical device.
[0013b] In a second aspect there is provided use of a sustained release formulation of colchicine
according to the first aspect, for the manufacture of a medicament for preventing and/or treating
a cardiovascular disease in a subject in need thereof.
[0013c] In a third aspect there is provided use of a sustained release formulation of colchicine
according to the first aspect, for the manufacture of a medicament for preventing and/or treating
an inflammatory disease in a subject in need thereof.
[0013d] In a fourth aspect there is provided a process of preparing a colchicine-sustained release
formulation comprising:
(A) forming a granulate by dissolving 0.5 mg of colchicine or a pharmaceutically
acceptable salt thereof in an acceptable solvent;
(B) adding a first hydroxypropyl methylcellulose (HPMC) of 6 mPa •s in an amount of
0.5% to 1.5% (w/w) of the formulation, a filling agent comprising lactose
monohydrate in an amount of 10% to 80% (w/w) of the formulation, and
pregelatinized starch to Step A, and forming a wet granulate;
(C) drying the wet granulate of Step B;
(D) blending the dried granulate from Step C with a retarding agent, wherein the release
retarding agent is in an amount of 10% to 30% (w/w) of the formulation, and
wherein the release retarding agent is equal parts of a second HPMC of 4000 mPa •s,
and lactose monohydrate; and
(E) compressing the final granulation from step D.
According to aspects of the invention illustrated herein, there is provided a sustained
release formulation of colchicine as an active ingredient, the formulation comprising colchicine
or a pharmaceutically acceptable salt thereof; a retarding agent; and at least one
pharmaceutically acceptable excipient.
According to aspects of the invention illustrated herein, there is provided a method for
treating and/or preventing a cardiovascular disease in a subject, comprising administering to the
subject a therapeutically effective amount of a sustained release formulation of colchicine.
According to aspects of the invention illustrated herein, there is provided a method for
treating and/or preventing an inflammatory disease in a subject, comprising administering
AH26(25575208_1):RTK
WE
Claims (30)
1. A sustained release formulation of colchicine, comprising: (a) granules comprising 0.5 mg of colchicine or a pharmaceutically acceptable salt thereof, and a first hydroxypropyl methylcellulose (HPMC) in an amount of 0.5% to 1.5% (w/w) of the formulation; (b) a release retarding agent admixed with the colchicine granules in an amount of 10% to 30% w/w of the formulation, wherein the release retarding agent is equal parts (w/w) of a second HPMC and lactose monohydrate; and (c) at least one pharmaceutically acceptable excipient admixed with the granules; wherein the viscosity of the second HPMC is higher than the viscosity of the first HPMC, wherein the formulation is in a form of a pill, a capsule, a caplet, a suppository, sublingual formulation, a pouch, a dermal patch, sprinkles, or in fixed combination with a surgically insertable medical device.
2. The formulation of claim 1, wherein less than 70% of the colchicine is released in vitro within 2 hours at 37 °C.
3. The formulation of claims 1 or 2, wherein the formulation releases at least about 20% of the colchicine in vitro within the first 30 minutes.
4. The formulation of any one of claims 1-3, wherein the first HPMC has a viscosity of 6 mP a •s and the second HPMC has a viscosity of 4000 mP a •s.
5. The formulation of any one of claims 1 to 4, wherein the pharmaceutically acceptable excipient comprises one or more of a binder, a filling agent, a glidant, and a lubricant.
6. The formulation of any one of claims 1 to 5, wherein the pharmaceutically acceptable excipient comprises a binder, and wherein the binder comprises one or more of starches, gelatin, polyvinylpyrrolidone, cellulose derivatives, and polyvinyl alcohol.
7. The formulation of claim 6, wherein the cellulose derivative is HPMC or hydroxypropyl cellulose (HPC).
8. The formulation of claim 6, wherein the cellulose derivative forms a hydrophilic matrix. AH26(25575208_1):RTK
9. The formulation of any one of claims 1 to 8, wherein the pharmaceutically acceptable excipient comprises a filling agent , and wherein the filling agent comprises one or more of sucrose, lactose, trehalose, maltose, mannitol, sorbitol, croscarmellose sodium, crospovidone, alginic acid, sodium alginate, methacrylic acid divinyl benzene (DVB), cross-linked polyvinylpyrrolidone (PVP), microcrystalline cellulose, polacrilin potassium, sodium starch glycolate, starch, and pregelatinized starch.
10. The formulation of claim 9, wherein the total amount of filling agent in the formulation is between about 5.0 wt % and 90.0 wt % of the formulation.
11. The formulation of any one of claims 1 to 10, wherein the pharmaceutically acceptable excipient is a glidant, and wherein the glidant comprises one or more of colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, talc, and tribasic calcium phosphate
12. The formulation of claim 11, wherein total amount of glidant in the formulation is between about 0.5 wt % to about 5 wt % of the formulation.
13. The formulation of any one of claims 1 to 12, wherein the pharmaceutically acceptable excipient is a lubricant, and wherein the lubricant comprises one or more of glyceryl behenate, stearic acid, hydrogenated vegetable oils, stearyl alcohol, leucine, polyethylene glycol, magnesium stearate, glyceryl monostearate, polyethylene glycol, ethylene oxide polymers, sodium lauryl sulfate, magnesium lauryl sulfate, sodium oleate, sodium stearyl fumarate, DL- leucine, and colloidal silica.
14. The formulation of claim 13, wherein the lubricant is included in an amount between about 0.5 wt % to about 5 wt % of the formulation.
15. The formulation of any one of claims 1 to 14, wherein the excipient is a starch, gelatin, polyvinylpyrrolidone (PVP), microcrystalline cellulose, hydroxypropyl cellulose (HPC), polyvinyl alcohol, or a mixture thereof.
16. The formulation of any one of claims 1 to 15, wherein the total amount of colchicine in the formulation is between about 0.25 wt % and about 0.75 wt % of the formulation.
17. The formulation of any one of claims 1 to 16, wherein the formulation comprises no immediate release component or layer. AH26(25575208_1):RTK
18. The formulation of any one of claims 1 to 17, wherein the formulation is formulated for once daily administration.
19. The formulation of any one of claims 1 to 18, wherein the formulation further comprises a statin.
20. The formulation of claim 19, wherein the statin is admixed with the formulation.
21. The formulation of claim 19 or claim 20, wherein the statin is one or more of atorvastatin, rosuvastatin, simvastatin, and pravastatin, or a salt thereof.
22. Use of a sustained release formulation of colchicine according to any one of claims 1-21, for the manufacture of a medicament for preventing and/or treating a cardiovascular disease in a subject in need thereof.
23. The use of claim 22, wherein the cardiovascular disease is acute pericarditis, recurrent pericarditis, post-pericardiotomy syndrome (PPS), or cardiovascular events in subjects with stable coronary disease.
24. The use of claim 22 or claim 23, wherein the composition further comprises a conventional therapy for long-term prevention of an acute cardiovascular event in subjects with established stable coronary disease.
25. The use of claim 24, wherein the acute cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke.
26. Use of a sustained release formulation of colchicine according to any one of claims 1 to 21, for the manufacture of a medicament for preventing and/or treating an inflammatory disease in a subject in need thereof.
27. The use of claim 26, wherein the inflammatory disease is gout, familial Mediterranean fever, Behcet´s disease, age-related macular degeneration, or Alzheimer´s disease.
28. A process of preparing a colchicine-sustained release formulation comprising: (A) forming a granulate by dissolving 0.5 mg of colchicine or a pharmaceutically acceptable salt thereof in an acceptable solvent; (B) adding a first hydroxypropyl methylcellulose (HPMC) of 6 mPa •s in an amount of AH26(25575208_1):RTK 0.5% to 1.5% (w/w) of the formulation, a filling agent comprising lactose monohydrate in an amount of 10% to 80% (w/w) of the formulation, and pregelatinized starch to Step A, and forming a wet granulate; (C) drying the wet granulate of Step B; (D) blending the dried granulate from Step C with a retarding agent, wherein the release retarding agent is in an amount of 10% to 30% (w/w) of the formulation, and wherein the release retarding agent is equal parts of a second HPMC of 4000 mPa •s, and lactose monohydrate; and (E) compressing the final granulation from step D.
29. The process of claim 28, further comprising adding talc as a glidant in Step D, and adding stearic acid as a lubricant in Step D.
30. The process of claims 28 or 29, wherein the amount of each component in the colchicine- sustained release formulation is as follows: Ingredient mg / Tablet Tablet Colchicine 0.500 0.5 Lactose monohydrate 59.00 59.0 Pregelatinized Starch 7.50 7.5 HPMC 6 mPa •s 1.000 1.0 Purified water q.s. q.s. lactose monohydrate 10.0 - 30.00 10.0 - and 30.0 HPMC 4000 mPa •s, (
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ751885A NZ751885B2 (en) | 2013-04-16 | 2014-04-16 | Sustained-release formulations of colchicine and methods of using same |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361812514P | 2013-04-16 | 2013-04-16 | |
| US61/812,514 | 2013-04-16 | ||
| EP13194505 | 2013-11-26 | ||
| EPEP13194505.7 | 2013-11-26 | ||
| PCT/IB2014/001201 WO2014170755A2 (en) | 2013-04-16 | 2014-04-16 | Sustained-release formulations of colchicine and methods of using same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ713151A NZ713151A (en) | 2021-01-29 |
| NZ713151B2 true NZ713151B2 (en) | 2021-04-30 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2593582T5 (en) | Coated tablet formulation and method | |
| JP2017222705A5 (en) | ||
| ES2465478T3 (en) | Pharmaceutical compositions comprising brivaracetam | |
| JP2015506377A5 (en) | ||
| CN110944638A (en) | Nilaparib compositions | |
| EP0749308B1 (en) | Film coated tablet of paracetamol and domperidone | |
| JP2015501808A5 (en) | ||
| KR101272470B1 (en) | Immediate-release and sustained-release pharmaceutical composition comprising levodropropizine | |
| CA3097053A1 (en) | Edaravone pharmaceutical composition | |
| KR20180083239A (en) | Oral composition of sustained-release formular containing limaprost or limaprost alfadex | |
| ES2508490T3 (en) | Formulation of trimetazidine with different release profiles | |
| US20150366850A1 (en) | Modified release pharmaceutical compositions of dexmethylphenidate or salts thereof | |
| KR101497354B1 (en) | Slow release pharmaceutical composition having Eperisone as active ingredient | |
| ES2693156T3 (en) | Sustained-release tablet containing levodropropizine and method to prepare it | |
| KR100844256B1 (en) | Pharmaceutical composition and preparation for treatment of metabolic bone disease comprising risedronate and vitamin d | |
| NZ713151B2 (en) | Sustained-release formulations of colchicine and methods of using same | |
| NZ713151A (en) | Sustained-release formulations of colchicine and methods of using same | |
| KR20120120519A (en) | Combination preparations comprising niacin and hmg-coa reductase inhibitor and the preparation method thereof | |
| WO2013154512A1 (en) | Pharmaceutical formulations comprising dexibuprofen | |
| WO2019209217A2 (en) | Modified release formulations of flurbiprofen | |
| RU2603469C2 (en) | Controlled-release pharmaceutical tablet for oral administration methods for preparation thereof | |
| BRPI0617184A2 (en) | delayed-release pralnacasan formulation | |
| NZ751885B2 (en) | Sustained-release formulations of colchicine and methods of using same | |
| JP2020125335A5 (en) | ||
| KR20160059442A (en) | Novel formulation of cilostazol, a quinolinone-derivative used for alleviating the symptom of intermittent claudication in patients with peripheral vascular disease |