TR2021001817A2 - A FILM COATED TABLET CONTAINING NALTREXONE HYDROCHLORIDE - Google Patents
A FILM COATED TABLET CONTAINING NALTREXONE HYDROCHLORIDEInfo
- Publication number
- TR2021001817A2 TR2021001817A2 TR2021/001817A TR2021001817A TR2021001817A2 TR 2021001817 A2 TR2021001817 A2 TR 2021001817A2 TR 2021/001817 A TR2021/001817 A TR 2021/001817A TR 2021001817 A TR2021001817 A TR 2021001817A TR 2021001817 A2 TR2021001817 A2 TR 2021001817A2
- Authority
- TR
- Turkey
- Prior art keywords
- film
- coated tablet
- sodium
- naltrexone hydrochloride
- tablet according
- Prior art date
Links
- 239000007941 film coated tablet Substances 0.000 title claims abstract description 39
- 229960000858 naltrexone hydrochloride Drugs 0.000 title claims abstract description 34
- ZFSXKSSWYSZPGQ-UHFFFAOYSA-N (2-hydroxycyclopentyl)azanium;chloride Chemical compound Cl.NC1CCCC1O ZFSXKSSWYSZPGQ-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 239000002245 particle Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 7
- 239000011230 binding agent Substances 0.000 claims description 13
- 239000003826 tablet Substances 0.000 claims description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 229930195725 Mannitol Natural products 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 11
- 239000000594 mannitol Substances 0.000 claims description 11
- 235000010355 mannitol Nutrition 0.000 claims description 11
- 229960001855 mannitol Drugs 0.000 claims description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- 239000008109 sodium starch glycolate Substances 0.000 claims description 8
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 8
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 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
- 239000007884 disintegrant Substances 0.000 claims description 5
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 238000007873 sieving Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000378 calcium silicate Substances 0.000 claims description 4
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 4
- 235000012241 calcium silicate Nutrition 0.000 claims description 4
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 229940032147 starch Drugs 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- 238000005550 wet granulation Methods 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 239000008121 dextrose Substances 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 claims description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate 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)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 229920000148 Polycarbophil calcium Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- 229960004977 anhydrous lactose Drugs 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 235000001465 calcium Nutrition 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims description 2
- 229960003340 calcium silicate Drugs 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229940096516 dextrates Drugs 0.000 claims description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 2
- RRPFCKLVOUENJB-UHFFFAOYSA-L disodium;2-aminoacetic acid;carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O.NCC(O)=O RRPFCKLVOUENJB-UHFFFAOYSA-L 0.000 claims description 2
- 229960000878 docusate sodium Drugs 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 2
- 239000000832 lactitol Substances 0.000 claims description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 2
- 235000010448 lactitol Nutrition 0.000 claims description 2
- 229960003451 lactitol Drugs 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229960001021 lactose monohydrate Drugs 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 2
- 239000000395 magnesium oxide Substances 0.000 claims description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 2
- 229960000869 magnesium oxide Drugs 0.000 claims description 2
- 235000012245 magnesium oxide Nutrition 0.000 claims description 2
- 239000000391 magnesium silicate Substances 0.000 claims description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 claims description 2
- 235000019792 magnesium silicate Nutrition 0.000 claims description 2
- 229960002366 magnesium silicate Drugs 0.000 claims description 2
- VIOAGOMGEZTUHG-UHFFFAOYSA-L magnesium;2-hydroxyacetate;octadecanoate Chemical compound [Mg+2].OCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O VIOAGOMGEZTUHG-UHFFFAOYSA-L 0.000 claims description 2
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000008188 pellet Substances 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 229940070721 polyacrylate Drugs 0.000 claims description 2
- 229950005134 polycarbophil Drugs 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 150000004804 polysaccharides Chemical class 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229960003975 potassium Drugs 0.000 claims description 2
- 235000007686 potassium Nutrition 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229940083542 sodium Drugs 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229940080281 sodium chlorate Drugs 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims 1
- 235000010980 cellulose Nutrition 0.000 claims 1
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- 235000019700 dicalcium phosphate Nutrition 0.000 claims 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims 1
- HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical compound C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 claims 1
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000009472 formulation Methods 0.000 abstract description 3
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 6
- 229960003086 naltrexone Drugs 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229940005483 opioid analgesics Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- -1 or other opioids Chemical compound 0.000 description 2
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- 238000010561 standard procedure Methods 0.000 description 2
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Abstract
Mevcut buluş naltrekson hidroklorür ve farmasötik olarak kabul edilebilir en az bir yardımcı madde içeren film kaplı bir tabletle ilgili olup burada naltrekson hidroklorür 50 µm’#&den küçük bir d (0.9) parçacık boyutuna sahiptir. Buna ilaveten, mevcut buluş, naltrekson hidroklorür içeren film kaplı bir tablet formülasyonunun hazırlanmasına ilişkin bir prosesi de açıklamaktadır. Söz konusu proses basit, hızlı, fiyat olarak uygun, zaman kazandıran ve endüstriyel olarak uygun bir prosestir.The present invention relates to a film-coated tablet containing naltrexone hydrochloride and at least one pharmaceutically acceptable excipient, wherein naltrexone hydrochloride has a d (0.9) particle size of less than 50 µm. In addition, the present invention discloses a process for preparing a film-coated tablet formulation containing naltrexone hydrochloride. The process in question is simple, fast, affordable, time-saving and industrially suitable.
Description
TARIFNAME NALTREKSON HIDROKLORÜR IÇEREN BIR FILM KAPLI TABLET Bulusun Alani Mevcut bulus naltrekson hidroklorür ve farmasötik olarak kabul edilebilir en az bir yardimci madde içeren film kapli bir tabletle ilgili olup burada naltrekson hidroklorür 50 um"den küçük bir d (0.9) parçacik boyutuna sahiptir. Buna ilaveten, mevcut bulus, naltrekson hidroklorür içeren film kapli bir tablet formülasyonunun hazirlanmasina iliskin bir prosesi de açiklamaktadir. Söz konusu proses basit, hizli, fiyat olarak uygun, zaman kazandiran ve endüstriyel olarak uygun bir prosestir. Bulusun Arka Plani Opioidler, kullanilan farmasötik maddeye bagli olarak farkli derecelerde potenslere sahip analjezik ve antinosiseptif bir yanit üreten ilaçlardir. Naltrekson, uygulanan hem opioid agonistlerinin hem de opioid sisteminden türetilen endojen agonistlerin farmakolojik etkilerini inhibe edebilen bir opioid antagonistidir. Naltrekson Hidroklorür, rekabetçi opioid antagonistik aktiviteye sahip bir noroksimorfon türevi olan naltreksonun hidroklorür tuzudur. Naltrekson hidroklorürün kimyasal adi 17- (Siklopropilmetil)-4,5-alfa-epoksi-3,14-dihidroksi-morfinan-6-on hidroklorür olup kimyasal yapisi Formül 1'de gösterilmektedir. Formül I Naltrekson bilesigi ve söz konusu bilesigin sentezi için yöntemler ABD Patent No. 3,332,950'de tarif edilmektedir. Morfin, eroin ya da diger opioidlerle birlikte kronik olarak yeterli miktarda uygulandiginda, naltrekson opioidlere fiziksel bagimliligin insidansini azaltabilmektedir. Naltrekson hidroklorür, alkol bagimliliginin tedavisi ve eksojen olarak uygulanan opioidlerin bloke edilmesi için tablet formunda ticari olarak temin edilebilmektedir (Revia®, DuPont). Naltrekson hidroklorür, çözünürlügü çok düsük bir ilaçtir. Farmasötik kompozisyonun gerçek üretiminde, genellikle düsük çözünme ya da hatta niteliksizlik gibi problemlerle karsilasilmaktadir. Buna ilaveten, farmasötik olarak kabul edilebilir bir kompozisyon için gerekliliklerden biri, kompozisyonun üretimi ile hasta tarafindan kullanilmasi arasindaki süre boyunca etken maddenin önemli ölçüde ayrismasini sergilemeyecek sekilde kararli olmasi gerektigidir. Naltrekson hidroklorürün, muhtemelen isi, isik ve/veya oksijen nedeniyle depolama esnasinda bozunabilecegi bulunmustur. Bu basvuruda, naltrekson hidroklorür, teknigin bilinenen durumunda açiklanan sorunlarin üstesinden gelmek için 50 um'den küçük bir d (0.9) parçacik boyutuna sahiptir. Ayrica, film kapli bir tablet farmasötik bir kompozisyon olarak da kullanilmaktadir. Bu sekilde, bu, tablet için istenen çözünürlügü, içerik bütünlügünü ve sikistirilabilirligi saglamaktadir. Ayrica, film kapli tablet, basit ve uygun maliyetli yöntemler olan standart teknikler kullanilarak gelistirilmistir. Bulusun Detayli Açiklamasi Mevcut bulusun temel amaci naltrekson hidroklorür içeren film kapli bir tablet saglamak olup burada tablet, naltrekson hidroklorürün üretimi, depolanmasi ve dagitimi sirasinda yeterli stabiliteye sahiptir ve ayrica tablet, istenen çözünme profiline sahiptir. Mevcut bulusun bir diger amaci da iyilestirilmis içerik bütünlügüne ve sikistirilabilirlige sahip film kapli birtablet saglamaktir. Mevcut bulusun bu düzenlemesine göre, naltreksonun hassas bir molekül olmasindan ötürü en iyi oral formun film kapli bir tablet oldugunu bulduk. Film kapli bir tablet naltrekson hidroklorürün bir farmasötik formu olarak kullanilmaktadir. Film kaplama, etken maddenin stabilitesini korumak için neme ve isiga karsi korumaktadir. Asagidaki parçacik boyutlarina sahip olan naltrekson hidroklorürün formülasyon için çok önemli oldugunu bulduk. Özellikle çözünme özelliklerini ve toz homojenizasyonunu olumlu bir biçimde etkilemektedir. Elde edilen tabletler istenen çözünme profiline sahiptir. Toz daha homojendir. Daha homojen tozdan elde edilen tabletlerin içerik bütünlügü daha idealdir. Bu sebeple, daha iyi bir biyoyararlanim saglamaktadir. Burada kullanildigi sekliyle "parçacik boyutu" lazer kirinimi yöntemi (yani malvern analizi) gibi konvansiyonel olarak kabul görmüs herhangi bir yöntem ile test edilen kümülatif hacim boyut dagilimi anlamina gelmektedir. D (0.1) terimi, parçaciklarin hacimce % 10'unun daha ince oldugu boyut anlamina gelmekte ve d (0.5), parçaciklarin hacimce % 50'sinin daha ince oldugu boyut anlamina gelmekte ve d (0.9), parçaciklarin hacimce % 90"inin daha ince oldugu boyut anlamina gelmektedir. Mevcut bulusun bu düzenlemesine göre, film kapli bir tablet naltrekson hidroklorür ve en az bir farmasötik olarak kabul edilebilir yardimci madde içermekte olup, burada naltrekson hidroklorür 50 um'den küçük bir d (0.9) parçacik boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, naltrekson hidroklorür 45 um'den küçük, tercihen de 40 um"den küçük bir d (0.9) parçacik boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, naltrekson hidroklorür 20 um'den küçük, tercihen de 18 um"den küçük bir d (0.5) parçacik boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, naltrekson hidroklorür 10 um'den küçük, tercihen de 8 um'den küçük bir d (0.1) parçacik boyutuna sahiptir. Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette naltrekson hidroklorürün Mevcut bulusun bu düzenlemesine göre, farmasötik olarak kabul edilebilir yardimci maddeler dolgu maddeleri, baglayicilar, dagiticilar, kayganlastiricilar/kaydiricilar ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Uygun dolgu maddeleri mikrokristalin selüloz, mannitol, laktoz monohidrat, susuz laktoz, sorbitol, sukroz, inorganik tuzlar, kalsiyum tuzlari, püskürtülerek kurutulmus laktoz, kalsiyum silikat, polisakkaritler, dekstroz, sodyum klorür, dekstratlar, laktitol, seker peleti, nisasta, maltodekstrin, dibazik kalsiyum fosfat ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bu düzenlemesine göre, dolgu maddesi mikrokristalin selüloz ya da mannitol ya da bunlarin karisimidir. Baglayicilarin kullanilmasi istenen çözünme profillerinin elde edilmesine yardimci olmaktadir. Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette dolgu maddelerinin miktari Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette mannitolün miktari Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette mikrokristalin selülozün Uygun baglayicilar, polivinilpirolidon, hidroksipropil metilselüloz, önceden jelatinize edilmis nisasta, misir nisastasi, dogal zamkIar, jelatin, karbomerler, karboksimetilselüloz sodyum, selüloz asetat ftalat, kitosan, dekstroz, etilselüloz, gliseril behenat, hidroksietil selüloz, hidroksietilmetil selüloz, hidroksipropil selüloz, hidroksipropil nisasta, magnezyum alüminyum silikat, poloksamer, polikarbofil, polidekstroz, polietilen oksit, polimetakrilatlar, alümina hidroksit, setostearil alkol, polioksietilen-alkil eterler ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Mevcut bulusun bu düzenlemesine göre, baglayici polivinilpirolidondur. Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette baglayicilarin miktari agirlikça % 1.0 ile % 7.0 arasinda, tercihen agirlikça % 1.0 ile % 5.0 arasindadir. Raf ömrü süresince ideal dagilma süresini elde etmek için yardimci maddelerin seçimi daha da önemlidir. Özellikle dagitici seçimi büyük rol oynamaktadir. Bu nedenle de uygun bir parçalayici ve en uygun kullanim seviyesinin seçimi, yüksek bir dagilma orani saglamak açisindan çok önemlidir. Uygun dagiticilar, krospovidon, povidon, kroskarmeloz sodyum, düsük ikameli hidroksipropil selüloz, sodyum karboksimetil selüloz, kalsiyum karboksimetil selüloz, karboksimetil selüloz, dokusat sodyum, poliakrilat potasyum, sodyum aljinat, alginik asit, magnezyum alüminyum silika, sülfat, poloksamer, sodyum glisin karbonat ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Bulusun bu düzenlemesine göre, dagitici sodyum nisasta glikolattir. Mevcut bulusun bu düzenlemesine göre, toplam film kapli tablette dagiticilarin miktari agirlikça % 2.0 ile % 10.0 arasinda, tercihen agirlikça % 3.0 ile % 8.0 arasindadir. Uygun kayganlastiricilar/kaydiricilar magnezyum stearat, sodyum stearil fumarat, kolloidal silikon dioksit, kalsiyum stearat, çinko stearat, talk, silikon dioksit, talk, alüminyum silikat, kalsiyum silikat, magnezyum silikat, magnezyum oksit, nisasta, sodyum klorat, magnezyum lauril sülfat, sodyum oleat, sodyum asetat, sodyum benzoat, polietilen glikol, stearik asit, fumarik asit, gliseril palmito sülfat, sodyum lauril sülfat ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Bulusun bu düzenlemesine göre, kayganlastirici/kaydirici magnezyum stearattir. Mevcut bulusun film kapli tableti örnegin dogrudan sikistirma, islak ya da kuru granülasyon, sicak eriyik granülasyoun, sicak eriyik ekstrüzyon, akiskan yatakli granülasyon, ekstrüzyon/sferonizasyon, slugging, püskürtmeli kurutma ve çözücü buharlastirma gibi teknigin mevcut durumunda iyi bilinen standart teknikler ya da üretim prosesleri kullanilarak hazirlanabilir. Bulusun bu düzenlemesine göre, mevcut bulusun film kapli tableti islak granülasyon kullanilarak hazirlanabilmektedir. Bu sekilde, etken maddenin dezavantajlarini ortadan kaldirmak için kolay bir yöntem gelistirilmistir. Mevcut bulusun bu düzenlemesine göre, islak granülasyonda bir çözücü kullanilmaktadir. Uygun çözücüler saf su, diklorometan, 0.1N HCI, metanol, etanol, izopropil alkol, benzil alkol, propilen glikol, polietilen glikol, gliserin, siklometikon, gliserin triasetat, dietilen glikol monoetil eter ya da bunlarin karisimlarini içeren gruptan seçilmektedir. Çözücü tercihen sudur. Mevcut bu bulusta, film kapli tabletin istenen bir sikistirilabilirligi ve istenen bir içerik bütünlügü saglanmistir ve endüstriyel üretim lehine basit bir hazirlik prosesine sahiptir. Mevcut bulusun bu düzenlemesine göre, film kapli tablet sunlari içermektedir; - Naltrekson hidroklorür - Mannitol - Mikrokristalin selüloz - Polivinilpirolidon - Sodyum nisasta glikolat - Magnezyum stearat. Mevcut bulusun bu düzenlemesine göre, film kapli tabletin hazirlanmasi için bir proses ayrica asagidaki adimlari içermektedir: a) Naltrekson hidroklorür, mannitol, mikrokristalin selüloz ve sodyum nisasta glikolatin elekten geçirilmesi ve ardindan islak granülatörde karistirilmasi, b) Polivinilpirolidonun suda çözülmesi ve bir baglayici çözeltinin elde edilmesi, c) (a) adimindaki karisim ve (b) adimindaki baglayici çözeltinin karistirilmasi, d) Islak granüllerin kurutulmasi, e) Kuru granüllerin elekten geçirilmesi, f) Magnezyum stearat eklenmesi ve ardindan karistirilmasi, g) Hazirlanmis olan karisimin tabletler olusturmak üzere sikistirilmasi, h) Bu tabletlerin film kaplama ile kaplanmasi. Örnek 1: Naltrekson hidroklorür içeren film kapli tablet agirliginin %'si cinsinden) Naltrekson hidroklorür 12.0 - 25.0 Mannitol 41.0 - 60.0 Mikrokristalin selüloz 14.0 - 25.0 Polivinilpirolidon 1.0 - 7.0 Sodyum nisasta glikolat 2.0 - 10.0 Magnezyum stearat. 0.5 - 3.0 Film kaplama 2.0 - 5.0 Toplam 100 Örnek 1 için bir proses: Naltrekson hidroklorür, mannitol, mikrokristalin selüloz ve sodyum nisasta glikolatin elekten geçirilmesi ve ardindan islak granülatörde karistirilmasi, Polivinilpirolidonun suda çözülmesi ve bir baglayici çözeltinin elde edilmesi, (a) adimindaki karisim ve (b) adimindaki baglayici çözeltinin karistirilmasi, Kuru granüllerin elekten geçirilmesi, Magnezyum stearat eklenmesi ve ardindan karistirilmasi, Hazirlanmis olan karisimin tabletler olusturmak üzere sikistirilmasi, Bu tabletlerin film kaplama ile kaplanmasi. TR TR TR TR DESCRIPTION A FILM-COATED TABLET CONTAINING NALTREXONE HYDROCHLORIDE Field of the Invention The present invention relates to a film-coated tablet comprising naltrexone hydrochloride and at least one pharmaceutically acceptable excipient, wherein the naltrexone hydrochloride has a particle size d (0.9) of less than 50 µm. The present invention also discloses a process for the preparation of a film-coated tablet formulation containing naltrexone hydrochloride. The process is simple, rapid, affordable, time-saving and industrially suitable. Background of the Invention Opioids differ depending on the pharmaceutical substance used. Naltrexone is an opioid antagonist that can inhibit the pharmacological effects of both opioid agonists and endogenous agonists derived from the opioid system. It is the hydrochloride salt of naltrexone, a noroxymorphone derivative with competitive opioid antagonistic activity. The chemical name of naltrexone hydrochloride is 17- (Cyclopropylmethyl)-4,5-alpha-epoxy-3,14-dihydroxy-morphinan-6-one hydrochloride and its chemical structure is shown in Formula 1. The compound of Formula I Naltrexone and methods for synthesizing said compound are disclosed in US Patent No. It is described in No. 3,332,950. When administered chronically in sufficient amounts in combination with morphine, heroin, or other opioids, naltrexone may reduce the incidence of physical dependence to opioids. Naltrexone hydrochloride is commercially available in tablet form for the treatment of alcohol dependence and for blocking exogenously administered opioids (Revia®, DuPont). Naltrexone hydrochloride is a drug with very low solubility. In the actual production of the pharmaceutical composition, problems such as low solubility or even lack of quality are often encountered. In addition, one of the requirements for a pharmaceutically acceptable composition is that the composition must be stable so as not to exhibit significant degradation of the active ingredient during the period between its manufacture and use by the patient. Naltrexone hydrochloride has been found to degrade during storage, possibly due to heat, light and/or oxygen. In this application, naltrexone hydrochloride has a particle size d (0.9) of less than 50 µm to overcome the problems disclosed in the prior art. Additionally, a film-coated tablet is also used as a pharmaceutical composition. In this way, this provides the desired solubility, content integrity and compressibility for the tablet. Moreover, the film-coated tablet was developed using standard techniques, which are simple and cost-effective methods. Detailed Description of the Invention The primary object of the present invention is to provide a film-coated tablet containing naltrexone hydrochloride, wherein the tablet has sufficient stability during the production, storage and distribution of naltrexone hydrochloride and furthermore, the tablet has the desired dissolution profile. Another object of the present invention is to provide a film-coated tablet with improved content integrity and compressibility. According to this embodiment of the present invention, we have found that the best oral form is a film-coated tablet because naltrexone is a sensitive molecule. A film-coated tablet is used as a pharmaceutical form of naltrexone hydrochloride. The film coating protects against moisture and light to maintain the stability of the active ingredient. We found that naltrexone hydrochloride having the following particle sizes is very important for the formulation. It particularly affects dissolution properties and powder homogenization positively. The resulting tablets have the desired dissolution profile. The powder is more homogeneous. The content integrity of tablets obtained from more homogeneous powder is more ideal. For this reason, it provides better bioavailability. As used herein, "particle size" means the cumulative volume size distribution tested by any conventionally accepted method, such as the laser diffraction method (i.e., malvern analysis). The term d (0.1) means the size at which 10% of the particles by volume are finer, d (0.5) means the size at which 50% of the particles by volume are finer, and d (0.9) means the size at which 90% of the particles by volume are finer. According to this embodiment of the present invention, a film-coated tablet comprises naltrexone hydrochloride and at least one pharmaceutically acceptable excipient, wherein the naltrexone hydrochloride has a particle size d (0.9) of less than 50 µm. According to its embodiment, naltrexone hydrochloride has a particle size d (0.9) of less than 45 µm, preferably less than 40 µm. According to this embodiment of the present invention, naltrexone hydrochloride has a particle size d (0.5) of less than 20 µm, preferably less than 18 µm. According to this embodiment of the present invention, naltrexone hydrochloride has a particle size of less than 10 µm, preferably less than 8 µm. According to this embodiment of the present invention, naltrexone hydrochloride in the total film-coated tablet has a small particle size d (0.1). According to this embodiment of the present invention, pharmaceutically acceptable excipients are from the group comprising fillers, binders, dispersants, lubricants, or mixtures thereof. Suitable fillers are selected: microcrystalline cellulose, mannitol, lactose monohydrate, anhydrous lactose, sorbitol, sucrose, inorganic salts, calcium salts, spray-dried lactose, calcium silicate, polysaccharides, dextrose, sodium chloride, dextrates, lactitol, sugar pellet, starch, maltodextrin. According to this embodiment of the present invention, the filler is microcrystalline cellulose or mannitol, or mixtures thereof. The use of binders helps to obtain the desired dissolution profiles. According to this embodiment of the present invention, the amount of fillers in the total film-coated tablet. According to this embodiment of the present invention, the amount of mannitol in the total film-coated tablet. According to this embodiment of the present invention, the amount of microcrystalline cellulose in the total film-coated tablet. Suitable binders include polyvinylpyrrolidone, hydroxypropyl methylcellulose, pregelatinized starch, corn starch, natural gums, gelatin, carbomers, carboxymethylcellulose sodium, cellulose acetate phthalate, chitosan, dextrose, ethylcellulose, glyceryl behenate, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hydroxypropyl starch, magnesium aluminum silicate, polycarbophil. , polydextrose, polyethylene oxide , polymethacrylates, alumina hydroxide, cetostearyl alcohol, polyoxyethylene-alkyl ethers, or mixtures thereof. According to this embodiment of the present invention, the binder is polyvinylpyrrolidone. According to this embodiment of the present invention, the amount of binders in the total film-coated tablet is between 1.0 and 7.0% by weight, preferably between 1.0 and 5.0% by weight. The selection of excipients is even more important to achieve the ideal disintegration time during shelf life. Particularly the choice of distributor plays a big role. Therefore, choosing a suitable shredder and the most appropriate usage level is very important to ensure a high dispersion rate. Suitable disintegrants are crospovidone, povidone, croscarmellose sodium, low substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, docusate sodium, polyacrylate potassium, sodium alginate, alginic acid, magnesium aluminum silica, sulfate, poloxamer, sodium glycine carbonate or is selected from the group containing mixtures of these. According to this embodiment of the invention, the dispersant is sodium starch glycolate. According to this embodiment of the present invention, the amount of disintegrants in the total film-coated tablet is between 2.0 and 10.0% by weight, preferably between 3.0 and 8.0% by weight. Suitable lubricants/lubricants are magnesium stearate, sodium stearyl fumarate, colloidal silicon dioxide, calcium stearate, zinc stearate, talc, silicon dioxide, talc, aluminum silicate, calcium silicate, magnesium silicate, magnesium oxide, starch, sodium chlorate, magnesium lauryl sulfate, sodium. oleate, sodium acetate, sodium benzoate, polyethylene glycol, stearic acid, fumaric acid, glyceryl palmito sulfate, sodium lauryl sulfate, or mixtures thereof. According to this embodiment of the invention, the lubricant is magnesium stearate. The film-coated tablet of the present invention can be manufactured using standard techniques or manufacturing processes well known in the state of the art, such as direct compression, wet or dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, slugging, spray drying and solvent evaporation. It can be prepared using . According to this embodiment of the invention, the film-coated tablet of the present invention can be prepared using wet granulation. In this way, an easy method has been developed to eliminate the disadvantages of the active ingredient. According to this embodiment of the present invention, a solvent is used in wet granulation. Suitable solvents are selected from the group consisting of pure water, dichloromethane, 0.1N HCl, methanol, ethanol, isopropyl alcohol, benzyl alcohol, propylene glycol, polyethylene glycol, glycerin, cyclomethicone, glycerin triacetate, diethylene glycol monoethyl ether, or mixtures thereof. The solvent is preferably water. In this present invention, a desired compressibility and a desired content integrity of the film-coated tablet is achieved and has a simple preparation process in favor of industrial production. According to this embodiment of the present invention, the film-coated tablet includes; - Naltrexone hydrochloride - Mannitol - Microcrystalline cellulose - Polyvinylpyrrolidone - Sodium starch glycolate - Magnesium stearate. According to this embodiment of the present invention, a process for preparing the film-coated tablet further includes the following steps: a) Sifting naltrexone hydrochloride, mannitol, microcrystalline cellulose and sodium starch glycolate and then mixing in a wet granulator, b) Dissolving polyvinylpyrrolidone in water and obtaining a binder solution. , c) Mixing the mixture in step (a) and the binder solution in step (b), d) Drying the wet granules, e) Sieving the dry granules, f) Adding magnesium stearate and then mixing, g) Compressing the prepared mixture to form tablets, h) ) These tablets are coated with film coating. Example 1: (in % of weight of film-coated tablet containing Naltrexone hydrochloride) Naltrexone hydrochloride 12.0 - 25.0 Mannitol 41.0 - 60.0 Microcrystalline cellulose 14.0 - 25.0 Polyvinylpyrrolidone 1.0 - 7.0 Sodium starch glycolate 2.0 - 10.0 Magnesium stear horse 0.5 - 3.0 Film coating 2.0 - 5.0 Total 100 A process for Example 1: Sieving naltrexone hydrochloride, mannitol, microcrystalline cellulose and sodium starch glycolate and then mixing in a wet granulator, Dissolving polyvinylpyrrolidone in water and obtaining a binder solution, the mixture in step (a) and mixing the binder solution in step (b), sieving the dry granules, adding magnesium stearate and then mixing, compressing the prepared mixture to form tablets, coating these tablets with film coating. TR TR TR TR
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| TR2021/001817A TR2021001817A2 (en) | 2021-02-09 | 2021-02-09 | A FILM COATED TABLET CONTAINING NALTREXONE HYDROCHLORIDE |
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| Application Number | Priority Date | Filing Date | Title |
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| TR2021/001817A TR2021001817A2 (en) | 2021-02-09 | 2021-02-09 | A FILM COATED TABLET CONTAINING NALTREXONE HYDROCHLORIDE |
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