WO2012120364A2 - Novel immediate release film coating compositions - Google Patents
Novel immediate release film coating compositions Download PDFInfo
- Publication number
- WO2012120364A2 WO2012120364A2 PCT/IB2012/000431 IB2012000431W WO2012120364A2 WO 2012120364 A2 WO2012120364 A2 WO 2012120364A2 IB 2012000431 W IB2012000431 W IB 2012000431W WO 2012120364 A2 WO2012120364 A2 WO 2012120364A2
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- WO
- WIPO (PCT)
- Prior art keywords
- composition
- range
- group
- polymer
- phthalate
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- 239000000203 mixture Substances 0.000 title claims abstract description 118
- 239000007888 film coating Substances 0.000 title claims abstract description 35
- 238000009501 film coating Methods 0.000 title claims abstract description 35
- 239000012729 immediate-release (IR) formulation Substances 0.000 title claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 31
- 229920000642 polymer Polymers 0.000 claims description 65
- 239000002131 composite material Substances 0.000 claims description 43
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 42
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 26
- 239000011248 coating agent Substances 0.000 claims description 26
- 238000000576 coating method Methods 0.000 claims description 26
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 26
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 26
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 26
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 25
- 239000004014 plasticizer Substances 0.000 claims description 21
- 239000006185 dispersion Substances 0.000 claims description 19
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 19
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 19
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000004615 ingredient Substances 0.000 claims description 18
- 239000003995 emulsifying agent Substances 0.000 claims description 17
- 239000000080 wetting agent Substances 0.000 claims description 17
- 239000000758 substrate Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 14
- 229920000053 polysorbate 80 Polymers 0.000 claims description 14
- 239000000049 pigment Substances 0.000 claims description 13
- 239000003086 colorant Substances 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 12
- 229940068968 polysorbate 80 Drugs 0.000 claims description 12
- -1 sorbitan ester Chemical class 0.000 claims description 11
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 239000004408 titanium dioxide Substances 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 7
- 239000003605 opacifier Substances 0.000 claims description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 claims description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 5
- 229940031954 dibutyl sebacate Drugs 0.000 claims description 5
- 235000013305 food Nutrition 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004166 Lanolin Substances 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 4
- 229920001219 Polysorbate 40 Polymers 0.000 claims description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 4
- 235000009508 confectionery Nutrition 0.000 claims description 4
- 235000015872 dietary supplement Nutrition 0.000 claims description 4
- MQHNKCZKNAJROC-UHFFFAOYSA-N dipropyl phthalate Chemical compound CCCOC(=O)C1=CC=CC=C1C(=O)OCCC MQHNKCZKNAJROC-UHFFFAOYSA-N 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 235000003599 food sweetener Nutrition 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 229940039717 lanolin Drugs 0.000 claims description 4
- 235000019388 lanolin Nutrition 0.000 claims description 4
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 4
- 239000003765 sweetening agent Substances 0.000 claims description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 4
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 4
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 3
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 3
- 239000008213 purified water Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 claims description 2
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical class CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 claims description 2
- 108010011485 Aspartame Proteins 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
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- 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 claims description 2
- YIKYNHJUKRTCJL-UHFFFAOYSA-N Ethyl maltol Chemical compound CCC=1OC=CC(=O)C=1O YIKYNHJUKRTCJL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 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 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 235000021314 Palmitic acid Nutrition 0.000 claims description 2
- 239000004264 Petrolatum Substances 0.000 claims description 2
- 229920002675 Polyoxyl Polymers 0.000 claims description 2
- 239000004349 Polyvinylpyrrolidone-vinyl acetate copolymer Substances 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 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 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000004203 carnauba wax Substances 0.000 claims description 2
- 235000013869 carnauba wax Nutrition 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 229960001777 castor oil Drugs 0.000 claims description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 claims description 2
- 229960000541 cetyl alcohol Drugs 0.000 claims description 2
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 2
- 235000019864 coconut oil Nutrition 0.000 claims description 2
- 239000003240 coconut oil Substances 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 229920001531 copovidone Polymers 0.000 claims description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 2
- 229960000878 docusate sodium Drugs 0.000 claims description 2
- 150000002148 esters Chemical class 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
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
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- 229940093503 ethyl maltol Drugs 0.000 claims description 2
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- 239000008103 glucose Substances 0.000 claims description 2
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- 229960005150 glycerol Drugs 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 150000002314 glycerols Chemical class 0.000 claims description 2
- 229940049654 glyceryl behenate Drugs 0.000 claims description 2
- 229940046813 glyceryl palmitostearate Drugs 0.000 claims description 2
- 150000002334 glycols Chemical class 0.000 claims description 2
- 239000011874 heated mixture Substances 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
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- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
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- 235000010445 lecithin Nutrition 0.000 claims description 2
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- 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
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
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- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
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- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 claims description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
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- 239000011787 zinc oxide Substances 0.000 claims description 2
- 235000010216 calcium carbonate Nutrition 0.000 claims 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 claims 1
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- 238000004519 manufacturing process Methods 0.000 claims 1
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- 239000002245 particle Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 2
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 2
- 235000019645 odor Nutrition 0.000 description 2
- 238000007781 pre-processing Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 1
- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 description 1
- QFMDFTQOJHFVNR-UHFFFAOYSA-N 1-[2,2-dichloro-1-(4-ethylphenyl)ethyl]-4-ethylbenzene Chemical compound C1=CC(CC)=CC=C1C(C(Cl)Cl)C1=CC=C(CC)C=C1 QFMDFTQOJHFVNR-UHFFFAOYSA-N 0.000 description 1
- NMSBTWLFBGNKON-UHFFFAOYSA-N 2-(2-hexadecoxyethoxy)ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCO NMSBTWLFBGNKON-UHFFFAOYSA-N 0.000 description 1
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960002380 dibutyl phthalate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940086721 perfect coat Drugs 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Definitions
- the present invention relates to novel immediate release film coating compositions having enhanced adhesion and tensile strength.
- the invention relates to the field of coating compositions for substrates like pharmaceutical tablets, nutritional supplements, food products, confectionery, agricultural seeds and the like.
- Film coating is a process in which substrate like tablet, confectionary or a seed is enveloped by a thin layer of polymeric material. Most pharmaceutical materials, food products, confectionery, nutritional supplements, agricultural seeds and the like, need coating on their surface. The reasons for coating may be various and include protection of unstable compositions, protection in the stomach with enteric coating, improving the appearance of the tablet, separation of the ingredients of a tablet if they are incompatible, and masking objectionable odors and taste.
- PVA polyvinyl alcohol
- WO20061 11980 discloses a dry /liquid film coating composition having polyvinyl alcohol and self-emulsifying glyceryl monostearate (GMS)as an anti-tack agent.
- GMS self-emulsifying glyceryl monostearate
- This application utilizes hot water for the reconstitution of the anti-tack agent toprovide final film coating. This may not be suitable for heat sensitive ingredients/drugs.
- maintaining a high temperature during spraying is cumbersome in an Industrial set up.Notwithstanding, the viscosity of the final film coating composition resulting from the disclosure in this application is very high which may lead to spray related problems.
- WO2003/GB03195 also attempts to eliminate tackiness by combiningEudragit with GMS along with surface active agent.
- the composition needs to be solubilized at a high temperature to provide working film coating formulationand hence not suitable at several instances.
- US 2010/0291 159 provides a method of using waxy detackifier such as glyceryl monostearate (GMS) through micronization, further thispublication exemplifies the use of micronized GMS to yield coating compositions.
- Glycerol monostearate is a waxy substance and micronization process of waxy substances is not uniform and yields variable particle sizes, which interfere with spraying process.
- pre-processing is required. Since pre-processing step is required for processing every batch, which includes steps such as sieving (material wastage), manual processing, time consuming selection, equipment dependent piucess, etc., Lhere is a huge wastage of time and material. It also draws serious limitation of applicability to small sized industries and research and development laboratories requiring lower amount of micronized GMS. Further, such composition retains its hydrophobic property and is difficult to disperse during reconstitution.
- An object of the present invention is to provide a novel immediate release, non-tacky film coating composition of PVA that is completely dispersed at ambient temperature and the process for producing the same.
- plasticizer in combination withwaxy emulsifierwetting agent and the polymer results in a composition which is non-tacky and disperses easily in ambient temperature, which also results in a smooth coating. Further the resultant film exhibits good adhesion and tensile strength.
- Film coating is the process whereby a tablet, capsule, or pellet is surrounded by a thin layer of polymeric material. Coating tablet with a thin polymeric film is commonly performed to modify drug release, mask the taste of therapeutic agents, to enhance the stability of the drug within the gastrointestinal fluids or may be used for pure aesthetic reasons.
- 'polymer composite base' comprises the dry mass obtained by mixing the polymer in heated plasticizer, emulsifier and wetting agent.
- ambient temperature shall be understood to mean temperatures generally in the range ol ' irom about 20°C (68°F) to about 30°C (86°F) +/-3°C.
- An immediate release film coating composition of the present invention comprises a dry polymer composite base along with pharmaceutically acceptable excipients.
- the dry polymer composite base of present invention comprises a polymer, awaxy emulsifier, a plasticizer and a wetting agent.
- the present invention provides a novel immediate release film coating composition
- a novel immediate release film coating composition comprising a polymer, awaxy emulsifier, a plasticizer, a wetting agent and optionally an opacifier, a pigment,a diluent, lubricant or other pharmaceutically acceptable excipients.
- the novel immediate release film coating composition of the present invention includes a polymer which forms a good filmlacks toxicity and has a suitable solubility profile upon ingestion.
- the film must provide a tough, yet elastic film even in the presence of powdered additives such as pigments.
- the film must be stable to heat, light, moisture and be free from undesirable taste and odor.
- the polymer may be selected fromthe group comprising polyvinyl alcohol (PVA), copolymers of PVA, polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), polyvinylacetate phthalate, methacrylic acid copolymers, hypromellose (hydroxypropylmethyl cellulose), hydroxypropylcellulose, sodium carboxymethyl cellulose, ethyl cellulose.
- PVA polyvinyl alcohol
- copovidone polyvinylpyrrolidone-vinyl acetate copolymer
- methacrylic acid copolymers hypromellose (hydroxypropylmethyl cellulose), hydroxypropylcellulose, sodium carboxymethyl cellulose, ethyl cellulose.
- the polymer may be preferably polyvinyl alcohol.
- Polyvinyl alcohol is an odorless and tasteless, translucent, white or cream colored granular powder. All grades of polyvinyl alcohol may be used in the present invention.
- the amount of polymer used in the composition of the present invention may be range of 50- 90%, preferably 55to 85% w/w, more preferably 60-80% by weight of the polymer composite base.
- Plasticizer of the present invention may be selected from the groupcomprising phthalate esters, phosphate esters, and other esters like citrates, stearates, sebacate, oleate, oils, glycerols, glycols etc.
- the plasticizer of the present invention is selected from the group comprising polyethylene glycol, ethyl phthalate, methyl phthalate, propylene glycol, fractionated coconut oil, lecithin, castor oil, dibutylsebacate, diethyl phthalate, dipropyl phthalate, dibutyl phthalate, triacetin, liquid paraffin, triethyl citrate, and combinations thereof. More preferably, the plasticizer is dibutylsebacate, diethyl phthalate, and dibutyl phthalate.
- the amount of plasticizer used in the composition of the present invention may be range of 2 to 30% w/w, preferably 5-25% by weight of the polymer composite base.
- the composition of the present invention comprises a waxy emulsifier.
- a non-limiting list of materials that may be used as 'waxy emulsifier' includes glyceryl monostearate, glycerylbehenate (e.g. Compritol 888 ATO), glycerylpalmitostearate (e.g. Precirol ATO 05), sorbitan ester (e.g. sorbitan monopalmitate— Span 40), palmitic acid, polyoxyethylene alkyl ether (e.g. Cremophor AG; Brij 52; Brij 72; Volpo S2; and Ethylan 2512), lauroylpolyoxylglyceride (e.g.
- Gelucire 44/14) and stearoylpolyoxylglyceride e.g. Gelucire 50/13
- ceresin cetostearyl alcohol, cetyl alcohol, docusate sodium, ethyl maltol, ethylene glycol stearates, glycerylmonooleate, lanolin, myristic acid, petrolatum/lanolin alcohol, polyoxyl 6 stearate, polyoxyl 8 stearate, propylene glycol monostearate, sorbitan tristearate, sodium stearylfumarate, stearyl alcohol, hydrogenated vegetable oil, carnauba wax, microcrystalline wax and zinc stearate, and the like.
- the wetting agent is polysorbate 80.
- the amount of waxy emulsifier used in the composition may be in the range of 1 % w/w to 20 % w/w, preferably in the range of 3% w/w to 15% by weight of the polymer composite base.
- Wetting agents of the present invention may be selected from the group comprising Tween 20(polysorbate 20 or poloxyethylene (20) sorbitan monolaurate), Tween 40 (polysorbate 40 or polyoxyethylene (20) sorbitan monopalmitate), Tween 60 (polysorbate 60 or polyoxyethylene (20) sorbitan monostearate), Tween 80 (polysorbate 80 or polyoxyethylene (20) sorbitan monoleate), sodium lauryl sulphate and combinations thereof.
- the amount of wetting agent used in the composition of the present invention may be in the range of 0, 1% w/w to! 5% w/w, preferably in the range of 0.5% w/w to 10% by weight of the polymer composite base
- composition of the present invention may additionally comprise other ingredients such as an opacifier, a colorant, adiluent, a lubricant, a flavoring agent and/or a sweetening agent etc.
- Opacifiers of the present invention may be selected from the group comprising titanium dioxide, zinc oxide, calcium carbonate, magnesium oxide and the like.
- a pigment may be used to provide color to the film coating.
- pigments of the present invention may include iron oxide colors, Lake or soluble colors, natural colors, candurin colors and the like or any food approved colors or dyes or combinations thereof.
- Diluent of the present invention may include Tri basic calcium phosphate, Micro-crystalline cellulose, calcium phosphate and the like.
- Lubricants of the present invention may be selected from the group comprisingmagnesium stearate, calcium stearate, zinc stearate, stearic acid, mineral oil, and combinations thereof.
- Sweeteners of the present invention may be selected from the group comprising glucose, fructose, sorbitol, aspartame, glycerol, saccharin, xylitol and the like.
- Flavoring agents of the present invention may be selected from the group comprising powder, liquid, encapsulated flavors either natural or syntheticorigin.
- Substrates of the present invention comprise but are not limited to pharmaceutical materials, nutritional supplements, food, confectionery forms, agricultural seeds, and the like.
- the present invention provides a coating composition, wherein the dry polymer composite base present may be present in the range of 50 to 90%, preferably in the range of 60 % w/w to 80%, with other pharmaceutical excipients.
- the pharmaceutical excipients may include anopacifier in the range of 0.1-25% w/w, a pigment in the range of 0.1-25% w/w, a diluent in the range ofO.1- 15% w/w, a lubricant in the range of 0.1-5% w/w or combinations thereof.
- the coating composition may additionally comprise other pharmaceutically acceptable excipients.
- composition of the present invention may be, prepared by a process comprising the steps of:
- step 3 adding the polymer to the heated mixture of step 1 to obtain the polymer composite base in dry powder form;
- the process of preparing the composition of the present invention includes combining the waxy emulsifier, wetting agent and liquefied plasticizer.
- the combination may be achieved by several processes such as mixing, stirring etc.
- the resultant mixture obtained, on combining the liquefied plasticizer with the waxy emulsifierand wetting agent may be heated in the temperature range of about 60-90 °C (degree Celsius), more preferably about 70-80°C, for a period of 5-10 min to obtain a homogenous liquid dispersion.
- the polymer of the present invention may be added to the homogenous liquid dispersion to obtain the polymer composite base.
- other components of the composition as described above may be added to the polymer composite base.
- the present invention provides a method for coating substrates comprising reconstituting the film coating composition and applying the coating solution onto the substrates to form a film coating on the substrates, and drying the film coating on said substrates.
- the polymer composite base of the present invention is reconstituted in purified water, de-mineralized water, and Iike.
- the amount of solid present after reconstitution may be in the range of 5-20% w/v, preferably 5 to 15% w/v.
- composition of the present invention is reconstituted in solvents selected from the group comprising aqueous solutions, purified water, de-mineralized water, and Iike.
- solvents selected from the group comprising aqueous solutions, purified water, de-mineralized water, and Iike.
- the amount of solidpresent after reconstitution may be in the range of 10-40% w/v, preferably 1 to 30% w/v.
- the polymer composite baseor the composition of the present invention may be coated by methods such as simple pan coating, fluidized bed coating, pans with one-way air flow through the tablet bed and the like.
- the film coating process may be carried out in conventional pan. Operation variables such as speed of pan, rotation, angle of pan axis, and temperature and humidity control, optimum spray rate may beadjusted whichhelp in increasing the efficiency of the process and to obtain the desired coating effect.
- the composition of the present invention displayed good spray delivery rates even at such high solids contents in the coating suspension.
- the composite base or the composition of the present invention may be sprayed by adapting the following coating parameters, such as Inlet air temperature in the range of 50-70 degree Celsius, Tablet bed temperature in the range of 30-50 degree Celsius, suitable pump •speed, pan speed, an atomizing air pressure in the range of 1.4-3.0KG/cm sq. as per requirement of lot size to be coated.
- coating parameters such as Inlet air temperature in the range of 50-70 degree Celsius, Tablet bed temperature in the range of 30-50 degree Celsius, suitable pump •speed, pan speed, an atomizing air pressure in the range of 1.4-3.0KG/cm sq. as per requirement of lot size to be coated.
- the composition of the present invention uses aliydrophobic plasticizer in combination with other ingredients and PVA, which results in a composition which provides a smooth coating, which is non-tacky and disperses easily in ambient temperature. Further the resultant film exhibits good adhesion and tensile strength.
- the process of preparing the composition of the present invention using a combination of heating and marinating the mixture at appropriate temperatures and addition of the composition in sequence. It is postulated that the plasticizer interacts with the waxy emulsifier thereby surprisingly reducing the relative size of GMS and hydrophobicity of mixture. Such a mixture is easily dispersed in the polymer, thereby easing reconstitution.
- composition of the present invention is synergistic, is easily dispersible, readily reconstitutable and eliminates the problems of prior art.
- the present invention relates to the intimate mixture obtained by heating the plasticizer and wetting agent to a temperature of about 60-85°C and subsequent addition of waxy emulsifier with continuous mixing of 10-15 minutes.
- the intimate mixture thus obtained has a desirable particle size.
- This intimate mixture is capable of freely passing through #120 mesh to #325 mesh, 38 micron, 28 micron sieves.
- Subsequently addition of polymer to this intimate mixture provides granules having ranges of #100 mesh to #120 mesh.
- composition of the present invention When the composition of the present invention is coated over a 100 kg batch of substrate, at weight gain of 2.5 % w/w,time period for spraying reconstituted solution is about2 Hours.
- the composition of the present invention provides uniform film formation.
- the present invention uses a wetting agent with a waxy emulsifier and a liquefied plasticizer in raised temperature, thereby dissolving the waxy emulsifier easilyand hence eliminating the problem of prior art.
- composition of the present invention may be adapted to provide colorless and transparent film coat to the materialswith the enhanced film properties like finish, aesthetics, moisture barrier and luster.
- composition of the present invention has minimum tackiness, good adhesion, good tensile strength, high stability and high percentage of reconstitution.
- composition of the present invention is simple and the high solid content does not lead to any viscosity problem for spray and does not dry at the orifice of the spray gun.
- composition of the present invention may be carried out in water, and thereby eliminates the use of harmful organic solvents.
- composition of the present invention provides a uniform and nearly perfect coat in relatively less time.
- High solid content of the present composition helps to build up necessary weight and coating thickness quicker than other compositions thus increasing the speed of the process and thereby decreases the time consumed and is more economic.
- compositions of the present invention are highly stable with respect to storing after reconstitution for long hours.
- the formulation of the present invention solves the problems of prior art, with regards to the use of glycerol monostearate in a composition.
- composition of the present invention reduces the dispersion time of the composition and renders ease of constitution.
- the composition of the present invention is reconstituted within a time period of 20-25 minutes, whereas the compositions of prior art are reconstituted only in about 35-40 minutes.
- the solid content of the composition of the present invention is much higher than that of prior art.
- Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
- This polymer composite base is reconstituted in water at ambient temperature and the suspension thus obtained is used as film coating to coat various substrates.
- the film coating can be applied as part of a pan coating or spray coating process commonly used to coat such articles. The amount of coating applied will depend upon several factors, including the nature and functionality of the film coating, the substrate to be coated and the apparatus employed to apply the coating, etc.
- types of tablet used were medium sized, round, plane on both sides with sharp edges with diameter 10 mm, thickness mm and hardness of core 4.2 kg/cm sq.
- Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Dibutyl sebacate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
- Process of preparation of Polymer compositebase comprises of heating 85.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 12.68% w/w of Glyceryl monostearate, 2.23% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
- Process of preparation of Polymer compositebase comprises of heating 38.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 32.23% w/w of Glyceryl monostearate, 29.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
- the polymer composite base is taken from any of the preceding examples andblended with Other pharmaceutical ingredients.
- the Polymer composite base is taken in amounts of 57% w/w, PEG 6000 in amounts of 8% w/w,magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
- the powder mixtures are prepared using standard dry blending or mixing techniques.
- the ingredients are individually weighed, added to high speed mixer, blended for a sufficient time until a substantially uniform mixture of the ingredients is obtained. The time required to achieve such substantial uniformity will, of course, depend upon the batch size. This mixture is then passed through a 40 mm sieve to ensure smoothness of the mixture.
- any of the powder composition'singredients are liquids, they are added only after all of the dry ingredients have been sufficiently blended, and the combination of wet and dry ingredients is blended for an additional amount of time to ensure homogeneity once all of the liquid is introduced.
- the methods in accordance with the present invention include applying the film coating compositions as described herein as aqueous suspensions to the surfaces of orally ingestible substrates.
- the film coating can be applied as part of a pancoating or spray coating process commonly used to coat such articles.
- the amount of coatingapplied will depend upon several factors, including the nature and functionality of the filmcoating, the substrate to be coated and the apparatus employed to apply the coating, etc. In this case types of tablet used were medium sized, round, plane on both sides with sharpedges with diameter 10 mm,thickness 5mm and hardness of core 4.2 kg/cm sq.
- the polymer composite base is taken from any of the preceding examples and blended with other pharmaceutical ingredients.
- the Polymer composite base is taken in amounts of 57 % w/w, PEG 6000 in amounts of 4% w/w, calcium carbonate 4% w/w, magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
- the powder mixtures are blended, sifted, reconstituted, sprayed on tablet as explained in example 5.
- the polymer composite base is taken from any of the preceding examples and blended with other pharmaceutical ingredients.
- the Polymer composite base is taken in amounts of 80% w/w, PEG 6000 in amounts of 1U% w/w, calcium carbonate 7% w/w, Titanium dioxide in amounts of 3% w/w.
- the powder mixtures are blended, sifted, reconstituted, sprayed on tablet as explained in example 5.
- Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
- the above composite base is used as a ready mix to be blended with color, lake colors, titanium dioxide and Magnesium stearate to produce the desired product.
- step-II The Polymer composite base of step-II is then taken in amounts of 55 % w/w, PEG 6000 in amounts of 10% w/w,magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
- the powder mixtures are prepared using standard dry blending or mixing techniques.
- the ingredients are individually weighed, added to high speed mixer, blended for a sufficient time until a substantially uniform mixture of the ingredients is obtained. The time required to achieve such substantial uniformity will, of course, depend upon the batch size. This mixture is then passed through a 40mm sieve to ensure smoothness of the mixture.
- the film coating can be applied as part of a pan coating or spray coating process commonly used to coat such articles.
- the amount of coating applied will depend upon several factors, including the nature and functionality of the film coating, the substrate to be coated and the apparatus employed to apply the coating, etc. In this case types of tablet used were medium sized, round, plane on both sides with sharp edges with diameter 10mm, thickness 5mm and hardness of core 4.2 kg/cm sq.
- Process of preparation of Polymer composite base comprises heating of Diethyl phthalate to 80 degree Celsius and Glyceryl monostearate in amounts as given in table no 10. Heat the mixture to 70-80 °C for 5-10 min.
- the dry film coating composition (25grams) is dispersed into 75grams of water at ambienttemperature to make an aqueous coating suspension having 25% w/w non-water ingredients.
- the water is weighed into a vessel with a diameter approximately equal to the depth of thefinal dispersion.
- a low shear mixer is lowered into the water and turned on to create a vortexfrom the edge of the vessel down to just above the mixing blade to prevent entrapment of air.
- the 25grams of dry film coating composition is added to the vortex at a rate where there is noexcessive buildup of dry powder.
- the speed and depth of the mixing blade is adjusted to avoidair being drawn into the suspension so as to avoid foaming.
- the suspension is stirred to form ahomogeneous aqueous dispersion suitable for coating.
- the average coating parameters were: Inlet air temperature 55-60 degree Celsius, tablet bed temperature 40-43 degree Celsius, pump RPMlrpm, pan speed 35-38 rpm,atomizing air pressure 1.4-2.0KG/cm sq.
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Abstract
The invention provides a novel immediate release, non-tacky film coating composition of PVA that is completely dispersed at ambient temperature and the process for the same.
Description
NOVEL IMMEDIATE RELEASE FILM COATING COMPOSITIONS
FIELD OF INVENTION
The present invention relates to novel immediate release film coating compositions having enhanced adhesion and tensile strength. The invention relates to the field of coating compositions for substrates like pharmaceutical tablets, nutritional supplements, food products, confectionery, agricultural seeds and the like.
BACKGROUND OF INVENTION
Film coating is a process in which substrate like tablet, confectionary or a seed is enveloped by a thin layer of polymeric material. Most pharmaceutical materials, food products, confectionery, nutritional supplements, agricultural seeds and the like, need coating on their surface. The reasons for coating may be various and include protection of unstable compositions, protection in the stomach with enteric coating, improving the appearance of the tablet, separation of the ingredients of a tablet if they are incompatible, and masking objectionable odors and taste.
One of the polymers frequently used in coating is polyvinyl alcohol (PVA). Polyvinyl alcohol is very sticky in nature and renders tackiness to the final composition. Hence, there have been several attempts in prior art to use PVA in film coating without the resultant tackiness.
WO20061 11980discloses a dry /liquid film coating composition having polyvinyl alcohol and self-emulsifying glyceryl monostearate (GMS)as an anti-tack agent. This application, however utilizes hot water for the reconstitution of the anti-tack agent toprovide final film coating. This may not be suitable for heat sensitive ingredients/drugs. Moreover, maintaining a high temperature during spraying is cumbersome in an Industrial set up.Notwithstanding, the viscosity of the final film coating composition resulting from the disclosure in this application is very high which may lead to spray related problems.
WO2003/GB03195 also attempts to eliminate tackiness by combiningEudragit with GMS along with surface active agent. Herein again, the composition needs to be solubilized at a high
temperature to provide working film coating formulationand hence not suitable at several instances.
US 2010/0291 159 provides a method of using waxy detackifier such as glyceryl monostearate (GMS) through micronization, further thispublication exemplifies the use of micronized GMS to yield coating compositions.However, Glycerol monostearate is a waxy substance and micronization process of waxy substances is not uniform and yields variable particle sizes, which interfere with spraying process. Additionally to get micronized GMS pre-processing is required. Since pre-processing step is required for processing every batch, which includes steps such as sieving (material wastage), manual processing, time consuming selection, equipment dependent piucess, etc., Lhere is a huge wastage of time and material. It also draws serious limitation of applicability to small sized industries and research and development laboratories requiring lower amount of micronized GMS. Further, such composition retains its hydrophobic property and is difficult to disperse during reconstitution.
Hence, there is a need to have an alternative process and/or composition that eliminates the problems of prior art and simultaneously reduces the tackiness of film coating compositions based on PVA.
OBJECT OF INVENTION
An object of the present invention is to provide a novel immediate release, non-tacky film coating composition of PVA that is completely dispersed at ambient temperature and the process for producing the same.
SUMMARY OF THE INVENTION
It has been surprisingly found that the use of plasticizer in combination withwaxy emulsifierwetting agent and the polymer results in a composition which is non-tacky and disperses easily in ambient temperature, which also results in a smooth coating. Further the resultant film exhibits good adhesion and tensile strength.
DETAILED DESCRIPTION
Unless otherwise stated all terms used in the following description, shall constitute the same meaning as understood by a person skilled in the art. All terms used here in the specification carry the same meaning as in common scientific parlance.
Film coating is the process whereby a tablet, capsule, or pellet is surrounded by a thin layer of polymeric material. Coating tablet with a thin polymeric film is commonly performed to modify drug release, mask the taste of therapeutic agents, to enhance the stability of the drug within the gastrointestinal fluids or may be used for pure aesthetic reasons.
For the purpose of present invention, 'polymer composite base' comprises the dry mass obtained by mixing the polymer in heated plasticizer, emulsifier and wetting agent.
For the purpose of present invention,'ambient temperature' shall be understood to mean temperatures generally in the range ol'irom about 20°C (68°F) to about 30°C (86°F) +/-3°C.
An immediate release film coating composition of the present invention comprises a dry polymer composite base along with pharmaceutically acceptable excipients.
The dry polymer composite base of present invention comprises a polymer, awaxy emulsifier, a plasticizer and a wetting agent.
The present invention provides a novel immediate release film coating composition comprising a polymer, awaxy emulsifier, a plasticizer,a wetting agent and optionally an opacifier, a pigment,a diluent, lubricant or other pharmaceutically acceptable excipients.
The novel immediate release film coating composition of the present invention includes a polymer which forms a good filmlacks toxicity and has a suitable solubility profile upon ingestion. The film must provide a tough, yet elastic film even in the presence of powdered
additives such as pigments. The film must be stable to heat, light, moisture and be free from undesirable taste and odor.
The polymer may be selected fromthe group comprising polyvinyl alcohol (PVA), copolymers of PVA, polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), polyvinylacetate phthalate, methacrylic acid copolymers, hypromellose (hydroxypropylmethyl cellulose), hydroxypropylcellulose, sodium carboxymethyl cellulose, ethyl cellulose. The polymer may be preferably polyvinyl alcohol.
Polyvinyl alcohol is an odorless and tasteless, translucent, white or cream colored granular powder. All grades of polyvinyl alcohol may be used in the present invention.
The amount of polymer used in the composition of the present invention may be range of 50- 90%, preferably 55to 85% w/w, more preferably 60-80% by weight of the polymer composite base.
Plasticizer of the present invention may be selected from the groupcomprising phthalate esters, phosphate esters, and other esters like citrates, stearates, sebacate, oleate, oils, glycerols, glycols etc. Preferably, the plasticizer of the present invention is selected from the group comprising polyethylene glycol, ethyl phthalate, methyl phthalate, propylene glycol, fractionated coconut oil, lecithin, castor oil, dibutylsebacate, diethyl phthalate, dipropyl phthalate, dibutyl phthalate, triacetin, liquid paraffin, triethyl citrate, and combinations thereof. More preferably, the plasticizer is dibutylsebacate, diethyl phthalate, and dibutyl phthalate.
The amount of plasticizer used in the composition of the present invention may be range of 2 to 30% w/w, preferably 5-25% by weight of the polymer composite base.
The composition of the present invention comprises a waxy emulsifier. A non-limiting list of materials that may be used as 'waxy emulsifier' includes glyceryl monostearate, glycerylbehenate (e.g. Compritol 888 ATO), glycerylpalmitostearate (e.g. Precirol ATO 05), sorbitan ester (e.g. sorbitan monopalmitate— Span 40), palmitic acid, polyoxyethylene alkyl
ether (e.g. Cremophor AG; Brij 52; Brij 72; Volpo S2; and Ethylan 2512), lauroylpolyoxylglyceride (e.g. Gelucire 44/14) and stearoylpolyoxylglyceride (e.g. Gelucire 50/13), ceresin, cetostearyl alcohol, cetyl alcohol, docusate sodium, ethyl maltol, ethylene glycol stearates, glycerylmonooleate, lanolin, myristic acid, petrolatum/lanolin alcohol, polyoxyl 6 stearate, polyoxyl 8 stearate, propylene glycol monostearate, sorbitan tristearate, sodium stearylfumarate, stearyl alcohol, hydrogenated vegetable oil, carnauba wax, microcrystalline wax and zinc stearate, and the like. Preferably the wetting agent is polysorbate 80.
The amount of waxy emulsifier used in the composition may be in the range of 1 % w/w to 20 % w/w, preferably in the range of 3% w/w to 15% by weight of the polymer composite base.
Wetting agents of the present invention may be selected from the group comprising Tween 20(polysorbate 20 or poloxyethylene (20) sorbitan monolaurate), Tween 40 (polysorbate 40 or polyoxyethylene (20) sorbitan monopalmitate), Tween 60 (polysorbate 60 or polyoxyethylene (20) sorbitan monostearate), Tween 80 (polysorbate 80 or polyoxyethylene (20) sorbitan monoleate), sodium lauryl sulphate and combinations thereof.
The amount of wetting agent used in the composition of the present inventionmay be in the range of 0, 1% w/w to! 5% w/w, preferably in the range of 0.5% w/w to 10% by weight of the polymer composite base
The composition of the present invention may additionally comprise other ingredients such as an opacifier, a colorant, adiluent, a lubricant, a flavoring agent and/or a sweetening agent etc.
Opacifiers of the present invention may be selected from the group comprising titanium dioxide, zinc oxide, calcium carbonate, magnesium oxide and the like.
A pigment may be used to provide color to the film coating. For instance, pigments of the present invention may include iron oxide colors, Lake or soluble colors, natural colors, candurin colors and the like or any food approved colors or dyes or combinations thereof.
Diluent of the present invention may include Tri basic calcium phosphate, Micro-crystalline cellulose, calcium phosphate and the like.
Lubricants of the present invention may be selected from the group comprisingmagnesium stearate, calcium stearate, zinc stearate, stearic acid, mineral oil, and combinations thereof.
Sweeteners of the present invention may be selected from the group comprising glucose, fructose, sorbitol, aspartame, glycerol, saccharin, xylitol and the like.
Flavoring agents of the present invention may be selected from the group comprising powder, liquid, encapsulated flavors either natural or syntheticorigin.
Substrates of the present invention comprise but are not limited to pharmaceutical materials, nutritional supplements, food, confectionery forms, agricultural seeds, and the like.
The present invention provides a coating composition, wherein the dry polymer composite base present may be present in the range of 50 to 90%, preferably in the range of 60 % w/w to 80%, with other pharmaceutical excipients. The pharmaceutical excipients may include anopacifier in the range of 0.1-25% w/w, a pigment in the range of 0.1-25% w/w, a diluent in the range ofO.1- 15% w/w, a lubricant in the range of 0.1-5% w/w or combinations thereof. The coating composition may additionally comprise other pharmaceutically acceptable excipients.
In another aspect the composition of the present invention may be, prepared by a process comprising the steps of:
1. combining the liquefied plasticizer with the waxy emulsifier and wetting agent;
2. heating the above said mixture to obtain a homogenous liquid dispersion;
3. adding the polymer to the heated mixture of step 1 to obtain the polymer composite base in dry powder form;
4. Optionally adding other pharmaceutical excipients to obtain the composition of the present invention.
The process of preparing the composition of the present invention includes combining the waxy emulsifier, wetting agent and liquefied plasticizer. The combination may be achieved by several processes such as mixing, stirring etc. The resultant mixture obtained, on combining the liquefied plasticizer with the waxy emulsifierand wetting agent may be heated in the temperature range of about 60-90 °C (degree Celsius), more preferably about 70-80°C, for a period of 5-10 min to obtain a homogenous liquid dispersion.
The polymer of the present invention may be added to the homogenous liquid dispersion to obtain the polymer composite base. In addition other components of the composition as described abovemay be added to the polymer composite base.
In another embodiment, the present invention provides a method for coating substrates comprising reconstituting the film coating composition and applying the coating solution onto the substrates to form a film coating on the substrates, and drying the film coating on said substrates.
In another aspect of the invention, the polymer composite base of the present invention is reconstituted in purified water, de-mineralized water, and Iike.The amount of solid present after reconstitution may be in the range of 5-20% w/v, preferably 5 to 15% w/v.
In another aspect of the invention, the composition of the present invention is reconstituted in solvents selected from the group comprising aqueous solutions, purified water, de-mineralized water, and Iike.The amount of solidpresent after reconstitution may be in the range of 10-40% w/v, preferably 1 to 30% w/v.
The polymer composite baseor the composition of the present invention may be coated by methods such as simple pan coating, fluidized bed coating, pans with one-way air flow through the tablet bed and the like.
The film coating process may be carried out in conventional pan. Operation variables such as speed of pan, rotation, angle of pan axis, and temperature and humidity control, optimum spray rate may beadjusted whichhelp in increasing the efficiency of the process and to obtain the desired coating effect. Surprisingly,the composition of the present invention, displayed good spray delivery rates even at such high solids contents in the coating suspension.
For instance, the composite base or the composition of the present invention may be sprayed by adapting the following coating parameters, such as Inlet air temperature in the range of 50-70 degree Celsius, Tablet bed temperature in the range of 30-50 degree Celsius, suitable pump •speed, pan speed, an atomizing air pressure in the range of 1.4-3.0KG/cm sq. as per requirement of lot size to be coated.
Without being limited by theory, the composition of the present invention uses aliydrophobic plasticizer in combination with other ingredients and PVA, which results in a composition which provides a smooth coating, which is non-tacky and disperses easily in ambient temperature. Further the resultant film exhibits good adhesion and tensile strength. Moreover, the process of preparing the composition of the present invention, using a combination of heating and marinating the mixture at appropriate temperatures and addition of the composition in sequence. It is postulated that the plasticizer interacts with the waxy emulsifier thereby surprisingly reducing the relative size of GMS and hydrophobicity of mixture. Such a mixture is easily dispersed in the polymer, thereby easing reconstitution.
Hence, the composition of the present invention is synergistic, is easily dispersible, readily reconstitutable and eliminates the problems of prior art.
In another aspect, the present invention relates to the intimate mixture obtained by heating the plasticizer and wetting agent to a temperature of about 60-85°C and subsequent addition of waxy emulsifier with continuous mixing of 10-15 minutes. The intimate mixture thus obtained has a desirable particle size. This intimate mixture is capable of freely passing through #120 mesh to #325 mesh, 38 micron, 28 micron sieves. Subsequently addition of polymer to this intimate mixture provides granules having ranges of #100 mesh to #120 mesh.
FC U0t)U4HA
When the composition of the present invention is coated over a 100 kg batch of substrate, at weight gain of 2.5 % w/w,time period for spraying reconstituted solution is about2 Hours.The composition of the present invention provides uniform film formation.
ADVANTAGES
1. The present invention uses a wetting agent with a waxy emulsifier and a liquefied plasticizer in raised temperature, thereby dissolving the waxy emulsifier easilyand hence eliminating the problem of prior art.
2. The composition of the present invention may be adapted to provide colorless and transparent film coat to the materialswith the enhanced film properties like finish, aesthetics, moisture barrier and luster.
3. The composition of the present invention has minimum tackiness, good adhesion, good tensile strength, high stability and high percentage of reconstitution.
4. The reconstitution of composition of the present invention is simple and the high solid content does not lead to any viscosity problem for spray and does not dry at the orifice of the spray gun.
5. The reconstitution of the composition of the present invention may be carried out in water, and thereby eliminates the use of harmful organic solvents.
6. The composition of the present invention provides a uniform and nearly perfect coat in relatively less time.
7. High solid content of the present composition helps to build up necessary weight and coating thickness quicker than other compositions thus increasing the speed of the process and thereby decreases the time consumed and is more economic.
8. During reconstitution of the composition, there is no sedimentation or floating of the particles thereby eliminating continuous stirring. Thus the compositions of the present invention are highly stable with respect to storing after reconstitution for long hours.
9. The formulation of the present invention solves the problems of prior art, with regards to the use of glycerol monostearate in a composition.
10. The composition of the present invention reduces the dispersion time of the composition and renders ease of constitution. The composition of the present invention is reconstituted within a time period of 20-25 minutes, whereas the compositions of prior art are reconstituted only in about 35-40 minutes.
11. The solid content of the composition of the present invention is much higher than that of prior art.
The invention illustratively disclosed herein suitably may be practiced in the absence of any component, ingredient, or step which is not specifically disclosed herein. Several examples are set forth below to further illustrate the nature of the invention and the manner of carrying it out. However, the invention should not be considered as being limited to the details thereof.
EXAMPLES
The present invention will next be described in further detail based on examples and comparative examples, although the present invention shall not be limited by the following examples. All units and percentages in the examples are by weight.
Example 1: Preparation of the composition of present invention
Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
Take 28% w/w of the above liquid dispersion (at a temperature 70-80°C) and mix with 72% w/w poly vinyl alcohol to prepare the desired polymer composite base. The same is gradually cooled to room temperature to obtain a dry powder base. The powder obtained is sifted through sieve of 40 mesh to ensure the absence of lumps or agglomerates. The final composition of the dry polymer composite base thus obtained is given in table 1.
Table 1
Component Percentage in
Polymer composite
base
Diethyl phthalate 16.5452
Glyceryl Monostearate 8.1844
Polysorbate 80 3.2704
Poly vinyl alcohol 72
Total 100
This polymer composite base is reconstituted in water at ambient temperature and the suspension thus obtained is used as film coating to coat various substrates.The film coating can be applied as part of a pan coating or spray coating process commonly used to coat such articles. The amount of coating applied will depend upon several factors, including the nature and functionality of the film coating, the substrate to be coated and the apparatus employed to apply the coating, etc.
In this case types of tablet used were medium sized, round, plane on both sides with sharp edges with diameter 10 mm, thickness mm and hardness of core 4.2 kg/cm sq.
Example 2
Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Dibutyl sebacate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
Take 25% w/w of the above liquid dispersion (at a temperature 70-80°C) and mix with 75% w/w poly vinyl alcohol to prepare the desired polymer composite base. The same is gradually cooled to room temperature to obtain a dry powder base. The powder obtained is sifted through sieve of 40 mesh to ensure the absence of lumps or agglomerates. The final composition of the dry polymer composite base thus obtained is given in table 2
Table 2
Powder is sifted, reconstituted, sprayed on tablet as explained in example 1 Example 3
Process of preparation of Polymer compositebase comprises of heating 85.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 12.68% w/w of Glyceryl monostearate, 2.23% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
Take 35% w/w of the above liquid dispersion (at a temperature 70-80°C) and mix with 65% w/w poly vinyl alcohol to prepare the desired polymer composite base. The same is gradually cooled to room temperature to obtain a dry powder base. The powder obtained is sifted through sieve of 40 mesh to ensure the absence of lumps or agglomerates. The final composition of the dry polymer composite base thus obtained is given in table 3.
Table 3
Component Percentage in
Polymer composite
base
dibutyl phthalate 29.7815
Glyceryl Monostearate 4.438
Polysorbate 80 0.7805
Poly vinyl alcohol 65
Total 100
Powder is sifted, reconstituted, sprayed on tablet as explained in example 1 Example 4
Process of preparation of Polymer compositebase comprises of heating 38.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 32.23% w/w of Glyceryl monostearate, 29.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
Take 28% w/w of the above liquid dispersion (at a temperature 70-80°C) and mix with 72% w/w poly vinyl alcohol to prepare the desired polymer composite base. The same is gradually cooled to room temperature to obtain a dry powder base. The powder obtained is sifted through sieve of 40 mesh to ensure the absence of lumps or agglomerates. The final composition of the dry polymer composite base thus obtained is given in table 4.
Table 4
Powder is sifted, reconstituted, sprayed on tablet as explained in example 1 Example 5:
The polymer composite base is taken from any of the preceding examples andblended with Other pharmaceutical ingredients.
Table 5
Ingredient Percentage by weight Weight in grams
Polymer composite 57% 570
base
Polyethylene glycol 8% 80
6000
Magnesium Stearate 3% 30
Titanium Dioxide 15% 150
Pigment 17% 170
Total 100% 1000
The Polymer composite baseis taken in amounts of 57% w/w, PEG 6000 in amounts of 8% w/w,magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
The powder mixtures are prepared using standard dry blending or mixing techniques. The ingredients are individually weighed, added to high speed mixer, blended for a sufficient time until a substantially uniform mixture of the ingredients is obtained. The time required to achieve such substantial uniformity will, of course, depend upon the batch size. This mixture is then passed through a 40 mm sieve to ensure smoothness of the mixture.
If any of the powder composition'singredients are liquids, they are added only after all of the dry ingredients have been sufficiently blended, and the combination of wet and dry ingredients is blended for an additional amount of time to ensure homogeneity once all of the liquid is introduced. As will be described below, the methods in accordance with the present invention include applying the film coating compositions as described herein as aqueous suspensions to the surfaces of orally ingestible substrates.
The film coating can be applied as part of a pancoating or spray coating process commonly used to coat such articles. The amount of coatingapplied will depend upon several factors, including the nature and functionality of the filmcoating, the substrate to be coated and the apparatus employed to apply the coating, etc.
In this case types of tablet used were medium sized, round, plane on both sides with sharpedges with diameter 10 mm,thickness 5mm and hardness of core 4.2 kg/cm sq.
Example 6:
The polymer composite base is taken from any of the preceding examples and blended with other pharmaceutical ingredients.
Table 6
The Polymer composite base is taken in amounts of 57 % w/w, PEG 6000 in amounts of 4% w/w, calcium carbonate 4% w/w, magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
The powder mixtures are blended, sifted, reconstituted, sprayed on tablet as explained in example 5.
Example 7:
The polymer composite base is taken from any of the preceding examples and blended with other pharmaceutical ingredients.
Table 7
Ingredient Percentage by weight Weight in grams
Polymer composite 80% 800
base
Polyethylene glycol 10% 100
6000
Micro-crystalline 7% 70
cellulose
Titanium Dioxide 3% 30
Total 100% 1000
The Polymer composite base is taken in amounts of 80% w/w, PEG 6000 in amounts of 1U% w/w, calcium carbonate 7% w/w, Titanium dioxide in amounts of 3% w/w.
The powder mixtures are blended, sifted, reconstituted, sprayed on tablet as explained in example 5.
Example 8:
Process of preparation of Polymer compositebase comprises of heating 59.09% w/w of Diethyl phthalate to 80 degree Celsius and adding 29.23% w/w of Glyceryl monostearate, 1 1.68% w/wof Polysorbate 80 to form a homogenous liquid dispersion.
Take 28% w/w of the above liquid dispersion (at a temperature 70-80"C) and mix with 72% w/w poly vinyl alcohol to prepare the desired polymer composite base. The same is gradually cooled to room temperature to obtain a dry powder base. The powder obtained is sifted through sieve of 40 mesh to ensure the absence of lumps or agglomerates. The final composition of the dry polymer composite base thus obtained is given in table 8.
Table 8
Component Percentage in
Polymer composite
base
Diethyl phthalate 16.5452
Glyceryl. Monostearate 8.1844
Polysorbate 80 3.2704
Poly vinyl alcohol 72
Total 100
The above composite base is used as a ready mix to be blended with color, lake colors, titanium dioxide and Magnesium stearate to produce the desired product.
Table 9
The Polymer composite base of step-II is then taken in amounts of 55 % w/w, PEG 6000 in amounts of 10% w/w,magnesium stearate in amounts of 3% w/w, Titanium dioxide in amounts of 15% w/w, and pigment in amounts of 17% w/w.
The powder mixtures are prepared using standard dry blending or mixing techniques. The ingredients are individually weighed, added to high speed mixer, blended for a sufficient time until a substantially uniform mixture of the ingredients is obtained. The time required to achieve such substantial uniformity will, of course, depend upon the batch size. This mixture is then passed through a 40mm sieve to ensure smoothness of the mixture.
The film coating can be applied as part of a pan coating or spray coating process commonly used to coat such articles. The amount of coating applied will depend upon several factors, including the nature and functionality of the film coating, the substrate to be coated and the apparatus employed to apply the coating, etc.
In this case types of tablet used were medium sized, round, plane on both sides with sharp edges with diameter 10mm, thickness 5mm and hardness of core 4.2 kg/cm sq.
Example 9:
Process of preparation of Polymer composite base comprises heating of Diethyl phthalate to 80 degree Celsius and Glyceryl monostearate in amounts as given in table no 10. Heat the mixture to 70-80 °C for 5-10 min.
Table no 10
When mixtcire obtained from above is taken in amounts of 28% w/w and mixed with 72% w/wpolyvinyl alcoholit results in the formation of a powder.Powder thus obtained is re-dispersed in water, however homogenous dispersion is not achieved.The properties expected to result that were not comparable to those of earlier compositions suggesting that presence of each component is necessary to obtain the desired properties.
Example 10:Preparation of the Aqueous Dispersion:
The dry film coating composition (25grams) is dispersed into 75grams of water at ambienttemperature to make an aqueous coating suspension having 25% w/w non-water ingredients.
The water is weighed into a vessel with a diameter approximately equal to the depth of thefinal dispersion. A low shear mixer is lowered into the water and turned on to create a vortexfrom the edge of the vessel down to just above the mixing blade to prevent entrapment of air.
The 25grams of dry film coating composition is added to the vortex at a rate where there is noexcessive buildup of dry powder. The speed and depth of the mixing blade is adjusted to avoidair being drawn into the suspension so as to avoid foaming. The suspension is stirred to form ahomogeneous aqueous dispersion suitable for coating.
The average coating parameters were: Inlet air temperature 55-60 degree Celsius, tablet bed temperature 40-43 degree Celsius, pump RPMlrpm, pan speed 35-38 rpm,atomizing air pressure 1.4-2.0KG/cm sq.
Claims
1. An immediate release film coating composition comprising a dry polymer composite base along with pharmaceutically acceptable excipients.
2. A dry polymer composite base as claimed in claim 1, comprising a polymer, awaxy emulsifier, a plasticizer and a wetting agent.
3. An immediate release film coating composition as claimed in claim 1, comprising a polymer, a waxy emulsifier, a plasticizer, a wetting agent and optionally an opacifier, a pigment, a diluent, lubricant or other pharmaceutically acceptable excipients.
4. The composition as claimed in claims 2 and 3, wherein the polymer is selected from the group comprising polyvinyl alcohol (PVA), copolymers based on PVA, polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), polyvinylacetate phthalate, methacrylic acid copolymers, hypromellose (hydroxypropylmethyl cellulose), hydroxypropylcellulose, sodium carboxymethyl cellulose, ethyl cellulose.
5. The composition as claimed in claims 2 and 3, wherein the polymer is polyvinyl alcohol.
6. The composition as claimed in claims 2 and 3claims 2 and 3, wherein the polymer is in the range of 50to 90%w/w, more preferably 60-80% w/w of the composition.
7. The composition as claimed in claims 2 and 3, wherein the plasticizer is selected from the group comprising phthalate esters, phosphate esters, and other esters like citrates, stearates, sebacate, oleate, oils, glycerols, glycols etc.
8. The composition as claimed in claims 2 and 3, wherein the plasticizer is selected from the group comprising polyethylene glycol, ethyl phthalate, methyl phthalate, propylene
glycol, fractionated coconut oil, lecithin, castor oil, dibutylsebacate, diethyl phthalate, dipropyl phthalate, dibutyl phthalate and combinations thereof, more preferably dibutylsebacate, diethyl phthalate, dibutyl phthalate
9. The composition as claimed in claims 2 and 3, wherein the plasticizer is in the range of 2 to 30% w/w, preferably 5-25% w/w of the composition
10. The composition as claimed in claims 2 and 3, wherein the waxy emulsifier is selected from the group comprising glyceryl monostearate, glycerylbehenate, , glycerylpalmitostearate, sorbitan ester, palmitic acid, polyoxyethylene alkyl ether, lauroylpolyoxylglyceride and stearoylpolyoxylglyceride, eresin, cetostearyl alcohol, cetyl alcohol, docusate sodium, ethyl maltol, ethylene glycol stearates, glycerylmonooleate, lanolin, myristic acid, petrolatum/lanolin alcohol, polyoxyl 6 stearate, polyoxyl 8 stearate, propylene glycol monostearate, sorbitan tristearate, sodium stearylfumarate, stearyl alcohol, hydrogenated vegetable oil, carnauba wax, microcrystalline wax and zinc stearate.
1 1. The composition as claimed in claims 2 and 3, wherein the waxy emulsifier is in the range of 1 % w/w to 20 % w/w, more preferably in the range of 3 % w/w to 15% w/w.
12. The composition as claimed in claims 2 and 3, wherein the wetting agent is selected from the group comprising Tween 20 (polysorbate 20 or poloxyethylene (20) sorbitan monolaurate), Tween 40 (polysorbate 40 or polyoxyethylene (20) sorbitan monopalmitate), Tween 60 (polysorbate 60 or polyoxyethylene (20) sorbitan monostearate), Tween 80 (polysorbate 80 or polyoxyethylene (20) sorbitan monoleate), sodium lauryl sulphate and combinations thereof, preferably the wetting agent is polysorbate 80.
13. The composition as claimed in claims 2 and 3, wherein the wetting agent is in the range of 0.1 % w/w to 15% w/w, preferably in the range of 0.5% w/w to 10% w/w.
14. The composition as claimed in claims 2 and 3, wherein the opacifier is selected from the group comprising titanium dioxide, zinc oxide, calcium carbonate, magnesium oxide.
15. The composition as claimed in claims 2 and 3, wherein the opacifier is in the range of 0.1 % w/w to 25% w/w.
16. The composition as claimed in claims 2 and 3, optionally comprising other ingredients such as, a colorant, a diluent, a lubricant, a pigment, a flavoring agent or a sweetening agent.
17. The composition as claimed in claim 16 , wherein the pigment is selected from the group comprising, iron oxide colors, Lake or soluble colors, natural colors, candurin colors and the like.
18. The composition as claimed in claim 16, wherein the diluent is selected from the group comprising calcium carbonate, calcium phosphate, magnesium trisilicate, tri basic calcium phosphate, micro-crystalline cellulose and the like.
19. The composition as claimed in claim 16, wherein the diluent is selected from the group comprising magnesium stearate, calcium stearate, zinc stearate, stearic acid, mineral oil, and combinations thereof.
20. The composition as claimed in claim 16, wherein the flavoring agent is selected from the group comprisingpowder, liquid, encapsulated flavors either natural or syntheticorigin.
21. The composition as claimed in claim 16, wherein the sweetener is selected from the group comprising glucose, fructose, sorbitol, aspartame, glycerol, saccharin, xylitol.
22. A composition as claimed in claim 16, wherein the dry polymer composite base present is the range of 40 to 90%, preferably in the range of 45 % w/w to 80%, along with an
opacifier in the range of 0.1-25% w/w, a pigment in the range of 0.1-25% w/w, a diluent in the range of 0.1-15% w/w, a lubricant in the range of 0.1-5.0% w/w or combinations thereof along with other pharmaceutically acceptable excipients.
23. A process for preparing the composition as claimed in claims 2 and 3 comprising the steps of:
1. combining the liquefied plasticizer with the waxy emulsifier and wetting agent;
2. heating the above said mixture to obtain a homogenous liquid dispersion;
3. adding the polymer to the heated mixture of step 1 to obtain the polymer composite base in dry powder form;
4. optionally adding other pharmaceutical excipients to obtain the composition of the present invention.
24. The composition as claimed in claims 2 and 3, when reconstituted in a solvent selected from the group comprising aqueous solutions, water, de-mineralized water, preferably purified water, having solid content in the range of 10-40% w/w, preferably 15 to 30% w/w of solvent.
25. The composition as claimed in claim 24, comprisingsolid contentof 15% to 30% by weight in the suspension on reconstitution.
26. A method of coating a substrate with the composition of claims 2 and 3, wherein the substrate is selected from the group comprising pharmaceutical materials, nutritional supplements, food, confectionery forms, agricultural seeds.
27. An orally ingestible substrate coated with the dry film coating composition of claims 2 and 3.
28. A dry film coating composition and method of coating as described in the specification with reference to forgoing examples.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN646MU2011 | 2011-03-09 | ||
| IN646/MUM/2011 | 2011-03-09 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2012120364A2 true WO2012120364A2 (en) | 2012-09-13 |
| WO2012120364A3 WO2012120364A3 (en) | 2012-11-08 |
| WO2012120364A8 WO2012120364A8 (en) | 2013-10-24 |
Family
ID=46798600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2012/000431 WO2012120364A2 (en) | 2011-03-09 | 2012-03-07 | Novel immediate release film coating compositions |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2012120364A2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2848246A1 (en) * | 2013-09-13 | 2015-03-18 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
| WO2015036512A1 (en) * | 2013-09-13 | 2015-03-19 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
| WO2016108250A1 (en) | 2015-01-01 | 2016-07-07 | Ideal Cures Pvt. Ltd. | Novel film coating composition |
| CN105916598A (en) * | 2014-01-21 | 2016-08-31 | Bpsi控股有限责任公司 | Immediate release film coatings containing medium chain glycerides and substrates coated therewith |
| US11937600B1 (en) * | 2023-03-14 | 2024-03-26 | King Faisal University | Seed germination activator for control of broomrape |
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| CN1720916A (en) * | 2000-07-04 | 2006-01-18 | Lts罗曼治疗方法有限公司 | Rapidly decomposing administrable form for releasing active ingredient in oral cavity or bodily cavity |
| CN101484142A (en) * | 2006-03-24 | 2009-07-15 | 奥克思利尤姆国际控股公司 | Stabilized compositions containing alkaline labile drugs |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1720916A (en) * | 2000-07-04 | 2006-01-18 | Lts罗曼治疗方法有限公司 | Rapidly decomposing administrable form for releasing active ingredient in oral cavity or bodily cavity |
| CN101484142A (en) * | 2006-03-24 | 2009-07-15 | 奥克思利尤姆国际控股公司 | Stabilized compositions containing alkaline labile drugs |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2848246A1 (en) * | 2013-09-13 | 2015-03-18 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
| WO2015036512A1 (en) * | 2013-09-13 | 2015-03-19 | Bayer Pharma Aktiengesellschaft | Pharmaceutical compositions containing refametinib |
| JP2016531151A (en) * | 2013-09-13 | 2016-10-06 | バイエル ファーマ アクチエンゲゼルシャフト | Pharmaceutical composition containing refametinib |
| CN105916598A (en) * | 2014-01-21 | 2016-08-31 | Bpsi控股有限责任公司 | Immediate release film coatings containing medium chain glycerides and substrates coated therewith |
| WO2016108250A1 (en) | 2015-01-01 | 2016-07-07 | Ideal Cures Pvt. Ltd. | Novel film coating composition |
| US11937600B1 (en) * | 2023-03-14 | 2024-03-26 | King Faisal University | Seed germination activator for control of broomrape |
| US11944094B1 (en) * | 2023-03-14 | 2024-04-02 | King Faisal University | Seed germination activator for control of broomrape |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012120364A3 (en) | 2012-11-08 |
| WO2012120364A8 (en) | 2013-10-24 |
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