WO2022254277A1 - Extended release composition and its process for the preparation - Google Patents
Extended release composition and its process for the preparation Download PDFInfo
- Publication number
- WO2022254277A1 WO2022254277A1 PCT/IB2022/054668 IB2022054668W WO2022254277A1 WO 2022254277 A1 WO2022254277 A1 WO 2022254277A1 IB 2022054668 W IB2022054668 W IB 2022054668W WO 2022254277 A1 WO2022254277 A1 WO 2022254277A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- single layer
- extended release
- layer matrix
- matrix tablet
- tablet composition
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 116
- 238000013265 extended release Methods 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 239000002356 single layer Substances 0.000 claims abstract description 63
- 239000013563 matrix tablet Substances 0.000 claims abstract description 57
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 claims abstract description 36
- 239000011764 pyridoxine hydrochloride Substances 0.000 claims abstract description 36
- KBAUFVUYFNWQFM-UHFFFAOYSA-N Doxylamine succinate Chemical group OC(=O)CCC(O)=O.C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 KBAUFVUYFNWQFM-UHFFFAOYSA-N 0.000 claims abstract description 35
- 229960005008 doxylamine succinate Drugs 0.000 claims abstract description 34
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims abstract description 33
- 239000008187 granular material Substances 0.000 claims abstract description 30
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000002156 mixing Methods 0.000 claims abstract description 26
- 229960004172 pyridoxine hydrochloride Drugs 0.000 claims abstract description 26
- 230000003111 delayed effect Effects 0.000 claims abstract description 25
- 238000009501 film coating Methods 0.000 claims abstract description 9
- 239000007888 film coating Substances 0.000 claims abstract description 9
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 26
- 239000000463 material Substances 0.000 claims description 26
- 229940011671 vitamin b6 Drugs 0.000 claims description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 20
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- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 17
- 238000009505 enteric coating Methods 0.000 claims description 15
- 239000002702 enteric coating Substances 0.000 claims description 15
- 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 13
- 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 13
- 239000003085 diluting agent Substances 0.000 claims description 13
- 229960001021 lactose monohydrate Drugs 0.000 claims description 13
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 13
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 13
- 239000000377 silicon dioxide Substances 0.000 claims description 13
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
- 235000012239 silicon dioxide Nutrition 0.000 claims description 12
- 235000008160 pyridoxine Nutrition 0.000 claims description 11
- 239000011677 pyridoxine Substances 0.000 claims description 11
- 239000000945 filler Substances 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 241000518994 Conta Species 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 9
- 229940069428 antacid Drugs 0.000 claims description 8
- 239000003159 antacid agent Substances 0.000 claims description 8
- 230000001458 anti-acid effect Effects 0.000 claims description 8
- 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 description 8
- 239000007884 disintegrant Substances 0.000 claims description 8
- 229960005178 doxylamine Drugs 0.000 claims description 8
- HCFDWZZGGLSKEP-UHFFFAOYSA-N doxylamine Chemical compound C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 HCFDWZZGGLSKEP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003979 granulating agent Substances 0.000 claims description 8
- 239000000391 magnesium silicate Substances 0.000 claims description 8
- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 8
- 229940099273 magnesium trisilicate Drugs 0.000 claims description 8
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 7
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
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- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 239000001913 cellulose Substances 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 6
- 239000000395 magnesium oxide Substances 0.000 claims description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 6
- 235000012245 magnesium oxide Nutrition 0.000 claims description 6
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
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- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 5
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 5
- -1 glidant Substances 0.000 claims description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 229920002261 Corn starch Polymers 0.000 claims description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- 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 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 4
- 229920000881 Modified starch Polymers 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
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 4
- 239000008116 calcium stearate Substances 0.000 claims description 4
- 235000013539 calcium stearate Nutrition 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 4
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 4
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- 229920002678 cellulose Polymers 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
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- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
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- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 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 3
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- 229940005550 sodium alginate Drugs 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920000856 Amylose Polymers 0.000 claims description 2
- 241000416162 Astragalus gummifer Species 0.000 claims description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 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
- 239000004471 Glycine Substances 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
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- 240000007472 Leucaena leucocephala Species 0.000 claims description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 2
- 235000019759 Maize starch Nutrition 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 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
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 229930006000 Sucrose Natural products 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
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- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 2
- JIFPTBLGXRKRAO-UHFFFAOYSA-K aluminum;magnesium;hydroxide;sulfate Chemical compound [OH-].[Mg+2].[Al+3].[O-]S([O-])(=O)=O JIFPTBLGXRKRAO-UHFFFAOYSA-K 0.000 claims description 2
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 claims description 2
- 239000000440 bentonite Substances 0.000 claims description 2
- 229910000278 bentonite Inorganic materials 0.000 claims description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 235000010338 boric acid Nutrition 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 235000010216 calcium carbonate Nutrition 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
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- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 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
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 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
- 229940049654 glyceryl behenate Drugs 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
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 2
- 229940046813 glyceryl palmitostearate Drugs 0.000 claims description 2
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- 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
- 230000001050 lubricating effect Effects 0.000 claims description 2
- 229960004018 magaldrate Drugs 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 239000000347 magnesium hydroxide Substances 0.000 claims description 2
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- 229940037627 magnesium lauryl sulfate Drugs 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
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- 239000002480 mineral oil Substances 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 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
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- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
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- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Definitions
- the present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules.
- the present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion does not involve granulation.
- the present invention more specifically relates to method for the preparation of extended release single layer matrix tablet composition comprising steps of sifting, direct mixing, granulating, blending, compression and film coating.
- the present invention more specifically relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, prepared by a process comprising steps of sifting, direct mixing, granulating, blending, compression and film coating.
- Extended release solid compositions can be in the form of tablets or capsules, wherein the release of the active ingredient is controlled by using a reservoir or a matrix system.
- extended release solid compositions suffer from certain drawbacks such as maintaining therapeutic window and bioavailability of the active medicament for 24 hours.
- Doxylamine succinate is in a class of medications called antihistamines. It works by blocking the action of certain natural substances in the body that may contribute to nausea and vomiting.
- Pyridoxine (vitamin B6) is a vitamin. It is given because a lack of pyridoxine in the body may also be a factor in causing nausea and vomiting during pregnancy.
- Doxylamine Succinate Doxylamine is a first-generation antihistamine and is a potent anticholinergic agent first reported in 1949 as sleep aid with weak hypnotic and calming effects.
- Doxylamine acts primarily as an antagonist or inverse agonist of the histamine H1 receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of the muscarinic acetylcholine receptors, an action responsible for its minor hypnotic, anticholinergic, and (at high doses) deliriant effects.
- Doxylamine in its succinic acid salt form in combination with vitamin B6 (pyridoxine) used to prevent morning sickness in pregnant women.
- Doxylamine succinate is chemically, ethanamine, N,N-dimethyl-2-[1-phenyl-1- (2-pyridinyl)ethoxy]-, butanedioate (1:1).
- Doxylamine succinate is a white to creamy white powder, is an antihistamine with sedative and hypnotic properties. It is very soluble in water and alcohol, freely soluble in chloroform and very slightly soluble in ether and benzene.
- Pyridoxine Hydrochloride Pyridoxine (also called pyridoxol) is one form of vitamin B6. Its hydrochloride salt, pyridoxine hydrochloride, is used as a vitamin B6 dietary supplement. Pyridoxine hydrochloride is a vitamin B6 analog.
- pyridoxine hydrochloride is 5-hydroxy-6-methyl-3,4-pyridinedimethanol, hydrochloride.
- the empirical formula is C 8 H 11 NO 3 •HCl and the molecular mass is 205.64 g/mol and the structural formula is:
- Pyridoxine HCl is a white or practically white crystalline powder or crystals. Pyridoxine HCl is freely soluble in water, slightly soluble in alcohol and insoluble in ether. Pyridoxine is one of the compounds analog with pyridoxal and pyridoxamine that are referred to as vitamin B6. Pyridoxine HCl is used in oral vitamin supplements and injectable vitamin formulation products.
- the present invention is an improvement over the prior art in that it delivers doxylamine succinate and pyridoxine hydrochloride extended release tablet composition as a single layer for the treatment of nausea and vomiting.
- US Pat No. 6,340,695 B1 discloses the formulation comprising combination of doxylamine succinate and pyridoxine HCl, preferably in the form of an enterically coated tablet, a medicament comprising synergistic duo of active ingredients is useful in the treatment of nausea and vomiting, during pregnancy “NVP”, wherein the “rapid onset” formulation comprising the following non-active excipients: a filler or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent, wherein the formulation exhibiting a dissolution profile indicative of a rapid onset.
- US Pat No. 9,089,489 B2 discloses the dual release oral dosage system comprising doxylamine or analog, derivative, prodrug, metabolite and salt thereof and pyridoxine or analog, derivative, prodrug, metabolite and salt thereof, wherein said dual release oral dosage system comprising an immediate release component and delayed release component contains one or more coating layers, wherein immediate release granules preparation involves granulation.
- US Pub. No. 2014/0335176 A1 discloses the disintegrant-free delayed release doxylamine succinate and pyridoxine HC1 formulation and a manufacturing process by using direct compression or dry granulation.
- doxylamine succinate and pyridoxine hydrochloride available as a delayed-release tablet (releases the medication in the intestine to delay when the medication will start working) and as an extended-release (long-acting) tablet for oral use. It is usually taken on an empty stomach (at least 1 hour before or 2 hours after a meal). At first, tablet to be taken once a day at bedtime. If the symptoms of nausea and vomiting are not better, then the delayed-release tablets two or three times a day, or the extended-release tablet two times a day are prescribed.
- Another objective of the present invention is to provide extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, prepared by a process comprising steps of sifting, direct mixing, granulating, blending, compression and film coating.
- One embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules.
- Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion is prepared by direct mixing and said composition further comprises pharmaceutically acceptable excipients.
- Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride, wherein said composition further comprising granulating agent/enteric coating agent, antacid, disintegrants, diluents/fillers, glidant, lubricant, coating agent and other pharmaceutically acceptable excipients.
- Another embodiment of the present invention relates to an extended release single layer matrix tablet composition
- an extended release single layer matrix tablet composition comprising; (a) 0.1% to 10% (w/w) of first active ingredient, (b) 0.1% to 10% (w/w) of second active ingredient, (c) 0.5% to 2.5% (w/w) of disintegrant, (d) 0.5% to 5% (w/w) of glidant, (e) 1% to 10 (w/w) of antacid, (f) 0.5% to 3% (w/w) of lubricant, (g) 35% to 65% (w/w) of diluent or filler, (h) 1% to 10% (w/w) of granulating agent/enteric coating agent, (i) 0.1% to 5% (w/w) of coating agent and (j) 0.01% to 5% other pharmaceutically acceptable excipients.
- an extended release single layer matrix tablet composition comprising; (a) 0.1% to 10% (w/w) of doxylamine or its salt, (b) 0.1% to 10% (w/w) of pyridoxine or its salt, (c) 0.5% to 2.5% (w/w) of croscarmellose sodium, (d) 0.5% to 5% (w/w) of silicon dioxide and (e) 1% to 10 (w/w) magnesium trisilicate, (f) 0.5% to 3% (w/w) of magnesium stearate, (g) 35% to 65% (w/w) of microcrystalline cellulose and lactose monohydrate, (h) 1% to 10% (w/w) of Acryl-Eze Aqueous Acrylic Enteric System White, (i) 0.1% to 5% (w/w) of OPADRY Pink 85F94320, and (j) 0.01% to 5% other pharmaceutically acceptable excipients.
- Another embodiment of the present invention relates to a process for preparing extended release single layer matrix tablet composition, wherein said process comprising steps of; 1) preparing immediate release blend comprising; (a) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (b) co-sifting of Pyridoxine HCl with the blend obtained from step a), (c) sifting lactose monohydrate and microcrystalline cellulose through suitable sieve separately, (d) adding sifted materials in conta blender in the following order of half quantity of materials obtained from step (c), step (b) material and remaining quantity of step (c) materials, blending for 30 minutes, (e) sifting of croscarmellose sodium and magnesium trisilicate separately through suitable sieve, adding and blending with step (d) blended materials in conta blender for 10 minutes, 2) preparing delayed release granules comprising; (f) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (g) co-sif
- the term “comprising”, which is synonymous with “including”, “containing”, or “characterized by” here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.
- the “active ingredients” used in the present invention can be used as pharmaceutically acceptable salts.
- the pharmaceutically acceptable salts used in the present invention are doxylamine in its succinate salt form as first active ingredient and pyridoxine in its hydrochloride salt form as second active ingredient.
- the extended release single layer tablet composition of the invention comprises first active ingredient is doxylamine succinate.
- the concentration of doxylamine succinate used in the extended release single layer matrix tablet composition of the invention is from 0.1% to 10%.
- the extended release single layer tablet composition of the invention comprises second active ingredient is pyridoxine hydrochloride.
- the concentration of pyridoxine hydrochloride used in the solid oral composition of the invention is from 0.1% to 10%.
- Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein said immediate release blend comprising antacid, disintegrants, diluents/fillers, glidant and lubricant.
- Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein said delayed release granules comprising granulating agent/enteric coating agent, diluents/fillers, glidant, lubricant and other pharmaceutically acceptable excipients.
- the extended release single layer matrix tablet composition according to the present invention comprise granulating agent/enteric coating agent which includes acacia, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, Acryl- Eze Aqueous Acrylic Enteric System White, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, ethylcellulose, disodium pyrosulfite, polyvinyl alcohol, gelatin, glucose, guar gum, magnesium aluminum silicate, maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth, maize starch and zein.
- granulating agent/enteric coating agent which includes acacia, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, Acryl
- the granulating agent/enteric coating agent used in the extended release single layer matrix tablet composition is Acryl-Eze Aqueous Acrylic Enteric System White.
- the concentration of granulating agent/enteric coating agent used in the extended release single layer matrix tablet composition of present invention is from 1% to 10% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise antacid which includes magnesium trisilicate, calcium carbonate, sodium bicarbonate, magnesium hydroxide, aluminum hydroxide, magnesium oxide, magnesium carbonate, aluminum phosphate, magaldrate.
- the antacid used in the extended release single layer matrix tablet composition is magnesium trisilicate.
- the concentration of antacid used in the extended release single layer matrix tablet composition of present invention is from 1% to 10% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise disintegrants which includes croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, crospovidone, methylcellulose, polacrilin potassium, sodium alginate, sodium starch glycolate, starch, disodium disulfite, disodium edathamil, disodium edetate, disodiumethylenediaminetetraacetate (EDTA) crosslinked polyvinylpyrollidines, pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose.
- disintegrants which includes croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose
- the disintegrant used in the extended release single layer matrix tablet composition is croscarmelose sodium.
- concentration of disintegrant used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 2.5% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise diluent/filler which includes cellulose or derivatives, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, cellulose acetate, hydroxypropylcellulose, lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, corn starch, potato starch and combinations thereof.
- the diluent or filler used in the extended release single layer matrix tablet composition are lactose monohydrate and microcrystalline cellulose.
- the concentration of diluent or filler used in the extended release single layer matrix tablet composition of present invention is from 35% to 65% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise glidants which includes include silicon dioxide, calcium stearate, magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behanate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, combination of sodium benzoate and sodium acetate.
- the glidant used in the extended release single layer matrix tablet composition are silicon dioxide.
- the concentration of glidants used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 5% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise lubricant which include magnesium oxide, grades of magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate.
- the lubricant used in the extended release single layer matrix tablet composition is grades of magnesium stearate.
- the concentration of lubricant used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 3% (w/w) of total weight of the composition.
- the extended release single layer matrix tablet composition according to the present invention comprise coating agent which includes polyvinyl acetate polymer, OPADRY Pink 85F94320, acrylic resin, polymers or coplymers of acrylic acid, methyl acrylate, ethyl acrylate, methacrylic acid, methyl methacrylate, ethyl methacrylate and the like which may contain quaternary ammonium groups such as ammonio (meth)acrylate copolymers.
- Preferred examples are copolymers of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride.
- Such an acrylic polymer is available under the name Eudragit RS which is a water-insoluble copolymer (poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, manufactured by Rh6m Pharma, Germany) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof which may be used for coating, for example Eudragit RS 30D.
- Eudragit RS is a water-insoluble copolymer (poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, manufactured by Rh6m Pharma, Germany) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof which may be used for coating, for example Eudragit RS 30D.
- Another acrylic polymer may be Eudragit RL which consists of the same components as Eudragit RS but has a different molar ratio (Eudragit RL: poly(ethylacrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride; 1:2:0.2) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof, for example Eudragit RL 30D.
- the coating agent used in the extended release single layer matrix tablet composition is OPADRY Pink 85F94320.
- the concentration of coating agent used in the extended release single layer matrix tablet composition of present invention is from 0.1% to 5% (w/w) of total weight of the composition.
- Blend I (Immediate Release Blend) 1. Dispense the ingredients of the core tablets, 2. Co-sift Doxylamine succinate and Silicon dioxide through suitable sieve, 3. Co-sift Pyridoxine HCl with the step 2 sifted materials through suitable sieve, 4. Sift Lactose Monohydrate and MCC through suitable sieve separately, 5.
- Blend II (Delayed Release Granules) 1. Dispense the ingredients of the core tablets, 2. Co-sift Doxylamine succinate and Silicon dioxide through suitable sieve, 3. Co-sift Pyridoxine HCl with the step 2 sifted materials through suitable sieve, 4.
- Blending of Blend I and Blend II 1. Add Immediate Release blend from step 6 and Delayed Release Granules from step 11 in to suitable blender and mix for 15 minutes at 12 rpm, 2. Sift Magnesium stearate though suitable sieve and lubricate the step 1 blend in Conta blender at 12 rpm for 5 mins. Compression 1.Compress the lubricated blend using suitable punch (round, standard concave punches plain on both sides).
- Example 1 Dissolution data Comparative Dissolution Bonjesta (RLD Product) Vs.
- Example 1 composition is as given below:
Abstract
The present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules. The present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion does not involve granulation. The present invention more specifically relates to method for the preparation of extended release single layer matrix tablet composition comprising steps of sifting, direct mixing, granulating, blending, compression and film coating. The present invention more specifically relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, prepared by a process comprising steps of sifting, direct mixing, granulating, blending, compression and film coating.
Description
EXTENDED RELEASE COMPOSITION AND ITS PROCESS FOR THE PREPARATION FIELD OF THE INVENTION The present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules. The present invention also relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion does not involve granulation. The present invention more specifically relates to method for the preparation of extended release single layer matrix tablet composition comprising steps of sifting, direct mixing, granulating, blending, compression and film coating. The present invention more specifically relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, prepared by a process comprising steps of sifting, direct mixing, granulating, blending, compression and film coating. BACKGROUND OF THE INVENTION Extended release solid compositions can be in the form of tablets or capsules, wherein the release of the active ingredient is controlled by using a reservoir or a matrix system. However, extended release solid compositions suffer from certain drawbacks such as maintaining therapeutic window and bioavailability of the active medicament for 24 hours. Many of technologies have developed and being used to provide the more bioavailability of the active medicament, still facing certain problems maintaining bioavailability of the active medicament particularly for certain groups of patients, especially pregnant woman.
Pregnant women often require flexibility of dosage regimen and also requires more bioavailability by providing immediate release and extended release of medicament upto 24 hours in order to reduce frequency of taking tablets for morning sickness. Nausea and vomiting of pregnancy, commonly known as “morning sickness,” affects approximately 80 percent of pregnant women. Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. The combination of doxylamine succinate and pyridoxine hydrochloride is used to treat nausea and vomiting in pregnant women whose symptoms have not improved after changing their diet or using other non-medicine treatments. Doxylamine succinate is in a class of medications called antihistamines. It works by blocking the action of certain natural substances in the body that may contribute to nausea and vomiting. Pyridoxine (vitamin B6) is a vitamin. It is given because a lack of pyridoxine in the body may also be a factor in causing nausea and vomiting during pregnancy. Doxylamine Succinate: Doxylamine is a first-generation antihistamine and is a potent anticholinergic agent first reported in 1949 as sleep aid with weak hypnotic and calming effects. Doxylamine acts primarily as an antagonist or inverse agonist of the histamine H1 receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of the muscarinic acetylcholine receptors, an action responsible for its minor hypnotic, anticholinergic, and (at high doses) deliriant effects. Doxylamine in its succinic acid salt form in combination with vitamin B6 (pyridoxine) used to prevent morning sickness in pregnant women. Doxylamine succinate is chemically, ethanamine, N,N-dimethyl-2-[1-phenyl-1- (2-pyridinyl)ethoxy]-, butanedioate (1:1). The empirical formula is C17H22N2O• C4H6O4 and the molecular mass is 388.46 g/mol, the structural formula is:
Doxylamine succinate is a white to creamy white powder, is an antihistamine with sedative and hypnotic properties. It is very soluble in water and alcohol, freely soluble in chloroform and very slightly soluble in ether and benzene. Pyridoxine Hydrochloride: Pyridoxine (also called pyridoxol) is one form of vitamin B6. Its hydrochloride salt, pyridoxine hydrochloride, is used as a vitamin B6 dietary supplement. Pyridoxine hydrochloride is a vitamin B6 analog. The chemical name for pyridoxine hydrochloride is 5-hydroxy-6-methyl-3,4-pyridinedimethanol, hydrochloride. The empirical formula is C8H11NO3•HCl and the molecular mass is 205.64 g/mol and the structural formula is:
Pyridoxine HCl is a white or practically white crystalline powder or crystals. Pyridoxine HCl is freely soluble in water, slightly soluble in alcohol and insoluble in ether. Pyridoxine is one of the compounds analog with pyridoxal and pyridoxamine that are referred to as vitamin B6. Pyridoxine HCl is used in oral vitamin supplements and injectable vitamin formulation products. The present invention is an improvement over the prior art in that it delivers doxylamine succinate and pyridoxine hydrochloride extended release tablet composition as a single layer for the treatment of nausea and vomiting. US Pat No. 6,340,695 B1 discloses the formulation comprising combination of doxylamine succinate and pyridoxine HCl, preferably in the form of an enterically coated tablet, a medicament comprising synergistic duo of active ingredients is useful in the treatment of nausea and vomiting, during pregnancy “NVP”, wherein the “rapid
onset” formulation comprising the following non-active excipients: a filler or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent, wherein the formulation exhibiting a dissolution profile indicative of a rapid onset.
US Pat No. 9,089,489 B2 discloses the dual release oral dosage system comprising doxylamine or analog, derivative, prodrug, metabolite and salt thereof and pyridoxine or analog, derivative, prodrug, metabolite and salt thereof, wherein said dual release oral dosage system comprising an immediate release component and delayed release component contains one or more coating layers, wherein immediate release granules preparation involves granulation.
US Pub. No. 2014/0335176 A1 discloses the disintegrant-free delayed release doxylamine succinate and pyridoxine HC1 formulation and a manufacturing process by using direct compression or dry granulation.
The combination of doxylamine succinate and pyridoxine hydrochloride available as a delayed-release tablet (releases the medication in the intestine to delay when the medication will start working) and as an extended-release (long-acting) tablet for oral use. It is usually taken on an empty stomach (at least 1 hour before or 2 hours after a meal). At first, tablet to be taken once a day at bedtime. If the symptoms of nausea and vomiting are not better, then the delayed-release tablets two or three times a day, or the extended-release tablet two times a day are prescribed.
All the prior art references discloses the doxylamine succinate and pyridoxine hydrochloride extended release single layer matrix tablets comprising immediate release granules and delayed release granules, wherein immediate release granules involve granulation step. None of the prior art references uses extended release single layer matrix tablets comprising immediate release blend involves direct mixing. Hence, inventors of the present invention provides extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules as a single layer tablet.
OBJECTIVE OF INVENTION One objective of the present invention is to provide an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules. Another objective of the present invention is to provide an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion does not involve granulation, and prepared by direct mixing and composition further, comprises pharmaceutically acceptable excipients. Another objective of the present invention is to provide a method for the preparation of extended release single layer matrix tablet composition comprising steps of sifting, direct mixing, granulating, blending, compression and film coating. Another objective of the present invention is to provide extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, prepared by a process comprising steps of sifting, direct mixing, granulating, blending, compression and film coating. SUMMARY OF INVENTION One embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion is prepared by direct mixing and said composition further comprises pharmaceutically acceptable excipients. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride, wherein said composition further comprising granulating agent/enteric
coating agent, antacid, disintegrants, diluents/fillers, glidant, lubricant, coating agent and other pharmaceutically acceptable excipients. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition comprising; (a) 0.1% to 10% (w/w) of first active ingredient, (b) 0.1% to 10% (w/w) of second active ingredient, (c) 0.5% to 2.5% (w/w) of disintegrant, (d) 0.5% to 5% (w/w) of glidant, (e) 1% to 10 (w/w) of antacid, (f) 0.5% to 3% (w/w) of lubricant, (g) 35% to 65% (w/w) of diluent or filler, (h) 1% to 10% (w/w) of granulating agent/enteric coating agent, (i) 0.1% to 5% (w/w) of coating agent and (j) 0.01% to 5% other pharmaceutically acceptable excipients. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition comprising; (a) 0.1% to 10% (w/w) of doxylamine or its salt, (b) 0.1% to 10% (w/w) of pyridoxine or its salt, (c) 0.5% to 2.5% (w/w) of croscarmellose sodium, (d) 0.5% to 5% (w/w) of silicon dioxide and (e) 1% to 10 (w/w) magnesium trisilicate, (f) 0.5% to 3% (w/w) of magnesium stearate, (g) 35% to 65% (w/w) of microcrystalline cellulose and lactose monohydrate, (h) 1% to 10% (w/w) of Acryl-Eze Aqueous Acrylic Enteric System White, (i) 0.1% to 5% (w/w) of OPADRY Pink 85F94320, and (j) 0.01% to 5% other pharmaceutically acceptable excipients.
Another embodiment of the present invention relates to a process for preparing extended release single layer matrix tablet composition, wherein said process comprising steps of; 1) preparing immediate release blend comprising; (a) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (b) co-sifting of Pyridoxine HCl with the blend obtained from step a), (c) sifting lactose monohydrate and microcrystalline cellulose through suitable sieve separately, (d) adding sifted materials in conta blender in the following order of half quantity of materials obtained from step (c), step (b) material and remaining quantity of step (c) materials, blending for 30 minutes, (e) sifting of croscarmellose sodium and magnesium trisilicate separately through suitable sieve, adding and blending with step (d) blended materials in conta blender for 10 minutes, 2) preparing delayed release granules comprising; (f) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (g) co-sifting of Pyridoxine HCl with the blend obtained from step f), (h) sifting lactose monohydrate and microcrystalline cellulose through suitable sieve separately, (i) adding sifted materials in rapid mixer granulator/ fluidized bed processor in the following order of half quantity of materials obtained from step (h), step (g) material and remaining quantity of step (h) materials, mixing for 10 minutes, (j) stirring purified water in mechanical stirrer by adding small quantities of Acryl-Eze aqueous enteric coating system upto 20 minutes, (k) granulating step (i) with step (j) enteric coating solution, (l) drying and sifting the dried granules through suitable sieve, 3) blending and compressing of immediate release blend and delayed release granules comprising; (m) adding Blend I and Blend II into blender, mixing for 15 minutes,
(n) sifting Magnesium stearate though suitable sieve and lubricating the step (m) blend in Conta blender for 5 minutes, (o) compressing the obtained blend from step (n) and film coating with the Opadry Pink to obtain extended release single layer matrix tablet. DETAILED DESCRIPTION OF THE INVENTION The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise. The “active ingredients” used in the present invention can be used as pharmaceutically acceptable salts. The pharmaceutically acceptable salts used in the present invention are doxylamine in its succinate salt form as first active ingredient and pyridoxine in its hydrochloride salt form as second active ingredient. In a preferred embodiment, the extended release single layer tablet composition of the invention comprises first active ingredient is doxylamine succinate. The concentration of doxylamine succinate used in the extended release single layer matrix tablet composition of the invention is from 0.1% to 10%. In a preferred embodiment, the extended release single layer tablet composition of the invention comprises second active ingredient is pyridoxine hydrochloride. The concentration of pyridoxine hydrochloride used in the solid oral composition of the invention is from 0.1% to 10%. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein said immediate release blend comprising antacid, disintegrants, diluents/fillers, glidant and lubricant. Another embodiment of the present invention relates to an extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine
hydrochloride comprising immediate release blend and delayed release granules, wherein said delayed release granules comprising granulating agent/enteric coating agent, diluents/fillers, glidant, lubricant and other pharmaceutically acceptable excipients. The extended release single layer matrix tablet composition according to the present invention comprise granulating agent/enteric coating agent which includes acacia, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, Acryl- Eze Aqueous Acrylic Enteric System White, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, ethylcellulose, disodium pyrosulfite, polyvinyl alcohol, gelatin, glucose, guar gum, magnesium aluminum silicate, maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth, maize starch and zein. Preferably, the granulating agent/enteric coating agent used in the extended release single layer matrix tablet composition is Acryl-Eze Aqueous Acrylic Enteric System White. The concentration of granulating agent/enteric coating agent used in the extended release single layer matrix tablet composition of present invention is from 1% to 10% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise antacid which includes magnesium trisilicate, calcium carbonate, sodium bicarbonate, magnesium hydroxide, aluminum hydroxide, magnesium oxide, magnesium carbonate, aluminum phosphate, magaldrate. Preferably, the antacid used in the extended release single layer matrix tablet composition is magnesium trisilicate. The concentration of antacid used in the extended release single layer matrix tablet composition of present invention is from 1% to 10% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise disintegrants which includes croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium,
hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, crospovidone, methylcellulose, polacrilin potassium, sodium alginate, sodium starch glycolate, starch, disodium disulfite, disodium edathamil, disodium edetate, disodiumethylenediaminetetraacetate (EDTA) crosslinked polyvinylpyrollidines, pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose. Preferably, the disintegrant used in the extended release single layer matrix tablet composition is croscarmelose sodium. The concentration of disintegrant used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 2.5% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise diluent/filler which includes cellulose or derivatives, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, cellulose acetate, hydroxypropylcellulose, lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, corn starch, potato starch and combinations thereof. Preferably, the diluent or filler used in the extended release single layer matrix tablet composition are lactose monohydrate and microcrystalline cellulose. The concentration of diluent or filler used in the extended release single layer matrix tablet composition of present invention is from 35% to 65% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise glidants which includes include silicon dioxide, calcium stearate, magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behanate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, combination of sodium benzoate and sodium acetate. Preferably, the glidant used in the extended release single layer matrix tablet composition are silicon dioxide.
The concentration of glidants used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 5% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise lubricant which include magnesium oxide, grades of magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate. Preferably, the lubricant used in the extended release single layer matrix tablet composition is grades of magnesium stearate. The concentration of lubricant used in the extended release single layer matrix tablet composition of present invention is from 0.5% to 3% (w/w) of total weight of the composition. The extended release single layer matrix tablet composition according to the present invention comprise coating agent which includes polyvinyl acetate polymer, OPADRY Pink 85F94320, acrylic resin, polymers or coplymers of acrylic acid, methyl acrylate, ethyl acrylate, methacrylic acid, methyl methacrylate, ethyl methacrylate and the like which may contain quaternary ammonium groups such as ammonio (meth)acrylate copolymers. Preferred examples are copolymers of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride. Such an acrylic polymer is available under the name Eudragit RS which is a water-insoluble copolymer (poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.1, manufactured by Rh6m Pharma, Germany) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof which may be used for coating, for example Eudragit RS 30D. Another acrylic polymer may be Eudragit RL which consists of the same components as Eudragit RS but has a different molar ratio (Eudragit RL: poly(ethylacrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride; 1:2:0.2) e.g. in form of organic-based polymeric solutions or aqueous-based polymeric dispersions thereof, for example Eudragit RL 30D. Preferably, the coating agent used in the extended release single layer matrix tablet composition is OPADRY Pink 85F94320.
The concentration of coating agent used in the extended release single layer matrix tablet composition of present invention is from 0.1% to 5% (w/w) of total weight of the composition. The present invention is further illustrated by the following examples which are provided merely to be exemplary of the inventions and is not intended to limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. EXAMPLES Example 1
Manufacturing procedure: Blend I (Immediate Release Blend) 1. Dispense the ingredients of the core tablets, 2. Co-sift Doxylamine succinate and Silicon dioxide through suitable sieve, 3. Co-sift Pyridoxine HCl with the step 2 sifted materials through suitable sieve, 4. Sift Lactose Monohydrate and MCC through suitable sieve separately, 5. Add the sifted materials in Conta blender in the following order: Half quantity of Diluents (Lactose Monohydrate and MCC), step 3 material and remaining quantity of Diluents, blend the materials for 30 mins at 12 rpm, 6. Sift Magnesium trisilicate and Croscarmellose sodium separately through suitable sieve and blend with step 5 blended materials in Conta blender at 12 rpm for 10 mins. Blend II (Delayed Release Granules) 1. Dispense the ingredients of the core tablets, 2. Co-sift Doxylamine succinate and Silicon dioxide through suitable sieve, 3. Co-sift Pyridoxine HCl with the step 2 sifted materials through suitable sieve, 4. Sift Lactose Monohydrate and MCC through suitable sieve separately,
5. Add the sifted materials in RMG/FBP in the following order: Half quantity of Diluents (Lactose Monohydrate and MCC), step 3 material and remaining quantity of Diluents & mix for 10 minutes, 6. Dispense Acryl-Eze Aqueous Enteric Coating System and Purified water. Stir Purified water using Mechanical stirrer and add small quantities of Acryl-Eze Aqueous Enteric Coating System to it, 7. Continue the stirring for about 20 minutes, 8. Granulate step 5 with step 7 enteric coating solution at inlet temp.50ºC. 9. Dry at inlet temperature 50ºC till get desired LOD. 10. Sift dried granules through suitable sieve. Blending of Blend I and Blend II 1. Add Immediate Release blend from step 6 and Delayed Release Granules from step 11 in to suitable blender and mix for 15 minutes at 12 rpm, 2. Sift Magnesium stearate though suitable sieve and lubricate the step 1 blend in Conta blender at 12 rpm for 5 mins. Compression 1.Compress the lubricated blend using suitable punch (round, standard concave punches plain on both sides). Film Coating 1.Dispense Opadry Pink 85F94320 and Purified water, 2.Stir Purified water using Mechanical stirrer and add small quantities of Opadry Clear 02O190000 to it, 3.Continue the stirring for about 45 minutes, 4.Coat the tablets in Tablet coating machine with the dispersion till the required weight gain is achieved. Stir the dispersion continuously using suitable stirrer during the coating operation.
Example 2
Example 3
Compositions of examples 2-3 were also prepared using the similar method used for the preparation of example 1 composition. Dissolution data Comparative Dissolution Bonjesta (RLD Product) Vs. Example 1 composition is as given below:
Claims
WE CLAIM: 1. An extended release single layer matrix tablet composition of doxylamine succinate and pyridoxine hydrochloride comprising immediate release blend and delayed release granules, wherein immediate release portion is prepared by direct mixing and said composition further comprises pharmaceutically acceptable excipients.
2. The extended release single layer matrix tablet composition as claimed in claim 1, wherein said excipients are granulating agent/enteric coating agent, antacid, disintegrants, diluents/fillers, glidant, anti-adherent, lubricant, coating agent.
3. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said granulating agent/enteric coating agent selected from acacia, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, acryl-eze aqueous acrylic enteric system white, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, ethylcellulose, disodium pyrosulfite, polyvinyl alcohol, gelatin, glucose, guar gum, magnesium aluminum silicate, maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth, maize starch and zein.
4. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said antacid is selected from magnesium trisilicate, calcium carbonate, sodium bicarbonate, magnesium hydroxide, aluminum hydroxide, magnesium oxide, magnesium carbonate, aluminum phosphate, magaldrate.
5. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said disintegrants are selected from croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, crospovidone, methylcellulose, sodium starch glycolate, starch, crosslinked polyvinylpyrollidines,
pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose.
6. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said diluents/fillers selected from cellulose or derivatives, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, cellulose acetate, hydroxypropylcellulose, lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, corn starch, potato starch and combinations thereof.
7. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said glidants which includes include silicon dioxide, calcium stearate, magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behanate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, combination of sodium benzoate and sodium acetate. Preferably, the glidant used in the extended release single layer matrix tablet composition are silicon dioxide.
8. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said lubricant is selected from magnesium oxide, grades of magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate.
9. The extended release single layer matrix tablet composition as claimed in claim 2, wherein said coating agent selected from polyvinyl acetate polymer, OPADRY Pink 85F94320, acrylic resin, polymers or coplymers of acrylic acid, methyl acrylate, ethyl acrylate, methacrylic acid, methyl methacrylate, ethyl methacrylate and the like which may contain quaternary ammonium groups such as ammonio (meth)acrylate copolymers.
10. An extended release single layer matrix tablet composition comprising; 0.1% to 10% (w/w) of doxylamine or its salt, 0.1% to 10% (w/w) of pyridoxine or its salt, 0.5% to 2.5% (w/w) of croscarmellose sodium, 0.5% to 5% (w/w) of silicon dioxide and 1% to 10 (w/w) magnesium trisilicate, 0.5% to 3% (w/w) of magnesium stearate, 35% to 65% (w/w) of microcrystalline cellulose and lactose monohydrate, 1% to 10% (w/w) of Acryl-Eze Aqueous Acrylic Enteric System White, 0.1% to 5% (w/w) of OPADRY Pink 85F94320, and 0.01% to 5% other pharmaceutically acceptable excipients.
11. A process for preparing extended release single layer matrix tablet composition, wherein said process comprising steps of; 1) preparing immediate release blend comprising; (a) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (b) co-sifting of Pyridoxine HCl with the blend obtained from step a), (c) sifting lactose monohydrate and microcrystalline cellulose through suitable sieve separately, (d) adding sifted materials in conta blender in the following order of half quantity of materials obtained from step (c), step (b) material and remaining quantity of step (c) materials, blending for 30 minutes, (e) sifting of croscarmellose sodium and magnesium trisilicate separately through suitable sieve, adding and blending with step (d) blended materials in conta blender for 10 minutes, 2) preparing delayed release granules comprising; (f) co-sifting of doxylamine succinate and silicon dioxide through the sieve, (g) co-sifting of Pyridoxine HCl with the blend obtained from step f), (h) sifting lactose monohydrate and microcrystalline cellulose through suitable sieve separately,
(i) adding sifted materials in rapid mixer granulator/ fluidized bed processor in the following order of half quantity of materials obtained from step (h), step (g) material and remaining quantity of step (h) materials, mixing for 10 minutes, (j) stirring purified water in mechanical stirrer by adding small quantities of Acryl-Eze aqueous enteric coating system upto 20 minutes, (k) granulating step (i) with step (j) enteric coating solution, (l) drying and sifting the dried granules through suitable sieve, 3) blending and compressing of immediate release blend and delayed release granules comprising; (m) adding Blend I and Blend II into blender, mixing for 15 minutes, (n) sifting Magnesium stearate though suitable sieve and lubricating the step (m) blend in Conta blender for 5 minutes, (o) compressing the obtained blend from step (n) and film coating with the Opadry Pink to obtain extended release single layer matrix tablet.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN202121024252 | 2021-05-31 | ||
| IN202121024252 | 2021-05-31 |
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| WO2022254277A1 true WO2022254277A1 (en) | 2022-12-08 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140335176A1 (en) * | 2011-12-07 | 2014-11-13 | Pharmascience Inc. | Disintegrant-free delayed release doxylamine and pyridoxine formulation and process of manufacturing |
| US20150366808A1 (en) * | 2012-02-22 | 2015-12-24 | Duchesnay Inc. | Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof |
| CN106606502A (en) * | 2015-10-27 | 2017-05-03 | 四川海思科制药有限公司 | Doxylamine succinate-pyridoxine hydrochloride enteric-coated tablet pharmaceutical composition and preparation method thereof |
| US10500196B2 (en) * | 2015-08-17 | 2019-12-10 | Alpha To Omega Pharmaceutical Consultants, Inc. | Transdermal and/or topical delivery systems composed of doxylamine succinate and pyridoxine hydrochloride in combination, or alone |
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2022
- 2022-05-19 WO PCT/IB2022/054668 patent/WO2022254277A1/en unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20140335176A1 (en) * | 2011-12-07 | 2014-11-13 | Pharmascience Inc. | Disintegrant-free delayed release doxylamine and pyridoxine formulation and process of manufacturing |
| US20150366808A1 (en) * | 2012-02-22 | 2015-12-24 | Duchesnay Inc. | Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof |
| US10500196B2 (en) * | 2015-08-17 | 2019-12-10 | Alpha To Omega Pharmaceutical Consultants, Inc. | Transdermal and/or topical delivery systems composed of doxylamine succinate and pyridoxine hydrochloride in combination, or alone |
| CN106606502A (en) * | 2015-10-27 | 2017-05-03 | 四川海思科制药有限公司 | Doxylamine succinate-pyridoxine hydrochloride enteric-coated tablet pharmaceutical composition and preparation method thereof |
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