CN103189434B - The polysaccharide of compressible high viscosity and polyol powder - Google Patents
The polysaccharide of compressible high viscosity and polyol powder Download PDFInfo
- Publication number
- CN103189434B CN103189434B CN201180052432.1A CN201180052432A CN103189434B CN 103189434 B CN103189434 B CN 103189434B CN 201180052432 A CN201180052432 A CN 201180052432A CN 103189434 B CN103189434 B CN 103189434B
- Authority
- CN
- China
- Prior art keywords
- powder
- tablet
- polysaccharide
- present
- polyhydric alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000843 powder Substances 0.000 title claims abstract description 109
- 150000004676 glycans Polymers 0.000 title claims abstract description 85
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 85
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 85
- 150000004804 polysaccharides Polymers 0.000 title claims abstract description 85
- 229920005862 polyol Polymers 0.000 title claims abstract description 24
- 150000003077 polyols Chemical class 0.000 title claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 26
- 238000001694 spray drying Methods 0.000 claims description 22
- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 claims description 18
- FBPFZTCFMRRESA-KVTDHHQDSA-N Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 18
- 239000000594 mannitol Substances 0.000 claims description 18
- 235000010355 mannitol Nutrition 0.000 claims description 18
- 229920000881 Modified starch Polymers 0.000 claims description 16
- 239000006188 syrup Substances 0.000 claims description 13
- 235000020357 syrup Nutrition 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 12
- VUKAUDKDFVSVFT-UHFFFAOYSA-N 2-[6-[4,5-bis(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound COC1C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)OC1OC1C(COCC(C)O)OC(OC)C(OCC(C)O)C1OCC(C)O VUKAUDKDFVSVFT-UHFFFAOYSA-N 0.000 claims description 10
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 10
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000000725 suspension Substances 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 8
- 241000196324 Embryophyta Species 0.000 claims description 7
- -1 hydroxyl Propyl Chemical group 0.000 claims description 7
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 claims description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 6
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 6
- 229940072056 alginate Drugs 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 235000010418 carrageenan Nutrition 0.000 claims description 5
- 229920001525 carrageenan Polymers 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- 239000001913 cellulose Substances 0.000 claims description 5
- 235000010980 cellulose Nutrition 0.000 claims description 5
- 238000007385 chemical modification Methods 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 230000001256 tonic Effects 0.000 claims description 5
- 241001597008 Nomeidae Species 0.000 claims description 4
- 229920001817 Agar Polymers 0.000 claims description 3
- 241000195493 Cryptophyta Species 0.000 claims description 3
- GJCOSYZMQJWQCA-UHFFFAOYSA-N Xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 3
- 239000008272 agar Substances 0.000 claims description 3
- 235000010419 agar Nutrition 0.000 claims description 3
- 238000007906 compression Methods 0.000 claims description 3
- 239000002537 cosmetic Substances 0.000 claims description 3
- 239000003599 detergent Substances 0.000 claims description 3
- 238000005243 fluidization Methods 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- 238000005461 lubrication Methods 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 229920001285 xanthan gum Polymers 0.000 claims description 3
- 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
- 235000013339 cereals Nutrition 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 230000001788 irregular Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 240000008529 Triticum aestivum Species 0.000 claims 1
- 231100000167 toxic agent Toxicity 0.000 claims 1
- 239000003440 toxic substance Substances 0.000 claims 1
- 235000021307 wheat Nutrition 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 22
- 238000007907 direct compression Methods 0.000 abstract description 9
- 239000003826 tablet Substances 0.000 description 27
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 15
- 239000011159 matrix material Substances 0.000 description 14
- 238000001035 drying Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 244000024675 Eruca sativa Species 0.000 description 8
- 235000014755 Eruca sativa Nutrition 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 229960000278 Theophylline Drugs 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000006069 physical mixture Substances 0.000 description 7
- WNLRTRBMVRJNCN-UHFFFAOYSA-N Adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 230000003321 amplification Effects 0.000 description 5
- 229920001222 biopolymer Polymers 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- ZTHKPSBRWLGUIK-XORBCWOASA-N (2R,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6S)-6-[[(2R,3S,4R,5R,6R)-3-[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-6-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3S,4R Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](OC[C@@H]2[C@H]([C@H](O)[C@@H](O)[C@@H](O[C@@H]3[C@H](O[C@H](O[C@@H]4[C@H](O[C@H](O)[C@H](O)[C@H]4O)CO)[C@H](O)[C@H]3O)CO)O2)O[C@@H]2[C@@H]([C@@H](O)[C@H](O[C@@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)[C@@H](CO)O2)O)[C@H](O)[C@H]1O ZTHKPSBRWLGUIK-XORBCWOASA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- XAPRFLSJBSXESP-UHFFFAOYSA-N Oxycinchophen Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=C(O)C=1C1=CC=CC=C1 XAPRFLSJBSXESP-UHFFFAOYSA-N 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- 239000001361 adipic acid Substances 0.000 description 3
- 235000011037 adipic acid Nutrition 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- GKFPPCXIBHQRQT-UHFFFAOYSA-N 6-(2-carboxy-4,5-dihydroxy-6-methoxyoxan-3-yl)oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(OC)C(C(O)=O)O1 GKFPPCXIBHQRQT-UHFFFAOYSA-N 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920002488 Hemicellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-YOLKTULGSA-N Maltose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)O[C@H]1CO)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 GUBGYTABKSRVRQ-YOLKTULGSA-N 0.000 description 2
- 241000143392 Oar Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000000249 desinfective Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OMDQUFIYNPYJFM-XKDAHURESA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[[(2R,3S,4R,5S,6R)-4,5,6-trihydroxy-3-[(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2S,3S,4S,5S,6R)-2-[(2R,3S,4R,5R,6S)-6-[(2R,3S,4R,5S,6S)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,4R,5S,6R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 1
- 244000247812 Amorphophallus rivieri Species 0.000 description 1
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- UNXHWFMMPAWVPI-QWWZWVQMSA-N D-Threitol Natural products OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000019749 Dry matter Nutrition 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N Erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 Erythritol Drugs 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 240000003598 Fraxinus ornus Species 0.000 description 1
- 235000002917 Fraxinus ornus Nutrition 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 229920002581 Glucomannan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N Inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 229940029339 Inulin Drugs 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- 229920002752 Konjac Polymers 0.000 description 1
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M Monopotassium phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 150000008444 O-glycosides Chemical class 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 240000004713 Pisum sativum Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 210000002381 Plasma Anatomy 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 1
- 229960004674 Theophylline anhydrous Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N Trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940046240 glucomannan Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 230000000887 hydrating Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000000252 konjac Substances 0.000 description 1
- 235000010485 konjac Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 238000011031 large scale production Methods 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000003287 optical Effects 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000000717 retained Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003068 static Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
Abstract
The present invention relates to a kind of cold-soluble polysaccharide and polyol powder, described powder is high viscosity and applicable direct compression in water.The invention still further relates to a kind of method for preparing described powder and relate to and application thereof, this powder is specifically intended for preparing the solid form of the active component with controlled release.
Description
Invention field
The present invention relates to a kind of cold solvable polysaccharide and polyol powder, described powder is high viscosity in water and is suitable for
Direct compression.The invention still further relates to a kind of method for preparing described powder and relate to and application thereof, this powder is particularly intended to
With being to prepare the solid form of the active component with controlled release.
Prior art
In the field of medicine and tonic excipient, controlled release matrix compositions, also referred to as controlled release matrix, permit
Permitted to give in a long time the active component of an effective dose with a kind of constant and uniform plasma concentration.Therefore for suffering from
For person, controlled release matrix is advantageous particularly, because they can optimize treatment, reduces simultaneously and must take the frequency of tablet also
And the plasma peaks of reduction active component, and the therefore potential side effect come.
At several years of the past, the hydrophilic matrix of controlled release obtained broad development.In the base composition of the type,
Active component is dispersed in the hydrophilic matrix of solid.Contact with described substrate by biological fluid so that active component is from this
Substrate discharges.More properly, biological fluid migrates across substrate, makes described matrix expansion, and dissolves active component, so
These active component rear diffuse through hydrating substrate network.Active component progressively spreads through substrate, have adjusted release stream.
In oral form available for release is controlled for active component, the sheet that can be obtained by direct compression
Agent is very interested for pharmaceuticals industry, because for the angle of drug technique, they are readily produced, and they
Release characteristics can be easily adjusted.
Under room temperature, water-soluble a lot of polymer (cold soluble polymer) have been proposed to be used in control release hydrophilic matrix.
In these preparations in most popular polymer, acrylic acid and the synthetic polymer of methacrylic acid and copolymer, with
And cold solvable polysaccharide (being the most especially derived from the galactomannan of plant gum), cellulose derivative (such as hydroxypropyl methyl
Cellulose (HPMC)) and pregelatinized starch have representative widely.
These polysaccharide have following facts jointly, and i.e. they are high viscosity in water.This high viscosity makes to obtain it
Powder type is complicated.Additionally, their molecule is very big, limits their crystallization and cause their powder to exist
The most unbodied, elastic and the most fibrous, this makes them be difficult to grind.Therefore, it is thus achieved that tool
The polysaccharide powder having precise physical characteristic is complicated.Therefore, these polysaccharide powder are difficult to flow and are not can to suppress very much
So that they are difficult to use in production tablet.
Mention the example of the technical problem run into during the commercial Application of cold solvable polysaccharide, can mention pregelatinized
The concrete condition of starch.This polysaccharide is the most attractive biopolymer as the excipient for controlling release matrix
One of, because it can carry out large-scale production, purity is high and Financial cost is low.Additionally, starch is biocompatible, biological
Degradable and avirulent, and the most therefore may be used for tonic purpose.It also has highly expanded ability in water.
Additionally, starch has the advantage that can act as extender, binding agent or diluent.But, its high viscosity and small particle are composed
Give the flow behavior that it is excessively poor.The high resiliency of starch gives its relatively low compressibility, and this character can not make by directly
Connect tabletting and carry out tablet manufacturing.Therefore, pregelatinized starch is used the most in a small amount.
In order to remedy this situation, the known practice of expert in the art is to use a kind of pregelatinized starch, wherein it
The step of production method is made up of precipitation in organic solvent.The pregelatinized starch generated not only has pregelatinized starch
Known advantage, the most particularly its controlled release hydrophilic matrix characteristic, but also can easily carry out tabletting, and allow to pass through
Direct compression produces tablet.
Unfortunately, these technology need to use a large amount of organic solvent, so that their industrialized production is the most difficult
To implement.
Further, it is necessary to organic solvent is collected, to prevent them to be distributed in air.
Finally, the malicious solvent of trace can be retained in end product.
In other words, owing to a large amount of organic solvent of especially needed use and needs overcome many technical limitations, so these
The preparation of compositions causes extra high environment and Financial cost.
In order to improve excipient, and the rheological behavior of the coldest solvable polysaccharide, those of ordinary skill in the art is
Know and they are combined with other excipient, and/or (such as pelletize, simple or multi-stage spray is dried, capsule bag to use particular technology
Envelope, agglomeration etc.) construct them.
In these excipient being most commonly encountered for prepared by tablet, can it should be particularly mentioned is lactose, sucrose, Portugal
Grape sugar, trehalose, mannitol, sorbitol, erythritol, maltose alcohol and hydroxyl isomaltulose.
Mannitol is due to the agent of low hygroscopicity of its crystal form, it is possible to constitute excellent excipient.Additionally, at solubility figuration
In agent, mannitol, by the highest chemical inertness of its relative activity composition, is a kind of for medicinal solid form offer maximum
The excipient of stability.
It has been proposed that can obtain sweet by spray drying in its patent application FR 08.54584 before the applicant
Dew alcohol granule and the granule of granular starch, and it is characterized in that they make it possible to direct compression and prepare especially
There is the mouth dispersible tablet of notable hardness.
Unfortunately, at the specific field of controlled release matrix, the problem of structure is not granular starch insoluble in water,
But the cold solvable polysaccharide of high viscosity in an aqueous medium.
Along with its generation, those of ordinary skill in the art is known (as especially table in patent US4.156.020
Bright), cold solvable polysaccharide or comprise the compositions of solvable polysaccharide, particularly pregelatinized starch, when this starch is with cold expansion
And in the presence of the state of viscosity, can not be made an uproar by spray dried and construct.Really, even if using steam jet, dehydration
Cold soluble product also cause viscosity, non-can the formation of building block.
In patent application WO 2010/017358, it has been suggested that by prepare the suspension of described polysaccharide and mannitol/
Solution is spray-dried cold solvable polysaccharide (particularly guar gum or inulin).If the owner with application WO 2010/017358
For, the suspension/solution that mannitol adds to polysaccharide makes the viscosity of described solution decline, and then it can be atomized dry
Dry.But, this technology has a considerable amount of shortcoming.Particularly, the suspension/solution only containing low concentration product can be by
(by weight, the polysaccharide concentration of suspension/solution is 0.25% to 1.0% to spray drying, and the ratio of polysaccharide/mannitol is 1/05
To 1/10), and this causes polysaccharide strong aquation before structure, and be difficult to be dried described polysaccharide.Additionally, the final product generated
Thing shows spherical, and in graininess, polysaccharide disappears, and small particle (between 1 μm and 20 μm), is not suitable for direct compression,
This technology cause less than the granule of 40 μm minimum can energy content, total powder of desirably less than 5% (w/w).This
Outward, end product self does not allows for producing the tablet that can be obtained by direct compression.A large amount of microcrystalline Cellulose must be added
In compositions, so that it can be suppressed.
From all those mentioned above, occur in that, to the unsatisfied needs with a kind of product, this product self has
There is following characteristics: be suitable for the hydrophilic matrix of commercial production controlled release, and be suitable for obtain tablet by direct compression, this
It is generally characterized by incompatible a bit.
Therefore, the applicant to one's credit opposes the technology foreknowledge restrained oneself for many years, and the most successfully solves
Determine above-mentioned rheological charactristics.
Therefore, a first object of the present invention is to provide a kind of product, and its own has the feature that and is suitable for industry life
Produce the hydrophilic matrix of controlled release, and fit through the tablet of direct compression.
One second target of the present invention is to provide a kind of substrate controlling release, being formed between batch not of this substrate
Notable change, and keep stable in time.
It is also an object of the present invention to provide and biocompatible, biodegradable and avirulent can easily make
Standby controlled release matrix.
It is also an object of the present invention to provide controlled release matrix, the production cost of this substrate is in economy and environment side
It is low for face.
Still another target of the present invention includes producing powder composition, and their mobility is the best, and therefore fits
It is combined in high-speed production solid form on tablet machine.
Still another target of the present invention includes producing the tablet showing high composition homogeneity, because of according to the present invention's
Powder does not induce solid to form any lamination problem of normal discovery in industry.
Finally, it is also an object of the present invention to provide a kind of method for preparing powder, this powder is suitable for cold solvable
Polysaccharide, is particularly suitable at room temperature showing in water any polysaccharide of high viscosity.
Summary of the invention
One theme of the present invention is a kind of cold-soluble polysaccharide and polyol powder, and this polysaccharide and polyhydric alcohol are at them
Between show secondary or physical bond, this polysaccharide is in particulate form and this polyhydric alcohol is mainly in crystal form.
The invention still further relates to the method for preparing the powder according to the present invention, it is characterised in that it includes a structure step
Suddenly, including:
-a kind of polyol syrup is sprayed on the cold solvable polysaccharide of particulate form, and simultaneously
-it is dried described polyol syrup.
Finally, a theme of the present invention is to include the solid form of the powder according to the present invention and for controlled release
The purposes of active component.
Brief Description Of Drawings
Fig. 1 show according to the present invention and the active component (theophylline) containing different powder in addition to the present invention by controlled release
Put.
Fig. 2 to Fig. 5 represents the observation photo shot with scanning microscope with different amplification, wherein has according to this
Four kinds of powder of invention.
Describe in detail
Present invention firstly relates to a kind of cold-soluble polysaccharide and polyol powder.According to the present invention, it is in particulate form
Polysaccharide and the powder of the polyhydric alcohol that is in crystal form there is secondary or physical bond between which.
In the present invention, term " cold solvable polysaccharide " is intended to refer to be made up of the some monosaccharide being connected to each other via O-glycosides key
Any polymer, in 20 DEG C ± 2 DEG C by weight its described polysaccharide, at least 90% is soluble in water.At 20 DEG C this
The dissolubility of sample makes it possible to the dissolubility guaranteeing this polysaccharide under the human body temperature of about 37 DEG C.As example, cold solvable
In polysaccharide, following material can be mentioned:
The cellulose derivative of-chemical modification, such as hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC) or hydroxypropyl
Ylmethyl cellulose (HPMC),
-the natural or hemicellulose of modification,
-pregelatinized starch, no matter they are natural or chemical modification,
-it is derived from the polysaccharide of plant, such as pectin, guar gum, Konjac glucomannan, karaya, tracasol or Radix Acaciae senegalis,
-it is derived from the polysaccharide of algae, such as agar, carrageenin, alginate and their salt,
-it is derived from the polysaccharide of microorganism, such as Xanthan gun or Pul,
And the most above-mentioned polysaccharide derivates, and their mixture.
Therefore, the invention still further relates to a kind of polysaccharide powder and polyol powder, wherein this polysaccharide is selected from lower group, and it is constituted
For: pregelatinized starch, the cellulose derivative of chemical modification, hemicellulose, it is derived from the polysaccharide of plant, is derived from algae or is derived from
The polysaccharide of microorganism, the derivant of these polysaccharide and their mixture.
Preferably, a theme of the present invention is a kind of polysaccharide powder and polyol powder, and wherein this polysaccharide is selected from lower group,
Consist of: hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC) or hydroxypropyl methyl cellulose (HPMC), natural or
The pregelatinized starch of chemical modification, agar, carrageenin, alginate and their salt, Xanthan gun, Pul,
The derivant of these polysaccharide and their mixture.
In the present invention, term " polysaccharide of particulate form " is intended to refer to the polysaccharide of a kind of powder type, forms this powder
The volume mean diameter D4 of granule, 3 between 10 μm and 200 μm, preferably between 20 μm and 150 μm and the most preferential
Between 50 μm and 100 μm.These polyoses grains also have high viscosity in water, especially press dry (DM) weight when them
Count with from 1% to 5% ratio in the solution time, viscosity be more than 200mPa.s-1。
In the present invention, term " polyol " is intended to refer to the compound selected from lower group, and the composition of this group is: mannitol, mountain
Pears alcohol, hydroxyl isomaltulose and their mixture.
In the present invention, term " secondary or physical bond " is intended to the agglomeration referring to be dried the polysaccharide with particulate form with polyhydric alcohol,
Described agglomeration is that (or dehydration) is formed by being dried by the described polyol syrup being sprayed on polysaccharide or about.Cause
This, this being dried creates the adhesion between this polysaccharide and this polyhydric alcohol or secondary or physical bond, and this polyhydric alcohol becomes from dissolved state
For mainly crystal or microcrystal state.Term " mainly crystal " or " being mostly in crystal form " are intended at this refer to following thing
Real, i.e. pass through polyol weight present in DSC (differential scanning calorimetry) measurement and the powder with respect to the present invention
Carry out weigh (polyhydric alcohol % by weight), fusion enthalpy (the Δ H of the polyhydric alcohol of this powderPowder) at least above again by DSC
Fusion enthalpy (the Δ H of the independent crystal polyhydric alcohol measuredIndividually polyhydric alcohol) 70%, it may be assumed that
ΔHPowder＞ 0.7x ((Δ HIndividually polyhydric alcohol) x (polyhydric alcohol % by weight)/100)
Therefore, the powder of the present invention, by feat of its existence form and therefore by feat of its technical characteristic, is different from simple
Physical mixture, this polysaccharide and polyhydric alcohol are presented in independence in the mixture, the most unconjugated entity.The present invention
Powder also by feat of its existence form and its technical characteristic, be different from by being dried a kind of polysaccharide and the suspension of polyhydric alcohol
Liquid/solution and the co-agglomerated body that produces, in this suspension/solution, this polysaccharide and polyhydric alcohol have covalent chemical between which
Key, such as hydrogen bond.
Can obtain the powder according to the present invention by following methods, the method includes a constitution step, this step bag
Include and polyol syrup is sprayed on the cold solvable polysaccharide of particulate form, be dried described polyol syrup simultaneously.
During this constitution step, the polysaccharide of particulate form can be introduced by continuous mode or batch mode.
In the present invention, term " is sprayed " and is intended to refer to by means of nozzle or turbine, and polyol syrup is separated into small droplet.
In order to spray, the temperature of this polyol syrup being maintained between 40 DEG C and 120 DEG C, the most such temperature allows to this
Polyhydric alcohol is maintained at dissolved state.This polyol syrup also has dry (DM) between 15% and 95% by weight and contains
Amount.
This constitution step must be allowed for sufficiently fast being dried, to prevent the hydration of the polysaccharide of particulate form, and also
It is used for preventing this polyol syrup and/or this polysaccharide sedimentation solid.
In the present invention, term " is dried " and is intended to refer to no matter will will be taken off through the polyol syrup of spraying by any means
Water.Especially it is possible to by convection current, by conducting or being dried by ripple (particularly microwave or infrared waves).According to this
One preference pattern of invention, uses temperature air between 40 DEG C and 300 DEG C to be dried.
Preferably, this constitution step can be carried out in spray drying tower or fluidization air bed comminutor.
One concrete pattern of the method according to the invention, (is such as equipped with high-pressure spray-drying nozzle at spray drying tower
MSD (i.e. plate dryer) type spray drying tower) carry out this constitution step.
The spray drying chamber of this spray drying tower includes a spraying being equipped with main dry air (upstream air) entrance
District (in this ceiling portion).This spray drying chamber is additionally included in has the quiet of special air (static bed air) entrance bottom this room
State fluid bed.The temperature of inlet porting air in the following manner:
The upstream air of-top of tower: temperature between 120 DEG C and 240 DEG C,
-static bed air: temperature is between 40 DEG C and 120 DEG C.
Preferably, this spray drying chamber includes that two dust a little, one be positioned at this ceiling portion and one be positioned at the bottom of this room
Portion, is used for introducing polysaccharide.
This spray drying tower is additionally advantageously furnished with cyclone system, this outlet air making it possible to reclaim spray drying chamber
The fine particle (the most advantageously, the particle diameter of these granules is less than 100 μm) that stream carries.Therefore, according to the present invention, according to the party
One concrete pattern of method, this constitution step also includes the recirculation of powder part.Term " powder part " is intended to finger at this will
The fine particle recirculation of powder, and optionally refer to a part according to the powder of the present invention, these powder are to grind or not
Grind.
In the case of using MSD type spray drying tower, can be by spraying into powder at top, spray drying chamber or bottom
Part carries out recirculation.
According to the present invention, according to a concrete pattern of the method, this powder experienced by one optionally after constitution step
Additional drying step.Such as can carry out this extra drying steps in fluidization air bed.
After this constitution step or after this optional additional drying step, this powder experienced by a cooling step.Root
According to a preference pattern of the method for the present invention, it is cooled to the temperature less than 30 DEG C and carries out on fluid bed, this fluid bed
Air themperature be between 15 DEG C and 25 DEG C.
This optional additional drying step can combine with cooling step in vibratory liquefaction airbed, this fluid bed by
Liang Ge district composition (one for drying steps and another for cooling step).
According to the present invention, according to a concrete pattern of the method, this powder experienced by an optional screening step.Tool
Body ground, uses one or two cloth or sieve to carry out described screening step.Therefore, it can remove meticulous and/or the thickest powder
Part.Additionally, that sift out and undesired powder part can be with recirculation (directly or grind after) for constitution step.
Therefore, the method according to the invention makes it possible to obtain cold-soluble polysaccharide and polyol powder.It is in micro-
The polysaccharide of the described powder of particle shape formula and the polyhydric alcohol being mainly in crystal form are physically to be connected to each other.According to this
The ratio of the polyhydric alcohol/polysaccharide of the powder of invention is between 95/5 and 30/70, preferably between 90/10 and 40/60, and very
To more preferably between 85/15 and 50/50.
Powder particle according to the present invention has shape (Fig. 2 to Fig. 5) irregular, the most aspheric.In basis
In the surface of the described granule of the present invention or on surface, the polysaccharide being in graininess is the most high-visible, mainly with crystal or micro-
The polyhydric alcohol that crystal state exists also is so (especially Fig. 5).
Powder according to the present invention can also have between 50 μm and 500 μm, preferably between 80 μm and 300 μm and
And even more preferential particle diameter D4 between 100 μm and 250 μm, 3.
In the present invention, according to technical manual and the description of manufacturer, from the U.S.'s limited public affairs of Beckman Kurt
Department (Beckman-Coulter), it is equipped with the LS 13-320 laser diffraction granularity analyzer of powder dispersed modules (dry method flow process)
On determine the particle diameter of these powdered product.
The operating condition of sub-hopper (subhopper) screw speed and the oscillation intensity of dispersion skewed slot are determined so that
Optical concentration is between 4% and 12%, it would be desirable to 8%.
The measurement scope of this LS 13-320 laser diffraction granularity analyzer is to 2000 μm from 0.04 μm.Result is calculated as
Percentage ratio by volume, and represent in units of μm.
This grading curve makes it possible to determine volume mean diameter (arithmetic mean of instantaneous value) D4, the numerical value of 3.
Preferably, assessed according to the test A of following description, according to the powder of the present invention viscosity in water be
100mPa.s-1And 10000Pa.s-1Between, preferably at 200mPa.s-1And 5000Pa.s-1Between, and even more preferentially exist
400mPa.s-1And 1000Pa.s-1Between.
Test A includes:
-there is sample to be tested by being incorporated in 90.0g distilled water to prepare by 10.0g sample at 20 DEG C ± 2 DEG C
Suspension/solution；
-make this suspension/solution be hydrated 1h, and make it uniform by stirring；
-according to the explanation of manufacturer and suggestion, use Physica MCR301 flow graph to measure viscosity at 20 DEG C ± 2 DEG C,
This flow graph is equipped with the measure geometry structure of cone-plate type, diameter 5cm, and angle 1 °, by Anton Paar company (Anton
Paar) sell (by by rad.s-1The angular velocity of meter is given and is fixed on 5s-1Shear gradient).
Preferably, determining according to test b, the flowing time having according to the powder of the present invention is between 3 seconds and 15 seconds, excellent
It is selected between 4 seconds and 12 seconds, and even more preferential between 5 seconds and 10 seconds.
Test b includes the measuring method according to European Pharmacopoeia suggestion, and (EP 5.0 rolls up 1,01/2005:20916,2.9.1.6
Section；Equipment according to Fig. 2 .9.16.-2), determine the time necessary to the flowing of 100.0g powder.
Additionally, be more advantageously characterised by its bulk density and tap density according to the powder of the present invention, they are according to tool
Corresponding to European Pharmacopoeia, (EP 5.1 rolls up 1,01/2005:20915,2-9-15 section to body；Equipment according to Fig. 2-9-15-1) built
The test C of the measuring method of view determines, and is further characterized in that its compressibility.
Briefly, test C include being incorporated in 250ml graduated cylinder 100g powder, the diameter of this graduated cylinder be 35mm also
And height is 335mm.Use such as Stampf volumenometer STAV 2003 device, in this 100g powder institute of any jolt ramming pre-test
The volume (jolt ramming front volume) accounted for, and after giving 2500 jolt ramming from top to bottom, then measure volume (volume after jolt ramming)
(declining 3mm+/-0.2).Therefore, this device make it possible to standardized and reproducible under the conditions of, by calculate pine close
Degree, tap density draw the compressibility of powder, and from these data, according to below equation calculating compressibility:
Bulk density=100 (g)/jolt ramming front volume (ml)
Volume (ml) after tap density=100 (g)/jolt ramming
Compressibility (%)=[(tap density-bulk density)/bulk density] x 100
Powder according to the present invention advantageously has:
-between 0.25g/ml and 0.65g/ml, preferably between 0.30g/ml and 0.60g/ml and the most preferential
Bulk density between 0.35g/ml and 0.55g/ml,
-between 0.40g/ml and 0.80g/ml, preferably between 0.45g/ml and 0.75g/ml and the most preferential
Tap density between 0.50g/ml and 0.70g/ml, and
-between 5% and 45%, preferably between 10% and 40% and even more preferentially between 12% and 35%
Compressibility.
According to test D, advantageously make it possible to obtain 400mg ± 10mg according to the powder of the present invention, hardness is 100N
The tablet of ± 10N, the pressure of these tablets is between 5kN and 50kN, preferably between 8kN and 40kN, even more preferentially exist
Between 10kN and 25kN and even more preferentially between 9kN and 25kN.
Test D includes measurement power, represents in units of kN, and this requires that obtaining hardness is the tablet of 100N ± 10N, this tablet
Using XL1 type laboratory reciprocating presses to prepare, this tablet machine is by Korsch Company and is equipped with a diameter of
The flat punch of 10mm, this tablet is to prepare from the described co-agglomerated body lubricated by the magnesium stearate of 0.5% to 2.0%.This
Lubrication is by having enough to meet the need blender (epicyclic mixer) (Willy A.Bachofen AG in Turbula T2C type
Maschinenfabrik company, CH-4005 Basel) in this powder mixed with magnesium stearate 5 minutes carry out.By tabletting
Machine could be adjusted to produce 400mg ± 10mg and hardness is the tablet of 100N ± 10N.This tablet is the cylinder with plane,
A diameter of 10mm.According to manufacturer's recommendation, the hard of these tablets measured by Erweka TBH 30 GMD type hardness tester tester
Degree or crushing strength.
Powder according to the present invention advantageouslys allow for the preparation of solid form, the most particularly tablet or capsule.Therefore, originally
One theme of invention or a kind of solid form, including the powder according to the present invention and at least one active component.At this
In invention, term " active component " be intended to refer to introduce solid form and particularly food, medicine, tonic, veterinary,
Plant quarantine, cosmetics, disinfectant and detergent applications have any molecule of application.Therefore, a theme of the present invention is also
It it is the purposes in field mentioned above of the solid form according to the present invention.
Solid form according to the present invention advantageously has the controlled release of one or more active component that it is comprised
Characteristic.Therefore, the theme of the present invention or solid form, it is characterised in that according to test E, after the 1h time period by weight
Meter, less than 80%, preferably smaller than 60% and the most preferentially this active component less than 40% be released.Therefore, according to this
The solid form of invention is additionally advantageously characterised by according to test E, after the 6h time period by weight, less than 80%, the least
In 60% and the most preferentially less than 50% this active component be released.
Test E includes:
-Turbula T2C type have enough to meet the need blender (Willy A.Bachofen AG Maschinenfabrik company,
CH-4005 Basel) in 196.0mg had powder to be tested and 2.0mg magnesium stearate, 2.0mg silicon dioxide (silicon dioxide
Aeroge 200) and 200.0mg active component (by weight, have purity more than 99% theophylline anhydrous, by Sigma company
Sell) mix 5 minutes,
-use the Fette Exacta 21 type reciprocating presses of the flat punch being equipped with a diameter of 10mm to prepare 400mg
± 10mg tablet.Tablet machine be could be adjusted to produces 400mg ± 10mg and hardness is the tablet of 100N ± 10N.Obtain
Tablet is the cylinder with plane, a diameter of 10mm,
-molten in the Sotax AT7 intelligence being equipped with Sotax CY 7-50 piston pump and Sotax C613 fraction collector
Solve and carry out on controlled system dissolving test.This dissolution system be configured to 2 types, therefore it is furnished with oar.Dissolving bath temperature is 37 DEG C,
And oar speed is 50 revs/min.Dissolve test the first step be to be immersed in by tablet containing 500ml, pH be 1.2 hydrochloric acid saline
In the dissolving bath of solution.During this first step, take out six samples (15 minutes from this dissolving bath；30 minutes；45 points
Clock；60 minutes；90 minutes；120 minutes).Second step is to add 500ml phosphate buffered solution (NaOH+KH2PO4), this
Sample makes have 1L buffer solution, pH 6.8, adds described phosphate buffered solution immediately after taking out the sample of 120 minutes.
During this second step, take out 12 samples (2.5 hours from this dissolving bath；3 hours；3.5 hour；4 hours；5 hours；6
Hour；7 hours；8 hours；9 hours；10 hours；11 hours；12 hours).Finally, by spectrophotometer method at 272nm wavelength
Place measures the theophylline comprised in the sample thus taken.Finally, a theme of the present invention is the solid form according to the present invention
Purposes in food, medicine, tonic, veterinary, plant quarantine, cosmetics, disinfectant and detergent applications.
The present invention is by means of following instance and accompanying drawing thereof it will be appreciated that ground is clearer, and the purpose of these materials is non-limiting
And be illustrative, and simply mean to some embodiment of the powder according to the present invention and some advantageous feature.
Example 1: according to the preparation of the powder of the present invention
1.1 Pregelatinized starch powder and mannitol powder
Use the Niro MSD spray drying tower of the evaporated quantity of water with about 80kg/h to prepare cold solvable pregelatinized shallow lake
Powder powder and polyol powder.
Use high pressure nozzle spraying system (SK 60*21), in spray drying chamber under 40 bars (HP pressure), spray sweet
The aqueous syrup (by dry matter weight gauge 40%, temperature is 80 DEG C) of dew alcohol.Meanwhile, via dose weight device in this spray dried
The top of dry room, according to make it possible to obtain mannitol/pregelatinized starch dry/ratio of dry weight is 54/46 (M/P ratio)
Flow velocity, sprays into the powdery pregelatinized starch (PREGEFLO sold by the applicant continuouslyCH10)。
Adjust spray drying tower temperature so that upstream air temperature is 135 DEG C (T ° of upstreams), and still air bed tempertaure
It is 77 DEG C (T ° of SFB), hence in so that the spray drying tower outlet air temperature (T ° of outlet) of 63 DEG C may be obtained.By outlet sky
The whirlwind of gas reclaims the fine particle (or fine powder) of pregelatinized starch and mannitol, and at the head of this spray drying chamber
They are sprayed into by (top, spray drying chamber) again.
On vibrated fluidized bed, the powder obtained in spray drying chamber's outlet being cooled to temperature is 20 DEG C.Then, at sieve
Hole size is to screen powder on the sieve of 500 μm, and particle diameter is removed more than the powder part of 500 μm.Therefore, collect according to the present invention
Pregelatinized starch powder and mannitol powder, they are later referred to as PREGEL-MAN 1.
1.2 Polysaccharide powder and mannitol powder
According to the method that carries out indicated above, the parameter listed in change table 1 and following cold solvable polysaccharide simultaneously
Character:
The mixture crosslinking of-PREGEL-MAN 1 and 2=and adipate ester reagent, the mixture of acetic anhydride and adipic acid
Waxy corn starch, pregelatinated on drum type drying machine, and sold (PREGEFLO by the applicantCH10,
ROQUETTE FRERES company)
-PREGEL-MAN 3 and 8=potato starch pregelatinized on drum type drying machine, and by the applicant
Sell (PREGEFLOP100, ROQUETTE FRERES company)
-PREGEL-MAN 4 and 5=pregelatinized waxy corn starch on drum type drying machine, and by the applicant
Sell (PREGEFLOC100, batch S0960, ROQUETTE FRERES company)
-PREGEL-MAN 9 and 10=waxy corn starch pregelatinized on drum type drying machine, and by this Shen
Ask someone to sell (PREGEFLOC100, batch S0988, ROQUETTE FRERES company)
The corn starch that-PREGEL-MAN 6=is pregelatinized on drum type drying machine, and sold by the applicant
(PREGEFLOM, ROQUETTE FRERES company)
The pea starch of-PREGEL-MAN 7=substitution value (DS) hydroxypropylation between 0.16 and 0.21, and
Pregelatinated on drum type drying machine
-HPMC-MAN 1,2,3 and 4=is by the HPMC (BENECEL of AQUALON CompanyK4M PH CR, IMCD)
-CARRA-MAN 1 and 2=is by the carrageenin (VISCARIN of FMC BIOPOLYMER CompanyGP 209
NF, IMCD)
-ALGI-MAN=is by the alginate (PROTANAL of FMC BIOPOLYMER CompanyLF 120M, IMCD).
Table 1
Example 2: according to the feature of the powder of the present invention with compare
Illustrate the powder (table 1) according to the present invention in the above example, it is characterised in that following aspect:
-flowing time, measured with the second, and assessed according to test b,
-bulk density and tap density, measure with g/ml, and according to test C assessment,
-compressibility, is evaluated as % according to test C,
-viscosity, measures with Pa/s, and according to test A assessment,
-volume mean diameter D4,3, measure with μm, and as previously explained, having from U.S.'s Beckman Kurt
Determine on the LS 13-320 laser diffraction granularity analyzer of limit company.
The feature of the powder according to the present invention also compares (table 2) with those features separating taken polysaccharide:
The Waxy maize of the mixture crosslinking of-PREGEL=and adipate ester reagent, the mixture of acetic anhydride and adipic acid
Starch, pregelatinated on drum type drying machine, and sold (PREGEFLO by the applicantCH10, ROQUETTE FRERES
Company)
-HPMC=is by the HPMC (BENECEL of AQUALON CompanyK4MPH CR, IMCD)
-CARRA=is by the carrageenin (VISCARIN of FMC BIOPOLYMER CompanyGP 209 NF, IMCD)
-ALGI=is by the alginate (PROTANAL of FMC BIOPOLYMER CompanyLF 120 M, IMCD)
And compare with those features of the simple physical mixture of polysaccharide/mannitol:
-PREGEL+MAN=mannitol (PEARLITOL160C, ROQUETTE FRERES company) and and adipate ester
Physical mixture (the M/P by weight of the waxy corn starch of the mixture crosslinking of reagent, the mixture of acetic anhydride and adipic acid
Ratio is 50/50), this starch is pregelatinated on drum type drying machine, and is sold (PREGEFLO by the applicantCH10,
ROQUETTE FRERES company)
-HPMC+MAN=mannitol (PEARLITOL160C, ROQUETTEFRERES company) and by AQUALON company
HPMC (the BENECEL soldK4MPH CR, IMCD) physical mixture (by weight, the ratio of M/P is 83/17).
Table 2
∞=Infinite Time；Nf=does not finds.
With separate taken polysaccharide or compared with simple physical mixture, according to the powder of the present invention show excellence stream
Dynamic (flowing time is less than 15 seconds), lower viscosity and higher volume mean diameter D4,3.
Example 3: assess according to the compressibility of the powder of the present invention and compare
The powder (table 1) according to the present invention that illustrates in example 1, separate some polysaccharide and polysaccharide/manna taken
The simple physical mixture of alcohol is characterised by the compressibility (table 3) according to test D.
Table 3
X=uses great pressure all can not prepare the tablet with required hardness
Contrary with separating taken polysaccharide and contrary, according to the present invention's with some polysaccharide/mannitol physical mixture
Powder makes it possible to according to test D, under the compression force less than 25kN, it is thus achieved that hardness is the tablet of 100N ± 10N.
Example 4: according to the dissolution characteristics curve of the solid form of the present invention with compare
The controlled release characteristics of the active component (theophylline) of the solid form according to the present invention, and from separating certain taken
The controlled release characteristics of the active component of the solid form that a little polysaccharide obtain, and mix from the simple physical of polysaccharide/mannitol
Thing obtain solid form active component controlled release characteristics, these all according to test E be estimated (Fig. 1)。
Solid form according to the present invention is after the 1h time period, and the theophylline showing the theophylline being less than 80% by weight is subject to
Controlled release is put.Additionally, according to some solid form of the present invention additionally advantageously after the period of 6h, show and be less than by weight
The theophylline controlled release of the theophylline of 60%.
Example 5: observe according to the scanning microscope of the powder of the present invention
The powder according to the present invention is observed by scanning electron microscope ESEM-FEI-Quanta FEG 200.Fig. 2 is to figure
5 is these photographic result observed.
Fig. 2: PREGEL-MAN 4 (amplification: 136 times)
Fig. 3: PREGEL-MAN 4 (amplification: 340 times)
Fig. 4: PREGEL-MAN 1 (amplification: 680 times)
Fig. 5: PREGEL-MAN 5 (amplification: 680 times)
Claims (17)
1. comprising a tablet for powder, the granule of described powder is made up of cold solvable polysaccharide and polyhydric alcohol, described powder
Grain has irregular aspheric shape, and this polysaccharide and polyhydric alcohol have secondary or physical bond between which, wherein at described granule
In: this polysaccharide is in particulate form and high-visible at described particle surface, and this polyhydric alcohol is mainly in crystal form.
2. tablet as claimed in claim 1, wherein the weight ratio of this polyhydric alcohol/polysaccharide is between 95/5 and 30/70.
3. tablet as claimed in claim 1, wherein this polyhydric alcohol is selected from lower group, consists of: mannitol, sorbitol, different wheat
Bud sugar alcohol and their mixture.
4. tablet as claimed in claim 1, wherein this polysaccharide is selected from lower group, consists of: pregelatinized starch, be derived from plant
Polysaccharide, be derived from algae or be derived from the polysaccharide of microorganism, the derivant of these polysaccharide and their mixture.
5. tablet as claimed in claim 1, wherein this polysaccharide is selected from lower group, consists of: hydroxyethyl cellulose (HEC), hydroxyl
Propyl cellulose (HPC) or hydroxypropyl methyl cellulose (HPMC), the natural or pregelatinized starch of chemical modification, agar,
Carrageenin, alginate, Xanthan gun, Pul, the derivant of these polysaccharide and their mixture.
6. tablet as claimed in claim 1, the volume mean diameter that wherein said powder has be 50 μm and 500 μm it
Between.
7. tablet as claimed in claim 1, the viscosity that described powder has in water is at 100mPa s-1With 10
000Pa·s-1Between, described viscosity is according to following mensuration:
-there is the suspension of sample to be tested by being incorporated in 90.0g distilled water to prepare by 10.0g sample at 20 DEG C ± 2 DEG C
Liquid/solution；
-make this suspension/solution be hydrated 1h, and make it uniform by stirring；
-according to the explanation of manufacturer and suggestion, use Physica MCR301 flow graph to measure viscosity, this stream at 20 DEG C ± 2 DEG C
Become instrument and be equipped with the measure geometry structure of cone-plate type, diameter 5cm, angle 1 °, by Anton Paar Company, be fixed on 5s-1
Shear gradient by by rad.s-1The angular velocity of meter is given.
8. tablet as claimed in claim 1, the flowing time that described powder has is between 3 seconds and 15 seconds, described flowing
Time is according to following mensuration: according to European Pharmacopoeia EP 5.0, rolls up 1,01/2005:20916,2.9.1.6 section；According to figure
The measuring method of equipment suggestion 2.9.16.-2, determines the time necessary to the flowing of 100.0g powder.
9. tablet as claimed in claim 1, the compressibility that described powder has is between 5% and 45%, described compressibility
According to following mensuration:
-100g powder is incorporated in 250ml graduated cylinder, the diameter of this graduated cylinder is 35mm and height is 335mm；
-at the volume (jolt ramming front volume) shared by this 100g powder of any jolt ramming pre-test, and then giving from top to bottom
After 2500 jolt ramming measure volume (volume after jolt ramming), decline 3mm+/-0.2, use standardized and reproducible under the conditions of
The device of the compressibility of powder can be measured by calculating bulk density, tap density, and from these data, according to following public affairs
Formula calculating compressibility:
Bulk density=100 (g)/jolt ramming front volume (ml)
Volume (ml) after tap density=100 (g)/jolt ramming
Compressibility (%)=[(tap density-bulk density)/bulk density] x 100.
10. tablet as claimed in claim 1, described powder obtains under following compression force that to have hardness be 100N ± 10N's
Tablet: between 5kN and 50kN, described compression force is by following mensuration: measures power, represents in units of kN, and this requires to obtain
Hardness is the tablet of 100N ± 10N, this tablet use XL1 type laboratory reciprocating presses prepare, this tablet machine by
Korsch Company and be equipped with the flat punch of a diameter of 10mm, this tablet be from 0.5% to 2.0% magnesium stearate
Prepared by the described powder of lubrication；This lubrication is by having enough to meet the need blender Willy in Turbula T2C type
A.BachofenAG Maschinenfabrik company, mixes with magnesium stearate 5 minutes by this powder in CH-4005 Basel
Row；Tablet machine be could be adjusted to produces 400mg ± 10mg and hardness is the tablet of 100N ± 10N；This tablet is to have
The cylinder of plane, a diameter of 10mm；According to manufacturer's recommendation, Erweka TBH 30 GMD type hardness tester tester is measured
The hardness of these tablets or crushing strength.
11. tablets as claimed in claim 1, wherein said powder prepared by the method including a constitution step, this step
Suddenly include:
-a kind of polyol syrup is sprayed on the cold solvable polysaccharide of particulate form, and simultaneously
-it is dried described polyol syrup.
12. tablets as claimed in claim 11, wherein this constitution step also includes the recirculation of a powder part.
13. tablets as claimed in claim 11, wherein carry out this constitution step in a spray drying tower.
14. tablets as claimed in claim 11, wherein carry out this constitution step in a fluidization air bed comminutor.
15. such as powder defined in claim 1 for preparing the purposes of tablet.
16. purposes as claimed in claim 15, wherein said tablet is food, medicine, veterinary, plant quarantine, cosmetics, disappears
Tablet in toxic agent and detergent applications.
17. purposes as claimed in claim 15, wherein said tablet is the tablet in tonic field.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1059024 | 2010-11-02 | ||
| FR1059024A FR2966828B1 (en) | 2010-11-02 | 2010-11-02 | POLYSACCHARIDE AND POLYOL POWDER, COMPRESSABLE AND HIGH VISCOSITY |
| PCT/FR2011/052559 WO2012059689A1 (en) | 2010-11-02 | 2011-11-02 | Compressible, highly viscous polysaccharide and polyol powder |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103189434A CN103189434A (en) | 2013-07-03 |
| CN103189434B true CN103189434B (en) | 2016-12-14 |
Family
ID=
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1175899A1 (en) * | 2000-07-27 | 2002-01-30 | Roquette Frˬres | Starch and lactose granulate |
| FR2826549A1 (en) * | 2001-06-28 | 2003-01-03 | Roquette Freres | PROCESS FOR THE PREPARATION OF A COMPRESSED EDULCORANT TABLET AND A COMPRESSED EDULCORANT THUS OBTAINED |
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1175899A1 (en) * | 2000-07-27 | 2002-01-30 | Roquette Frˬres | Starch and lactose granulate |
| FR2826549A1 (en) * | 2001-06-28 | 2003-01-03 | Roquette Freres | PROCESS FOR THE PREPARATION OF A COMPRESSED EDULCORANT TABLET AND A COMPRESSED EDULCORANT THUS OBTAINED |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9101155B2 (en) | Functional starch powder | |
| Nayak et al. | Plant polysaccharides in pharmaceutical applications | |
| US10314786B2 (en) | Hydroxyalkyl alkyl cellulose, method for producing the same, and solid preparation | |
| CN103501817A (en) | Novel polysaccharide derivatives and dosage forms | |
| CN102204895A (en) | Film-form preparation and method for producing the same | |
| CN104382868B (en) | The dispersible mannitol in oral cavity | |
| JP6850237B2 (en) | Hydroxyalkylalkylcellulose and its production method and solid preparation | |
| Nayak et al. | Tamarind polysaccharide based multiple units for oral drug delivery | |
| KR101804607B1 (en) | Compressible, highly viscous polysaccharide and polyol powder | |
| Gil-Chávez et al. | Application of Aquasolv Lignin in ibuprofen-loaded pharmaceutical formulations obtained via direct compression and wet granulation | |
| CN106511348B (en) | Huperzine skeleton particle, oral disintegrating tablet and preparation method thereof | |
| CN103189434B (en) | The polysaccharide of compressible high viscosity and polyol powder | |
| US20180049990A1 (en) | Low-substituted hydroxypropyl cellulose and solid preparation | |
| CN101790541A (en) | High-amylose sodium carboxymethyl starch sustained release excipient and preparation method thereof | |
| CN106890162A (en) | Film-form preparation and its manufacture method | |
| CN103025315B (en) | Control the method that active component discharges from dosage form | |
| Zhou et al. | Hydroxyethyl Pachyman as a novel excipient for sustained-release matrix tablets | |
| Rahi | Review Article on Superdisintegrants Agents Used in Formulations of Sublingual Tablets. | |
| CN107174665A (en) | Solid pharmaceutical preparation and its production method containing alkylcellulose | |
| Rahi | of Sublingual Tablets |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant |