CN115737582A - Hydrotalcite chewable tablet and preparation method thereof - Google Patents
Hydrotalcite chewable tablet and preparation method thereof Download PDFInfo
- Publication number
- CN115737582A CN115737582A CN202211629120.9A CN202211629120A CN115737582A CN 115737582 A CN115737582 A CN 115737582A CN 202211629120 A CN202211629120 A CN 202211629120A CN 115737582 A CN115737582 A CN 115737582A
- Authority
- CN
- China
- Prior art keywords
- granules
- chewable tablet
- corn starch
- hydrotalcite
- dry granulation
- 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.)
- Pending
Links
- 239000007910 chewable tablet Substances 0.000 title claims abstract description 73
- 229940068682 chewable tablet Drugs 0.000 title claims abstract description 49
- 229960001545 hydrotalcite Drugs 0.000 title claims description 50
- 229910001701 hydrotalcite Inorganic materials 0.000 title claims description 50
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 title claims 6
- 238000002360 preparation method Methods 0.000 title abstract description 31
- 239000008187 granular material Substances 0.000 claims abstract description 60
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 44
- 229920002261 Corn starch Polymers 0.000 claims abstract description 41
- 239000008120 corn starch Substances 0.000 claims abstract description 41
- 238000007908 dry granulation Methods 0.000 claims abstract description 34
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 22
- 239000000945 filler Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims description 49
- 238000002156 mixing Methods 0.000 claims description 30
- 239000002245 particle Substances 0.000 claims description 25
- 239000000796 flavoring agent Substances 0.000 claims description 21
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 19
- 229930195725 Mannitol Natural products 0.000 claims description 19
- 239000000594 mannitol Substances 0.000 claims description 19
- 235000010355 mannitol Nutrition 0.000 claims description 19
- 235000013355 food flavoring agent Nutrition 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 14
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 10
- 239000011777 magnesium Substances 0.000 claims description 10
- 229910052749 magnesium Inorganic materials 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 8
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- 230000004580 weight loss Effects 0.000 claims description 8
- 239000000811 xylitol Substances 0.000 claims description 8
- 235000010447 xylitol Nutrition 0.000 claims description 8
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 8
- 229960002675 xylitol Drugs 0.000 claims description 8
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 5
- 229940085605 saccharin sodium Drugs 0.000 claims description 5
- 240000008790 Musa x paradisiaca Species 0.000 claims description 3
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- 239000007967 peppermint flavor Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 abstract description 21
- 235000019640 taste Nutrition 0.000 abstract description 15
- UJOHNXQDVUADCG-UHFFFAOYSA-L aluminum;magnesium;carbonate Chemical compound [Mg+2].[Al+3].[O-]C([O-])=O UJOHNXQDVUADCG-UHFFFAOYSA-L 0.000 abstract description 12
- HLLSOEKIMZEGFV-UHFFFAOYSA-N 4-(dibutylsulfamoyl)benzoic acid Chemical compound CCCCN(CCCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 HLLSOEKIMZEGFV-UHFFFAOYSA-N 0.000 abstract 1
- 239000000463 material Substances 0.000 description 47
- PWZFXELTLAQOKC-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide;tetrahydrate Chemical compound O.O.O.O.[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O PWZFXELTLAQOKC-UHFFFAOYSA-A 0.000 description 43
- 230000008569 process Effects 0.000 description 36
- 229920002472 Starch Polymers 0.000 description 15
- 239000008107 starch Substances 0.000 description 15
- 235000019698 starch Nutrition 0.000 description 15
- 229940032147 starch Drugs 0.000 description 15
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 13
- 229940069428 antacid Drugs 0.000 description 13
- 239000003159 antacid agent Substances 0.000 description 13
- 230000001458 anti-acid effect Effects 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 239000011230 binding agent Substances 0.000 description 12
- 238000005550 wet granulation Methods 0.000 description 12
- 239000000853 adhesive Substances 0.000 description 9
- 230000001070 adhesive effect Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 235000020985 whole grains Nutrition 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000003825 pressing Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000001156 gastric mucosa Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 210000004211 gastric acid Anatomy 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 238000000227 grinding Methods 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 235000006679 Mentha X verticillata Nutrition 0.000 description 3
- 235000002899 Mentha suaveolens Nutrition 0.000 description 3
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 3
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000007767 bonding agent Substances 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 230000001055 chewing effect Effects 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229910017053 inorganic salt Inorganic materials 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000013441 quality evaluation Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229940013618 stevioside Drugs 0.000 description 3
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 3
- 235000019202 steviosides Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108091005508 Acid proteases Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 235000016623 Fragaria vesca Nutrition 0.000 description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 235000019606 astringent taste Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- -1 hydrotalcite tetrahydrate Chemical class 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 244000307700 Fragaria vesca Species 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 206010067171 Regurgitation Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 208000019790 abdominal distention Diseases 0.000 description 1
- 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 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000013070 direct material Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Abstract
The invention discloses an aluminum magnesium carbonate chewable tablet and a preparation method thereof, and the chewable tablet comprises a granule A, a granule B and magnesium stearate, wherein the granule A contains 50 percent of aluminum magnesium carbonate and 4 to 8 percent of corn starch; the granule B contains 3-7% of corn starch and the rest of filler, and is prepared by dry granulation. The chewable tablet has good overall characteristics, good taste, short disintegration time, rapid acid resistance, long acid resistance maintaining time and suitable hardness.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a hydrotalcite chewable tablet and a preparation method thereof.
Background
The hydrotalcite is a novel long-acting antacid, the molecular structure of which is arranged according to layered crystal lattices, and has various pharmacological actions. Firstly, the gastric acid neutralization: 1g of hydrotalcite can neutralize 27.1 mmol-27.8 mmol of hydrochloric acid to generate two insoluble salts, water and carbon dioxide. When the pH is less than 3, the medicine starts to perform a neutralization reaction; when the pH is =5, the reaction is terminated; when the pH is less than 3, the reaction is restarted. Therefore, the medicine can maintain the pH value of the stomach between 3 and 5, neutralize 99 percent of gastric acid and inactivate 80 percent of pepsin. The product has antacid effect, and has the advantages of rapid action, mild effect, and long action time. Secondly, the product has the functions of adsorption and combination: can directly inhibit the activity of gastric acid protease by adsorbing and combining the gastric acid protease, and is beneficial to the repair of ulcer surfaces; the medicine can also combine bile acid and adsorb lysophosphorylcholine, thereby preventing the damage and destruction of the gastric mucosa by the substances. In addition, the product also has the mucosa protection function: the composition can stimulate gastric mucosa to increase prostaglandin E2 synthesis, thereby enhancing gastric mucosa barrier effect. In addition, the hydrotalcite can promote the release of epidermal growth factor in gastric mucosa, increase the content of phospholipid in the hydrophobic layer of the lower layer of mucus, and prevent the gastric mucosa from being damaged.
The product is clinically used for gastric ulcer and duodenal ulcer; acute and chronic gastritis and duodenal ampungitis; reflux esophagitis; and is used for symptomatic treatment of stomach discomfort associated with hyperchlorhydria, such as burning pain, acid regurgitation and abdominal distention, nausea, vomiting, etc.
The hydrotalcite is an antacid, and the key quality attribute is the antacid capacity expressed as the antacid capacity. Further, the quality evaluation may be performed by an in vitro antacid test to evaluate the antacid rate and the antacid duration.
The original preparation on the market of the product is the hydrotalcite chewable tablet of German Bayer, with the trade name of Daxi. According to the published data, the prescription has simple composition, and only contains corn starch, mannitol, saccharin sodium, magnesium stearate, mint essence and banana essence except the main medicine. The formula is simple, and good taste can be maintained. In addition, the antacid has excellent performance in terms of acid resistance rate, acid resistance maintenance time, and the like.
In 2018, the FDA in the united states issued guidelines for quality evaluation of chewable tablets, discussed the specificity of chewable tablets compared to common tablets, and reviewed quality evaluation studies of chewable tablets in terms of hardness, mouthfeel, disintegration time limit, and the like. For hardness, the FDA generally recommends that chewable tablets should be of lower hardness, e.g., an average hardness of less than 120N.
It is relatively easy for the product to meet the acidity index specified by the pharmaceutical standards. However, achieving the quality characteristics of the original developer with good performance in all aspects is a challenging task. Specifically, the excellent combination of properties of the product should include the following: (1) excellent mouthfeel; (2) shorter disintegration time; (3) faster acid-resistant speed; (4) long duration of acid resistance; (5) suitable hardness.
There are numerous prior art disclosing formulation compositions and methods of preparation of hydrotalcite chewable tablets, mostly using wet granulation processes, later developed methods of preparation including direct compression and dry granulation, summarized as follows:
(1) And (3) a wet granulation process:
CN200710093165.8 discloses a hydrotalcite preparation and a preparation process thereof. The prescription of the scheme contains mannitol, carboxymethyl starch sodium, magnesium stearate, sodium cyclamate and mint essence, and the preparation method is characterized in that pre-crosslinked starch slurry is used as a bonding agent, and the pre-crosslinked starch slurry is firstly cut and granulated and then is further granulated. The proposal adopts a mode of combining two wet granulation processes, the process is complex, and because of using the adhesive, the teeth are easily stuck and the mouth is easily astringent.
CN201610610562.7 discloses an aluminum magnesium carbonate chewable tablet and a preparation process thereof. The prescription of the scheme contains lactose, mannitol, stevioside, pineapple essence and magnesium stearate, the process is a wet granulation process, and polyvinylpyrrolidone K30 aqueous solution is used as a binder. The adhesive adopted by the technical scheme brings bad experience in the aspect of mouthfeel.
CN202210378555.4 discloses an aluminosilicate magnesium carbonate chewable tablet and a preparation method thereof, wherein the formula of the scheme comprises mannitol, corn starch, saccharin sodium, carboxymethyl starch sodium, purified water, powdered mint essence and magnesium stearate, and the process comprises wet granulation and adopts corn starch pulping as a binding agent. The scheme adopts a wet granulation process, has simple working procedures, but easily causes tooth sticking and astringent taste due to the use of starch slurry, and influences the taste.
CN202110036123.0 discloses an alundum carbonate chewable tablet and a preparation method thereof, wherein the formula of the scheme comprises alundum carbonate, a diluent, a lubricant and a flavoring agent, wherein the alundum carbonate needs to be micronized, and has a particle size D 90 Controlling the thickness to be 15-10 μm. The scheme adopts a shearing wet granulation process and adopts purified water as a wetting agent. The finished product prepared by the scheme has higher acid resistance speed, but the main drug needs micronization, the particle size control range is narrower, the industrial large-scale production is not easy to carry out, and the main drug is easy to be stuck to teeth and the taste is influenced by adopting a wet granulation process by taking water as a bonding agent.
202210713526.9 discloses a hydrotalcite chewable tablet and its preparation method, the filler of the technical scheme comprises a mixture of sugar alcohol and inorganic salt, wherein the inorganic salt comprises alumina, magnesium oxide, etc. The preparation method of the scheme adopts some special measures, for example, materials need to be wetted by low-temperature pure water vapor or atomized pure water, and the mixed materials are firstly tabletted, then dried, granulated and secondarily tabletted to obtain the finished product. The inorganic salt used in the filling agent of the scheme is not a common auxiliary material of the chewable tablet, and can cause poor mouthfeel; the process needs material wetting and secondary tabletting, which causes complex process and difficult industrial mass production.
(2) The direct tabletting process comprises the following steps:
CN201811603597.3 discloses a hydrotalcite chewable tablet and a preparation process thereof, wherein the formula of the formula comprises mannitol, pre-crosslinked starch, microcrystalline cellulose, a sweetening agent, an aromatic, a flavoring agent and magnesium stearate. The method adopts direct mixing and tabletting, and has the characteristics of simple process, low energy consumption and low production cost. The technical scheme needs to use materials with better compressibility, such as microcrystalline cellulose, in order to adapt to direct material compression, and the addition of the materials is a negative factor for mouthfeel.
CN202011055907.X discloses a process for preparing hydrotalcite chewable tablet and its application. The formula of the technical scheme comprises xylitol, pre-crosslinked starch, microcrystalline cellulose, croscarmellose sodium, a sweetening agent, a flavoring agent, magnesium stearate and silicon dioxide. In the technical scheme, in order to adapt to direct tabletting, microcrystalline cellulose with better compressibility is also used, and meanwhile, in order to ensure disintegration, a disintegrant sodium croscarmellose is added. The addition of these materials also inevitably affects the mouthfeel.
(3) And (3) dry granulation process:
CN202110195247.3 discloses an aluminum magnesium carbonate chewable tablet and a preparation method thereof. The prescription of the scheme contains a diluent, a binder, a lubricant, a glidant and a flavoring agent, wherein the binder is selected from povidone, hydroxypropyl cellulose and hydroxypropyl methyl cellulose. The preparation method adopts a common dry granulation process. The technical scheme has the characteristics of stable quality, simple process and low energy consumption. This solution, in order to be suitable for dry granulation processes, requires the addition of binders, and such formulation is also a disadvantage with respect to mouthfeel.
In the prior art, the production or quality problems of the product are mostly solved only from a certain aspect or aspects. While some problems have been solved, other problems have been raised, and excellent overall characteristics have not been achieved. For example, when a wet granulation process is adopted, a binder or wetting agent needs to be adopted, and after the binder or wetting agent interacts with raw materials and auxiliary materials, on one hand, the problems of mouth feel such as tooth sticking, astringent taste, gritty feel and the like can be caused, and on the other hand, the disintegration time can be prolonged, so that the acid resistance speed is influenced; when a direct tabletting process is adopted, a filling agent with good compressibility is required to be added in order to improve the compressibility of the product, and a disintegrating agent is required to ensure disintegration, and the materials are not common materials for chewable tablets and are not beneficial to mouthfeel; when the dry granulation process is adopted, in order to ensure the tabletting formation, a binding agent needs to be added, and the addition of the auxiliary materials can cause tooth sticking and is not good for the mouthfeel.
In summary, the prior art has certain drawbacks. The prepared product has poor comprehensive properties. The inventor carries out intensive research on various preparation methods of the variety, and tries to use fewer auxiliary materials to ensure good mouthfeel and have excellent comprehensive characteristics in other aspects like the original product. As mentioned above, in the prior art, when wet granulation is adopted, an adhesive or a wetting agent needs to be added, and the wet granulation and the main drug and auxiliary materials interact with each other, so that poor taste of the drug is caused; when direct tabletting is adopted, the addition of materials with better compressibility can also affect the mouthfeel. The present inventors have also conducted intensive studies on a dry granulation process, which has the greatest challenge of being difficult to form and liable to cause chipping in tableting. As described in CN202110195247.3, a certain proportion of adhesive is added, and a large pressure is applied to press forming. The technical scheme has the following defects: 1. the adhesive is added, and the bonding property of the adhesive is adverse to the mouthfeel, so that the feeling of a patient when the adhesive is chewed and taken is influenced; 2. the hardness of the prepared finished product is larger, generally more than 130N, and the finished product does not meet the general characteristic requirements of the prior chewable tablet and is difficult for patients to take; 3. the finished product has higher hardness and longer disintegration time than the original ground product. The dry granulation process is adopted to prepare products with excellent characteristics in all aspects, and is a great challenge for the product.
Through the intensive research of the inventor, on the basis of a dry granulation process, the process formula of a product on the market and the prior art are improved, granules are creatively divided into two parts for granulation, the proportion of materials in each part of granules is researched, and finally the invention is completed.
Disclosure of Invention
The invention aims to provide the hydrotalcite chewable tablet and the preparation method thereof, and the hydrotalcite chewable tablet does not contain a bonding agent and has good mouthfeel; the chewable tablet can be pressed and formed under a small pressure, and the hardness of the prepared finished product meets the general requirements of FDA on the chewable tablet; meanwhile, the disintegration time is shorter and is equivalent to that of the original ground product. In addition, the product of the invention has faster acid resistance speed and longer acid resistance maintaining time. The granules are divided into two parts for granulation creatively, and the obtained product has unexpected quality characteristics, thereby solving various technical problems in the prior art. The method adopts a dry granulation process, and the prepared hydrotalcite chewable tablet has excellent comprehensive properties, and specifically comprises the following aspects: (1) excellent mouthfeel; (2) shorter disintegration time; (3) faster acid-resistant speed; (4) long duration of acid resistance; (5) suitable hardness.
To achieve the object of the present invention, the following embodiments are provided.
In one embodiment, the invention provides an hydrotalcite chewable tablet, which is characterized by comprising granules A and granules B and magnesium stearate, wherein the granules A contain 50% of hydrotalcite, 4% to 8% of corn starch and a proper amount of flavoring agent, and the granules B consist of 3% to 7% of corn starch and 33.0% to 42.1% of filling agent, and the magnesium stearate is 0.7% to 1.5%, wherein the drying weight loss of the corn starch is less than 7%, based on the total weight percentage of the tablet, and the chewable tablet is prepared by dry granulation and tabletting.
Preferably, the chewable tablet of the present invention is prepared by dry granulation and tabletting, wherein the granule a comprises 50% of hydrotalcite, 4% to 8% of corn starch and a proper amount of flavoring agent, the granule B comprises 3% to 7% of corn starch and 33.0% to 42.1% of filler, and the magnesium stearate comprises 0.7% to 1.5%, wherein the loss on drying of the corn starch is less than 7%.
Preferably, in the chewable tablet of the present invention, the flavoring agent comprises essence and sweetener.
Preferably, in the chewable tablet of the present invention, the flavoring agent is selected from one or more of peppermint flavor, banana flavor and saccharin sodium, and more preferably, the flavoring agent is selected from three.
Preferably, in the chewable tablet of the present invention, the filler is mannitol, xylitol or a mixture thereof.
Preferably, in the chewable tablet of the present invention, 90% of the hydrotalcite is smaller than 150 μm in particle size.
Preferably, in the chewable tablet of the present invention, 90% of the hydrotalcite is smaller than 120 μm in particle size.
Preferably, in the chewable tablet of the present invention, 90% of the hydrotalcite is smaller than 90 μm in particle size.
In another embodiment, a method for preparing the above-mentioned magnesium aluminocarbonate chewable tablet of the present invention comprises the following steps:
1) Uniformly mixing the hydrotalcite, the corn starch and the flavoring agent, and performing dry granulation to obtain granules A;
2) Mixing corn starch and filler uniformly, and granulating by a dry method to obtain granules B;
3) Mixing the granules A in the step 1) and the granules B in the step 2) with the additional magnesium stearate, uniformly mixing, tabletting to obtain the chewable tablets,
wherein, the steps 1) and 2) have no precedence requirement.
The above-mentioned hydrotalcite is hydrotalcite tetrahydrate meeting medicinal requirements, and its molecular formula is Al2Mg6 (OH) 16CO 3.4H 2O. The particle size of 90% of the hydrotalcite is less than 150 μm; preferably, 90% of the amount of particles have a size of less than 120 μm; further preferably, 90% of the amount of particles have a particle size of less than 90 μm.
The corn starch refers to the corn starch meeting the medicinal requirements. In order to carry out the invention, it is particularly desirable that the loss on drying of the corn starch is less than 7%. The pharmacopeia standard corn starch drying weight loss limit is 14%, the index is controlled below 7%, and the drying can be realized through various ways, such as drying, or the requirements are provided for material suppliers.
The bulking agent is selected from mannitol and xylitol; preferably, the bulking agent is selected from mannitol.
In order to achieve better taste effect, flavoring agents can be added into the prescription. The flavoring agent is selected from essence and sweetener. The essence is selected from herba Menthae essence and fructus Musae essence, and the sweetener is selected from saccharin sodium.
The following description will be made in conjunction with the prior art documents to explain the positive effects of the present invention:
the hydrotalcite chewable tablet contains the same types of auxiliary materials as the original preparation, only uses corn starch as a disintegrating agent, uses mannitol or xylitol as a filling agent and uses magnesium stearate as a lubricating agent. The technical proposal does not contain other auxiliary materials, such as polyvinylpyrrolidone K30 as a binder and carboxymethyl starch sodium as a disintegrant, which are needed by wet granulation; directly compressed microcrystalline cellulose; other binders needed by the dry granulation process are hydroxypropyl cellulose or hydroxypropyl methyl cellulose, and the like. The product needs to be taken after chewing, uses a few types of auxiliary materials, mainly uses the common auxiliary materials of the chewable tablet, can ensure good taste of the product, and is very important for the product. Except the main medicines, the product has small dosage of starch, and the auxiliary material with larger dosage is mannitol or xylitol. Mannitol absorbs heat when dissolved, has sweet taste and is comfortable to the oral cavity, and is widely used for manufacturing chewable tablets. Xylitol has the same sweetness as sucrose, can generate obvious cooling feeling when dissolved, is very effective in improving the taste of tablets and covering the unpleasant taste of certain medicines and auxiliary materials, and is also commonly used for producing chewable tablets. The use of less auxiliary material types can keep the same with the original grinding agent in design, so that the grinding agent has good taste.
The invention adopts a dry granulation process to divide the material into two parts of granules for granulation, namely aluminum-carbon-magnesium and corn starch, and mannitol and corn starch. Researches show that when the main drug, the starch and the mannitol are granulated together by a dry method and tabletted, tablets are easy to crack, and the prepared finished product has longer disintegration time limit and is obviously longer than the original preparation. One approach to solving the problem of splintering is to add an adhesive, such as the solution adopted in chinese patent application CN 202110195247.3. The splintering is mainly caused by poor binding force between materials, and the addition of the binder is beneficial to increasing the binding force between the materials, which is a common means for solving the problems in the field of preparation. However, the following problems still exist in the finished product prepared in this way: (1) Because of using the adhesive, the teeth are easily stuck, thereby affecting the taste; (2) The product can be pressed and formed only by large pressure, the hardness of the finished product is large, generally more than 130N, and the product does not meet the general characteristic requirements of the prior chewable tablet; (3) The larger hardness also leads the disintegration time limit of the finished product to be longer, which is obviously longer than that of the original grinding agent. In order to solve the problem, the inventor of the invention surprisingly discovers after intensive research that the problem of cracking can be solved by respectively carrying out dry granulation on the main drug, the corn starch, the mannitol and the corn starch by adopting a decomposition principle to prepare granules, mixing the granules and then tabletting. The sample prepared by the method can be pressed and formed under lower pressure, the average hardness can be controlled below 120N, and the requirement that the hardness of the chewable tablet is generally less than 120N is met.
The present inventors have conducted extensive studies on a two-part granulation process, and hopefully, this approach not only solves the problem of tablet breakage, but also results in a shorter disintegration time for the finished product. Research results show that the water content of the starch influences the disintegration time limit of the product. The pharmacopoeia stipulates that the drying weight loss limit of starch is 14%, in order to implement the invention, the water content of corn starch needs to be strictly controlled, and the drying weight loss needs to be controlled to be below 7%. This can be achieved in a number of ways, such as drying the starch, or placing a demand on the material supplier, etc. For two granules of aluminum magnesium carbonate and corn starch, mannitol and corn starch, starch is used as a disintegrating agent, the material dosage is researched, and for the granules of aluminum magnesium carbonate and corn starch, the dosage of the aluminum magnesium carbonate and corn starch is 4-8 percent, wherein the aluminum magnesium carbonate and corn starch contains 50 percent of the aluminum magnesium carbonate; for the granules consisting of mannitol or xylitol and starch, the using amount of the corn starch is 3 to 7 percent. Surprisingly, by controlling the moisture content of the corn starch and optimizing the dosage, the finished product has shorter disintegration time limit which is basically equivalent to that of the original preparation. The product has short disintegration time, and can achieve rapid antacid effect. The acid resistance research shows that the finished product of the invention also has longer acid resistance maintenance time.
In conclusion, the hydrotalcite chewable tablet prepared by the invention has excellent comprehensive properties, and specifically comprises the following aspects: (1) excellent mouthfeel; (2) shorter disintegration time; (3) faster acid resistance speed; (4) long duration of acid resistance; (5) suitable hardness.
Detailed Description
The following examples are merely representative for the purpose of illustration and to aid in understanding the spirit of the invention, and are not intended to limit the scope of the invention in any way. Any simple modifications and variations made within the spirit of the present invention are also within the scope of the present invention.
EXAMPLE 1 hydrotalcite chewable tablets
Prescription is shown in Table 1
Table 1 formulation of example 1
The preparation method comprises the following steps:
the hydrotalcite chewable tablet is prepared according to a dry granulation process, and the specific process is as follows:
1) Weighing raw and auxiliary materials of the granules A and the granules B respectively according to the prescription, wherein the particle size of 90 percent of the hydrotalcite is controlled to be less than 120 mu m, and the drying weight loss of the corn starch is less than 7 percent.
2) The materials of the particles A and the particles B are respectively mixed by a mixer, the mixing speed is 10rpm, and the mixing time is 10min.
3) Respectively granulating the mixed materials obtained in the step 2) into granules by adopting a dry granulation process to obtain granules A and granules B. The process conditions of the dry granulation of the granule A are as follows: the pressing rotating speed is 10 rpm-20 rpm, the pressure is 10 bar-20 bar, the material gap is 1.0 mm-2.5 mm, the whole grain rotating speed is 100 rpm-120 rpm, and the aperture of the screen mesh is 1.2mm; the process conditions of the dry granulation of the granules B are as follows: the pressing rotating speed is 8 rpm-15 rpm, the pressure is 40 bar-100 bar, the material gap is 1.0 mm-2.5 mm, the whole grain rotating speed is 100 rpm-120 rpm, and the aperture of the screen mesh is 1.2mm.
4) Mixing the granules A and B prepared in the step 3) and the additional magnesium stearate by using a mixer, wherein the mixing speed is 10rpm, and the mixing time is 10min.
5) Tabletting the mixed materials obtained in the step 4) to obtain the hydrotalcite chewable tablets. And adjusting proper pre-pressure and main pressure during tabletting, and controlling the friability to be below 1.0% to obtain a finished product with the average hardness of below 115N.
Example 2 hydrotalcite chewable tablets
Prescription is shown in Table 2
Table 2 formulation of example 2
The preparation method comprises the following steps:
the hydrotalcite chewable tablet is prepared according to a dry granulation process, and the specific process is as follows:
1) Weighing raw and auxiliary materials of the granules A and the granules B respectively according to the prescription, wherein the particle size of 90 percent of the hydrotalcite is controlled to be less than 150 mu m, and the drying weight loss of the corn starch is less than 7 percent.
2) The materials of the particles A and the particles B are respectively mixed by a mixer, the mixing speed is 10rpm, and the mixing time is 10min.
3) Respectively granulating the mixed materials obtained in the step 2) into granules by adopting a dry granulation process to obtain granules A and granules B. The process conditions of the dry granulation of the granule A are as follows: the pressing rotating speed is 10 rpm-20 rpm, the pressure is 10 bar-20 bar, the material gap is 1.0 mm-2.5 mm, the whole grain rotating speed is 100 rpm-120 rpm, and the aperture of the screen mesh is 1.2mm; the process conditions of the dry granulation of the granules B are as follows: the pressing rotating speed is 8-15 rpm, the pressure is 40-100 bar, the material gap is 1.0-2.5 mm, the whole grain rotating speed is 100-120 rpm, and the mesh aperture is 1.2mm.
4) Mixing the granules A and B prepared in the step 3) and the additional magnesium stearate by using a mixer, wherein the mixing speed is 10rpm, and the mixing time is 10min.
5) Tabletting the mixed materials obtained in the step 4) to obtain the hydrotalcite chewable tablets. And adjusting proper pre-pressure and main pressure during tabletting, and controlling the friability to be below 1.0% to obtain a finished product with the average hardness of below 115N.
Example 3 magnesium Aluminocarbonate chewable tablets
Prescription is shown in Table 3
Table 3 formulation of example 3
The preparation method comprises the following steps:
the hydrotalcite chewable tablet is prepared according to a dry granulation process, and the specific process is as follows:
1) Weighing raw and auxiliary materials of the granules A and the granules B respectively according to the prescription, wherein the particle size of 90 percent of the hydrotalcite is controlled to be less than 90 mu m, and the drying weight loss of the corn starch is less than 7 percent.
2) The materials of the particles A and the particles B are respectively mixed by a mixer, the mixing speed is 10rpm, and the mixing time is 10min.
3) Respectively granulating the mixed materials obtained in the step 2) into granules by adopting a dry granulation process to obtain granules A and granules B. The process conditions of the dry granulation of the granule A are as follows: the pressing rotating speed is 10 rpm-20 rpm, the pressure is 10 bar-20 bar, the material gap is 1.0 mm-2.5 mm, the whole grain rotating speed is 100 rpm-120 rpm, and the aperture of the screen mesh is 1.2mm; the process conditions of the dry granulation of the granules B are as follows: the pressing rotating speed is 8 rpm-15 rpm, the pressure is 40 bar-100 bar, the material gap is 1.0 mm-2.5 mm, the whole grain rotating speed is 100 rpm-120 rpm, and the aperture of the screen mesh is 1.2mm.
4) Mixing the granules A and B prepared in the step 3) and the additional magnesium stearate by using a mixer, wherein the mixing speed is 10rpm, and the mixing time is 10min.
5) Tabletting the mixed materials obtained in the step 4) to obtain the hydrotalcite chewable tablets. And adjusting proper pre-pressure and main pressure during tabletting, and controlling the friability to be below 1.0% to obtain a finished product with the average hardness of below 115N.
Comparative example 1
Samples were prepared as disclosed in example 1 of chinese patent application CN 202110195247.3. The prescription is shown in Table 4
TABLE 4 formula of hydrotalcite chewable tablets of comparative example 1
| Component (A) | Prescription ratio | The dosage per tablet (mg) | The dosage (g) of each 1000 tablets |
| Aluminum magnesium carbonate | 50％ | 500 | 500 |
| Mannitol | 34.1％ | 341 | 341 |
| Sorbitol | 10％ | 100 | 100 |
| Povidone | 4％ | 40 | 40 |
| Magnesium stearate | 0.8％ | 8 | 8 |
| Talcum powder | 1％ | 10 | 10 |
| Stevioside | 0.04％ | 0.4 | 0.4 |
| Strawberry essence | 0.06％ | 0.6 | 0.6 |
| Is totaled | 100.00％ | 1000 | 1000 |
The preparation method comprises the following steps: according to the method disclosed in the patent application, dry granulation is adopted, and the steps are as follows:
1) Weighing the raw materials and the auxiliary materials according to the mass ratio in the table.
2) Premixing: mixing the magnesium aluminum carbonate raw material medicine (particle diameter D) 90 Controlling the particle size below 180 μm), diluent (mannitol, sorbitol) and binder (polyvidone K30) in a mixer, and pre-mixing at 10rpm for 5min.
3) And (3) granulating: preparing the mixed powder premixed in the step 2) into granules by using a dry granulating machine. The conditions for dry granulation were as follows: the screw rotation speed is 20rpm, the compression roller rotation speed is 8rpm, the whole grain rotation speed is 150rpm, the compression roller pressure is 30bar, and the mesh opening is 1.Omm.
4) And (3) total mixing: and (4) mixing the granules prepared in the step 3) with an additional glidant (talcum powder), a lubricant (magnesium stearate) and a flavoring agent (stevioside and strawberry essence) in a mixer at a mixing speed of 10rpm for 5min.
5) Tabletting: tabletting by using a tabletting machine to obtain the hydrotalcite chewable tablets.
Comparative example 2
This original breed development, a hydrotalcite chewable tablet from bayer, germany, with trade name da xi, was purchased as comparative example 2.
Performance indicator detection
For the samples of examples 1-3, the samples of comparative examples 1-2 were tested for relevant performance indicators.
1. Hardness, disintegration time and acid limiting force detection
The hardness of the sample is detected by a hardness meter, the disintegration time is detected according to a pharmacopoeia method, the acid-making capacity is detected by a determination method under the term of the acid-making capacity in ' aluminum magnesium carbonate chewable tablets ' in ' 2020 edition of Chinese pharmacopoeia, and the results are shown in the following table 5.
TABLE 5 hardness, disintegration time and limiting acidity test results
The above results show that the samples of example 3 have two indexes of average hardness and disintegration time, which are similar to those of the original preparation, and the indexes of comparative example 1 are greatly different from those of the original preparation.
2. Evaluation of mouthfeel
25 volunteers evaluated the hydrotalcite chewable tablets in 5 batches by oral evaluation from difficulty in chewing, taste after chewing and comfort after taking. Points and criteria for scoring are shown in table 6 below.
TABLE 6 taste scoring Standard of magnesium Aluminocarbonate chewable tablets
The results of 5 samples evaluated for mouthfeel are shown in table 7 below (results are rounded off, with one significant figure remaining).
TABLE 7 taste scoring results for magnesium alumino-carbonate chewable tablets
The results show that the taste evaluation of the samples in the 3 examples is similar to that of the original grinding agent, and is obviously superior to that of the samples in the comparative example 1.
3. In vitro antacid evaluation
The acid resistance speed and the acid resistance maintaining time are evaluated by adopting a Rossett-Rice in-vitro acid resistance experiment.
The in vitro antacid test method is as follows: 30ml of water and 70ml of a 0.1mol/L hydrochloric acid solution were charged into a reaction vessel, and the reaction solution was controlled at 37 ℃. + -. 0.5 ℃ by a magnetic heating stirrer and a contact thermometer. The magnetic stirring was started at 400rpm, and the pH change in the reaction vessel was measured with a pH meter. The constant flow pump is started, and 0.1mol/L hydrochloric acid solution with constant temperature of 37 ℃ is pumped into the reaction vessel at the speed of (2.0 +/-0.1) ml/min. When the hydrotalcite chewable tablet (the hydrotalcite dose is 1 g) was added, the constant flow pump and the magnetic stirrer were immediately started, and the time and the pH value were recorded at the same time. The results are given in Table 8 below.
TABLE 8 results of in vitro antacid test of magnesium Aluminocarbonate chewable tablets
The results show that the time to reach pH3, the samples of examples 1-3 are equivalent to the original formulation and are significantly faster than the sample of comparative example 1, indicating that the sample of the present invention can take effect faster in acid-fast speed; the retention time is 3-5, and the sample of the example 3 is equivalent to the original preparation and is obviously longer than the sample of the comparative example 1, which shows that the sample of the invention can exert the drug effect for a longer time in the aspect of the acid-resistant maintenance time.
Claims (9)
1. The chewable tablet is characterized by comprising granules A, granules B and magnesium stearate, wherein the granules A are prepared by dry granulation and tabletting, the granules A comprise 50% of the hydrotalcite, 4% to 8% of corn starch and a proper amount of flavoring agent according to the total weight percentage of the tablet, the granules B comprise 3% to 7% of the corn starch and 33.0% to 42.1% of filling agent, and the magnesium stearate is 0.7% to 1.5%, wherein the drying weight loss of the corn starch is less than 7%.
2. Chewable tablets according to claim 1, consisting of granulate a consisting of 50% hydrotalcite, 4-8% corn starch and a suitable amount of flavoring agent, granulate B consisting of 3-7% corn starch and 33.0-42.1% filler, and magnesium stearate 0.7-1.5%, wherein the corn starch has a loss on drying of less than 7%, and magnesium stearate, and prepared by dry granulation and tabletting.
3. A chewable tablet as claimed in claim 1 or claim 2 wherein the flavouring agent comprises flavours and sweeteners.
4. The chewable tablet of claim 3, wherein the flavoring agent is selected from one or more of peppermint flavor, banana flavor, and saccharin sodium.
5. Chewable tablet according to claim 1 or 2, wherein the filler is mannitol, xylitol or a mixture thereof.
6. The magnesium aluminocarbonate chewable tablet of claim 1, wherein 90% of the magnesium aluminocarbonate particles have a particle size of less than 150 μm.
7. The magnesium aluminocarbonate chewable tablet of claim 1, wherein 90% of the magnesium aluminocarbonate particles have a particle size of less than 120 μm.
8. The hydrotalcite chewable tablet of claim 1, wherein 90% of the hydrotalcite is particles with a size of less than 90 μm.
9. A method for preparing the magnesium aluminocarbonate chewable tablet according to any one of claims 1 to 8, comprising the following steps:
1) Uniformly mixing the hydrotalcite, the corn starch and the flavoring agent, and performing dry granulation to obtain granules A;
2) Uniformly mixing corn starch and a filling agent, and performing dry granulation to obtain granules B;
3) Mixing the granules A in the step 1) and the granules B in the step 2) with the additional magnesium stearate, uniformly mixing, tabletting to obtain the chewable tablets,
wherein, the steps 1) and 2) have no precedence requirement.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211629120.9A CN115737582A (en) | 2022-12-14 | 2022-12-14 | Hydrotalcite chewable tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211629120.9A CN115737582A (en) | 2022-12-14 | 2022-12-14 | Hydrotalcite chewable tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115737582A true CN115737582A (en) | 2023-03-07 |
Family
ID=85346511
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211629120.9A Pending CN115737582A (en) | 2022-12-14 | 2022-12-14 | Hydrotalcite chewable tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115737582A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112957369A (en) * | 2021-02-20 | 2021-06-15 | 北京阳光诺和药物研究股份有限公司 | Hydrotalcite chewable tablet and preparation method thereof |
| CN114177154A (en) * | 2022-01-04 | 2022-03-15 | 四川健能制药有限公司 | Chewable tablet containing aluminum magnesium carbonate and preparation method thereof |
-
2022
- 2022-12-14 CN CN202211629120.9A patent/CN115737582A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112957369A (en) * | 2021-02-20 | 2021-06-15 | 北京阳光诺和药物研究股份有限公司 | Hydrotalcite chewable tablet and preparation method thereof |
| CN114177154A (en) * | 2022-01-04 | 2022-03-15 | 四川健能制药有限公司 | Chewable tablet containing aluminum magnesium carbonate and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 王春燕等: "《药剂学》", 31 July 2017, pages: 156 - 159 * |
| 钟海军等: "《高等院校药学类创新型系列教材 药剂学》", 31 July 2021, pages: 169 - 171 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101590115B1 (en) | Pharmaceutical compositions | |
| PT1145711E (en) | Flash-melt oral dosage formulation | |
| WO2005037319A1 (en) | Composition for tablet rapidly disintegrable in mouth | |
| CN101374503B (en) | Quickly disintegrating tablet produced by direct dry-tabletting | |
| WO2000078292A1 (en) | Quickly disintegrating solid preparations | |
| ES2820737T3 (en) | Pharmaceutical composition comprising phosphate chelator particles | |
| WO2007029376A1 (en) | Orally rapidly disintegrating tablet | |
| IE62728B1 (en) | Chewable tablet | |
| CN101516403A (en) | Orally disintegrating tablet and process for production thereof | |
| US20100092564A1 (en) | Composition of and Method for Preparing Orally Disintegrating Tablets | |
| JP2000095675A (en) | Oral solid pharmaceutical composition for treating rhinitis of intraoral soluble type or mastication type | |
| CN101461788B (en) | Phloroglucine orally disintegrating tablet and preparation method thereof | |
| JP2005507397A (en) | Fast-dissolving oral formulation | |
| CN114177154A (en) | Chewable tablet containing aluminum magnesium carbonate and preparation method thereof | |
| CA2748496C (en) | Disintegrable formulations of lanthanum carbonate | |
| CN115737582A (en) | Hydrotalcite chewable tablet and preparation method thereof | |
| CN102512402A (en) | Novel preparation of medicine for treating gastric and duodenal ulcers and preparation method thereof | |
| CN102872024B (en) | Misoprostol medicine combination used in mouths | |
| CN102018721B (en) | Chewable tablet of calcium carbonate dimeticone and preparation process | |
| CN101690720A (en) | Carteolol orally disintegrating tablets and preparation method thereof | |
| CN112957369A (en) | Hydrotalcite chewable tablet and preparation method thereof | |
| TWI831808B (en) | Pharmaceutical composition in the form of a chewable tablet of diosmin or a flavonoid fraction | |
| CN115708820B (en) | L-theanine sustained release preparation, double release preparation, application and medicament | |
| CN117919271A (en) | Aluminum magnesium carbonate tablet and preparation method thereof | |
| CN100394914C (en) | Aarin oral cavity disintegrating tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |