US3873694A - Direct compression tabletting composition and pharmaceutical tablets produced therefrom - Google Patents
Direct compression tabletting composition and pharmaceutical tablets produced therefrom Download PDFInfo
- Publication number
- US3873694A US3873694A US401322A US40132273A US3873694A US 3873694 A US3873694 A US 3873694A US 401322 A US401322 A US 401322A US 40132273 A US40132273 A US 40132273A US 3873694 A US3873694 A US 3873694A
- Authority
- US
- United States
- Prior art keywords
- weight
- vehicle
- maltodextrin
- dextrose
- tablets
- 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.)
- Expired - Lifetime
Links
- 238000007907 direct compression Methods 0.000 title claims abstract description 58
- 239000000203 mixture Substances 0.000 title claims description 137
- 229920002774 Maltodextrin Polymers 0.000 claims abstract description 128
- 239000005913 Maltodextrin Substances 0.000 claims abstract description 116
- 229940035034 maltodextrin Drugs 0.000 claims abstract description 116
- 235000000346 sugar Nutrition 0.000 claims abstract description 52
- 239000004480 active ingredient Substances 0.000 claims abstract description 40
- 239000007864 aqueous solution Substances 0.000 claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 239000011436 cob Substances 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 238000005507 spraying Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 45
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 43
- 239000008121 dextrose Substances 0.000 claims description 43
- 229960001031 glucose Drugs 0.000 claims description 43
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 36
- 229920002245 Dextrose equivalent Polymers 0.000 claims description 36
- 238000005469 granulation Methods 0.000 claims description 36
- 230000003179 granulation Effects 0.000 claims description 36
- 239000011149 active material Substances 0.000 claims description 30
- 239000000463 material Substances 0.000 claims description 28
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 claims description 25
- 229960000673 dextrose monohydrate Drugs 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 23
- 239000002245 particle Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000000314 lubricant Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 17
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 16
- 229920002472 Starch Polymers 0.000 claims description 16
- 235000019698 starch Nutrition 0.000 claims description 16
- 229960005070 ascorbic acid Drugs 0.000 claims description 15
- 235000010323 ascorbic acid Nutrition 0.000 claims description 15
- 239000011668 ascorbic acid Substances 0.000 claims description 15
- 239000008107 starch Substances 0.000 claims description 15
- 239000000413 hydrolysate Substances 0.000 claims description 13
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 claims description 11
- 229940042585 tocopherol acetate Drugs 0.000 claims description 11
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 8
- 239000007884 disintegrant Substances 0.000 claims description 8
- 239000011790 ferrous sulphate Substances 0.000 claims description 8
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 8
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 8
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 8
- 229960005489 paracetamol Drugs 0.000 claims description 8
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 7
- 239000001527 calcium lactate Substances 0.000 claims description 7
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 7
- 235000011086 calcium lactate Nutrition 0.000 claims description 7
- 229960002401 calcium lactate Drugs 0.000 claims description 7
- 239000000391 magnesium silicate Substances 0.000 claims description 7
- 229940099273 magnesium trisilicate Drugs 0.000 claims description 7
- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 7
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims description 7
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 229960004025 sodium salicylate Drugs 0.000 claims description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
- 229960001781 ferrous sulfate Drugs 0.000 claims description 5
- -1 coloring aids Substances 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- 238000004040 coloring Methods 0.000 claims description 2
- 239000002278 tabletting lubricant Substances 0.000 claims description 2
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 claims 2
- 239000003826 tablet Substances 0.000 description 141
- 238000002474 experimental method Methods 0.000 description 19
- 238000012360 testing method Methods 0.000 description 17
- 239000003814 drug Substances 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- 238000011156 evaluation Methods 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000004615 ingredient Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 229920001353 Dextrin Polymers 0.000 description 7
- 239000004375 Dextrin Substances 0.000 description 7
- 239000000654 additive Substances 0.000 description 7
- 235000019425 dextrin Nutrition 0.000 description 7
- 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 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000000454 talc Substances 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- 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 5
- 235000013339 cereals Nutrition 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000007906 compression Methods 0.000 description 5
- 230000006835 compression Effects 0.000 description 5
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 240000008042 Zea mays Species 0.000 description 4
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 239000012084 conversion product Substances 0.000 description 4
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 4
- 229940038472 dicalcium phosphate Drugs 0.000 description 4
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 229940069428 antacid Drugs 0.000 description 3
- 239000003159 antacid agent Substances 0.000 description 3
- 230000001458 anti-acid effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007891 compressed tablet Substances 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 229940089206 anhydrous dextrose Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
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- 230000005484 gravity Effects 0.000 description 2
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- 238000006703 hydration reaction Methods 0.000 description 2
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- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000013517 stratification Methods 0.000 description 2
- 230000009967 tasteless effect Effects 0.000 description 2
- 208000016261 weight loss Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- KXFNZUHMPODMRZ-UHFFFAOYSA-N 2-hydroxypropanoic acid;octadecanoic acid Chemical compound CC(O)C(O)=O.CCCCCCCCCCCCCCCCCC(O)=O KXFNZUHMPODMRZ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- 102000010029 Homer Scaffolding Proteins Human genes 0.000 description 1
- 108010077223 Homer Scaffolding Proteins Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001274197 Scatophagus argus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 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
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- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- DCOLOVHTJKNUOI-UHFFFAOYSA-J [OH-].[OH-].[OH-].[OH-].[Mg++].[Mg++] Chemical compound [OH-].[OH-].[OH-].[OH-].[Mg++].[Mg++] DCOLOVHTJKNUOI-UHFFFAOYSA-J 0.000 description 1
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- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 description 1
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- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
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- ZORPJCONVDWMSP-UHFFFAOYSA-J calcium;magnesium;tetraacetate Chemical compound [Mg+2].[Ca+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ZORPJCONVDWMSP-UHFFFAOYSA-J 0.000 description 1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
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- 150000003893 lactate salts Chemical class 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
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- GPRDLRZMTVQCHM-UHFFFAOYSA-L magnesium;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Mg+2] GPRDLRZMTVQCHM-UHFFFAOYSA-L 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
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- 230000003068 static effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C13—SUGAR INDUSTRY
- C13B—PRODUCTION OF SUCROSE; APPARATUS SPECIALLY ADAPTED THEREFOR
- C13B50/00—Sugar products, e.g. powdered, lump or liquid sugar; Working-up of sugar
- C13B50/002—Addition of chemicals or other foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- C—CHEMISTRY; METALLURGY
- C13—SUGAR INDUSTRY
- C13B—PRODUCTION OF SUCROSE; APPARATUS SPECIALLY ADAPTED THEREFOR
- C13B50/00—Sugar products, e.g. powdered, lump or liquid sugar; Working-up of sugar
- C13B50/02—Sugar products, e.g. powdered, lump or liquid sugar; Working-up of sugar formed by moulding sugar
Definitions
- This invention relates to direct compression tabletting compositions and the pharmaceutical tablets produced therefrom. More particularly, this invention relates to an improved direct compression tabletting composition prepared from a uniquely granulated mixture of a crystalline sugar such as dextrose monohydrate, and a maltodextrin having a measurable dextrose equivalent value not substantially above about 20.
- the improved direct compression tabletting compositions are capable of being directly compressed into commercially acceptable and hard tablets with large amounts of a variety of active materials.
- the new direct compression tablets can be used as the sole binder disintegrant without the aid of other adjuvants ordinarily used for this purpose.
- the compressed tablet is the most popular unit dosage form for medicinal substances.
- the tablet as a dosage form can be traced to well over 1,000 years ago when a procedure for molding solid forms containing medicinal ingredients was recorded.
- tablets are replacing all forms of pills, powders and capsules. Accordingly, tablets presently represent the largest production volume of all pharmaceuticals.
- tablets enable: (1) administration of medication in an accurate dose, (2) fast and accurate dispensing with less chance of error and contamination, (3) ease of administration, (4) administration in a form in which the time and area of contact between'the active ingredient and the taste buds is reduced, thus obviating the physiological problems associated with the oral administration of drugs that possess a bitter taste and, in the case of coated tablets, with drugs that possess a dis agreeable odor, (5) release of drugs at specific loca tions in the gastro-intestinal tract to: (a) prevent degradation of drugs sensitive to the low pH environment in the stomach, (b) prevent release of drugs that irritate the gastric mucosa in the stomach, (c) facilitate local action or preferential absorption at specific sites in the tract, (6) enhance stability by effecting a marked reduction in the surface of the drug exposed to the environment, (7) rapid production, and (8) economy and ease in storage, packaging and shipping.
- tablettin g There are currently three basic methods for tablettin g. They are the wet granulation method, the dry granulation method, and the direct compression method.
- the direct compression method is by far the desired method from the standpoint of processing procedures, equipment and materials. However, only a very limited number of pharmaceutically used substances possess enough cohesive strength and flowability to allow direct compression without previous granulation. Certain crystalline materials, such as potassium bromide and potassium chloride can be compressed without preliminary treatment. Also, aspirin, phenolthaline, chlorohydrate can be directly compressed.
- the ideal material to compress would be composed of crystals which, at the moment of compression, behaved like clay rather than rubber.
- the crystals should be such that on release of pressure they should not rebound into their original shape.
- most materials possess both plastic and elastic deformation properties. Therefore, most materials are not suitable for direct compression without previous granulation.
- An ideal direct compression vehicle should possess the following properties: (1) low elastic modules, (2) high dislocation density, (3) inert, non-potent and nontoxic, (4) high degree ofplastic deformation, (5) colorless, odorless, tasteless or without disagreeable taste, (6) free-flowing, (7) compatible with active ingredients and common additives like lubricants, colors, etc., (8) non-hygroscopic, or relatively low order of hygroscopicity, (9) fast disintegration properties, or should not delay the bioavailability of the drug, l0) limited range of particle size distribution, l l) stable effects of aging, and (12) reworkable and should possess high carrying capacity for active medicinal agents.
- Microcrystalline cellulose is a natural cellulose in a specially processed form which makes it digestible. lt normally produces good tablets with fast disintegration and drug release properties. lt has been found to give better results if stored in a dry condition before use exposure to a slightly humid atmosphere makes it compress less easily. It is quite fluffy by nature.
- Spray-dried lactose has a heavy appearance when poured and is spherical in shape. It cannot be re worked, as the spherical shape is lost when ground. lt has been disclosed that spray-dried lactose with 5-10% maize starch as a disintegrant and 0.5% magnesium stearate as a lubricant forms a useful direct compression base. However, it has the tendency to get brown in the presence of moisture, amines, phosphates, lactates and acetates. Borates and the stearate lubricants tend to retard the browning.
- Dicalcium phosphate dehydrate has good flow and compressibility properties.
- the tablets from dicalcium phosphate are also easily embossed.
- the increased flow is believed to be due to its high density. It cannot be re worked. Due to its alkaline pH, stability of ingredients like Vitamin C or aspirin may be effected.
- the vehicle mannitol absorbs heat from the surroundings when going into solution, and results in good mouth feel.” Thus, it is commonly used in chewable tablets. It has been reported that a change in the compression characteristics of mannitol occurs when spraycongealing the product.
- the vehicle known in the art as Cellutab is a spraydried dextrose product. It has excellent flow characteristics. It is relatively coarse compared to other vehicles and contains approximately 8% moisture.
- Encompress is essentially a blend of dicalcium phosphate dehydrate, unmilled; starch; Avacil; and magnesium stearate. It is free-flowing, self-lubricating and possesses good compression characteristics.
- the vehicle known in the art as Royal-T is essentially an agglomerated mixture of a crystalline sugar such as dextrose and a maltodextrin such as Mor-Rex Code 1918.
- the preparation of this bold and new pioneering discovery in the direct compression vehicle art is described in British Pat. No. 1,286,275, published Aug. 23, 1972 which generally corresponds to pending U.S. application Ser. No. 485,480, filed July 3,1974, which is a continuation-in-part of abandoned U.S. application Ser. No. 254,552, filed May 18, 1972, which in turn is a continuation-in-part of abandoned U.S. application Ser. No. 141,030, filed May 6, 1971, and which in turn is a continuation-impart of abandoned U.S. application Ser. No. 767,520, filed Oct. 14, 1968.
- Di Pac The vehicle known in the art as Di Pac is also a mixture of a crystalline sugar and a maltodextrin.
- the preparation ofthis product is generally described in the aforesaid British patent and, more specifically disclosed in U.S. Pat. No. 3,642,535, granted Feb. 15, 1972.
- measurable dextrose equivalent value not substantially above about 20 to form a uniform admixture and thereafter concurrently agitating and spraying said admixture with an aqueous solution containing dissolved therein the aforesaid maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said aqueous solution of dissolved maltodextrin being present in an amount sufficient to provide a damp mass of said uniform admixture and to cause binding and granulation of said uniform admixture.
- the granulated mixture is thereafter dried to a moisture content of less than about 10% by weight.
- the preferred direct compression compositions of this invention will contain from about 15% to about 35% by weight of said maltodextrin, preferably from about 20-30% by weight of said maltodextrin.
- the preferred crystalline sugar utilized includes dextrose monohydrate.
- compositionsof this invention provide a direct compression vehicle which can be directly compressed into commercially acceptable and hard tablets with large amounts of a variety of active materials and can be used as the sole'binder disintegrant without the aid of other adjuvants ordinarily used for this purpose.
- the crystalline sugars employed in the practice of the present invention include any type of crystalline sugar product, examples of which include dextrose, sucrose, lactose and blends thereof. Many of these crystalline sugars are wellknown in the art and are conventional articles of commerce sold under various trade names. Such sugars are generally produced and crystallized by conventional techniques.
- the preferred crystalline sugar employed in the practice of the present invention is dextrose, either in its monohydrate, anhydrous or dehydrated form. Dextrose monohydrate is particularly preferred as the crystalline sugar to be utilized in the practice of the invention.
- the maltodextrins having a measurable dextrose equivalent value not substantially above about 20 utilized in the practice of the present invention represent a known class of materials.
- the maltodextrins are also known as hydrolyzed cereal solids and such materials are commercially available under the tradenames Mor- Rex, manufactured and sold by CPC lnternational lnc., Maltrin. manufactured and sold by Grain Processing Corporation, Frodex, manufactured by American- Maize Products Company, and Star-Dry l5, manufactured by A. E. Staley Manufacturing Company.
- maltodextrins and hydrolyzed cereal solids
- starch conversion products having a relatively small amount of dextrose and maltose.
- the dextrose content of the maltodextrins in less than about 2.4% by weight and the amount of maltose is less than about 9% by weight.
- the dextrose equivalent value in a starch conversion product having a value above about 20 is generally referred to as a corn syrup solid; whereas starch conversion products having only a trace amount of dextrose are referred to as dextrins.
- the starch conversion products having a measurable dextrose equivalent value not substantially above about 20 and also having a trace amount of dextrose as hereinabove referred to, are known as hydrolyzed cereal solids or maltodextrins. lt is the maltodextrins described hereinabove which are employed in the practice of this invention for the preparation of the direct compression tabletting compositions.
- the corn syrup solids having a dextrose equivalent value greater than about 20 are not suitable in the practice of the present invention, since these products do not possess the proper properties to effectively cause granulation and thereby produce a tabletting composition having a high carrying capacity for the active material.
- the corn syrup solids are also extremely hygroscopic, a property undesirable from the standpoint of flowability and mixing during the direct compression procedure for preparing the tablets.
- the preferred maltodextrins or hydrolyzed cereal solids employed in the practice ofthe present invention are characterized as having a descriptive ratio of at least about 2.
- the descriptive ratio is the sum of the percentages (dry basis) of saccharides of the maltodextrin with a degree of polymerization of l to 6 divided by the dextrose equivalent value.
- An especially preferred class of maltodextrins employed in the practice of the present invention are derived from waxy starch hydrolysates and have a dextrose equivalent value in the range of from about 9 to about 13 and a descriptive ratio of at least about 2. These starch hydrolysates or maltodextrins are prepared by the method disclosed in British Pat. No.
- measurable dextrose equivalent value is defined as the reducing value of the hydrolysate material compared to the re as percent, dry basis, i.e.,
- dextrose equivalent value of a starch hydrolysate is a common expression in the art for describing the total reducing sugars content of a material calculated as dextrose and expressed as percent, dry basis.
- An essential aspect of the invention comprises admixing (e.g., by spraying or by any other convenient means) an aqueous solution containing from about 5 to about 60 weight/volume percent of the abovedescribed maltodextrin with a uniform mixture of a crystalline sugar and 10 to about 50% by weight of the above-described maltodextrin.
- the admixing of the aqueous solution of the maltodextrin should be conducted while the uniform mixture of the crystalline sugar and the maltodextrin is being agitated to achieve uniform and homogeneouscontact of the crystalline sugar particles and the maltodextrin with the aqueous solution containing the maltodextrin.
- the aqueous solution will contain from about 10 to about 30% weight/volume of the maltodextrin.
- the solution containing the maltodextrin is preferably admixed with the uniform mixture of the crystalline sugar and maltodextrin at ambient temperatures and pressures. Slight deviations may be imposed, provided that such conditions do not adversely affect the compositions.
- the amount of the solution containing the maltodex trin utilized may vary, depending on the characteristics of the crystalline sugar, the amount of moisture in the homogeneous mixture of the crystalline sugar and/or the maltodextrin, etc.
- the amount of the aqueous solution containing the maltodextrin utilized will be an amount such that its admixture with all of the materials provides a thoroughly admixed damp mass.
- Such amounts will generally be in the range of from about 20 ml. to about ml.' of the aqueous solution per one kilogram (kg) of the uniform mixture of the crystalline sugar and the maltodextrin.
- a suitable damp mass can be obtained under ordinary conditions utilizing from about 40 ml. to about 60 ml. of the aqueous solution per one kilogram (kg) ofthe uniform mixture.
- the entire admixture is thoroughly mixed to cause granulation.
- the granulated product is thereafter dried to a moisture content of less than about 10% by weight, preferably less than about 5% by weight moisture.
- the dried granulated product may be screened to provide a more homogeneous screen size.
- the final dried and screened product can be used as is as a direct compression tabletting composition whereupon it can simply be admixed with the desired active material and directly compressed into tablets.
- the crystalline sugar hereinabove described may be admixed in either dry or wet form with the maltodextrin.
- the crystalline sugar e.g., dextrose monohydrate
- the amount of water necessary to initially granulate the above-described composition of this invention, excluding water of hydration, is preferably from 1-8% by weight of the total composition.
- the initially granulated admixture may be dried, providing the amount of maltodextrin exceeds about 10% by weight of the total mixture.
- the amount of maltodextrin employed in the direct compression compositions of this invention is critical.
- the final composition will generally contain more than about by weight of the maltodextrin which is introduced into the matrix of the crystalline sugar composition, either by the initial blending of the maltodextrin with the crystalline sugar and/or by the admixture treatment with the aqueous solution containing the maltodextrin which follows the blending of the crystalline sugar and the maltodextrin.
- the tabletting composition will contain from about to about 35% by weight of the maltodextrin based on the total amount of the direct compression vehicle. Particularly good results are obtained when the level of maltodextrin in the tabletting composition is in the range of from about to about by weight.
- a premix is formed by admixing 80 parts by weight of dextrose monohydrate crystals and 20 parts by weight of maltodextrin having a dextrose equivalent value in the range of from about 9 to about 13, the water content of the mixture being in the range of from about 2 to about 15 by weight.
- the mixture is thereafter thoroughly agitated and sprayed with an aqueous solution containing the above-described maltodextrin in an amount such that a damp mass is formed.
- the amount of maltodextrin dissolved in the aqueous solution is preferably l0 to about 40% weight/volume. In a typical example, 50 ml.
- a 20% weight/volume aqueous solution contain ing the aforedescribed maltodextrin is sprayed onto 1 kg. of the dextrosemaltodextrin admixture (800 grams of dextrose and 200 grams of maltodextrin).
- the sprayed mixture is thereafter dried to a moisture content of less than about 10%, preferably less than about 5% by weight.
- the granulated mixture may be wet screened through a number 6 sieve prior to drying to the final desired moisture content. However, satisfactory results are obtained by drying the granulated mixture prior to screening.
- the particle size of the direct compression tabletting composition of the present invention is rather impor tant. Most pharmaceutical compounds have a particle size of less than 100 mesh. Accordingly, the carrier must be coarser or have a particle size larger than the pharmaceutical compound. If the particle size of the direct compression tabletting composition or vehicle is v broadly dispersed, stratification will occur and uniform amounts of ingredients in the respective tablets will not be successfully accomplished. Therefore, it is important that the particle size of the direct compression tabletting compositions of the present invention have a relatively narrow particle size distribution.
- the particle size distribution found to be most desirable should be such that the particles of the composition fall within the range of 20 to about +200. However, better results are obtained wherein the composition has a particle size in the range from about 30 to about and, more preferably, in the range of from about -40 to about +100.
- an active material ingredient is thoroughly mixed by any suitable dry blending technique with the above-described direct compression tabletting composition in relative amounts required to provide a resultant superficially dry, free-flowing formulation directly compressible into tablets, and the formulation is then tabletted by direct compression.
- Active ingredients contemplated to be employed in the preparation of tablets by the present invention constitute all active ingredients compatible with the abovedescribed direct compression tabletting compositions.
- the present invention is particularly suitable for the use in preparing tablets containing the well-known pharmaceutically active materials.
- Specific examples of pharmaceutically active ingredients which advantageously may be tabletted by the present invention include ascorbic acid, sodium salicylate, acetaminophen, sodium bicarbonate, aluminum hydroxide, magnesium trisilicate, Vitamin E acetate, calcium lactate, ferrous sulfate and mixtures thereof.
- Particularly preferred pharmaceutically active mate rials include ascorbic acid (Vitamin C), acetaminophen (APAP), aluminum hydroxide in combination with sodium bicarbonate (an antacid); citric acid in combination with sodium bicarbonate (an antacid), and magnesium trisilicate in combination with aluminum hydroxide (in a ratio of 2:1, respectively, as another antacid).
- ascorbic acid Vitamin C
- APAP acetaminophen
- aluminum hydroxide in combination with sodium bicarbonate
- citric acid in combination with sodium bicarbonate
- magnesium trisilicate in combination with aluminum hydroxide (in a ratio of 2:1, respectively, as another antacid).
- the pharmaceutically active materials may be present at relatively high levels in the tablets produced from the vehicles of the present invention. These tablets, even when they contain a high level of the active material, possess acceptable hardness and friability values, not possessed by other sugar-based tablets such as those described in British Pat. No. 1,286,275.
- the tablets of the present invention may be prepared by direct compression utilizing relatively small amounts of pressure in high speed tabletting machines. Due to the unusual structural integrity of the direct compression tabletting vehicles of the present invention, the vehicles may be simply dry mixed with the desired active materials, and, alternatively with conventional tabletting aids such as fillers, lubricants and the like, to obtain ac tive ingredient-containing formulations which are directly compressible into tablets in conventional tabletting equipment.
- These directly compressed tablets exhibit the desired hardness and friability even though they are sugar-based compositions.
- the fact that the tablets are sugar-based and also contain the new relatively tasteless maltodextrins renders the tablets quite suitable for chewable type formulations.
- the sugar in the tablets masks the undesirable flavor of many active materials.
- the present invention provides pleasant tasting chewable tablets which may contain a high level of active material therein and still have the appropriate hardness and friability necessary for commercial manufacture and shipping of these tablets.
- novel tabletting vehicles of the present invention are also characterized as having properties which satisfy the requirements of a binder for the active material and a disintegrant for the tablet in an aqueous medium.
- the compositions of the present invention are capable of being directly compressible into tablets having commercially acceptable hardness, friability and disintegration properties merely by blending the compositions of the present invention with an active material and compressing the mixture with conventional tabletting equipment.
- novel tabletting vehicles of the present invention are capable of carrying relatively high levels of active materials and still maintain commercially acceptable hardness. friability and disintegration properties when directly compressed at low pressures is not fully understood. These unusual properties are not as evident in the agglomerated" dextrose-maltodextrin tabletting compositions described in British Pat. No. 1,286,275. Not wishing to be bound by any theory, it is believed, however, that the addition of the aqueous solution containing the maltodextrin dissolved therein to the uniform mixture of the crystalline sugar and maltodextrin achieves a form of granulation which provides a unique structural integrity in the vehicle.
- the unique structural integrity of the direct compression vehicles of the invention which makes it possible for the granulated mixture ofa crystalline sugar such as dextrose and from about to about 50% by weight of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, wherein said granulated mixture contains less than about 10% by weight moisture, to be capable of being formed into hard, substantially non-friable tablets by direct compression when in admixture with up to 80% by weight of at least one pharmaceutically active ingredient, said tablets have a Strong Cobb Hardness Unit Value (S.C.H.U.) of about 6 or more, and are substantially non'friable.
- a Strong Cobb Hardness Unit Value S.C.H.U.
- the tablets of the invention which contain the aforesaid active ingredients will have a hardness value greater than about 7 S.C.H.U. and quite often greater than about 9 S.C.H.U.
- the hardness values referred to herein are generally obtainable by compressing the dry blended vehicle of the present invention with the active material at pressures as low as 2,000 pounds and, more consistently, such hardness values are obtained when the dry mix is compressed at pressures of 3,000 5,000 pounds (as is generally the case in some commercially available tabletting machines).
- the hardness and friability properties are further improved when the level of maltodextrin is increased to a value of from -35%, the most preferred levels being in the range of from about 30% by weight.
- a preferred embodiment of the invention comprises 21 directly compressed pharmaceutical composition in tablet form, comprising a dry-blended mixture of up to about 80% by weight of a pharniaceutically active ingredient such as ascorbic acid or acetaminophen and at least about 20% by weight of a granulated mixture of dextrose and about 15 to about 35% by weight of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said granulated mixture containing less than about 10% by weight moisture, said directly compressed pharmaceutical composition having a Strong Cobb Hardness Unit (S.C.H.U.) value of at least about 6.
- a pharniaceutically active ingredient such as ascorbic acid or acetaminophen
- a granulated mixture of dextrose and about 15 to about 35% by weight of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20
- said directly compressed pharmaceutical composition having a Strong Cobb
- the preferred tablets of the invention will contain from about 15 to about 35% by weight of the pharmaceuti cally active ingredient.
- the level of active ingredient in the tablet having the desired hardness value will vary from one active ingredient to another.
- higher levels of ascorbic acid can be tolerated as compared to Vitamin E acetate to attain the desired hardness values with the vehicles of the present invention at comparable pressures of preparation.
- a crystalline sugar such as dextrose based vehicle is capable of providing substantially non-friable, hard tablets when directly compressed with high levels of active ingredients.
- additives such as lubricants, fillers, colors and disintegrants may be added to the novel vehicles of the present invention for their known purposes.
- additives include magnesium stearate, talc, CabO-Sil, Cellutab, Sta-Rx 1500, Magnapol, etc. These additives may be present in amounts ranging from about 0.25% by weight to about 10% by weight or more.
- the amount of additive, such as the suitable libricant, will generally depend on the active material employed, and the speed and pressure of the tabletting machine utilized.
- tablet hardness tablet friability, weight variation, tablet disintegration, and accelerated stability study are defined as follows:
- Tablet Hardness A measure of the strength of tablets (average of ten or more tablets) and their ability to retain their physical integrity, expressed in terms of Strong Cobb Hardness Units (S.C.H.U.), as determined by conventional procedure using a Strong Cobb Hardness tester of the Strong-Cobb-Arner Company, Cleveland, Ohio, and the average of these readings is reported herein as mean hardness. The hardness tester was actuated by hand at 60i 5 strokes per minute.
- Tablet Friability A measure of the tendency of tablets (average of 10 or more tablets) to crumble and dust, expressed in terms of percent weight loss, as determined by the R0- che test described in the Journal of the American Pizarmaceutical Association, Scientific Edition, Vol. 45, pages 114-116 (1956). This is conducted by sampling ten or more tablets from each batch by first de-dusting the tablets and weighing the same. The tablets are then subjected to the friability test in a Roche Friabilator at 20 revolutions per minute. The tablets are allowed to roll and fall for 4 minutes and thereafter de-dusted and weighed again. The loss of weight is reported as percentage loss from the original weight. lt is well-known that an active ingredient-containing tablet displaying a weight loss of less than about 1% generally is considthe mean of these two limits is taken.
- Such a tablet characteristic is herein defined as substantially non-friable.
- Quantity ()t (iranulate HARDNESS ⁇ '. ⁇ i.iiis on a Syntron Test Sieve Shaker. Model: TSSZSB. man 01 Maltot ⁇ ilb 510k ufacturcd by the Syntron Company. Homer City. Pa, Dextrose d xtrin M soil. of zltliiio 4
- EXAMPLE 3 Granulation of Dextrose Monohydrate-Maltodextrin Mixture with Aqueous Solutions Containing Maltodextrin
- the above data are indicative that the granulation of a mixture of a crystalline sugar such as dextrose and at least about 10% by weight of a maltodextrin with an aqueous solution containing dissolved therein a maltodextrin provides a tabletting composition having excellent hardness profiles at commercially utilized pressures.
- these compositions can be used as direct compression tabletting compositions.
- the compositions described in Examples 1 and 2 are not acceptable as direct compression vehicles.
- Each of the active ingredients (ascrobic acid (granular), as supplied by Hoffman-LaRoche Inc. and ace1- aminophen (APAP), special power. supplied by S. B.
- Acceptable tablets are defined as those which pos- The vehicles with and without the active ingredient sess minimum friability, effective hardness and rapid were formed into tablets in a Stokes Model 8-2, 16 stadisintegration time. Samples of tablets produced at diftion rotary tablet machine which had been set up with ferent pressures were taken and subjected to tests for four inch s.c. tooling and a standard feed frame to hardness, weight variation, friability. disintegration and enable gravity feed. All samples of the granulation were 5 stability. The details of these experiments and their refirst inspected for physical appearance. In each insults are tabulated in Table 5.
- the granulated direct compression composition was indicated as having excellent cornpressibility characteristics and carrying capacity.
- the granulated direct compression composition exhibited excellent flowtl'rom the hopper to the dies of the tablet press.
- the flow properties of the APAP compositions were not quite as good as the ascorbic acid containing compositions.
- the vehicle was prepared by the granulation process of Example 3, wherein 80% by weight of dextrose monohydrate was admixed with 2071.11 weight of the maltodextrin (Mor-Rex Code 1918. a waxy starch hydrolysate having a DB. 019-1 3) bonate, aluminum hydroxide gel, dried; magnesium trisilicate, dried; (all three supplied by Rugar Chemical Co, New York), acetaminophen (APAP) regular powder, (as supplied by S. B. Penick & Co.) as indicated in Table 7.
- Each of the samples tested contained a lubricant.
- the mixtures of the vehicle and the active ingredient were placed in a Colton Model No. 204.
- the admixture was granulated with a 20% W/V aqueous solution of the maltodextrin (50ml. of the solution per 1.000 grams of dextrose monohydrate and maltodextrin admixture).
- a 20% W/V aqueous solution of the maltodextrin 50ml. of the solution per 1.000 grams of dextrose monohydrate and maltodextrin admixture.
- Each of the granulations tested was passed through a Fitz Mill using a suitable screen (No. 2A or No. 1) with knives forward at medium speed.
- the comminuted granulations were then hand sieved so as to obtain three particle size ranges, viz.: 20 +60. 40 +100, and -100 +200.
- the granulations (except the controls which did not contain active ingredient) were dry blended with sodium bicar weight variation (U.S.P.) test was also good to excel 19 lent. However, the 20 +60 and 40 +100 particle size
- EXAMPLE 8 The vehicle used in this experiment was prepared in I the same manner as previously described in Examples 3 6. The vehicle was a granulated admixture of 80% by weight of dextrose monohydrate and 20% by weight of the maltodextrin granulated with a 20% W/V solution of a maltodextrin. The final granulated admixture was screened to a particle size range of +100. The granulation was dried in an oven at different temperatures and for different lengths of time so as to obtain at least three different moisture content levels, 8.0, 4.0 and 2.0%. by weight. The tablets were prepared on a Colton Model No. 204, 4 station rotary tablet machine in the same manner described in the previous examples.
- each of the active ingredients (ascrobic acid (type S); calcium salicylate; ferrous sulfate (exicated); and Vitamin E acetate; 50% SD.) were mixed with the granulated vehicle of Example 3 and tested in exactly the same way as described in Example 4.
- Each of the blended mixtures of granulated vehicle and active medicinal ingredient had excellent flow characteristics from the hopper to the tablet die. The tablets also had a very narrow weight variation. All of the active ingredients were carried very well and the resulting tablets were of extremely high quality, having a friability of less than 2%.
- Sodium salicylate was carried the least and it required a larger amount (2%) oflubricant.
- Vitamin E acetate (111) was carried up to 55%.
- EXAMPLE 9 This experiment was performed to determine the effect of Sta-Rx 1500 (available from A. E. Staley Mfg. Co., Decatur, III.) on the disintegration time ofthe tablets of the granulations per se, as well as in combination with various active medicinal agents.
- Example 3 The same granulated vehicle used in the previous Example 3 was employed. which was an admixture of 80% by weight dextrose monohydrate and of the water soluble maltodextrin granulated with a 20% W/V solu- FORMUATION Active Active Carried 7r LUBRICANT EVALUATION Medicinal By Granulated Magnesium Hardness Disintegration 7r Agent Vehicle Stearate Talc Cab-O-Sil In S.C.H.U. In Min. Friability Calcium '35 1.0 12.5 12.0 0.14 I Lactate 1 Ferrous Sulfate. 0.5 7.6 25 0.31 Exicated Sodium 10 2.0 5.0 23 1.4 Salicylate ments measured less than 1%. All of the tablets had good hardness values.
- the hardness value for Vitamin E acetate tablets ranged from 3.8 to 4.0, simply because of the reference pressure for the control tablets to produce a hardness value of 10.8.
- the hardness value of these tablets could be increased to about 6 or TABLE 10 EFFECT OF STA-RX 1500 AS A DISINTEGRANT ON GRANULATED VEHICLE WITH AND WITHOUT ACTIVE MEDICINAL INGREDIENTS FORMULATION 7c ACTIVE Vitamin E 7c LUBRICANT EVALUATION Acetate Calcium Magnesium Capping, Hardness Disintegration 7t (509? SD.) Lactate Stearate Talc Cab-O-Sil Sta-Rx 1500 If Any In S.C.H.U. In Min.
- the dried granulated vehicle EXAMPLE 1() was screened to obtain a mesh size in the range of +100.
- the screened granulated vehicle (except the control) was blended with Sta-Rx 1500 to obtain 10% by weight of Sta-Rx of the total mixture.
- the Sta-Rx 1500 was also added to the formulations containing the active medicinal ingredients, displacing the granulated direct compression vehicle.
- the tablets were prepared in the same manner as described in Example 4, keeping the hardness the same as the tablets without Sta-Rx
- the tablets were evaluated for their weight variation, hardness, friability and disintegration.
- the addition of the directly compressible starch, Sta-Rx 1500 did not effect the carrying capacity of the granulated vehicle of the invention.
- very slight capping was observed in the case of the calcium lactate formulation] This result was expected.
- tablets containing starches have a tendency to cap.
- the reduction of time was about one-third of the original time.
- the flow from the hopper to the tablet die for all samples was excellent.
- the experiment was performed using the same granulated vehicle used in the previous Examples which had been prepared by admixing by weight of dextrose monohydrate with 20% by weight of the maltodextrin. and thereafter granulating the admixture with a 20% W/V aqueous solution of the maltodextrin (50 ml. of solution per 1,000 grams of dextrose monohydrate and maltodextrin admixture).
- Vitamin C and Vitamin E acetate were blended with several samples to provide 20 and 55% by weight of the active medicinal agent in the total blend, respectively.
- the rate of moisture pick-up of the granulated vehicle. per se. and in ct'imbination with the active medicinal agents was studied at 50%, 70 and 90% relative humidity at room temperature.
- the moisture pick-up of the samples tested was determined using the below-described procedure.
- test material which was placed in an aluminum pan (supported by a wire ring) was hooked onto the Surface Tensiometer with a thread passing through a 2-inch length of rubber tubing partly slipped over a 3-inch length of plastic tubing.
- the glass tubing was fitted into the tubulature of the desiccator top through a one-hole rubber stopper.
- the test material, the aluminum pan with the ring, the nylon thread were counterbalanced by necessary weights to produce a tensiometer reading of 0.00 mg. Readings were taken at the end of each hour and the increase in weight was noted.
- EXAMPLE ll This experiment demonstrates the excellent density and fluff characteristics possessed by the granulated vehicles of the present invention, which characteristics enable the vehicle to have the good flow properties from the hopper to the tablet die.
- the tablet thickness actually depends on the volume occupied by the vehicle in the die cavity. Tablet thickness is related to the density of the granulation as volume and is inversely proportional to the density. Thus, the denser the granulation, the less volume will be occupied at a given weight, producing thinner tablets. The thickness of the tablets determines the choice of a given packaging unit and even the toolings to be used in their manufacturing.
- This Example determines the fluff and top densities of the granulations; first, the weight of the material at a given volume, and secondly, the volume is evaluated at a given weight of material.
- the granulated vehicle was prepared as previously described in Example 3, using 80% by weight of dextrose monohydrate and 20% by weight of the maltodextrin.
- Top Density Each granulated vehicle sample (50 grams) was accurately weighed and transferred to a .l00-ml. cylinder. The cylinder was gently topped on a thick layer of cloth, until no further perceptible decrease in volume was observed. The weight of the granulations was divided by the volume obtained, and the result was reported as Top Density" in grams/ml.
- EXAMPLE 12 Several granulated vehicles were prepared utilizing the unique procedure described in Example 3, except that in place of Mor-Rex Code 1918, an acid hydrolysate having a DB of about 15 (Frodex, available from American Maize-Products), an enzyme hydrolysate having a E.E. of about 5 (Mor-Rex P908), and two dextrins (Globe Dextrin and Excello Dextrin, available from CPC International Inc.) were employed in amounts of l0, 20 and 30% by weight in the initial blend with the dextrose monohydrate.
- the respective maltodextrin or dextrin was placed in water and the solution or dispersion (containing 20% W/V of the maltodextrin or dextrin) was used to granulate the blend.
- the blends were dried to a moisture content of 3-5% and screened of oversize granules above a No. 14 mesh.
- Each of the granulated vehicles was mixed with 1.0% magnesium stearate for lubrication and was formed into tablets on a Model F single stroke tabletting machine set at a ratio of 45 strokes per minute and at 1% tons of pressure.
- the granulated vehicles were freeflowing and had acceptable compressibilities. Slight scoring of tablets was observed in the vehicles prepared from the acid hydrolysate (Frodex) and Mor-Rex P908, therefore, necessitating a higher amount of lubricant or inclusion of an anti-adherent. From a hardness and friability standpoint, all blends made acceptable tablets. All of the granulated vehicles demonstrated very little hygroscopicity at 50, and 90% relative humidity. The acid hydrolysate (Frodex) containing vehicles. However, the acid hydrolysate containing vehicles were slightly more hygroscopic than the other vehicles tested.
- the dextrin containing vehicles while they provided suitable tablets, were not acceptable because the tablets possessed a yellow color and had a burnt flavor. Thus, it is necessary to employ the maltodextrins to product commercially acceptablegranulated vehicles for use in the pharmaceutical industry.
- the present invention has now provided a unique granulated vehicle having an unusual structural integrity and density.
- the structural integrity and density of the granulated vehicles provides a tabletting composition having excellent flowability and capability of forming strong, hard and substantially non-friable tablets, even when the tablet contains up to about by weight of the tablet, a pharmaceutically active material.
- a substantially non-friable tablet it is meant a tablet which loses less than about 1% by weight, as determined by the Roche test described hereinabove.
- a method for producing a direct compression ve hicle for tabletting comprising:
- dextrose is a centrifuge cake containing up to about l6% by weight moisture, based upon the weight of the centrifuge cake.
- said maltodextrin is a waxy starch hydrolysate having a dextrose equivalent value in the range of from about 9 to about 13 and a descriptive ratio of at least about 2, said descriptive ratio being the sum of the percentages (dry basis) of saccharides of the maltodextrin with a degree of polymerization of 1 to 6 divided by the dextrose equivalent value.
- a method for producing a direct compression vehicle for tabletting comprising:
- a directly compressible tabletting vehicle comprising a granulated mixture of a crystalline sugar and from about 10 to about 50% by weight, based upon the weight of said vehicle, of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said granulated mixture containing less than about 10% by weight moisture, based upon the weight of said vehicle, said directly compressible tabletting vehicle in admixture with up to about by weight, based upon the weight of said vehicle, of at least one pharmaceutically active ingredient, being characterized as capable of being formed by direct compression at a pressure as low as about 2000 pounds into hard, substantially non-friable tablets having a Strong Cobb Hardness Unit (S.C.H.U.) value of at least about 6.
- S.C.H.U. Strong Cobb Hardness Unit
- a method for preparing tablets comprising forming an admixture of the product of claim 9 and an active material, said product comprising at least about 20% by weight of said vehicle, and compressing the mixture into tablets.
- a method for preparing tablets comprising forming an admixture of the product of claim 10 and an active material, said product comprising at least 20% of said vehicle, and compressing the mixture into tablets.
- said pharmaceutically active material is a member selected from the group consisting of ascorbic acid, sodium salicylate, acetaminophen, sodium bicarbonate, aluminum hydroxide, magnesium trisilicate, Vitamin E acetate, calcium lactate, ferrous sulfate and mixtures thereof.
- a directly compressed pharmaceutical composition in tablet form comprising a dry-blended mixture comprising:
- a at least one pharmaceutically active ingredient present in an amount up to about 80% by weight, based upon the weight of said directly compressed pharmaceutical composition
- Y b a directly compressible vehicle comprising a granulated mixture of a crystalline sugar and at least about 10% by weight.
- directly compressible vehicle based upon the weight of the directly compressible vehicle, of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said directly compressible vehicle containing less than about by weight moisture, said directly compressible vehicle being present in an amount of at least about 20% by weight, based upon the weight of said directly compressed pharmaceutical composition, said directly compressed pharmaceutical composition being characterized as being hard and substantially non-friable, and being further characterized as having a Strong Cobb Hardness Unit (S.C.H.U.) value of at least about 6.
- S.C.H.U. Strong Cobb Hardness Unit
- directly compressible vehicle comprises a granulated mixture of dextrose monohydrate granulated with to about 35% by weight, based upon the weight of the vehicle, of a maltodextrin having a measurable dextrose equivalent value not substantially above about 20.
- composition of claim 17 wherein said pharmaceutically active ingredient is a member selected from the group consisting of ascorbic acid, sodium salicylate, acetaminophen, sodium bicarbonate, aluminum hydroxide, magnesium trisilicate, Vitamin E acetate, calcium lactate, ferrous sulfate and mixtures thereof.
- the directly compressed pharmaceutical composition of claim 17, which additionally includes a small but effective amount of materials selected from the group consisting of lubricants, coloring aids, disintegrants, binders and mixtures thereof.
- a directly compressed pharmaceutical composition in tablet form comprising a dry-blended mixture comprising:
- a. ascorbic acid in an amount of up to about 80% by weight. based upon the weight of said pharmaceutical composition
- a directly compressible vehicle comprising a granulated mixture of dextrose and about 15% to about 35% by weight, based upon the weight of said vehicle, of water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said vehicle containing less than about 10% by weight moisture.
- said directly compressed pharmaceutical tablet being characterized as being hard and substantially nonfriable such that the tablet has a Strong Cobb Hardness Unit (S.C.H.U.) value of at least about 6.
- S.C.H.U. Strong Cobb Hardness Unit
- a directly compressible tabletting vehicle comprising a granulated mixture of dextrose and from about l5 to about 35% by weight, based upon the weight of the vehicle, of a water soluble maltodextrin having a measurable dextrose equivalent value not substantially above about 20, said granulated mixture containing less than about 5% by weight moisture, based upon the weight of said vehicle, said directly compressible tabletting vehicle in admixture with at least one pharmaceutically active ingredient in an amount of from about l5 to about 35% by weight, based upon the weight of the total composition, being characterized as capable of being formed by direct compression at a pressure as low as 2000 pounds into hard, substantially non-friable tablets having a Strong Cobb Hardness Unit (S.C.H.U.) value of at least about 6, said vehicle being further characterized as having a particle size in the range of from about 40 to about mesh screen.
- S.C.H.U. Strong Cobb Hardness Unit
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US401322A US3873694A (en) | 1973-09-27 | 1973-09-27 | Direct compression tabletting composition and pharmaceutical tablets produced therefrom |
GB4158774A GB1471564A (en) | 1973-09-27 | 1974-09-24 | Direct compression tabletting composition and tablets produced therefrom |
ES430431A ES430431A1 (es) | 1973-09-27 | 1974-09-26 | Varistor de oxido metalico. |
JP49110653A JPS5058219A (es) | 1973-09-27 | 1974-09-27 | |
MY34/78A MY7800034A (en) | 1973-09-27 | 1978-12-30 | Direct compression tabletting composition and tablets produced therefrom |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US401322A US3873694A (en) | 1973-09-27 | 1973-09-27 | Direct compression tabletting composition and pharmaceutical tablets produced therefrom |
Publications (1)
Publication Number | Publication Date |
---|---|
US3873694A true US3873694A (en) | 1975-03-25 |
Family
ID=23587269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US401322A Expired - Lifetime US3873694A (en) | 1973-09-27 | 1973-09-27 | Direct compression tabletting composition and pharmaceutical tablets produced therefrom |
Country Status (5)
Country | Link |
---|---|
US (1) | US3873694A (es) |
JP (1) | JPS5058219A (es) |
ES (1) | ES430431A1 (es) |
GB (1) | GB1471564A (es) |
MY (1) | MY7800034A (es) |
Cited By (42)
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US4262017A (en) * | 1978-05-22 | 1981-04-14 | Basf Aktiengesellschaft | Preparation of a vitamin E dry powder |
US4349542A (en) * | 1979-06-08 | 1982-09-14 | National Research Development Corporation | Mixture containing active ingredient and dendritic crystalline sugar for tableting |
EP0100168A2 (en) * | 1982-07-06 | 1984-02-08 | Alan George Rogerson | Processes for preparing tablets by a modified 'wet-granulation' technique |
US4465667A (en) * | 1979-07-09 | 1984-08-14 | Aktiebolaget Hassle | Process for the preparation of gastric acid neutralizing agents, gastric acid neutralizing agents, and a method for treating hyperacidity and disorders related thereto |
US4495177A (en) * | 1983-01-17 | 1985-01-22 | Shaklee Corporation | Gel tableting agent |
US4639458A (en) * | 1985-01-22 | 1987-01-27 | Merck & Co., Inc. | Tablet and formulation |
US4643894A (en) * | 1984-07-24 | 1987-02-17 | Colorcon, Inc. | Maltodextrin coating |
US4684534A (en) * | 1985-02-19 | 1987-08-04 | Dynagram Corporation Of America | Quick-liquifying, chewable tablet |
US4711894A (en) * | 1986-01-16 | 1987-12-08 | Henkel Corporation | Stabilized tocopherol in dry, particulate, free-flowing form |
US4894236A (en) * | 1988-01-12 | 1990-01-16 | Choong-Gook Jang | Direct compression tablet binders for acetaminophen |
US4985252A (en) * | 1987-04-07 | 1991-01-15 | R. I. Ph. Recherche Informatique Et Pharmacie (S.A.R.L.) | Medication, dietetic product and hygienic product in the form of a powered composition obtained by adsorption of active ingredients on a rapidly dissolving sugar and process for obtaining said composition |
US5037658A (en) * | 1989-09-14 | 1991-08-06 | Hoechst-Roussel Pharmaceuticals, Inc. | Direct dry compressible acetaminophen composition |
US5047246A (en) * | 1988-09-09 | 1991-09-10 | Bristol-Myers Company | Direct compression cyclophosphamide tablet |
US5130140A (en) * | 1989-09-14 | 1992-07-14 | Hoeschst-Roussel Pharmaceuticals Inc. | Method of making direct dry compressible acetaminophen composition |
US5164192A (en) * | 1989-02-07 | 1992-11-17 | Duphar International Research B.V. | Effervescent composition for oral rehydration |
US5198228A (en) * | 1989-09-14 | 1993-03-30 | Hoechst-Roussel Pharmaceuticals Inc. | Direct dry compressible acetaminophen tablet |
US5384130A (en) * | 1990-04-18 | 1995-01-24 | Asahi Kasei Kogyo Kabushiki Kaisha | Spherical seed cores, spherical granules and process for production thereof |
US5470581A (en) * | 1990-04-04 | 1995-11-28 | Berwind Pharmaceutical Services, Inc. | Aqueous maltodextrin and cellulosic polymer film coatings |
US5505983A (en) * | 1990-04-18 | 1996-04-09 | Asahi Kasei Kogyo Kabushiki Kaisha | Spherical seed cores, spherical granules and process for production thereof |
US5531983A (en) * | 1990-10-08 | 1996-07-02 | Purac Biochem B.V. | Oral hygiene preparation |
EP0745382A1 (en) * | 1994-01-31 | 1996-12-04 | Yamanouchi Pharmaceutical Co. Ltd. | Intraorally soluble compressed molding and process for producing the same |
US5804217A (en) * | 1993-04-14 | 1998-09-08 | Pharmacia & Upjohn Aktiebolag | Manufacturing matrices |
FR2769636A1 (fr) * | 1997-10-13 | 1999-04-16 | Saint Louis Sucre Sa | Produit hydrophobe a base de saccharose |
US5939459A (en) * | 1996-09-06 | 1999-08-17 | Cellular Sciences Inc. | Method and composition for treating mammalian disease caused by inflammatory response |
US6008187A (en) * | 1993-07-30 | 1999-12-28 | Alza Corporation | Peptide formulation |
US6080427A (en) * | 1997-04-17 | 2000-06-27 | Bristol-Myers Squibb Company | Cefadroxil monohydrate tablet formulation |
US6348264B1 (en) | 1998-04-27 | 2002-02-19 | Roquette Freres | Process for producing low de starch hydrolysates by nanofiltration fractionation, products obtained thereby, and use of such products |
US6432448B1 (en) | 1999-02-08 | 2002-08-13 | Fmc Corporation | Edible coating composition |
US6500462B1 (en) | 1999-10-29 | 2002-12-31 | Fmc Corporation | Edible MCC/PGA coating composition |
US6699315B2 (en) | 2000-11-28 | 2004-03-02 | Fmc Corporation | Edible PGA coating composition |
US6716453B1 (en) * | 1999-05-20 | 2004-04-06 | Verion, Inc. | Method for increasing the active loading of compressible composition forms |
US6723342B1 (en) | 1999-02-08 | 2004-04-20 | Fmc Corporation | Edible coating composition |
US20050095272A1 (en) * | 2000-11-28 | 2005-05-05 | Fmc Corporation | Edible PGA coating composition |
US20050143343A1 (en) * | 2003-12-30 | 2005-06-30 | Nerenberg Arnold P. | Nutritional supplement for enhancing the production and effect of natural human growth hormone |
US7282217B1 (en) | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
US20080069936A1 (en) * | 2006-09-18 | 2008-03-20 | ISON Renny | Cohesive non-free flowing sweeetener compositions containing a hygroscopic gluing agent and a desiccant |
EP2395972A1 (en) * | 2009-02-11 | 2011-12-21 | Liangping Yu | Particulate composition and the method of making the same |
WO2012019266A1 (en) * | 2010-08-13 | 2012-02-16 | Filho Jose Raimundo | Method and composition for reducing the color of sugar |
DE202015004009U1 (de) | 2015-06-09 | 2016-01-11 | Hermes Arzneimittel Gmbh | Schnell zerfallende Tabletten ohne Zerfallsbeschleuniger |
DE202016005032U1 (de) | 2016-08-19 | 2017-02-10 | Hermes Arzneimittel Gmbh | Schnell zerfallende Efeu-Trinktabletten ohne Zerfallsbeschleuniger |
US9919007B2 (en) | 2013-03-15 | 2018-03-20 | Braintree Laboratories, Inc. | Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof |
US10143656B1 (en) | 2017-08-04 | 2018-12-04 | Braintree Laboratories, Inc. | Solid oral sulfate salt formulations for cleaning a colon and methods of using same |
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AR226763A1 (es) * | 1980-12-22 | 1982-08-13 | Monsanto Co | Metodo de preparacion de una granulacion analgesica de acetaminofeno |
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Cited By (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4262017A (en) * | 1978-05-22 | 1981-04-14 | Basf Aktiengesellschaft | Preparation of a vitamin E dry powder |
US4349542A (en) * | 1979-06-08 | 1982-09-14 | National Research Development Corporation | Mixture containing active ingredient and dendritic crystalline sugar for tableting |
US4465667A (en) * | 1979-07-09 | 1984-08-14 | Aktiebolaget Hassle | Process for the preparation of gastric acid neutralizing agents, gastric acid neutralizing agents, and a method for treating hyperacidity and disorders related thereto |
EP0100168A2 (en) * | 1982-07-06 | 1984-02-08 | Alan George Rogerson | Processes for preparing tablets by a modified 'wet-granulation' technique |
EP0100168A3 (en) * | 1982-07-06 | 1984-11-28 | Sterwin Ag. | Processes for preparing tablets by a modified 'wet-granulation' technique |
US4495177A (en) * | 1983-01-17 | 1985-01-22 | Shaklee Corporation | Gel tableting agent |
AU574443B2 (en) * | 1984-07-24 | 1988-07-07 | Bpsi Holdings, Inc. | Maltodextrin coating |
US4643894A (en) * | 1984-07-24 | 1987-02-17 | Colorcon, Inc. | Maltodextrin coating |
AU618751B2 (en) * | 1984-07-24 | 1992-01-09 | Bpsi Holdings, Inc. | Coating composition |
US4725441A (en) * | 1984-07-24 | 1988-02-16 | Colorcon, Inc. | Maltodextrin coating |
US4639458A (en) * | 1985-01-22 | 1987-01-27 | Merck & Co., Inc. | Tablet and formulation |
US4684534A (en) * | 1985-02-19 | 1987-08-04 | Dynagram Corporation Of America | Quick-liquifying, chewable tablet |
US4711894A (en) * | 1986-01-16 | 1987-12-08 | Henkel Corporation | Stabilized tocopherol in dry, particulate, free-flowing form |
US4985252A (en) * | 1987-04-07 | 1991-01-15 | R. I. Ph. Recherche Informatique Et Pharmacie (S.A.R.L.) | Medication, dietetic product and hygienic product in the form of a powered composition obtained by adsorption of active ingredients on a rapidly dissolving sugar and process for obtaining said composition |
US4894236A (en) * | 1988-01-12 | 1990-01-16 | Choong-Gook Jang | Direct compression tablet binders for acetaminophen |
US5047246A (en) * | 1988-09-09 | 1991-09-10 | Bristol-Myers Company | Direct compression cyclophosphamide tablet |
US5164192A (en) * | 1989-02-07 | 1992-11-17 | Duphar International Research B.V. | Effervescent composition for oral rehydration |
US5037658A (en) * | 1989-09-14 | 1991-08-06 | Hoechst-Roussel Pharmaceuticals, Inc. | Direct dry compressible acetaminophen composition |
US5130140A (en) * | 1989-09-14 | 1992-07-14 | Hoeschst-Roussel Pharmaceuticals Inc. | Method of making direct dry compressible acetaminophen composition |
US5198228A (en) * | 1989-09-14 | 1993-03-30 | Hoechst-Roussel Pharmaceuticals Inc. | Direct dry compressible acetaminophen tablet |
US5470581A (en) * | 1990-04-04 | 1995-11-28 | Berwind Pharmaceutical Services, Inc. | Aqueous maltodextrin and cellulosic polymer film coatings |
US5384130A (en) * | 1990-04-18 | 1995-01-24 | Asahi Kasei Kogyo Kabushiki Kaisha | Spherical seed cores, spherical granules and process for production thereof |
US5505983A (en) * | 1990-04-18 | 1996-04-09 | Asahi Kasei Kogyo Kabushiki Kaisha | Spherical seed cores, spherical granules and process for production thereof |
US5531983A (en) * | 1990-10-08 | 1996-07-02 | Purac Biochem B.V. | Oral hygiene preparation |
US5804217A (en) * | 1993-04-14 | 1998-09-08 | Pharmacia & Upjohn Aktiebolag | Manufacturing matrices |
US6008187A (en) * | 1993-07-30 | 1999-12-28 | Alza Corporation | Peptide formulation |
EP0745382A1 (en) * | 1994-01-31 | 1996-12-04 | Yamanouchi Pharmaceutical Co. Ltd. | Intraorally soluble compressed molding and process for producing the same |
EP0745382A4 (en) * | 1994-01-31 | 1997-10-29 | Yamanouchi Pharma Co Ltd | INTRAORALLY SOLUBLE MOLDED PRESSURE AND METHOD FOR THE PRODUCTION THEREOF |
US5939459A (en) * | 1996-09-06 | 1999-08-17 | Cellular Sciences Inc. | Method and composition for treating mammalian disease caused by inflammatory response |
US6080427A (en) * | 1997-04-17 | 2000-06-27 | Bristol-Myers Squibb Company | Cefadroxil monohydrate tablet formulation |
FR2769636A1 (fr) * | 1997-10-13 | 1999-04-16 | Saint Louis Sucre Sa | Produit hydrophobe a base de saccharose |
EP0909824A1 (fr) * | 1997-10-13 | 1999-04-21 | Saint-Louis Sucre S.A. | Granule hydrophobe à base de saccharose |
US6348264B1 (en) | 1998-04-27 | 2002-02-19 | Roquette Freres | Process for producing low de starch hydrolysates by nanofiltration fractionation, products obtained thereby, and use of such products |
US6432448B1 (en) | 1999-02-08 | 2002-08-13 | Fmc Corporation | Edible coating composition |
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DE202015004009U1 (de) | 2015-06-09 | 2016-01-11 | Hermes Arzneimittel Gmbh | Schnell zerfallende Tabletten ohne Zerfallsbeschleuniger |
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Also Published As
Publication number | Publication date |
---|---|
GB1471564A (en) | 1977-04-27 |
ES430431A1 (es) | 1976-10-01 |
MY7800034A (en) | 1978-12-31 |
JPS5058219A (es) | 1975-05-21 |
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