EP2661252A1 - Water soluble dosage forms - Google Patents
Water soluble dosage formsInfo
- Publication number
- EP2661252A1 EP2661252A1 EP12707405.2A EP12707405A EP2661252A1 EP 2661252 A1 EP2661252 A1 EP 2661252A1 EP 12707405 A EP12707405 A EP 12707405A EP 2661252 A1 EP2661252 A1 EP 2661252A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- range
- water soluble
- weight
- formulations
- acarbose
- 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.)
- Withdrawn
Links
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 51
- 239000002552 dosage form Substances 0.000 title description 9
- 239000000203 mixture Substances 0.000 claims abstract description 72
- 229960002632 acarbose Drugs 0.000 claims abstract description 27
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims abstract description 26
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000009472 formulation Methods 0.000 claims description 69
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000013543 active substance Substances 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 15
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 10
- -1 glidant Substances 0.000 claims description 10
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 8
- 239000011230 binding agent Substances 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 239000005913 Maltodextrin Substances 0.000 claims description 7
- 229920002774 Maltodextrin Polymers 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 7
- 239000007884 disintegrant Substances 0.000 claims description 7
- 229940035034 maltodextrin Drugs 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- 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 claims description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- 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 claims description 5
- 239000001175 calcium sulphate Substances 0.000 claims description 5
- 235000011132 calcium sulphate Nutrition 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 235000010356 sorbitol Nutrition 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 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 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 4
- 235000010216 calcium carbonate Nutrition 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- 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 claims description 3
- 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 claims description 3
- 239000002518 antifoaming agent Substances 0.000 claims description 3
- 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 claims description 3
- 238000004040 coloring Methods 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000013355 food flavoring agent Nutrition 0.000 claims description 3
- 235000003599 food sweetener Nutrition 0.000 claims description 3
- 239000003906 humectant Substances 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000001095 magnesium carbonate Substances 0.000 claims description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 3
- 235000014380 magnesium carbonate Nutrition 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 239000003765 sweetening agent Substances 0.000 claims description 3
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000000395 magnesium oxide Substances 0.000 claims description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 2
- 235000012245 magnesium oxide Nutrition 0.000 claims description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 2
- 239000008188 pellet Substances 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 8
- 108090001061 Insulin Proteins 0.000 description 8
- 229940125396 insulin Drugs 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 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 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 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 5
- 238000000034 method Methods 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000011090 malic acid Nutrition 0.000 description 3
- 239000001630 malic acid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
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- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 2
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- 235000017803 cinnamon Nutrition 0.000 description 2
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- 230000029087 digestion Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
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- 150000004677 hydrates Chemical class 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
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- 229940127017 oral antidiabetic Drugs 0.000 description 2
- 230000003711 photoprotective effect Effects 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000001508 potassium citrate Substances 0.000 description 2
- 229960002635 potassium citrate Drugs 0.000 description 2
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 2
- 235000011082 potassium citrates Nutrition 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
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- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229940043353 maltol Drugs 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- VNKYTQGIUYNRMY-UHFFFAOYSA-N methoxypropane Chemical compound CCCOC VNKYTQGIUYNRMY-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 description 1
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 description 1
- 235000010434 neohesperidine DC Nutrition 0.000 description 1
- 235000019412 neotame Nutrition 0.000 description 1
- HLIAVLHNDJUHFG-HOTGVXAUSA-N neotame Chemical compound CC(C)(C)CCN[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 HLIAVLHNDJUHFG-HOTGVXAUSA-N 0.000 description 1
- 108010070257 neotame Proteins 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940125395 oral insulin Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- CFJYNSNXFXLKNS-UHFFFAOYSA-N p-menthane Chemical compound CC(C)C1CCC(C)CC1 CFJYNSNXFXLKNS-UHFFFAOYSA-N 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 239000010663 parsley oil Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001388 sodium aluminate Inorganic materials 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 229910052911 sodium silicate Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- 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 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000004260 weight control Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- 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
-
- 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
Definitions
- the present invention relates to water soluble pharmaceutical compositions comprising acarbose and use of these compositions in diabetes, adiposity and hyperlipoidemia.
- Diabetes is a chronic disease which is characterized by insufficient or lack of insulin production by the pancreas and leads to disorders of carbohydrate, lipid and protein metabolism. There are two major types of diabetes.
- Type I diabetes grows because beta cells in the pancreas can produce very little or no insulin associated with autoimmune mechanisms. Insulin is a hormone which is responsible for reducing elevated blood sugar. Blood sugar level rises depending on reduction in amount or in efficiency of insulin (hyperglycemia). Type I diabetes generally develops in children or young adults. Type II diabetes is the most common type of diabetes and characterized by insulin resistance. In this type of diabetes, insulin is released properly but it cannot be sufficiently effective.
- the primary treatment method for diabetic patients is diet and exercise. This treatment approach provides very little weight loss but regulates insulin sensitivity. Sometimes, it can be possible to control blood sugar level for a long period of time only with this treatment method. However, the tendency towards insulin resistance in these people never disappears; therefore, the diet, exercise and weight control should be maintained continuously. In the cases that diet and exercise are insufficient, the second step of the treatment is oral anti-diabetic drugs and insulin reinforcement.
- the main oral anti-diabetics used in treatment of Type II diabetes are sulfonylureas, biguanides and alpha glucosidase inhibitors,
- Acarbose which is an alpha glucosidase inhibitor was first disclosed in the patent document numbered DE2347782.
- Acarbose is produced by fermentation of the microorganism called Actinoplanes utahensis.
- Acarbose inhibits alpha glucosidase enzyme which is responsible for digestion of carbohydrates in lumen of the small intestine. Digestion and absorption of carbohydrates in the intestine are slowed down by inhibition of this enzyme; therefore elevation in blood sugar level after meals is prevented. Acarbose does not affect insulin release from the pancreas, insulin use in the tissues or glucose outflow from the liver. Therefore, acarbose does not cause hypoglycaemia when used singly.
- acarbose can be preferred as a primary treatment in the case that there is diabetes that cannot be controlled by diet or it can be preferred as combination treatment option in the case that postprandial hyperglycemias cannot be prevented during the treatments of sulfonurea, biguanide or insulin.
- the formulation comprising the active agent acarbose is marketed under the trade name Glucobay® in the form of 50 and 100 mg tablets.
- solid dosage forms such as tablet cause difficulty of use generally in geriatric, pediatric and disabled patients who have swallowing difficulty. Feeling of obstruction and choking can o uf ⁇ rr3 ⁇ 4drviduals due to the ⁇ rob1 ⁇ 2n ⁇ e €umng- & pharyngeal and esophageal motility and consequently taking drug can be disgustful and painful for patients. In line with this, the patient delays drug intake and this situation decreases efficiency of the treatment significantly and affects life quality of the patient.
- dosage forms which comprise the active agent acarbose and are easy-to-use for patients in order to be used in treatment of diabetes, adiposis and hyperlipidemia.
- Suspension forms which are presented as an alternative in order to overcome the problems caused by solid dosage forms cannot be performed in most of the active agents due to the reasons that suspension forms have the possibility of causing high and/or uncontrolled dose intake and furthermore there is problems in physical and chemical stabilities of suspension forms after diluted; production costs of suspension forms are high and they pose problem in using and carrying.
- acarbose is a hygroscopic molecule; therefore, it is quite hard to formulate acarbose in water soluble dosage forms such as suspension. Contact of the active agent with water leads to disintegration of the formulations in a shorter time than expected and quickly.
- the present invention relates to water soluble dosage forms comprising the active agent acarbose; the methods for preparing these dosage forms and usage areas thereof.
- Formulating the formulations of the present invention in water soluble dosage forms have enabled that required therapeutic benefit is provided by using less amount of active agent than the active agent amount comprised in the dosage forms in the prior art. Use of less active agent is also advantageous for the reason that it reduces side effect possibility that can be caused by the formulations.
- one water soluble iOrmulations of the present invention is that the formulations comprise acarbose in the range of 1 % to 10 % by weight, preferably in the range of 1% to 9 % by weight, more preferably in the range of 1% to 8% by weight.
- Another characteristic feature of the water soluble formulations of the present invention is that the formulations comprise acarbose in the range of 10-300 mg, preferably in the range of 20-200 mg, more preferably in the range of 50-150 mg.
- one characteristic feature of the water soluble formulations of the present invention is that the formulations are formulated in the form of powder, granule, pellet, micro tablet or tablet.
- the water soluble formulations of the present invention can comprise at least one pharmaceutically acceptable excipient selected from a group comprising effervescent couple, binder, lubricant, glidant, diluent, disintegrant, flavouring agent, sweetener, colouring agent, surfactant, antifoaming agent, viscosity agent, stabilizing agent, humectant or combinations thereof in addition to the active agent.
- a pharmaceutically acceptable excipient selected from a group comprising effervescent couple, binder, lubricant, glidant, diluent, disintegrant, flavouring agent, sweetener, colouring agent, surfactant, antifoaming agent, viscosity agent, stabilizing agent, humectant or combinations thereof in addition to the active agent.
- the binder that can be used in the water soluble formulations of the present invention can be selected from a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethylcellulose, methylcellulose, ethylcellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol; water or the combinations thereof.
- the binder used in the water soluble formulations of the present invention is selected from a group comprising lactose, sorbitol, polyethylene glycol or the combinations thereof.
- the amount of the binder that can be used in the water soluble formulations of the present invention is in the range of 0% to 10% by weight, preferably in the range of 0.5% to 2% by weight.
- the lubricant that can be used in the water soluble formulations of the present invention can be selected from sodium lauryl sulphate, calcium stearate, magnesium stearate, polyethylene glycol, polyvinyl alcohol, potassium benzoate, sodium benzoate, sodium chloride, carbowax 4000, talc or a combination thereof.
- the amount of the lubricant used in the formulations of the present invention is in the range of 0% to 5% by weight, preferably in the range of 0.3% to 2% by weight; the lubricant which is particularly preferred is polyethylene glycol.
- the glidant that can be used in the water soluble formulations of the present invention can be selected from talc, magnesium stearate, stearic acid, sodium stearyl fumarate, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof.
- the amount of the glidant used in the formulation of the present invention is in the range of 0% to 5% by weight.
- the diluent that can be used in the water soluble formulations of the present invention can be selected from lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch, calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, magnesium carbonate, magnesium oxide or a combination thereof.
- the inventors have unexpectedly found that the type and amount of the diluent used in the formulations prevent disintegration arising from hygroscopic characteristic of the active agent. According to this, stability of the formulations comprising small amount of the active agent acarbose could be preserved for a long period of time, for 24 months, with use of maltodextrin as diluent in the water soluble formulations of the present invention.
- the amount of the diluent used in the water soluble formulations of the present invention is in the range of 1% to 10% by weight, preferably in the range of 2% to 7% by weight, more preferably in the range of 3% to 5% by weight.
- one characteristic feature of the water soluble formulations of the present invention comprising acarbose is that the formulations comprise maltodextrin in the range of 1% to 10% by weight, preferably in the range of 2% to 7% by weight, more preferably in the range of 3% to 5% by weight.
- the disintegrant that can be used in the water soluble formulations of the present invention can be selected from starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose SOdium or micro crystalline cellulose; polyvinylpyrrolidone ; erospovidone;- aigini acid and its salts; chyles such as xanthan gum or veegum; ion-exchange resins or a combination thereof.
- the amount of the disintegrant used in the formulation of the present invention is in the range of 0% to 70% by weight, preferably in the range of 0% to 50% by weight; and the disintegrant which is particularly preferred is starch or cellulose derivative.
- the flavouring agent that can be used in the water soluble formulations of the present invention can be selected from natural aroma oils (such as peppermint oil, oil of wintergreen, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, menthane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, sage, eugenol, oxanon, alpha-irisone, marjoram, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, timole, linalol, cinnamaldehyde glycerol acetal, N-substituted p- ment
- the sweetener that can be used in the water soluble formulations of the present invention can be selected from sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulphame potassium, aspartame, D-tryptophan, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof.
- the colouring agent that can be used in the water soluble formulations of the present invention can be selected from carotenoids and
- the surfactant that can be used in the water soluble formulations of the present invention can be selected from sodium lauryl sulphate and magnesium lauryl sulphate or a combination thereof.
- the antifoaming agent that can be used in the water soluble formulations of the present invention can be selected from simethicone emulsion and dimethyl siloxane, silicone oil or a combination thereof.
- the viscosity agent that can be used in the water soluble formulations of the present invention can be selected from carboxymethyl cellulose, methyl cellulose, xanthan gum, gummi tragacanthae, gum arabic, aerosil 200, colloidon, agar-agar, bentonite, hydroxyethyl cellulose or a combination thereof.
- the stabilizing agent and/or agents that can be used in the water soluble formulations of the present invention can be selected from agents such as antioxidants, chelating agents, alkalinizing agents and photo-protectives.
- the antioxidants can be selected from substances such as butylated hydroxyanisole (BHA), sodium ascorbate, butylated hydroxytoluene (BHT), sodium sulphite, gallates (such as propyl gallate), tocopherol, citric acid, malic acid, ascorbic acid, acetylcysteine, fumaric acid, lecithin, ascorbil palmitate, ethylenediamine tetraacetate or a combination thereof.
- the chelating agents can be selected from disodium EDTA, edetic acid, citric acid, sodium citrate, potassium citrate or a combination thereof.
- the alkalizing agents can be selected from alkaline metal salts such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen ortophosphate, sodium aluminate; earth alkaline metal salts such as calcium carbonate, calcium hydroxide, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium acetate, calcium gluconate, calcium glycerophosphate, magnesium carbonate, magnesium hydroxide, magnesium sulphate, magnesium acetate, magnesium silicate, magnesium aluminate and organic compounds such as primary, secondary and tertiary amines, cyclic amines, N-N'-dibenzylethylenediamine, diethanoleamine, ethylenediamine, meglumine, monosodium glutamate, polyacryline sodium, sodium alginate or a combination thereof.
- alkaline metal salts such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen ortophosphat
- the photo-protective agents can be selected from metal oxides such as titanium oxide, iron oxide or zinc oxide or a combination thereof.
- the humectant mentioned herein can be selected from anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
- the water soluble formulations of the present invention can be optionally prepared in effervescent or non-effervescent characteristic.
- the formulations are prepared in effervescent form, the formulations also comprise a pharmaceutically acceptable effervescent couple in addition to the excipients specified above.
- the acidic agent that can be used in the water soluble formulations of the present invention can be selected from a group comprising acedic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid and/or hydrates, anhydrates or the combinations thereof.
- the amount of the acidic agent that can be used in the water soluble formulations of the present invention is in the range of 0% to 85% by weight, preferably in the range of 0% to 75% by weight; and the acidic agent which is particularly preferred is citric acid and/or malic acid.
- the basic agent that can be used in the water soluble formulations of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate and/or hydrates, anhydrates or the combinations thereof.
- the amount of the basic agent that can be used in the water soluble formulations of the present invention is in the range of 0% to 40% by weight, preferably in the range of 0% to 30% by weight; and the basic agent which is particularly preferred is sodium carbonate or sodium hydrogen carbonate.
- the water soluble formulations of the present invention basically comprise acarbose in the range of 1% to 10% by weight and the diluent in the range of 1% to 10% by weight.
- the water soluble formulations of the present invention can optionally comprise the excipients given below in addition to the active agent and the diluent;
- the water soluble formulations of the present invention can be produced by any one of the conventional production methods in the prior art such as wet granulation, dry granulation, dry blending.
- the formulation of the present invention can be used in treatment of diabetes, adiposity and hyperlipidemia. All of the components used within the scope of the present invention are pharmaceutically suitable.
- pharmaceutically suitable signifies that the component used is suitable for human use, has a few or no unexpected side effects (toxicity, irritations, allergic response) and provides a significant benefit to user.
- the granulation solution is prepared by mixing the binder and the diluent. Acarbose and the effervescent couple are mixed in fluid bed and granulated with the granulation solution prepared. The granules obtained are mixed with the lubricant and the other excipients.
- the formulation prepared can be packed in powder or granule form and also the formulation prepared can be compressed into tablets.
- the components in the given amounts are packed after formed into powder or granule by any of the methods in the prior art.
- the powder mixture which is sieved is filled into bottles or the components can be formed into dry powder by any of the methods in the prior art in order to be used in preparation of suspension.
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- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to effervescent pharmaceutical formulations comprising acarbose and use of these compositions in diabetes, adiposity and hyperlipoidemia.
Description
WATER SOLUBLE DOSAGE FORMS
Technical Field
The present invention relates to water soluble pharmaceutical compositions comprising acarbose and use of these compositions in diabetes, adiposity and hyperlipoidemia. The Prior Art
Diabetes is a chronic disease which is characterized by insufficient or lack of insulin production by the pancreas and leads to disorders of carbohydrate, lipid and protein metabolism. There are two major types of diabetes.
Type I diabetes grows because beta cells in the pancreas can produce very little or no insulin associated with autoimmune mechanisms. Insulin is a hormone which is responsible for reducing elevated blood sugar. Blood sugar level rises depending on reduction in amount or in efficiency of insulin (hyperglycemia). Type I diabetes generally develops in children or young adults. Type II diabetes is the most common type of diabetes and characterized by insulin resistance. In this type of diabetes, insulin is released properly but it cannot be sufficiently effective.
In treatment of diabetes, it is aimed to reduce symptoms, improve life quality, prevent acute and chronic symptoms. The primary treatment method for diabetic patients is diet and exercise. This treatment approach provides very little weight loss but regulates insulin sensitivity. Sometimes, it can be possible to control blood sugar level for a long period of time only with this treatment method. However, the tendency towards insulin resistance in these people never disappears; therefore, the diet, exercise and weight control should be maintained continuously. In the cases that diet and exercise are insufficient, the second step of the treatment is oral anti-diabetic drugs and insulin reinforcement. The main oral anti-diabetics used in treatment of Type II diabetes are sulfonylureas, biguanides and alpha glucosidase inhibitors,
Acarbose which is an alpha glucosidase inhibitor was first disclosed in the patent document numbered DE2347782. Acarbose (formula I), chemical name of which is 0-{4- Amino-4,6-dideoxy-N-((lS,4R,5S-,6S)-4,5,6-trihydroxy-3-hydroxymethylcyclohex-2- enyl)-alpha-D-glucopyranosyl } -( 1 ->4)-0-alpha-D-glucopyranosyl-( 1 ->4)-D-
glucopyranose, is an alpha glucosidase inhibitor. Acarbose is produced by fermentation of the microorganism called Actinoplanes utahensis.
(Formula 1) Acarbose inhibits alpha glucosidase enzyme which is responsible for digestion of carbohydrates in lumen of the small intestine. Digestion and absorption of carbohydrates in the intestine are slowed down by inhibition of this enzyme; therefore elevation in blood sugar level after meals is prevented. Acarbose does not affect insulin release from the pancreas, insulin use in the tissues or glucose outflow from the liver. Therefore, acarbose does not cause hypoglycaemia when used singly. Use of acarbose can be preferred as a primary treatment in the case that there is diabetes that cannot be controlled by diet or it can be preferred as combination treatment option in the case that postprandial hyperglycemias cannot be prevented during the treatments of sulfonurea, biguanide or insulin. Nowadays, the formulation comprising the active agent acarbose is marketed under the trade name Glucobay® in the form of 50 and 100 mg tablets.
However, solid dosage forms such as tablet cause difficulty of use generally in geriatric, pediatric and disabled patients who have swallowing difficulty. Feeling of obstruction and choking can o uf^rr¾drviduals due to the ^rob½n^^e€umng- & pharyngeal and esophageal motility and consequently taking drug can be disgustful and painful for patients. In line with this, the patient delays drug intake and this situation decreases efficiency of the treatment significantly and affects life quality of the patient.
When the prior art is taken into consideration, there is need for development of dosage forms which comprise the active agent acarbose and are easy-to-use for patients in order to be used in treatment of diabetes, adiposis and hyperlipidemia.
Suspension forms which are presented as an alternative in order to overcome the problems caused by solid dosage forms cannot be performed in most of the active agents due to the reasons that suspension forms have the possibility of causing high and/or uncontrolled dose intake and furthermore there is problems in physical and chemical stabilities of suspension forms after diluted; production costs of suspension forms are high and they pose problem in using and carrying. In other aspect, acarbose is a hygroscopic molecule; therefore, it is quite hard to formulate acarbose in water soluble dosage forms such as suspension. Contact of the active agent with water leads to disintegration of the formulations in a shorter time than expected and quickly.
However, the inventors have achieved to prepare new and improved water soluble dosage forms that can be produced without being affected by hygroscopic characteristic of the active agent.
Detailed Description of the Invention
The present invention relates to water soluble dosage forms comprising the active agent acarbose; the methods for preparing these dosage forms and usage areas thereof. Formulating the formulations of the present invention in water soluble dosage forms have enabled that required therapeutic benefit is provided by using less amount of active agent than the active agent amount comprised in the dosage forms in the prior art. Use of less active agent is also advantageous for the reason that it reduces side effect possibility that can be caused by the formulations. According to this, one
water soluble iOrmulations of the present invention is that the formulations comprise acarbose in the range of 1 % to 10 % by weight, preferably in the range of 1% to 9 % by weight, more preferably in the range of 1% to 8% by weight.
Another characteristic feature of the water soluble formulations of the present invention is that the formulations comprise acarbose in the range of 10-300 mg, preferably in the range of 20-200 mg, more preferably in the range of 50-150 mg.
According to this, one characteristic feature of the water soluble formulations of the present invention is that the formulations are formulated in the form of powder, granule, pellet, micro tablet or tablet.
The water soluble formulations of the present invention can comprise at least one pharmaceutically acceptable excipient selected from a group comprising effervescent couple, binder, lubricant, glidant, diluent, disintegrant, flavouring agent, sweetener, colouring agent, surfactant, antifoaming agent, viscosity agent, stabilizing agent, humectant or combinations thereof in addition to the active agent.
The binder that can be used in the water soluble formulations of the present invention can be selected from a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethylcellulose, methylcellulose, ethylcellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol; water or the combinations thereof. The binder used in the water soluble formulations of the present invention is selected from a group comprising lactose, sorbitol, polyethylene glycol or the combinations thereof.
In other aspect, the amount of the binder that can be used in the water soluble formulations of the present invention is in the range of 0% to 10% by weight, preferably in the range of 0.5% to 2% by weight. The lubricant that can be used in the water soluble formulations of the present invention can be selected from sodium lauryl sulphate, calcium stearate, magnesium stearate, polyethylene glycol, polyvinyl alcohol, potassium benzoate, sodium benzoate, sodium chloride, carbowax 4000, talc or a combination thereof. The amount of the lubricant used in the formulations of the present invention is in the range of 0% to 5% by weight, preferably in the range of 0.3% to 2% by weight; the lubricant which is particularly preferred is polyethylene glycol.
The glidant that can be used in the water soluble formulations of the present invention can be selected from talc, magnesium stearate, stearic acid, sodium stearyl fumarate, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof. The amount of the glidant used in the formulation of the present invention is in the range of 0% to 5% by weight.
The diluent that can be used in the water soluble formulations of the present invention can be selected from lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch, calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, magnesium carbonate, magnesium oxide or a combination thereof.
The inventors have unexpectedly found that the type and amount of the diluent used in the formulations prevent disintegration arising from hygroscopic characteristic of the active agent. According to this, stability of the formulations comprising small amount of the active agent acarbose could be preserved for a long period of time, for 24 months, with use of maltodextrin as diluent in the water soluble formulations of the present invention.
The amount of the diluent used in the water soluble formulations of the present invention is in the range of 1% to 10% by weight, preferably in the range of 2% to 7% by weight, more preferably in the range of 3% to 5% by weight.
In other words, one characteristic feature of the water soluble formulations of the present invention comprising acarbose is that the formulations comprise maltodextrin in the range of 1% to 10% by weight, preferably in the range of 2% to 7% by weight, more preferably in the range of 3% to 5% by weight.
The disintegrant that can be used in the water soluble formulations of the present invention can be selected from starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose SOdium or micro crystalline cellulose; polyvinylpyrrolidone ; erospovidone;- aigini acid and its salts; chyles such as xanthan gum or veegum; ion-exchange resins or a combination thereof.
The amount of the disintegrant used in the formulation of the present invention is in the range of 0% to 70% by weight, preferably in the range of 0% to 50% by weight; and the disintegrant which is particularly preferred is starch or cellulose derivative.
The flavouring agent that can be used in the water soluble formulations of the present invention can be selected from natural aroma oils (such as peppermint oil, oil of wintergreen, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, menthane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, sage, eugenol, oxanon, alpha-irisone, marjoram, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, timole, linalol, cinnamaldehyde glycerol acetal, N-substituted p- menthane-3-carboxamide, 3,1-methoxy propane 1.2-diol or a combination thereof.
The sweetener that can be used in the water soluble formulations of the present invention can be selected from sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulphame potassium, aspartame, D-tryptophan, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof. The colouring agent that can be used in the water soluble formulations of the present invention can be selected from carotenoids and chlorophyll or a combination thereof.
The surfactant that can be used in the water soluble formulations of the present invention can be selected from sodium lauryl sulphate and magnesium lauryl sulphate or a combination thereof. The antifoaming agent that can be used in the water soluble formulations of the present invention can be selected from simethicone emulsion and dimethyl siloxane, silicone oil or a combination thereof.
The viscosity agent that can be used in the water soluble formulations of the present invention can be selected from carboxymethyl cellulose, methyl cellulose, xanthan gum, gummi tragacanthae, gum arabic, aerosil 200, colloidon, agar-agar, bentonite, hydroxyethyl cellulose or a combination thereof.
The stabilizing agent and/or agents that can be used in the water soluble formulations of the present invention can be selected from agents such as antioxidants, chelating agents, alkalinizing agents and photo-protectives.
The antioxidants can be selected from substances such as butylated hydroxyanisole (BHA), sodium ascorbate, butylated hydroxytoluene (BHT), sodium sulphite, gallates (such as propyl gallate), tocopherol, citric acid, malic acid, ascorbic acid, acetylcysteine, fumaric acid, lecithin, ascorbil palmitate, ethylenediamine tetraacetate or a combination thereof. The chelating agents can be selected from disodium EDTA, edetic acid, citric acid, sodium citrate, potassium citrate or a combination thereof.
The alkalizing agents can be selected from alkaline metal salts such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen ortophosphate, sodium aluminate; earth alkaline metal salts such as calcium carbonate, calcium hydroxide, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium acetate, calcium gluconate, calcium glycerophosphate, magnesium carbonate, magnesium hydroxide, magnesium sulphate, magnesium acetate, magnesium silicate, magnesium aluminate and organic compounds such as primary, secondary and tertiary amines, cyclic amines, N-N'-dibenzylethylenediamine, diethanoleamine, ethylenediamine, meglumine, monosodium glutamate, polyacryline sodium, sodium alginate or a combination thereof.
The photo-protective agents can be selected from metal oxides such as titanium oxide, iron oxide or zinc oxide or a combination thereof.
The humectant mentioned herein can be selected from anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
The water soluble formulations of the present invention can be optionally prepared in effervescent or non-effervescent characteristic.
In the case that the formulations are prepared in effervescent form, the formulations also comprise a pharmaceutically acceptable effervescent couple in addition to the excipients specified above.
The term "effervescent couple" used here refers to use of an acidic agent and basic agent together.
The acidic agent that can be used in the water soluble formulations of the present invention can be selected from a group comprising acedic acid, citric acid, lactic acid, malic acid,
phosphoric acid, propionic acid, tartaric acid and/or hydrates, anhydrates or the combinations thereof.
The amount of the acidic agent that can be used in the water soluble formulations of the present invention is in the range of 0% to 85% by weight, preferably in the range of 0% to 75% by weight; and the acidic agent which is particularly preferred is citric acid and/or malic acid.
The basic agent that can be used in the water soluble formulations of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate and/or hydrates, anhydrates or the combinations thereof.
The amount of the basic agent that can be used in the water soluble formulations of the present invention is in the range of 0% to 40% by weight, preferably in the range of 0% to 30% by weight; and the basic agent which is particularly preferred is sodium carbonate or sodium hydrogen carbonate. The water soluble formulations of the present invention basically comprise acarbose in the range of 1% to 10% by weight and the diluent in the range of 1% to 10% by weight.
The water soluble formulations of the present invention can optionally comprise the excipients given below in addition to the active agent and the diluent;
- the effervescent acid in the range of 0-85%
- the effervescent base in the range of 0-40%
- the binder in the range of 0- 10%
- the lubricant in the range of 0- 10%
- the glidant in the range of 0-5%
- the disintegrant in the range of 0-70%
- the other excipients in the range of 1-20%
The water soluble formulations of the present invention can be produced by any one of the conventional production methods in the prior art such as wet granulation, dry granulation, dry blending.
The formulation of the present invention can be used in treatment of diabetes, adiposity and hyperlipidemia.
All of the components used within the scope of the present invention are pharmaceutically suitable. The term pharmaceutically suitable signifies that the component used is suitable for human use, has a few or no unexpected side effects (toxicity, irritations, allergic response) and provides a significant benefit to user.
The examples below are given in order to explain the invention. The scope of the invention is not limited to these examples and these examples are evaluated with the description above which is described in detail.
Example 1
The granulation solution is prepared by mixing the binder and the diluent. Acarbose and the effervescent couple are mixed in fluid bed and granulated with the granulation solution prepared. The granules obtained are mixed with the lubricant and the other excipients. The formulation prepared can be packed in powder or granule form and also the formulation prepared can be compressed into tablets.
Example 2
The components in the given amounts are packed after formed into powder or granule by any of the methods in the prior art.
Example 3
All of the components given are mixed and sieved. The powder mixture which is sieved is filled into bottles or the components can be formed into dry powder by any of the methods in the prior art in order to be used in preparation of suspension.
Claims
1. The formulations comprising acarbose characterized in that the formulations are formulated in water soluble form.
2. The water soluble formulations according to claim 1 characterized in that the formulations comprise acarbose in the range of 1 % to 10% by weight.
3. The water soluble formulations according to claims 1-2 characterized in that the formulations comprise acarbose in the range of 1 % to 9% by weight.
4. The water soluble formulations according to claims 1-3 characterized in that the formulations comprise acarbose in the range of 1% to 8% by weight.
5. The water soluble formulations according to any preceding claims characterized in that the formulations are formulated in powder, granule, pellet, micro tablet or tablet forms.
6. The water soluble formulations according to any preceding claims characterized in that the formulations comprise pharmaceutically suitable excipients in addition to the active agent acarbose.
7. The water soluble formulations according to claim 6 characterized in that the formulations comprise at least one pharmaceutically acceptable excipient selected from a group comprising effervescent couple, binder, lubricant, glidant, diluent, disintegrant, flavouring agent, sweetener, colouring agent, surfactant, antifoaming agent, viscosity agent, stabilizing agent, humectant or the combinations thereof in addition to the active agent.
8. The water soluble formulations according to claim 7 characterized in that the diluent comprised in the formulations is selected from a group comprising lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch, calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, magnesium carbonate, magnesium oxide or a combination thereof.
9. The water soluble formulations according to claim 8- characterized in that the diluent comprised in the formulations is maltodextrin.
10. The water soluble formulations according to claim 9 characterized in that the amount of the diluent is in the range of 1% to 10% by weight.
11. The water soluble formulations according to claims 9-10 characterized in that the amount of the diluent is in the range of 2% to 7% by weight.
12. The water soluble formulations according to claims 9-11 characterized in that the amount of the diluent is in the range of 3% to 5% by weight.
13. The water soluble formulations according to any preceding claims characterized in that the formulations comprise
- acarbose in the range of 1% to 10% by weight
- the effervescent acid in the range of 0-85% by weight
- the effervescent base in the range of 0-40% by weight
- the binder in the range of 0- 10% by weight
- the lubricant in the range of 0- 10% by weight
- the glidant in the range of 0-5% by weight
- the diluent in the range of 1 - 10% by weight
- the disintegrant in the range of 0-70% by weight and
- optionally the other excipients in the range of 1-20% by weight.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2011/00150A TR201100150A2 (en) | 2011-01-06 | 2011-01-06 | Water soluble dosage forms |
| PCT/TR2012/000003 WO2012093972A1 (en) | 2011-01-06 | 2012-01-06 | Water soluble dosage forms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2661252A1 true EP2661252A1 (en) | 2013-11-13 |
Family
ID=45809558
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP12707405.2A Withdrawn EP2661252A1 (en) | 2011-01-06 | 2012-01-06 | Water soluble dosage forms |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP2661252A1 (en) |
| TR (1) | TR201100150A2 (en) |
| WO (1) | WO2012093972A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013115745A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | A process for production of pharmaceutical (effervescent) composition comprising alpha - glucosidase inhibitor (e.g. vogliobose and metformin) |
| WO2013115744A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | A process for production of pharmaceutical (effervescent) composition comprising alpha - glucosidase inhibitor (e.g. vogliobose and metformin) |
| WO2013115742A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Pharmaceutical composition comprising alpha-glucosidase inhibitor |
| WO2013115741A1 (en) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Pharmaceutical compositions comprising alpha-glucosidase inhibitor |
| CA2922849A1 (en) | 2012-08-31 | 2014-03-06 | Ixchel Pharma, Llc | Agents useful for treating obesity, diabetes and related disorders |
| CN104013590A (en) * | 2014-05-09 | 2014-09-03 | 万特制药(海南)有限公司 | Acarbose-containing medicinal composition and preparation method thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2347782C3 (en) | 1973-09-22 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | Amino sugar derivatives, processes for their preparation and medicaments containing these compounds |
| DE19802700A1 (en) * | 1998-01-24 | 1999-07-29 | Bayer Ag | Preparation of fast-dissolving tablets for controlling blood sugar levels |
| DE19860698A1 (en) * | 1998-12-30 | 2000-07-06 | Hexal Ag | New pharmaceutical composition |
| JP4993246B2 (en) * | 2005-06-10 | 2012-08-08 | 日医工株式会社 | Method for formulating acarbose-containing tablets with excellent stability over time |
| CN101411715B (en) * | 2007-10-19 | 2012-03-28 | 杭州华东医药集团生物工程研究所有限公司 | Pharmaceutical composition containing acarbose |
| JP2011506279A (en) * | 2007-12-08 | 2011-03-03 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | Orally dispersible tablets |
| CA2797365A1 (en) * | 2010-04-27 | 2011-11-03 | Bayer Intellectual Property Gmbh | Orally disintegrating tablet containing acarbose |
-
2011
- 2011-01-06 TR TR2011/00150A patent/TR201100150A2/en unknown
-
2012
- 2012-01-06 EP EP12707405.2A patent/EP2661252A1/en not_active Withdrawn
- 2012-01-06 WO PCT/TR2012/000003 patent/WO2012093972A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2012093972A1 * |
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| WO2012093972A1 (en) | 2012-07-12 |
| TR201100150A2 (en) | 2012-07-23 |
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