CN113197878A - Acetaminophen taste masking granules and preparation method thereof - Google Patents
Acetaminophen taste masking granules and preparation method thereof Download PDFInfo
- Publication number
- CN113197878A CN113197878A CN202110440654.6A CN202110440654A CN113197878A CN 113197878 A CN113197878 A CN 113197878A CN 202110440654 A CN202110440654 A CN 202110440654A CN 113197878 A CN113197878 A CN 113197878A
- Authority
- CN
- China
- Prior art keywords
- taste
- acetaminophen
- masking
- granule
- layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 title claims abstract description 145
- 229960005489 paracetamol Drugs 0.000 title claims abstract description 76
- 239000008187 granular material Substances 0.000 title claims abstract description 49
- 230000000873 masking effect Effects 0.000 title claims description 26
- 238000002360 preparation method Methods 0.000 title abstract description 18
- 238000000576 coating method Methods 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 239000011248 coating agent Substances 0.000 claims abstract description 27
- 239000000463 material Substances 0.000 claims abstract description 24
- 238000002156 mixing Methods 0.000 claims abstract description 10
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical group O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 16
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 15
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 10
- 239000008188 pellet Substances 0.000 claims description 10
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 10
- 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 9
- 235000010356 sorbitol Nutrition 0.000 claims description 9
- 235000021355 Stearic acid Nutrition 0.000 claims description 8
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 8
- 239000000600 sorbitol Substances 0.000 claims description 8
- 239000008117 stearic acid Substances 0.000 claims description 8
- 229960004274 stearic acid Drugs 0.000 claims description 8
- 239000000454 talc Substances 0.000 claims description 8
- 235000012222 talc Nutrition 0.000 claims description 8
- 229910052623 talc Inorganic materials 0.000 claims description 8
- 239000004408 titanium dioxide Substances 0.000 claims description 8
- 235000010215 titanium dioxide Nutrition 0.000 claims description 8
- 229960005196 titanium dioxide Drugs 0.000 claims description 8
- 229960003943 hypromellose Drugs 0.000 claims description 7
- 238000002955 isolation Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000004376 Sucralose Substances 0.000 claims description 6
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 6
- 244000263375 Vanilla tahitensis Species 0.000 claims description 6
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 229940083037 simethicone Drugs 0.000 claims description 6
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 6
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 6
- 235000019408 sucralose Nutrition 0.000 claims description 6
- 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 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 235000005976 Citrus sinensis Nutrition 0.000 claims description 4
- 240000002319 Citrus sinensis Species 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229940093429 polyethylene glycol 6000 Drugs 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
- 229920000178 Acrylic resin Polymers 0.000 claims description 3
- 239000004925 Acrylic resin Substances 0.000 claims 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 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
- 229930195725 Mannitol Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 229930006000 Sucrose Natural products 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
- 239000004148 curcumin Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- 239000002518 antifoaming agent Substances 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 2
- 229940008099 dimethicone Drugs 0.000 claims description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 2
- 235000013399 edible fruits Nutrition 0.000 claims description 2
- 235000003599 food sweetener Nutrition 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 238000009499 grossing Methods 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- 239000003605 opacifier Substances 0.000 claims description 2
- 239000004014 plasticizer Substances 0.000 claims description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 235000013772 propylene glycol Nutrition 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 229960001462 sodium cyclamate Drugs 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000003765 sweetening agent Substances 0.000 claims description 2
- 239000001069 triethyl citrate Substances 0.000 claims description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 2
- 235000013769 triethyl citrate Nutrition 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 230000004888 barrier function Effects 0.000 claims 2
- 239000007968 orange flavor Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 40
- 229940079593 drug Drugs 0.000 abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 12
- 230000003044 adaptive effect Effects 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 210000000214 mouth Anatomy 0.000 description 8
- 239000002609 medium Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
- 206010013911 Dysgeusia Diseases 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 239000013558 reference substance Substances 0.000 description 6
- 229960002920 sorbitol Drugs 0.000 description 6
- 238000007865 diluting Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 210000003296 saliva Anatomy 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000000152 swallowing effect Effects 0.000 description 4
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229940097043 glucuronic acid Drugs 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000009747 swallowing Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000000889 atomisation Methods 0.000 description 2
- 239000000337 buffer salt Substances 0.000 description 2
- JZZIHCLFHIXETF-UHFFFAOYSA-N dimethylsilicon Chemical compound C[Si]C JZZIHCLFHIXETF-UHFFFAOYSA-N 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000036449 good health Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- -1 methoxyl group Chemical group 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229950005770 hyprolose Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an acetaminophen preparation, in particular to a novel acetaminophen taste-masking granule which is a water-free swallow granule and is prepared by coating acetaminophen with a taste-masking layer and an isolating layer and then mixing a taste-modifying auxiliary material composition. Compared with the prior art, the preparation method has the outstanding technical effects that the preparation method has the technical effect of anhydrous oral administration, breaks the problem that the conventional granule needs to be taken with water smoothly, improves the medication convenience and the medication compliance of patients, increases the adaptive population of the patients, and is favorable for improving the medication compliance of the patients, particularly children, except for effectively covering the bitter peculiar smell of acetaminophen and having good taste and medication compliance.
Description
The application has application date of 2015, 29.01 and application numbers of: 201510045401.3, entitled "Acetaminophen taste masking granule and its preparation method", and is a divisional application of the Chinese patent application.
Technical Field
The invention relates to a novel acetaminophen preparation, in particular to novel acetaminophen taste-masking granules, which are water-free swallowable granules. Belongs to the field of pharmaceutical preparation.
Background
The acetaminophen is N- (4-hydroxyphenyl) acetamide with the chemical name of C8H9NO2Structural formula (II)
Is usually white crystalline powder, has antipyretic and analgesic effects, and can be used for treating common cold, fever, arthralgia, neuralgia, migraine, cancer pain, postoperative pain, etc. The medicine is easy to absorb after being taken orally, the blood concentration reaches the peak value within 0.5-1 h, 95 percent of the medicine is combined with glucuronic acid or sulfuric acid in vivo to be inactivated, and 5 percent of the medicine is converted into metabolites which are toxic to the liver through hydroxylation and is discharged from urine. The plasma protein binding rate was 25%. 90-95% of the total metabolites are metabolized in the liver, mainly combined with glucuronic acid, sulfuric acid and cysteine. The intermediate metabolite has toxic effects on the liver. The half-life period is generally 1-4 hours (average 2 hours), the renal insufficiency is not changed, but the half-life period may be prolonged in some patients with liver diseases, prolonged in the elderly and neonates, and shortened in children. The product is mainly excreted from kidney in the form of glucuronic acid, and about 3% of the product is excreted with urine in the original form within 24 hours.
201210138734.7 discloses a method for preparing acetaminophen dry suspension, which comprises taking acetaminophen as raw material, and adjuvants including pregelatinized starch, lactose, sucrose, disintegrating agent, hypromellose, xanthan gum, steviosin, maltose, milk essence, and hyprolose. The preparation method comprises the following steps: the inventor finds that the acetaminophen dry-mixed suspension particles prepared by the technology still have original peculiar smell of the medicine because the acetaminophen is not coated with taste masking coating, so that the medicine taking compliance of patients is reduced, and the acetaminophen is prepared into syrup before being taken, so that the taking convenience is greatly reduced.
In the prior art, the acetaminophen taste-masking granules need to be taken with water to help the medicine to be taken smoothly, so that the acetaminophen taste-masking granules are not beneficial to or limit the inconvenience of taking the medicine with water smoothly, and the acetaminophen has bitter peculiar smell, so that the medication compliance of patients, particularly children patients, is greatly influenced.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a novel acetaminophen taste-masking granule which not only effectively masks the bitter peculiar smell of the medicine, has good taste, but also has smooth taste, and is beneficial to anhydrous oral administration.
The technical scheme of the invention is as follows:
the invention provides a paracetamol taste masking granule, which is prepared by using paracetamol raw materials or pellets prepared by a conventional method as a mother core, sequentially coating a taste masking layer and an isolating layer on the mother core, and mixing a taste masking auxiliary material composition outside the granules.
The acetaminophen taste-masking granule described above wherein:
the acrylic resin polymer is selected from one or more of Ewing E100, Ewing EPO and Ewing L30D-55;
the anti-sticking agent is selected from one or more of talcum powder, glyceryl monostearate and stearic acid;
the surfactant is selected from one or more of sodium dodecyl sulfate and sodium dodecyl sulfate;
the opacifier is titanium dioxide;
the defoaming agent is selected from one or more of simethicone and simethicone;
the hydroxypropyl methylcellulose is selected from one or more than one of viscosity grades from 3 mPa.s to 50 mPa.s;
the plasticizer is selected from one or more of castor oil, diethyl phthalate, polyethylene glycol, tween 80, triethyl citrate and propylene glycol;
the glidant is selected from one or more of talcum powder, superfine silica gel powder and magnesium stearate;
the smoothing agent is selected from one or more of sodium carboxymethylcellulose and carbomer;
the sweetener is one or more selected from sucrose, mannitol, maltose, xylitol, sucralose, aspartame, acesulfame potassium and sodium cyclamate;
the essence is selected from one or more of vanilla essence, sweet orange essence and fruit essence.
Wherein, the Esterqi E100, the Esterqi EPO and the Esterqi L30D-55 are all commercial pharmaceutical excipients. For example, Ewing EPO, an acrylic resin polymer, is chemically copolymerized from butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate (1:2:1), and is commercially available from Wingchunggsai.
Wherein the hypromellose 603 is a cellulose derivative mainly containing methoxyl group and hydroxypropyl group, has viscosity of about 6 mPa.s, and is commercially available from shin-Etsu chemical industries.
Wherein, the sorbitol is D-glucitol which is an isomer of mannitol, and the commercial source is Guangxi Nanning chemical pharmaceutical company Limited liability company.
Preferably, the acetaminophen taste-masked granule described above, wherein the taste-masking layer is made of EPO, talc, sodium lauryl sulfate, stearic acid, titanium dioxide and dimethicone.
Preferably, the acetaminophen taste-masking granule described above, wherein the isolating layer is made of hypromellose 603, polyethylene glycol 6000 and talc.
Preferably, the acetaminophen taste-masking granule is prepared from sorbitol, talcum powder, sodium carboxymethylcellulose, sucralose, vanilla essence, orange essence and magnesium stearate.
Preferably, the acetaminophen odor-masking granule comprises, by weight, 1.0-83.3% of acetaminophen, 0.5-50.0% of odor-masking layer, 0.1-30.0% of isolation layer, and 3.3-86.0% of flavoring auxiliary material composition.
Preferably, the acetaminophen taste-masking granule is characterized in that the taste-masking layer contains 10 to 70.0 wt% of the yuteqi EPO and 10.0 to 80.0 wt% of the talc.
Preferably, the acetaminophen odor-masking granule comprises, in percentage by weight of the isolation layer, 10% to 100% of hypromellose 603.
Preferably, the acetaminophen odor-masking granule is characterized in that the flavoring auxiliary material composition contains sorbitol 10-100 wt%.
More preferably, the acetaminophen odor-masking granule comprises, by weight, 16.8% to 46.8% of acetaminophen, 1.7% to 15.7% of odor-masking layer, 0.4% to 5.0% of isolating layer, and 40.6% to 80.6% of flavoring auxiliary material composition.
More preferably, the acetaminophen taste-masking granule described above, wherein the taste-masking layer comprises 30% to 50% of ewt EPO and 37.8% to 57.8% of talc, calculated as weight percentage of the taste-masking layer.
More preferably, the acetaminophen odor-masking granule described above, wherein the weight percentage of the isolating layer is 69.1% to 79.1% of hypromellose 603.
More preferably, the acetaminophen odor-masking granule described above, wherein the flavor-masking excipient composition comprises 60.0% to 96.0% sorbitol by weight of the flavor-masking excipient composition.
The acetaminophen taste-masked particles of the present invention, wherein the taste-masking layer and the separating layer are coated, can be coated by coating techniques conventional in the art, such as fluidized bed coating techniques. Preferably, the material temperature is controlled to be 30 +/-5 ℃ in the coating process of the taste-masking layer, and the material temperature is controlled to be 40 +/-5 ℃ in the coating process of the isolating layer.
In a preferred embodiment of the present invention, the acetaminophen taste-masking granules described above comprise, per formulation unit, the following components:
acetaminophen: 250.0 mg;
taste masking layer: 20.0mg of Ewing EPO, 24.0mg of talcum powder, 2.0mg of sodium dodecyl sulfate, 3.0mg of stearic acid, 1.2mg of titanium dioxide and 0.3mg of simethicone;
isolation layer: 6036.0 mg of hydroxypropyl methylcellulose, 60000.3 mg of polyethylene glycol and 1.8mg of talcum powder;
flavoring auxiliary material composition: 600.0mg of sorbitol, 3.0mg of sodium carboxymethylcellulose, 3.0mg of sucralose, 5.0mg of vanilla essence, 10.0mg of sweet orange essence, 10.0mg of talcum powder and 3.0mg of magnesium stearate.
As another object of the present invention, there is also provided a method for preparing the acetaminophen taste-masking granule described above, which comprises the steps of:
(1) coating a taste masking layer: preparing taste-masking layer coating solution from the taste-masking layer material by using purified water as a solvent, and performing taste-masking layer coating on acetaminophen by adopting a fluidized bed to prepare coated pellets;
(2) coating an isolation layer: preparing the isolating layer material into isolating layer coating solution by using purified water as a solvent, and performing isolating layer coating on the coated pellets prepared in the step (1) by adopting a fluidized bed to prepare coated pellets;
(3) mixing flavoring auxiliary material composition: and (3) uniformly mixing the coated pellets prepared in the step (2) and the taste-modifying auxiliary material composition to obtain the finished product of the acetaminophen taste-masking granules.
Compared with the prior art, the acetaminophen taste-masking granule has the outstanding technical effects that the acetaminophen taste-masking granule effectively masks the acetaminophen bitter peculiar smell, has good taste and drug compliance, has the technical effect of anhydrous oral administration, breaks through the problem that the conventional granule needs water for smooth administration, improves the medication convenience and the drug compliance of patients, increases the adaptive population of the patients, and is beneficial to improving the drug compliance of the patients, particularly children. In addition, the taste masking layer and the isolating layer of the acetaminophen taste masking granule of the invention do not influence the onset time and the drug absorption of the preparation, and the drug can be quickly released in a gastrointestinal system, thereby achieving the similar drug effect of a quick-release preparation.
Detailed Description
The following preferred examples are provided to further aid in explaining or illustrating the present disclosure, but are not to be construed as limiting the scope of the present invention.
Example 1: acetaminophen taste masking granules
Paracetamol taste-masking granules in a unit formulation, which are formulated as follows:
description of the preparation process:
coating acetaminophen with fluidized bed, coating taste masking layer and isolating layer, and mixing with taste-modifying supplementary material composition. The method comprises the following specific steps:
(1) preparation of taste masking layer solution and coating taste masking layer
Firstly, dissolving sodium dodecyl sulfate in 200.0mg of purified water, adding stearic acid in a high-speed dispersion state, dispersing to a dissolved state, adding Yttrium EPO in a dispersed state, dispersing until no solid floats on the surface, then adding titanium dioxide, talcum powder and dimethyl silicon oil, dispersing for 30min to form a uniform dispersion, and filtering by adopting a 0.5mm screen before coating to be used as a taste-masking layer coating solution. Coating acetaminophen with fluidized bed to obtain the taste-masked micropill. The temperature of the materials is controlled to be 30 +/-5 ℃ in the coating process.
(2) Preparation of isolating layer solution and coating isolating layer
Taking 112.0mg of purified water as a solvent, adding hydroxypropyl methylcellulose 603 and polyethylene glycol 6000 under stirring, stirring to a dissolved state, and adding talcum powder to form a final solution serving as an isolating layer coating solution. Coating the pellet with the taste-masking layer by fluidized bed to obtain coated pellet. The material temperature is controlled to be 40 +/-5 ℃ in the process of coating the isolation layer.
(3) Mixed flavoring auxiliary material composition
And (3) uniformly mixing the coated pellets prepared in the step (2) with the flavoring auxiliary material composition to obtain the final product, namely the acetaminophen taste-masking granules.
Evaluation of the effect of the preparation: dissolution rate, taste and no-water swallowing effect
Taking the product, adding 24ml of diluted hydrochloric acid into 1000ml of water as a dissolution medium according to a dissolution determination method (the second appendix XC of the second part of the version 2010 of Chinese pharmacopoeia), rotating at 75 revolutions per minute, operating according to the method, taking 10ml of solution after 30 minutes, filtering, precisely taking a proper amount of subsequent filtrate, diluting the solution with 0.04% sodium hydroxide solution to prepare a solution containing about 8 mu g of acetaminophen in each 1ml, and determining the absorbance at the wavelength of 257nm according to an ultraviolet-visible spectrophotometry method (the second appendix IV A of the second part of the version 2010 of Chinese pharmacopoeia). And taking a proper amount of acetaminophen reference substance, precisely weighing, dissolving by using 0.04% sodium hydroxide solution, and quantitatively diluting to prepare a solution containing about 8ug of acetaminophen reference substance in 1ml, wherein the solution is used as the reference substance solution. The measurement is carried out by the same method.
ph6.8 medium: phosphate buffer solution (3.4 g of monopotassium phosphate and 3.55g of anhydrous disodium hydrogen phosphate, adding a proper amount of water to dissolve, fixing the volume to 1000ml, and diluting twice to obtain the product)
The release data of the acetaminophen taste-masked particle samples prepared above in ph6.8 medium are as follows:
the pH environment of saliva in the oral cavity is similar to a medium with pH6.8, in order to simulate the drug release condition of the drug in the oral cavity, the pH6.8 buffer salt is used for detecting the release rate of the drug, 18.6% of drug release in 5min is obtained through results, 20 volunteers with good health states are searched for testing the drug, the drug does not taste bitter or peculiar smell in 5min in the oral cavity, and the drug reacts with the cool and light sensation in the oral cavity after being taken, so that the effect of covering the bad taste of the drug is achieved.
The effect of water-free swallowing: after oral administration of 20 volunteers, 18 volunteers can swallow smoothly within 1min under the state of no water and smooth throat, and the other 2 volunteers finish swallowing administration within 1.5min, which shows that the medicament achieves certain smooth effect after contacting saliva, and the swallowing effect meets the requirement of medicament quality.
Example 2: acetaminophen taste masking granules
1. Prescription composition and preparation
2. Preparation of taste-masking layer solution
Firstly, sodium dodecyl sulfate is dissolved in purified water, stearic acid is added in a high-speed dispersion state, the mixture is dispersed to a dissolved state, Uygur EPO is added in a dispersed state, the mixture is dispersed until no solid floats on the surface, then titanium dioxide, talcum powder and dimethyl silicon oil are added, the mixture is dispersed for 30min to form a uniform dispersion, and a 0.5mm screen is adopted for filtering before coating.
3. Preparing an isolating layer solution:
adding hydroxypropyl methylcellulose 603 and polyethylene glycol 6000 into purified water under stirring, stirring to dissolve, and adding pulvis Talci to obtain final solution.
4. Taste masking layer coating parameters list:
| art item | Parameter(s) |
| Batch number | 20141002 |
| Batch size | 500g of paracetamol as a base material |
| Atomization air pressure | 1.0bar |
| Temperature of the material | 30±5℃ |
| Rate of liquid supply | 9.5g/min |
| Air door | 14～18％ |
5. Coating parameters of the isolation layer:
| art item | Parameter(s) |
| Batch number | 20141002 |
| Batch size | 500g of taste masking layer material |
| Atomization air pressure | 1.0bar |
| Temperature of the material | 40±5℃ |
| Rate of liquid supply | 9.4g/min |
| Air door | 19～20％ |
Coating acetaminophen with fluidized bed, coating taste masking layer and isolating layer, and mixing with taste-modifying supplementary material composition.
6. Mixing a flavoring auxiliary material composition:
mixing the obtained acetaminophen coated pellet coated with the taste masking layer and the isolating layer in sequence with the taste-masking auxiliary material composition to obtain the final acetaminophen taste-masking granule.
Evaluation of the effect of the preparation: dissolution rate, taste and no-water swallowing effect
Taking the product, adding 24ml of diluted hydrochloric acid into 1000ml of water as a dissolution medium according to a dissolution determination method (the second appendix XC of the second part of the version 2010 of Chinese pharmacopoeia), rotating at 75 revolutions per minute, operating according to the method, taking 10ml of solution after 30 minutes, filtering, precisely taking a proper amount of subsequent filtrate, diluting the solution with 0.04% sodium hydroxide solution to prepare a solution containing about 8 mu g of acetaminophen in each 1ml, and determining the absorbance at the wavelength of 257nm according to an ultraviolet-visible spectrophotometry method (the second appendix IV A of the second part of the version 2010 of Chinese pharmacopoeia). And taking a proper amount of acetaminophen reference substance, precisely weighing, dissolving by using 0.04% sodium hydroxide solution, and quantitatively diluting to prepare a solution containing about 8ug of acetaminophen reference substance in 1ml, wherein the solution is used as the reference substance solution. The measurement is carried out by the same method.
ph4.0 medium: acetate buffer [ 0.05mol/L acetic acid-0.05 mol/L sodium acetate (16.4:3.6) ].
ph6.0 medium: according to the preparation of buffer solution in United states Pharmacopeia, 6.805g of monopotassium phosphate and 0.224g of sodium hydroxide are added with a proper amount of water to be dissolved and the volume is adjusted to 1000 ml.
ph6.8 medium: phosphate buffer solution (3.4 g of monopotassium phosphate and 3.55g of anhydrous disodium hydrogen phosphate, which is dissolved by adding a proper amount of water and is diluted by one time until the volume is 1000 ml).
And (3) measuring results: 20141002 the test results for the samples are as follows:
the pH environment of saliva in the oral cavity is similar to a medium with pH6.8, in order to simulate the drug release condition of the drug in the oral cavity, the pH6.8 buffer salt is used for detecting the release degree of the drug, the result shows that the drug is released for 20.9% in 5min, 20 volunteers with good health states are searched for testing the drug, the drug does not taste bitter or peculiar smell in 5min in the oral cavity, and the drug reacts with the cool and light sensation in the oral cavity after being taken, so that the effect of covering the bad taste of the drug is achieved.
The effect of water-free swallowing: after oral administration of 20 volunteers, the 20 volunteers can swallow smoothly within 1min under the state of no water and smooth throat, which shows that the medicine achieves certain smooth effect after contacting saliva, and the swallowing effect meets the quality requirement of the medicine.
The detection result shows that the acetaminophen taste-masking granule of the invention releases the drug rapidly under the acidic condition, and meets the quality requirement of the product.
Claims (10)
1. The acetaminophen taste-masking granule is prepared by using an acetaminophen raw material or a pellet prepared by a conventional method as a mother core, sequentially coating a taste-masking layer and an isolating layer on the mother core, and mixing a taste-masking auxiliary material composition outside the granule.
2. An acetaminophen taste-masking particle according to claim 1 wherein:
the acrylic resin polymer is selected from one or more of Ewing E100, Ewing EPO and Ewing L30D-55;
the anti-sticking agent is selected from one or more of talcum powder, glyceryl monostearate and stearic acid;
the surfactant is selected from one or more of sodium dodecyl sulfate and sodium dodecyl sulfate;
the opacifier is titanium dioxide;
the defoaming agent is selected from one or more of simethicone and simethicone;
the hydroxypropyl methylcellulose is selected from one or more than one of viscosity grades from 3 mPa.s to 50 mPa.s;
the plasticizer is selected from one or more of castor oil, diethyl phthalate, polyethylene glycol, tween 80, triethyl citrate and propylene glycol;
the glidant is selected from one or more of talcum powder, superfine silica gel powder and magnesium stearate;
the smoothing agent is selected from one or more of sodium carboxymethylcellulose and carbomer;
the sweetener is one or more selected from sucrose, mannitol, maltose, xylitol, sucralose, aspartame, acesulfame potassium and sodium cyclamate;
the essence is selected from one or more of vanilla essence, sweet orange essence and fruit essence.
3. Paracetamol taste masking granules according to claims 1-2, wherein the taste masking layer consists of EPO, talc, sodium lauryl sulfate, stearic acid, titanium dioxide and dimethicone.
4. A paracetamol taste masking granule according to claims 1 to 3 wherein the barrier layer consists of hypromellose 603, polyethylene glycol 6000 and talc.
5. Acetaminophen taste-masking granules according to claims 1-4, wherein the taste-masking excipient composition consists of sorbitol, talc, sodium carboxymethylcellulose, sucralose, vanilla, orange flavour and magnesium stearate.
6. An acetaminophen taste-masked granule as claimed in claims 1 to 5 wherein, in weight percent of the granule, acetaminophen is 1.0% to 83.3%, taste-masking layer is 0.5% to 50.0%, barrier layer is 0.1% to 30.0%, and taste-modifying excipient composition is 3.3% to 86.0%.
7. The acetaminophen taste-masked granules of claims 1-6 wherein the taste-masking layer comprises 10% to 70.0% of Ewing EPO and 10.0% to 80.0% of talc, calculated as weight percent of the taste-masking layer.
8. An acetaminophen taste-masked granule according to claims 1 to 7 wherein the isolating layer comprises between 10% and 100% by weight of hypromellose 603.
9. Paracetamol taste masking granules according to claims 1 to 8, wherein the taste-modifying excipient composition comprises sorbitol in an amount of between 10% and 100% by weight of the taste-modifying excipient composition.
10. Paracetamol taste masking granules according to claims 1 to 9, wherein the following components are contained per formulation unit: acetaminophen: 250.0 mg;
taste masking layer: 20.0mg of Ewing EPO, 24.0mg of talcum powder, 2.0mg of sodium dodecyl sulfate, 3.0mg of stearic acid, 1.2mg of titanium dioxide and 0.3mg of simethicone;
isolation layer: 6036.0 mg of hydroxypropyl methylcellulose, 60000.3 mg of polyethylene glycol and 1.8mg of talcum powder;
flavoring auxiliary material composition: 600.0mg of sorbitol, 3.0mg of sodium carboxymethylcellulose, 3.0mg of sucralose, 5.0mg of vanilla essence, 10.0mg of sweet orange essence, 10.0mg of talcum powder and 3.0mg of magnesium stearate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110440654.6A CN113197878A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen taste masking granules and preparation method thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110440654.6A CN113197878A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen taste masking granules and preparation method thereof |
| CN201510045401.3A CN105982859A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen granule with odor masked and preparation method of same |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510045401.3A Division CN105982859A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen granule with odor masked and preparation method of same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113197878A true CN113197878A (en) | 2021-08-03 |
Family
ID=57035738
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510045401.3A Pending CN105982859A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen granule with odor masked and preparation method of same |
| CN202110440654.6A Pending CN113197878A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen taste masking granules and preparation method thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510045401.3A Pending CN105982859A (en) | 2015-01-29 | 2015-01-29 | Acetaminophen granule with odor masked and preparation method of same |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN105982859A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926530A (en) * | 2018-08-17 | 2018-12-04 | 江苏科瑞达药业有限公司 | A kind of paracetamol liquid preparation with efficient suspension effect |
| CN113057950A (en) * | 2020-01-02 | 2021-07-02 | 上海信谊万象药业股份有限公司 | Oral pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate granule preparation and preparation process thereof |
| CN112587483A (en) * | 2020-12-16 | 2021-04-02 | 上海应用技术大学 | Compound infant cold dry suspension with taste masking effect and preparation method and application thereof |
| CN114306284B (en) * | 2021-11-30 | 2023-11-03 | 南京正济医药研究有限公司 | Monnpiravir taste masking granule and preparation method thereof |
| GR1010682B (en) * | 2023-02-03 | 2024-04-29 | Ιουλια Κλεωνος Τσετη | Paracetamol pharmaceutical composition for direct swallowing without water with taste enhancer compatible with paracetamol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101548953A (en) * | 2008-04-03 | 2009-10-07 | 上海医药工业研究院 | Medicine granule, preparation method thereof, and preparation containing same |
| CN104274409A (en) * | 2013-07-10 | 2015-01-14 | 北京科信必成医药科技发展有限公司 | Easily-swallowed drug-loaded microsphere and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100427088C (en) * | 2004-05-17 | 2008-10-22 | 杭州民生药业集团有限公司 | Paracetamol pseudoephedrine hydrochloride and cholrphenamine maleate oral cavity disintegration tablet for treating cold and preparation method thereof |
| CN101985044B (en) * | 2010-07-16 | 2013-10-23 | 钟术光 | Taste-masking medicinal coating composition |
| CN103536538B (en) * | 2013-10-23 | 2016-06-29 | 海南康芝药业股份有限公司 | A kind of expansive pellet of effective taste masking and preparation method thereof |
| CN103990132B (en) * | 2014-05-07 | 2016-03-30 | 北京化工大学 | A kind of method of preparing drug taste-masking preparation with acrylic resin mixed water dispersion |
-
2015
- 2015-01-29 CN CN201510045401.3A patent/CN105982859A/en active Pending
- 2015-01-29 CN CN202110440654.6A patent/CN113197878A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101548953A (en) * | 2008-04-03 | 2009-10-07 | 上海医药工业研究院 | Medicine granule, preparation method thereof, and preparation containing same |
| CN104274409A (en) * | 2013-07-10 | 2015-01-14 | 北京科信必成医药科技发展有限公司 | Easily-swallowed drug-loaded microsphere and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 肖进迈: "复方对乙酰氨基酚口腔崩解片的研制", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105982859A (en) | 2016-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2527766C2 (en) | Tablets and granulated powders containing 6-fluor-3-hydroxy-2-pyrazincarboxamide | |
| EP2246052B1 (en) | Orally rapidly disintegrating tablet comprising imidafenacin | |
| ES2347968T3 (en) | SOLID PREPARATION THAT DISAPPEARS RAPIDLY. | |
| US8722133B2 (en) | Method for production of orally rapidly disintegrating tablet comprising imidafenacin as active ingredient | |
| JP6392207B2 (en) | Orally administered formulation masking the bitter taste of silodosin | |
| US20090311321A1 (en) | Oral disintegrating tablet having masked bitter taste and method for production thereof | |
| JP4740740B2 (en) | Drug-containing particles and solid preparation containing the particles | |
| CN113197878A (en) | Acetaminophen taste masking granules and preparation method thereof | |
| CN105982858A (en) | Azithromycin dry-suspended granule with odor masked and preparation method thereof | |
| WO2016051782A1 (en) | Oral preparation in which bitter taste of bitter-tasting drug is masked | |
| KR100957731B1 (en) | Formulations containing Franlukast hydrate with reduced bitterness | |
| JP3899522B2 (en) | Formulation containing pranlukast hydrate with reduced bitterness | |
| CN115252619B (en) | Pharmaceutical composition, preparation method thereof and application thereof in treating diseases caused by coronavirus | |
| CN110167552B (en) | Pharmaceutical composition and method for producing the same | |
| CN113081983B (en) | Lurasidone sublingual tablet and preparation method thereof | |
| JP2008094751A (en) | Pranlukast hydrate-containing pharmaceutical composition | |
| JP6112696B1 (en) | Tablets containing solithromycin | |
| CN107625733B (en) | A kind of clarithromycin anhydrous swallow granule and preparation method thereof | |
| JP2005139086A (en) | Quick-disintegration preparation | |
| JP2011225468A (en) | Solid formulation | |
| CN112386578A (en) | Montelukast sodium chewable tablet and preparation method thereof | |
| KR20210003323A (en) | Pharmaceutical compositions including tamsulosin or its hydrochloride salt and preparation method thereof | |
| JP2011195518A (en) | Crospovidone and crospovidone-containing tablet | |
| TW201818928A (en) | Pharmaceutical composition containing memantine or pharmaceutically acceptable salt thereof | |
| JP2006316051A (en) | Pranlukast hydrate-containing preparation having relieved bitterness |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20230421 Address after: 8639, Floor 6, Building 3, No. 3, Yongchang North Road, Daxing District, Beijing, 100176 Applicant after: Beijing Kexin Jurun Pharmaceutical Technology Co.,Ltd. Address before: Room 5, 15 / F, block a, Tiangong building, No. 30 Xueyuan Road, Haidian District, Beijing 100083 Applicant before: COSCI MED-TECH Co.,Ltd. |