CN105326813B - Paroxetine slow release composition and preparation method thereof - Google Patents
Paroxetine slow release composition and preparation method thereof Download PDFInfo
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- CN105326813B CN105326813B CN201410355326.6A CN201410355326A CN105326813B CN 105326813 B CN105326813 B CN 105326813B CN 201410355326 A CN201410355326 A CN 201410355326A CN 105326813 B CN105326813 B CN 105326813B
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- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 title claims abstract description 30
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 22
- 238000013268 sustained release Methods 0.000 claims abstract description 44
- 239000012730 sustained-release form Substances 0.000 claims abstract description 44
- 239000008188 pellet Substances 0.000 claims abstract description 42
- 239000010410 layer Substances 0.000 claims abstract description 39
- 239000003814 drug Substances 0.000 claims abstract description 38
- 229940079593 drug Drugs 0.000 claims abstract description 36
- 239000000463 material Substances 0.000 claims abstract description 33
- 238000002955 isolation Methods 0.000 claims abstract description 29
- 239000011247 coating layer Substances 0.000 claims abstract description 25
- 239000000853 adhesive Substances 0.000 claims abstract description 15
- 230000001070 adhesive effect Effects 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000004014 plasticizer Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 3
- 239000000935 antidepressant agent Substances 0.000 claims abstract 2
- 229940005513 antidepressants Drugs 0.000 claims abstract 2
- 238000000576 coating method Methods 0.000 claims description 29
- 230000004584 weight gain Effects 0.000 claims description 28
- 235000019786 weight gain Nutrition 0.000 claims description 28
- 239000002775 capsule Substances 0.000 claims description 23
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 23
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 23
- 229960005183 paroxetine hydrochloride Drugs 0.000 claims description 23
- 239000011248 coating agent Substances 0.000 claims description 21
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 21
- 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 21
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 16
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 16
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 16
- 239000006187 pill Substances 0.000 claims description 16
- 235000013311 vegetables Nutrition 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 14
- 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 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 238000001125 extrusion Methods 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 11
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 238000005563 spheronization Methods 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 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 9
- 229920003081 Povidone K 30 Polymers 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- 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 8
- 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 8
- 229930006000 Sucrose Natural products 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 229960003511 macrogol Drugs 0.000 claims description 8
- 239000005720 sucrose Substances 0.000 claims description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 8
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 7
- 239000001069 triethyl citrate Substances 0.000 claims description 7
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 7
- 235000013769 triethyl citrate Nutrition 0.000 claims description 7
- 229920003163 Eudragit® NE 30 D Polymers 0.000 claims description 5
- -1 sorbierite Polymers 0.000 claims description 5
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 4
- 230000021736 acetylation Effects 0.000 claims description 4
- 238000006640 acetylation reaction Methods 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000008117 stearic acid Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 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
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 2
- 235000009508 confectionery Nutrition 0.000 claims description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- 229940069328 povidone Drugs 0.000 claims 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 239000002552 dosage form Substances 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract description 2
- 238000005457 optimization Methods 0.000 abstract description 2
- 230000001430 anti-depressive effect Effects 0.000 abstract 1
- 208000021017 Weight Gain Diseases 0.000 description 26
- 238000003756 stirring Methods 0.000 description 12
- 238000013270 controlled release Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000005303 weighing Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000000889 atomisation Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 238000013265 extended release Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 230000004888 barrier function Effects 0.000 description 5
- 230000036571 hydration Effects 0.000 description 5
- 238000006703 hydration reaction Methods 0.000 description 5
- 238000005550 wet granulation Methods 0.000 description 5
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 4
- 229920003157 Eudragit® RL 30 D Polymers 0.000 description 4
- 229920003161 Eudragit® RS 30 D Polymers 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000003825 pressing Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940095674 pellet product Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
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- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
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- 125000006850 spacer group Chemical group 0.000 description 1
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- 230000001502 supplementing effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
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- 230000000946 synaptic effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of paroxetine slow release composition, including pellet core, isolation coat layer and sustained-release coating layer, pellet core includes Paxil or its pharmaceutically acceptable salt, filler and adhesive；Isolation coat layer includes isolated material and plasticizer；Sustained-release coating layer includes slow-release material and antiplastering aid.The present invention also provides the methods for preparing the sustained release pharmaceutical composition, and its purposes in preparation antidepressant and resisting mental disease drug.The present invention is screened by a large amount of dosage form formulation optimizations, obtains the paroxetine slow release composition with good drug release behavior, simultaneously, the slow releasing composition has preferable roundness, heap density and yield, and preparation method is simple, and cost is relatively low, has a good application prospect.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to paroxetine slow release composition and preparation method thereof.
Background technique
(-)-trans- -4- (4- fluorophenyl) -3- { [(3', 4'- methylene-dioxy) phenoxy group] methyl }-piperidines also known as pa
Luo Xiting (paroxetine) is a kind of serotonin (5-HT) reuptaking inhibitor (Selective of efficient selective
Serotonin receptor inhibitors, SSRI), by selective depression nervous centralis presynaptic membrane to 5-HT again
Intake, increases the effective concentration of the 5-HT at synaptic cleft, to activate the psychomotor of patient, improves mood, and play town
Quiet effect antianxity.
Paxil structural formula is as follows:
Its hydrochloride semi-hydrate molecular formula is C19H20FNO3HCl1/2H2O, molecular weight: 374.8 (free radical shapes
Formula 329.4), it is a kind of white or off-white color crystalline powder, odorless, mildly bitter flavor.
Paroxetine hydrochloride ordinary tablet gastrointestinal side effect incidence is higher (25%), patient generate after the tablet has been ingested nausea,
Side effects, reason and the conventional tablets such as vomiting are higher related in stomach and small intestine upper section local concentration, it is therefore necessary to be prepared into
Enteric-coated sustained-release preparation.
Enteric coated preparations, which refer to, not to be discharged under one's belt at the appointed time or hardly discharges drug, and is entered in intestines,
A part of intestines can largely or entirely discharge the preparation of drug.Enteric coated preparations, which have, avoids drug to the strong thorn of gastric mucosa
Swash, avoid drug by the destruction of enzyme in gastric acid or stomach, sustained release effect is provided, will mainly be use up by the drug of small intestinal absorption
So far position may be transmitted with maximum concentration, improve the advantages such as bioavilability.
GlaxoSmithKline PLC drugmaker, Britain develops paroxetine hydrochloride enteric-coated sustained-release tablet, trade name Paxil CR,
Ratified to list through U.S. FDA in 2 months 1999, for treating various types of depression.US5422123 discloses Paxil
Controlled release tablet, the tablet are double-layer structure, and one layer is the erodible block layer without active constituent, and another layer is containing for hydrophilic matrix
Medicine layer, casing film have delayed the starting of drug release, just start drug release after tablet leaves stomach, also reachable in vivo
To the effect of Drug controlled release rate, patient is made to have more stable plasma drug level, better curative effect and tolerance.
Chinese patent CN103371982A discloses hydrochloric acid pa hydrochloric acid Luo Xiting enteric controlled release tablets new recipe and freshly prepared side
Method, the piece are double-layer tablets, and one layer is the medicated layer of hydrophilic matrix with hydroxypropyl methylcellulose (HPMC K4M), and one layer sweet with behenic acid
Grease and ethyl cellulose are the not drug containing corrosion layer of controlled-release material, and two layers obtained by tabletting after wet granulation, with this hair
Bright prepared paroxetine hydrochloride enteric-soluble controlled-release capsule has differences.But there may be the unstable, parts that releases the drug for Dospan
The problems such as stimulation is big or bioavilability is low, and individual difference is big, it is still necessary to develop that Release Performance is more preferable, prescription more preferably dosage form.
Summary of the invention
The purpose of the present invention is to provide one kind to have more preferable drug release feature, prescription more preferably paroxetine slow release composition
And preparation method thereof.
The first aspect of the present invention is related to a kind of paroxetine slow release composition, including pellet core, isolation coat layer and
Sustained-release coating layer, in which:
The pellet core includes Paxil or its pharmaceutically acceptable salt, filler and adhesive；
The isolation coat layer includes isolated material and plasticizer；
The sustained-release coating layer includes slow-release material and antiplastering aid.
Described in any item slow releasing compositions according to a first aspect of the present invention further include outermost capsule layer, it is preferable that
The capsule floor is No. 1 capsulae enterosolubilis.
Described in any item slow releasing compositions according to a first aspect of the present invention, the Paxil or its is pharmaceutically acceptable
Salt: isolated material: slow-release material weight ratio is (3~5): 1:(3~5).
Described in any item slow releasing compositions according to a first aspect of the present invention, the isolation coat layer weight gain is 3-5%.
Described in any item slow releasing compositions according to a first aspect of the present invention, the sustained-release coating layer weight gain is 10-20%.
Described in any item slow releasing compositions according to a first aspect of the present invention, the pharmaceutically acceptable salt of Paxil are
Paroxetine hydrochloride.
In embodiments of the invention, the pharmaceutically acceptable salt of the Paxil is half hydration paroxetine hydrochloride.
Described in any item slow releasing compositions according to a first aspect of the present invention, the filler are selected from microcrystalline cellulose, silicon
Change one of microcrystalline cellulose, starch, pregelatinized starch, lactose, sucrose, mannitol, sorbierite, dextrin or a variety of, preferably
One of microcrystalline cellulose, lactose, sucrose are a variety of.
Described in any item slow releasing compositions according to a first aspect of the present invention, described adhesive are selected from polyvinylpyrrolidone
One of (PVP K30) aqueous solution, hydroxypropyl methylcellulose (HPMC E5) and hydroxypropyl cellulose (HPC) aqueous solution are a variety of.
Described in any item slow releasing compositions according to a first aspect of the present invention, the isolated material are selected from hydroxypropyl methylcellulose
(HPMC), one of polyvinylpyrrolidone (PVP K30) and hydroxypropyl cellulose (HPC) are a variety of.
Described in any item slow releasing compositions according to a first aspect of the present invention, the plasticizer be selected from triethyl citrate,
Triacetyl glycerine, polyethylene glycol 400, Macrogol 600, Macrogol 4000, Macrogol 6000, propylene glycol, glycerol and
One of acetylation triethyl citrate is a variety of, preferably polyethylene glycol 400.
Described in any item slow releasing compositions according to a first aspect of the present invention, the slow-release material are Utech NE30D
(Eudragit NE30D), Eudragit RL 30D (Eudragit RL30D), Eudragit RS 30D (Eudragit RS30D) and second
One of base cellulose (EC) is a variety of, preferably Utech NE30D (Eudragit NE30D).
Described in any item slow releasing compositions according to a first aspect of the present invention, the antiplastering aid are stearic acid or talcum
Powder, preferably talc powder.
The second aspect of the present invention provides the preparation method of the described in any item slow releasing compositions of first aspect present invention,
The following steps are included:
1) wet granular is made in Paxil or its pharmaceutically acceptable salt and auxiliary material comprising filler and adhesive；
2) wet granular obtained by step 1) is made extrusion spheronization to handle and dry, drug containing vegetable pill is made；
3) auxiliaries comprising isolated material and plasticizer are thrown drug containing vegetable pill obtained by step 2) at isolated coating liquid
Fluidized bed sprays the isolated coating liquid, dry, and isolation ball is made；
4) by the auxiliaries comprising slow-release material and antiplastering aid at sustained release coating liquid, by isolation ball investment obtained by step 3)
Fluidized bed sprays the sustained release coating liquid, dry, and the sustained release pharmaceutical composition is made, optional, it further include being sustained gained
The step of pharmaceutical composition is sieved, it is preferred that cross 16-30 mesh.
Preparation methods described in any item according to the second aspect of the invention further include being filled in the slow releasing composition
The step of capsule, the capsule are preferably No. 1 capsulae enterosolubilis.
Preparation methods described in any item according to the second aspect of the invention, it is characterised in that in the item of following (1)~(6)
It is one or more:
(1) filler selection microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, lactose, sucrose,
One of mannitol, sorbierite, dextrin are a variety of, one of preferably microcrystalline cellulose, lactose, sucrose or more than one are mixed
Close object；
(2) described adhesive is selected from polyvinylpyrrolidone (PVP K30) aqueous solution, hydroxypropyl methylcellulose (HPMC E5)
With one of hydroxypropyl cellulose (HPC) aqueous solution or a variety of, it is preferable that the concentration of described adhesive is 1-5%.
(3) isolated material is selected from hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP K30) and hydroxypropyl
One of cellulose (HPC) is a variety of；
(4) the plasticizer is selected from triethyl citrate, triacetyl glycerine, polyethylene glycol 400, Macrogol 600, gathers
One of ethylene glycol 4000, Macrogol 6000, propylene glycol, glycerol and acetylation triethyl citrate are a variety of, preferably poly-
Ethylene glycol 400.
(5) slow-release material is selected from Utech NE30D (Eudragit NE30D), Eudragit RL 30D (Eudragit
RL30D), one of Eudragit RS 30D (Eudragit RS30D) and ethyl cellulose (EC) or a variety of, preferably Utech
NE30D(Eudragit NE30D)；
(6) antiplastering aid described in is selected from stearic acid or talcum powder, preferably talc powder.
In embodiments of the invention, it is 60- that the condition of extrusion spheronization described in step 2), which is extrusion revolving speed,
100rpm, round as a ball revolving speed are 400-800rpm.
In embodiments of the invention, the drug containing vegetable pill between 30-40 mesh is collected in step 2).
In embodiments of the invention, the weight gain of control isolation coat is 3-5% in step 3).
In embodiments of the invention, the weight gain of control sustained release coating is 10-20% in step 4).In implementation of the invention
In scheme, step 3) and 4) in fluidized coating condition be selected from following a)-d) at least one of:
A) controls temperature of charge at 30-40 DEG C；
B) controls blower frequency in 30-40Hz；
C) control sprinkling coating solution atomizing pressure is in 0.15-0.2MPa；
D) controls hydrojet speed in 5-35rpm.
" drug containing vegetable pill " of the present invention has the same meaning with " pellet core ", indicates in production process through step
It is rapid 1) and the medicine-containing particle of step 2) obtained uncoated isolation coat layer and sustained-release coating layer afterwards.
The third aspect of the present invention is related to the described in any item slow releasing compositions of first aspect present invention in preparation antidepression
Purposes in medicine or resisting mental disease drug.
The present invention is screened by a large amount of dosage form formulation optimizations, and it is slow to obtain the Paxil with good drug release behavior
Composition is released, meanwhile, which has preferable roundness, heap density and yield, and preparation method is simple, cost
It is lower, it has a good application prospect.
The various terms and phrase that the present invention uses have the term referred to well known to a person skilled in the art general sense
With phrase if any meaning inconsistent with common art-recognized meanings, that the present invention of being subject to is stated.
Detailed description of the invention
Fig. 1 is the paroxetine hydrochloride enteric of the different sustained-release coating layer weight gains of self-control of a specific embodiment of the invention
Spansule and Paxil CR the release curve graph comparison diagram in pH7.5tris buffer；
Fig. 2 is that the self-control paroxetine hydrochloride enteric-soluble controlled-release capsule of a specific embodiment of the invention and Paxil CR exist
Release curve comparison figure in 0.1N HCl solution；
Fig. 3 is that the self-control paroxetine hydrochloride enteric-soluble controlled-release capsule of a specific embodiment of the invention and Paxil CR exist
Release curve comparison figure in pH 7.5tris buffer solution.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
It can be with conventional products that are commercially available.
Supplementary material:
Paroxetine hydrochloride (Zhejiang Huahai/5320-09-006)
Paxil CR (GlaxoSmithKline PLC/A053830)
Hydroxypropyl methylcellulose (Huzhou prospect/201207074)；
Hydroxypropyl cellulose (U.S. Aqualon/37332)；
Lactose (Germany's U.S. agent happy/1311)；
Microcrystalline cellulose (Asahi Chemical Industry/6262)；
PVP K30 (U.S. International Specialty Products/053323091)；
Polyethylene glycol 400 (Guangdong brilliance/20120419)；
Talcum powder (LONGSHENG IN GUANGXI magnificent/1306131)；
Utech (wins wound Degussa/C130714136)；
No. 1 capsulae enterosolubilis (Mt. Huang in Anhui capsule).
1 composition 1 of embodiment
(1) pellet core
(2) isolation coat layer
(3) sustained-release coating layer
Preparation process is as follows:
1) pellet core is prepared:
A. wet granulation: pressing recipe quantity, weigh half hydration paroxetine hydrochloride and auxiliary material, be placed in wet granulator, low
Speed mixing 300s, is added 4% HPMC aqueous solution, adds in 90s, and unlatching stirs at low speed paddle and cutter, makes into wet grain, out
Material.
B. extrusion spheronization, drying and screening: wet grain is set in extrusion spheronization machine, and control extruder revolving speed is 80rpm, spheronizator
Revolving speed is 600-700rpm, obtains the preferable drug containing vegetable pill of roundness, sets 45 DEG C drying 28 minutes in fluidized bed, collects 30-40
Purpose drug containing vegetable pill.
2) packet barrier gown:
A. match coating solution: weighing hydroxypropyl cellulose, polyethylene glycol and water by recipe quantity, stir evenly.
B. it is coated: pellet core is placed in fluidized bed, adjust blower frequency 30Hz, 30-40 DEG C of temperature of charge, atomization pressure
Power 0.15-0.2MPa, hydrojet speed 6-10rpm, control isolation coat layer weight gain about in 3%, 40 DEG C of dry 13min, it is obtained every
From ball.
3) packet extended release coatings:
A. match coating solution: weighing Utech aqueous dispersion, talcum powder and water by recipe quantity, stir evenly.
B. it is coated: isolation ball is placed in fluidized bed, adjust blower frequency 35-40Hz, 30-40 DEG C of temperature of charge, atomization
Pressure 0.15-0.2MPa, hydrojet speed 10-30rpm, control sustained-release coating layer weight gain is about in 14%, 40 DEG C of dry 15min, mistake
Sustained release pellet is made in 16-30 mesh.
4) capsule is filled: calculating loading amount according to content, gained sustained release pellet is filled in No. 1 enteric coated capsule.
The paroxetine hydrochloride capsulae enterosolubilis that specification is 37.5mg can be obtained in above-mentioned preparation method.
2 composition 2 of embodiment
(1) pellet core
(2) isolation coat layer
(3) sustained-release coating layer
Preparation process is as follows:
1) pellet core is prepared:
A. wet granulation: pressing recipe quantity, weigh half hydration paroxetine hydrochloride and auxiliary material, be placed in wet granulator, low
Speed mixing 300s, is added 4% HPMC aqueous solution, adds in 100s, and unlatching stirs at low speed paddle and cutter, makes into wet grain,
Discharging.
B. extrusion spheronization, drying and screening: wet grain is set in extrusion spheronization machine, and control extruder revolving speed is 90rpm, spheronizator
Revolving speed is 600-800rpm, obtains the preferable drug containing vegetable pill of roundness, sets 45 DEG C drying 25 minutes in fluidized bed, collects 30-40
Purpose drug containing vegetable pill.
2) packet barrier gown:
A. match coating solution: weighing hydroxypropyl cellulose, polyethylene glycol and water by recipe quantity, stir evenly.
B. it is coated: pellet core is placed in fluidized bed, adjust blower frequency 32Hz, 30-40 DEG C of temperature of charge, atomization pressure
Isolation is made about in 4%, 40 DEG C of dry 15min in power 0.15-0.2MPa, hydrojet speed 6-8rpm, the weight gain of control isolation coat layer
Ball.
3) packet extended release coatings:
A. match coating solution: weighing Utech aqueous dispersion, talcum powder and water by recipe quantity, stir evenly.
B. it is coated: isolation ball is placed in fluidized bed, adjust blower frequency 32-40Hz, 30-40 DEG C of temperature of charge, atomization
Pressure 0.15-0.2MPa, hydrojet speed 8-30rpm, control sustained-release coating layer weight gain is about in 15%, 40 DEG C of dry 15min, mistake
Sustained release pellet is made in 16-30 mesh.
4) capsule is filled: calculating loading amount according to content, gained sustained release pellet is filled in No. 1 enteric coated capsule.
The paroxetine hydrochloride capsulae enterosolubilis that specification is 37.5mg can be obtained in above-mentioned preparation method.
3 composition 3 of embodiment
(1) pellet core
(2) isolation coat layer
(3) sustained-release coating layer
Preparation process is as follows:
1) pellet core is prepared:
A. wet granulation: pressing recipe quantity, weigh half hydration paroxetine hydrochloride and auxiliary material, be placed in wet granulator, low
Speed mixing 300s, is added 4% HPMC aqueous solution, adds in 120s, and unlatching stirs at low speed paddle and cutter, makes into wet grain,
Discharging.
B. extrusion spheronization, drying and screening: wet grain is set in extrusion spheronization machine, and control extruder revolving speed is 80rpm, spheronizator
Revolving speed is 600-800rpm, obtains the preferable drug containing vegetable pill of roundness, sets 45 DEG C drying 30 minutes in fluidized bed, collects 30-40
Purpose drug containing vegetable pill.
2) packet barrier gown:
A. match coating solution: weighing hydroxypropyl cellulose, polyethylene glycol and water by recipe quantity, stir evenly.
B. it is coated: pellet core is placed in fluidized bed, adjust blower frequency 30Hz, 30-40 DEG C of temperature of charge, atomization pressure
Power 0.15-0.2MPa, hydrojet speed 5-10rpm, control isolation coat layer weight gain about in 3%, 40 DEG C of dry 18min, it is obtained every
From ball.
3) packet extended release coatings:
A. match coating solution: weighing Utech aqueous dispersion, talcum powder and water by recipe quantity, stir evenly.
B. it is coated: isolation ball is placed in fluidized bed, adjust blower frequency 32-35Hz, 30-40 DEG C of temperature of charge, atomization
Pressure 0.15-0.2MPa, hydrojet speed 8-32rpm, control sustained-release coating layer weight gain is about in 12%, 40 DEG C of dry 13min, mistake
Sustained release pellet is made in 16-30 mesh.
4) capsule is filled: calculating loading amount according to content, gained sustained release pellet is filled in No. 1 enteric coated capsule.
The paroxetine hydrochloride capsulae enterosolubilis that specification is 37.5mg can be obtained in above-mentioned preparation method.
4 composition 4 of embodiment
(1) pellet core
(2) isolation coat layer
(3) sustained-release coating layer
Preparation process is as follows:
1) pellet core is prepared:
A. wet granulation: pressing recipe quantity, weigh half hydration paroxetine hydrochloride and auxiliary material, be placed in wet granulator, low
Speed mixing 300s, is added 4% HPMC aqueous solution, adds in 100s, and unlatching stirs at low speed paddle and cutter, makes into wet grain,
Discharging.
B. extrusion spheronization, drying and screening: wet grain is set in extrusion spheronization machine, and control extruder revolving speed is 70rpm, spheronizator
Revolving speed is 600-700rpm, obtains the preferable drug containing vegetable pill of roundness, sets 45 DEG C drying 32 minutes in fluidized bed, collects 30-40
Purpose drug containing vegetable pill.
2) packet barrier gown:
A. match coating solution: weighing hydroxypropyl cellulose, polyethylene glycol and water by recipe quantity, stir evenly.
B. it is coated: pellet core is placed in fluidized bed, adjust blower frequency 30Hz, 30-40 DEG C of temperature of charge, atomization pressure
Power 0.15-0.2MPa, hydrojet speed 6-10rpm, control isolation coat layer weight gain about in 4%, 40 DEG C of dry 16min, it is obtained every
From ball.
3) packet extended release coatings:
A. match coating solution: weighing Utech aqueous dispersion, talcum powder and water by recipe quantity, stir evenly.
B. it is coated: isolation ball is placed in fluidized bed, adjust blower frequency 32-36Hz, 30-40 DEG C of temperature of charge, atomization
Pressure 0.15-0.2MPa, hydrojet speed 10-30rpm, control sustained-release coating layer weight gain is about in 15%, 40 DEG C of dry 12min, mistake
Sustained release pellet is made in 16-30 mesh.
4) capsule is filled: calculating loading amount according to content, gained sustained release pellet is filled in No. 1 enteric coated capsule.
The paroxetine hydrochloride capsulae enterosolubilis that specification is 37.5mg can be obtained in above-mentioned preparation method.
Experimental example 1 makes paroxetine hydrochloride sustained release pellet (specification: 37.5mg) physical property by oneself
It is micro- that the present invention investigates homemade paroxetine hydrochloride sustained release by these three aspects of roundness, heap density and yield
The physical property of ball.Above three physical parameter is tested by following method, the person that is not specified actual conditions, according to routine
Condition carries out:
Roundness: 1g pellet is set on a plate, and plate side is lifted, measurement pellet start roll lean forward tapered plane with
Angle folded by level (Φ).
Heap density: taking appropriate pellet that it is made slowly to pass through a glass funnel, is poured onto a graduated cylinder, measures the body of pellet
Product, calculates the heap density of pellet.
Yield: the pellet between 16-30 mesh, weighing, divided by theoretical pellet amount, calculated yield are collected.
Table 1
| Roundness Φ (°) | Heap density (g/ml) | Yield (%) | |
| Embodiment 1 | 14.6 | 0.857 | 85.6 |
| Embodiment 2 | 14.3 | 0.868 | 86.8 |
| Embodiment 3 | 13.8 | 0.851 | 85.9 |
| Embodiment 4 | 14.4 | 0.872 | 86.3 |
2 binder concn of experimental example influences experiment
It is formed by the main ingredient and auxiliary material of composition 1, respectively with pure water, concentration is respectively 1%, 3%, 5% and 7%
HPMC E5, which investigates binder concn as adhesive, influences granulation.As a result, insufficient formability, material glues using water as adhesive
The poor cause fine powder of property is more；When with the adhesive of 1%-5% concentration, the pellet rounding of preparation, smooth, non-breakable, high income；With
When the adhesive of 7% concentration, pellet bonding is agglomerating, therefore binder concn control is in 1-5%.
3 isolation coat layer of experimental example weight gain screening test
It is formed by the main ingredient and auxiliary material of 1 composition 1 of embodiment, respectively with spacer layer coating weight gain for 1%, 3%, 5%
Influence to sustained release coating process.As a result, weight gain is easily broken during packet extended release coatings for the pellet of 1% separation layer, fine powder is more,
Yield is low；Weight gain be 3% and 5% separation layer pellet during packet extended release coatings non-breakable, high income；It is as high again in increased weight,
Material and Coating times will be wasted, therefore select weight gain for the barrier layer of 3-5%.
Separation layer weight gain calculation method: (having wrapped separation layer pellet gross weight-drug containing vegetable pill)/drug containing vegetable pill gross weight * 100%
4 sustained-release coating layer of experimental example weight gain screening test
Release experiment is using extremely big day hair digestion instrument and Agilent HPLC measurement.
Drug release determination:
It is carried out by the second law regulation in " Chinese Pharmacopoeia " (version two in 2005) annex XD, agitating paddle (band sedimentation basket) turns
Fast 150rpm, bath temperature (37.0 ± 0.5) DEG C, dissolution medium are 0.1N HCl solution 750mL.By paroxetine hydrochloride enteric
Spansule is placed in sedimentation basket, in investment stripping rotor after 2h, piece is transferred in another digestion instrument, rotating speed of agitator is
150rpm, bath temperature (37.0 ± 0.5) DEG C, dissolution medium is pH7.5Tris Buffer solution 1000mL, respectively at 1,2,
4,6h sampling 5mL, with 0.45 μm of filtering with microporous membrane, while supplementing synthermal dissolution medium 5mL, subsequent filtrate are gone to carry out HPLC
Measurement.
According to the above method, the enteric-soluble controlled-release capsule according to made from 1 composition 1 of embodiment is tested, sustained-release coating layer is compared
Weight gain at 5%, 10%, 15%, 20% and 25% and Paxil CR release curve in pH7.5Tris Buffer solution,
As shown in Figure 1.
As a result, drug release is too fast when sustained-release coating layer weight gain 5%；When sustained-release coating layer weight gain 25%, 6h cannot be complete
Release；It is similar to Paxil CR release profiles when sustained-release coating layer weight gain is 10%, 15%, 20%, it meets the requirements, therefore slow
Coatings weight gain control is released in 10-20%.
Sustained-release coating layer weight gain calculation method: (having wrapped sustained-release coating layer pellet gross weight-packet isolation coat layer pellet gross weight)/
Packet isolation coat layer pellet gross weight * 100%
5 paroxetine hydrochloride enteric-soluble controlled-release capsule release behavior testing experiment of experimental example
Release experiment is measured according to method described in experimental example 4.
Paroxetine hydrochloride enteric-soluble controlled-release capsule made from each prescription is measured in embodiment 1-4 respectively in 0.1N HCl solution
With the release behavior in pH7.5Tris Buffer solution, and compared with Paxil CR, as a result as shown in Fig. 2 and Fig. 3.
Claims (27)
1. a kind of paroxetine slow release composition, including pellet core, isolation coat layer and sustained-release coating layer, in which:
The pellet core includes Paxil or its pharmaceutically acceptable salt, filler and adhesive；
The isolation coat layer includes isolated material and plasticizer；
The sustained-release coating layer includes slow-release material and antiplastering aid, wherein the slow-release material is Utech NE30D (Eudragit
NE30D)；Also,
The Paxil or its pharmaceutically acceptable salt: isolated material: slow-release material weight ratio is (3~5): 1:(3~5)；
The isolation coat layer weight gain is 3-5%；
The sustained-release coating layer weight gain is 10-20%.
2. slow releasing composition according to claim 1 further includes outermost capsule layer.
3. slow releasing composition as claimed in claim 2, wherein the capsule floor is No. 1 capsulae enterosolubilis.
4. slow releasing composition according to claim 1, the pharmaceutically acceptable salt of Paxil is paroxetine hydrochloride.
5. slow releasing composition according to claim 1, the filler be selected from microcrystalline cellulose, silicified microcrystalline cellulose,
One of starch, pregelatinized starch, lactose, sucrose, mannitol, sorbierite, dextrin are a variety of.
6. slow releasing composition according to claim 1, the filler in microcrystalline cellulose, lactose, sucrose one
Kind is a variety of.
7. slow releasing composition according to claim 1, described adhesive is selected from aqueous povidone solution, hydroxypropyl first
One of cellulose or hydroxypropyl cellulose aqueous solution are a variety of.
8. the slow releasing composition of claim 7, the polyvinylpyrrolidone is PVP K30.
9. the slow releasing composition of claim 7, the hydroxypropyl methylcellulose is HPMC E5.
10. slow releasing composition according to claim 1, the isolated material is selected from hydroxypropyl methylcellulose, polyvinyl pyrrole
One of alkanone and hydroxypropyl cellulose are a variety of.
11. the slow releasing composition of claim 10, the polyvinylpyrrolidone is PVP K30.
12. slow releasing composition according to claim 1, the plasticizer be selected from triethyl citrate, triacetyl glycerine,
Polyethylene glycol 400, Macrogol 600, Macrogol 4000, Macrogol 6000, propylene glycol, glycerol and acetylation citric acid three
One of ethyl ester is a variety of.
13. slow releasing composition according to claim 1, the plasticizer is polyethylene glycol 400.
14. slow releasing composition according to claim 1, the antiplastering aid is selected from stearic acid or talcum powder.
15. slow releasing composition according to claim 1, the antitackiness agent is talcum powder.
16. the preparation method of the described in any item slow releasing compositions of claim 1-15 comprising following steps:
1) wet granular is made in Paxil or its pharmaceutically acceptable salt and auxiliary material comprising filler and adhesive；
2) wet granular obtained by step 1) is made extrusion spheronization to handle and dry, drug containing vegetable pill is made；
3) by the auxiliaries comprising isolated material and plasticizer at isolated coating liquid, by the investment stream of drug containing vegetable pill obtained by step 2)
Change bed, sprays the isolated coating liquid, it is dry, isolation ball is made；
4) by the auxiliaries comprising slow-release material Utech NE30D and antiplastering aid at sustained release coating liquid, by obtained by step 3) every
Fluidized bed is put into from ball, sprays the sustained release coating liquid, it is dry, the slow releasing composition is made, optional, it further include by gained
The step of slow releasing composition is sieved.
17. preparation method according to claim 16 further includes the steps that the slow releasing composition being filled in capsule.
18. preparation method according to claim 17, wherein the capsule is No. 1 capsulae enterosolubilis.
19. preparation method according to claim 16, it is characterised in that one or more in the item of following (1)~(6):
(1) filler selects microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, lactose, sucrose, sweet dew
One of alcohol, sorbierite, dextrin are a variety of；
(2) described adhesive is in aqueous povidone solution, hydroxypropyl methylcellulose or hydroxypropyl cellulose aqueous solution
It is one or more；
(3) isolated material is selected from one of hydroxypropyl methylcellulose, polyvinylpyrrolidone and hydroxypropyl cellulose or more
Kind；
(4) the plasticizer is selected from triethyl citrate, triacetyl glycerine, polyethylene glycol 400, Macrogol 600, poly- second two
One of alcohol 4000, Macrogol 6000, propylene glycol, glycerol and acetylation triethyl citrate are a variety of；
(6) antiplastering aid described in is selected from stearic acid or talcum powder.
20. the preparation method of claim 19, polyvinylpyrrolidone described in (2) item is PVP K30.
21. the preparation method of claim 19, hydroxypropyl methylcellulose described in (2) item is HPMC E5.
22. the preparation method of claim 19, polyvinylpyrrolidone described in (3) item is PVP K30.
23. preparation method according to claim 16, wherein the filler is in microcrystalline cellulose, lactose, sucrose
One or more kinds of mixtures.
24. preparation method according to claim 16, wherein the concentration of described adhesive is 1-5%.
25. preparation method according to claim 16, wherein the plasticizer is polyethylene glycol 400.
26. preparation method according to claim 16, wherein the antitackiness agent is talcum powder.
27. the described in any item slow releasing compositions of claim 1-15 are preparing the use in antidepressants or resisting mental disease drug
On the way.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007052877A1 (en) * | 2005-11-04 | 2007-05-10 | Gl Pharmtech Corp. | An enteric sustained-release tablet comprising paroxetine |
| CN101371836A (en) * | 2007-08-23 | 2009-02-25 | 珠海天翼医药技术开发有限公司 | Paroxetine enteric sustained-release composition |
| CN103371982A (en) * | 2012-04-20 | 2013-10-30 | 王进京 | Novel prescription composition and preparation method of paroxetine hydrochloride enteric controlled release tablet |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1791531A1 (en) * | 2004-08-20 | 2007-06-06 | Alpharma, Inc. | Paroxetine formulations |
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2014
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007052877A1 (en) * | 2005-11-04 | 2007-05-10 | Gl Pharmtech Corp. | An enteric sustained-release tablet comprising paroxetine |
| CN101371836A (en) * | 2007-08-23 | 2009-02-25 | 珠海天翼医药技术开发有限公司 | Paroxetine enteric sustained-release composition |
| CN103371982A (en) * | 2012-04-20 | 2013-10-30 | 王进京 | Novel prescription composition and preparation method of paroxetine hydrochloride enteric controlled release tablet |
Non-Patent Citations (1)
| Title |
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| 人工神经网络预测盐酸帕罗西汀缓释微丸的药物释放;朱正怡等;《中国现代应用药学》;20081228;第25卷(第06期);第520-524页 |
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