CN109568278A - Mo Fanse forest tract agent and preparation method thereof - Google Patents
Mo Fanse forest tract agent and preparation method thereof Download PDFInfo
- Publication number
- CN109568278A CN109568278A CN201710899268.7A CN201710899268A CN109568278A CN 109568278 A CN109568278 A CN 109568278A CN 201710899268 A CN201710899268 A CN 201710899268A CN 109568278 A CN109568278 A CN 109568278A
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- China
- Prior art keywords
- fanselin
- polyethylene glycol
- tablet
- silicon dioxide
- adhesive
- Prior art date
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- 238000002360 preparation method Methods 0.000 title abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 18
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims abstract description 16
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 15
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 15
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000945 filler Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 9
- 229920000881 Modified starch Polymers 0.000 claims abstract description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 9
- 229920002472 Starch Polymers 0.000 claims abstract description 8
- 239000011734 sodium Substances 0.000 claims abstract description 8
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 8
- 239000008107 starch Substances 0.000 claims abstract description 8
- 235000019698 starch Nutrition 0.000 claims abstract description 8
- 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 abstract description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 6
- 239000008101 lactose Substances 0.000 claims abstract description 6
- 229960000913 crospovidone Drugs 0.000 claims abstract description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 5
- 229920002261 Corn starch Polymers 0.000 claims abstract description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract 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 abstract description 3
- 229920001353 Dextrin Polymers 0.000 claims abstract description 3
- 239000004375 Dextrin Substances 0.000 claims abstract description 3
- 229930195725 Mannitol Natural products 0.000 claims abstract description 3
- 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 abstract description 3
- 239000008120 corn starch Substances 0.000 claims abstract description 3
- 229940099112 cornstarch Drugs 0.000 claims abstract description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 3
- 235000019425 dextrin Nutrition 0.000 claims abstract description 3
- 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 abstract description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 3
- 239000000594 mannitol Substances 0.000 claims abstract description 3
- 235000010355 mannitol Nutrition 0.000 claims abstract description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims abstract description 3
- 229940032147 starch Drugs 0.000 claims abstract description 3
- 238000005469 granulation Methods 0.000 claims description 17
- 230000003179 granulation Effects 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 13
- 239000000853 adhesive Substances 0.000 claims description 12
- 230000001070 adhesive effect Effects 0.000 claims description 12
- 239000012467 final product Substances 0.000 claims description 11
- 239000002075 main ingredient Substances 0.000 claims description 9
- 239000011122 softwood Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 229940069328 povidone Drugs 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 5
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 206010013786 Dry skin Diseases 0.000 claims description 3
- 229960003511 macrogol Drugs 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- AQLLBJAXUCIJSR-UHFFFAOYSA-N OC(=O)C[Na] Chemical group OC(=O)C[Na] AQLLBJAXUCIJSR-UHFFFAOYSA-N 0.000 claims 1
- 239000007767 bonding agent Substances 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 238000005461 lubrication Methods 0.000 claims 1
- 229940080313 sodium starch Drugs 0.000 claims 1
- 238000005303 weighing Methods 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000000470 constituent Substances 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 229960001375 lactose Drugs 0.000 description 4
- RYDFXSRVZBYYJV-TYYBGVCCSA-N (e)-but-2-enedioic acid;sodium Chemical compound [Na].OC(=O)\C=C\C(O)=O RYDFXSRVZBYYJV-TYYBGVCCSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 1
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000013409 condiments Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- -1 hydroxyl Propyl Chemical group 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- RKEWSXXUOLRFBX-UHFFFAOYSA-N pimavanserin Chemical compound C1=CC(OCC(C)C)=CC=C1CNC(=O)N(C1CCN(C)CC1)CC1=CC=C(F)C=C1 RKEWSXXUOLRFBX-UHFFFAOYSA-N 0.000 description 1
- 229960003300 pimavanserin Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to field of pharmaceutical preparations, and in particular to one kind Mo Fanse forest tract agent and preparation method thereof.Described Mo Fanse forest tract by active constituent Mo Fanselin, colloidal silicon dioxide, polyethylene glycol, selected from dextrin, cornstarch, pregelatinized starch, microcrystalline cellulose, mannitol, lactose filler, selected from sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose, crospovidone disintegrating agent, selected from magnesium stearate, talcum powder, sodium stearyl fumarate lubricant composition.Mo Fanselin tablet stability of the invention is good, and can significantly improve drug dissolution and bioavilability.
Description
Technical field
The present invention relates to technical field of medicine, and in particular to Mo Fanse forest tract agent and preparation method thereof.
Background technique
Whole world parkinsonian about 7 million to one 10,000,000 at present, China just have 2,600,000, rank first in the world, often
Year will also increase by 100,000 neopathy patients.50% or more parkinsonian once had mental symptom (PDP).These spirit
Symptom is mainly shown as illusion and vain hope, and the treatment and tourniquet to parkinsonian carry out bigger challenge.Dopamine is pa
The main target of the gloomy disease treatment of gold, since most of antipsychotics can block dopamine in brain to lead to disturbances in patients with Parkinson disease
Dyskinesia deteriorate, be not suitable for such patient at present.
Mo Fanselin (Pimavanserin), chemical name, 1-(4- luorobenzyl) -3-(4- isobutoxy benzyl) -1-(1-
Methyl piperidine -4- base) urea, Yuan Yanwei Acadia drug company.The reversed and antagonism of Mo Fanselin to 5-HT2A receptor
It is selectively 40 times of 5-HT2C receptor and dopamine receptor with high targeting and specificity.Good effect, specificity is good, keeps away
Exempt from the deterioration of muscular movement, few side effects.Breakthrough treatment status title, April 29 in 2016 are authorized by FDA on 2 9th, 2014
By FDA approval for treat Parkinson illusion and vain hope, current first be also it is only be permitted for treatment Parkinson essence
The drug of refreshing disease.
In research find a Mo Fanselin ordinary preparation stability it is poor, in preparation storing process dissolution rate gradually under
Drop, it is therefore desirable to the more stable pharmaceutical preparation of the compound.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the defect of the prior art, provide it is a kind of it is stable, dissolution rate is high
Mo Fanse forest tract agent.
Mo Fanse forest tract agent of the invention by Mo Fanselin and colloidal silicon dioxide, polyethylene glycol and pharmaceutically may be used
The auxiliary material of receiving forms.
Wherein polyethylene glycol is selected from Macrogol 6000, PEG 8000；The weight of colloidal silicon dioxide and polyethylene glycol
Amount is than being 1:3~8.
Wherein the ratio of the total amount and Mo Fanselin of colloidal silicon dioxide and polyethylene glycol is 1:1~4.
Wherein pharmaceutically acceptable auxiliary material is filler, disintegrating agent, adhesive and lubricant.The filler choosing
From the one or more of dextrin, cornstarch, pregelatinized starch, microcrystalline cellulose, mannitol, lactose, preferably pregelatinized starch
And microcrystalline cellulose；Disintegrating agent is selected from sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose, friendship
Join povidone, preferably sodium carboxymethyl starch；Adhesive is selected from hypromellose, hydroxypropyl cellulose, povidone, preferably hydroxyl
Propyl cellulose；Lubricant is selected from magnesium stearate, talcum powder, sodium stearyl fumarate, preferably magnesium stearate.
Wherein active constituent Mo Fanselin accounts for the 10~20% of the tablet weight, colloidal silicon dioxide, polyethylene glycol
Total amount account for the 2.5~10% of the tablet weight, filler is the 55~80% of the tablet weight, disintegrating agent is 2~
8%, adhesive is 5~15%, and lubricant is 1~2%.
The present invention also provides a kind of preparation methods of Mo Fanse forest tract agent, by the Mo Fanselin of recipe quantity, colloidal state
Silica, polyethylene glycol after mixing, add filler, disintegrating agent mixing, then with the aqueous solution system of adhesive
Grain；Then with the lubricant total mix of recipe quantity, tabletting to obtain the final product.
Specifically, which comprises the steps of: first crosses a Mo Fanselin and all auxiliary materials 80 meshes respectively, standby
With；Weigh the colloidal silicon dioxide of recipe quantity, polyethylene glycol is added granulation pot together with main ingredient and is uniformly mixed；Add filling
Agent, disintegrating agent mix；The aqueous solution softwood of adhesive is added；24 meshes granulation, 55 DEG C drying 1 hour, 24 mesh sieves；Claim
Take the lubricant total mix of recipe quantity, tabletting to obtain the final product.
Wherein the concentration of described adhesive aqueous solution is 5~15%, preferably 10%.
The present inventor has found that the ordinary preparation stability of a Mo Fanselin is poor, molten in storing process in R&D process
Out-degree can be gradually reduced, during preparation prescription optimizes, surprisingly it has been found that the colloidal silicon dioxide of special ratios is added
And after polyethylene glycol, the stable preparation of available dissolution rate, reason may be preparation in storing process, and raw material has poly-
Collect phenomenon, after raw material is mixed with hydrophilicity condiment, reduce electrostatic interaction, avoid assembling, and plays stabilization.
Specific embodiment
Technical solution of the present invention is further illustrated combined with specific embodiments below, but does not limit the present invention.
Dissolution determination method: the dissolution determination method announced according to FDA, using 0.1M hydrochloric acid as dissolution medium, basket method,
Revolving speed is 100prm, is operated according to methods, after 30min, with high effective liquid chromatography for measuring dissolution rate.
Embodiment 1
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh colloidal silicon dioxide, the poly- second two of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min is added in alcohol and main ingredient together；It adds
Pregelatinized starch, microcrystalline cellulose and carboxyrnethyl starch sodium mix；It is slowly added to the aqueous solution softwood of 15% hydroxypropyl cellulose；
24 meshes granulation, 55 DEG C drying 1 hour, 24 mesh sieves；Weigh the magnesium stearate total mix of recipe quantity, tabletting to obtain the final product.
Embodiment 2
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh colloidal silicon dioxide, the poly- second two of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min is added in alcohol and main ingredient together；It adds
Pregelatinized starch, microcrystalline cellulose and carboxyrnethyl starch sodium mix；It is slowly added to the aqueous solution softwood of 10% hydroxypropyl cellulose；
24 meshes granulation, 55 DEG C drying 1 hour, 24 mesh sieves；Weigh the magnesium stearate total mix of recipe quantity, tabletting to obtain the final product.
Embodiment 3
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh colloidal silicon dioxide, the poly- second two of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min is added in alcohol and main ingredient together；It adds
Pregelatinized starch, microcrystalline cellulose and carboxyrnethyl starch sodium mix；It is slowly added to the aqueous solution softwood of 5% hydroxypropyl cellulose；24
Mesh granulation, 55 DEG C drying 1 hour, 24 mesh sieves；Weigh the magnesium stearate total mix of recipe quantity, tabletting to obtain the final product.
Embodiment 4
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh colloidal silicon dioxide, the poly- second two of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min is added in alcohol and main ingredient together；It adds
Lactose, microcrystalline cellulose and crospovidone mix；It is slowly added to the aqueous solution softwood of 10% povidone；The granulation of 24 meshes, 55
DEG C dry 1 hour, 24 mesh sieves；Weigh the hard fumaric acid sodium total mix of recipe quantity, tabletting to obtain the final product.
Comparative example 1
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh pregelatinized starch, the microcrystalline cellulose of recipe quantity
Element, carboxyrnethyl starch sodium and main ingredient are added pot of pelletizing together, dry-mixed under low whipping speed 500r/min, shear velocity 1000r/min
5min；It is slowly added to the aqueous solution softwood of 5% hydroxypropyl cellulose；24 meshes granulation, 55 DEG C drying 1 hour, 24 meshes are whole
Grain；Weigh the magnesium stearate total mix of recipe quantity, tabletting to obtain the final product.
Comparative example 2
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh the colloidal silicon dioxide and main ingredient of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min are added together；Add lactose, crystallite
Cellulose and crospovidone mix；It is slowly added to the aqueous solution softwood of 10% povidone；The granulation of 24 meshes, 55 DEG C of dryings 1 are small
When, 24 mesh sieves；Weigh the hard fumaric acid sodium total mix of recipe quantity, tabletting to obtain the final product.
Comparative example 3
Composition:
Preparation process:
Mo Fanselin and all auxiliary materials are first crossed to 80 meshes respectively, it is spare；Weigh the Macrogol 6000 and main ingredient of recipe quantity
Granulation pot, dry-mixed 5min under low whipping speed 500r/min, shear velocity 1000r/min are added together；Add lactose, crystallite
Cellulose and crospovidone mix；It is slowly added to the aqueous solution softwood of 10% povidone；The granulation of 24 meshes, 55 DEG C of dryings 1 are small
When, 24 mesh sieves；Weigh the hard fumaric acid sodium total mix of recipe quantity, tabletting to obtain the final product.
Dissolution Rate Testing
By the tablet of embodiment 1-4, comparative example 1-3, after aluminium-plastic bubble plate packing, it is placed in (40 DEG C of temperature of testing chamber for medicine stability
± 2 DEG C, relative humidity 75% ± 5%) interior placement 3 months, using 0.1M hydrochloric acid as dissolution medium, basket method, revolving speed 100prm, warp
It is as a result as follows with high effective liquid chromatography for measuring dissolution rate after 30min:
It is above-mentioned that the results showed that placing 3 months under the conditions of accelerated test, the Dissolution of Tablet of embodiment 1-4 is unchanged, and
The Dissolution of Tablet of comparative example 1-3 is remarkably decreased.Illustrate the tablet prepared according to the technique and scheme of the present invention dissolution stablize, not by
The influence of high temperature and humidity condition.
Claims (9)
1. Mo Fanse forest tract agent, it is characterised in that by Mo Fanselin and colloidal silicon dioxide, polyethylene glycol and pharmaceutically
Acceptable auxiliary material composition, wherein polyethylene glycol is selected from Macrogol 6000, PEG 8000；Colloidal silicon dioxide and poly- second
The weight ratio of glycol is 1:3~8.
2. tablet according to claim 1, it is characterised in that the total amount of colloidal silicon dioxide and polyethylene glycol and Mo Fanse
The ratio of woods is 1:1~4.
3. tablet according to claim 1, it is characterised in that auxiliary material used is filler, disintegrating agent, adhesive and profit
Lubrication prescription.
4. tablet according to claim 3, it is characterised in that filler is selected from dextrin, cornstarch, pregelatinized starch, micro-
The one or more of crystalline cellulose, mannitol, lactose, preferably pregelatinized starch and microcrystalline cellulose；Disintegrating agent is selected from carboxymethyl
Sodium starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose, crospovidone, preferably sodium carboxymethyl starch；Bonding
Agent is selected from hypromellose, hydroxypropyl cellulose, povidone, preferably hydroxypropyl cellulose；Lubricant be selected from magnesium stearate,
Talcum powder, sodium stearyl fumarate, preferably magnesium stearate.
5. tablet according to claim 4, it is characterised in that Mo Fanselin accounts for the 10~20% of the tablet weight, glue
State silica, polyethylene glycol total amount account for the 2.5~10% of the tablet weight, filler is the 55 of the tablet weight
~80%, disintegrating agent is 2~8%, and adhesive is 5~15%, and lubricant is 1~2%.
6. the method for preparing any one of the claim 1-5 tablet, it is characterised in that by the Mo Fanselin of recipe quantity, colloidal state
Silica, polyethylene glycol after mixing, add filler, disintegrating agent mixing, then with the aqueous solution system of adhesive
Grain；Then with the lubricant total mix of recipe quantity, tabletting to obtain the final product.
7. according to the method described in claim 6, it is characterized in that it is prepared by the following method: by Mo Fanselin and owning
Auxiliary material first crosses 80 meshes respectively, spare；Granulation pot is added in the colloidal silicon dioxide, polyethylene glycol and main ingredient for weighing recipe quantity together
It is uniformly mixed；Add filler, disintegrating agent mixes；The aqueous solution softwood of adhesive is added；The granulation of 24 meshes, 55 DEG C of dryings
1 hour, 24 mesh sieves；Weigh the lubricant total mix of recipe quantity, tabletting to obtain the final product.
8. according to the method described in claim 7, it is characterized in that the concentration of described adhesive aqueous solution is 5~15%.
9. according to the method described in claim 8, it is characterized in that the concentration of described adhesive aqueous solution is 10%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111671730A (en) * | 2020-07-24 | 2020-09-18 | 迪沙药业集团有限公司 | A kind of levamlodipine besylate composition and preparation method thereof |
| WO2022063097A1 (en) * | 2020-09-23 | 2022-03-31 | 南京凯旺药业有限公司 | Method for preparing solid formulation of pimavanserin |
| CN115177595A (en) * | 2022-07-06 | 2022-10-14 | 金陵药业股份有限公司 | Oxagolide sodium tablet and preparation method thereof |
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| CN101500568A (en) * | 2006-05-15 | 2009-08-05 | 阿卡蒂亚药品公司 | Pharmaceutical formulations of pimavanserin |
| CN106074415A (en) * | 2016-07-22 | 2016-11-09 | 南京正大天晴制药有限公司 | A kind of aripirazole tablets and preparation method thereof |
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| WO2004064738A2 (en) * | 2003-01-16 | 2004-08-05 | Acadia Pharmaceuticals Inc. | Selective serotonin 2a/2c receptor inverse agonists as therapeutics for neurodegenerative diseases |
| CN101500568A (en) * | 2006-05-15 | 2009-08-05 | 阿卡蒂亚药品公司 | Pharmaceutical formulations of pimavanserin |
| CN106074415A (en) * | 2016-07-22 | 2016-11-09 | 南京正大天晴制药有限公司 | A kind of aripirazole tablets and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111671730A (en) * | 2020-07-24 | 2020-09-18 | 迪沙药业集团有限公司 | A kind of levamlodipine besylate composition and preparation method thereof |
| CN111671730B (en) * | 2020-07-24 | 2022-02-18 | 迪沙药业集团有限公司 | Levamlodipine besylate composition and preparation method thereof |
| WO2022063097A1 (en) * | 2020-09-23 | 2022-03-31 | 南京凯旺药业有限公司 | Method for preparing solid formulation of pimavanserin |
| CN116635014A (en) * | 2020-09-23 | 2023-08-22 | 南京凯旺药业有限公司 | The preparation method of pimavanserin solid preparation |
| CN115177595A (en) * | 2022-07-06 | 2022-10-14 | 金陵药业股份有限公司 | Oxagolide sodium tablet and preparation method thereof |
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