CN106943368A - Mirtazapine tablet and preparation method thereof - Google Patents
Mirtazapine tablet and preparation method thereof Download PDFInfo
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- CN106943368A CN106943368A CN201710188989.7A CN201710188989A CN106943368A CN 106943368 A CN106943368 A CN 106943368A CN 201710188989 A CN201710188989 A CN 201710188989A CN 106943368 A CN106943368 A CN 106943368A
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- mirtazapine
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- tablet
- cellulose
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- 229960001785 mirtazapine Drugs 0.000 title claims abstract description 59
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 32
- 238000000576 coating method Methods 0.000 claims abstract description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229920002472 Starch Polymers 0.000 claims abstract description 17
- 239000000843 powder Substances 0.000 claims abstract description 17
- 239000000741 silica gel Substances 0.000 claims abstract description 17
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 17
- 239000011734 sodium Substances 0.000 claims abstract description 17
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 17
- 239000008107 starch Substances 0.000 claims abstract description 17
- 235000019698 starch Nutrition 0.000 claims abstract description 17
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 16
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 16
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 16
- 239000002245 particle Substances 0.000 claims abstract description 16
- 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 15
- 239000008101 lactose Substances 0.000 claims abstract description 15
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 15
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920000642 polymer Polymers 0.000 claims abstract description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 7
- 239000011247 coating layer Substances 0.000 claims abstract description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 7
- 238000002372 labelling Methods 0.000 claims abstract description 6
- 238000007873 sieving Methods 0.000 claims abstract description 6
- 235000020985 whole grains Nutrition 0.000 claims description 10
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 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 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group 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 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims 3
- 239000001913 cellulose Substances 0.000 claims 3
- 235000010980 cellulose Nutrition 0.000 claims 3
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 235000013339 cereals Nutrition 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 8
- 238000004090 dissolution Methods 0.000 abstract description 7
- 239000004408 titanium dioxide Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract 1
- 238000005550 wet granulation Methods 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000007415 Anhedonia Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 241000209094 Oryza Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- HHRFWSALGNYPHA-UHFFFAOYSA-N [N].C1CNCCN1 Chemical compound [N].C1CNCCN1 HHRFWSALGNYPHA-UHFFFAOYSA-N 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- -1 benzo nitrogen Chemical compound 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000003760 hair shine Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000037047 psychomotor activity Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000004580 weight loss Effects 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2813—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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention proposes a kind of Mirtazapine tablet and preparation method thereof, is made up of label and coatings, and label includes following supplementary material：1~3 part of 20~45 parts of Mirtazapine, 120~240 parts of lactose, 40~80 parts of sodium carboxymethyl starch, 30~60 parts of microcrystalline cellulose, 15~30 parts of low-substituted hydroxypropyl cellulose, 1~3 part of magnesium stearate and superfine silica gel powder；Coatings are the polymer coating layer containing titanium dioxide and polyethylene glycol.Preparation method, comprises the following steps：1) supplementary material of label is subjected to sieving for standby；2) piece core raw material progress wet granulation is obtained into label；3) label is coated, obtains Mirtazapine tablet.The Dissolution of Tablet has particle size dependence, and drug releasing rate is stable, can avoid the problem of drug releasing rate fluctuation causes side effect.
Description
Technical field
The invention belongs to antidepressant preparation technique field, and in particular to a kind of Mirtazapine tablet and preparation method thereof.
Background technology
Mirtazapine (Mirtazapine) is the well-known medicine for being used to treat depression, with tetracyclic structure, is belonged to
The tall and erect class compound of piperazine-nitrogen.As a kind of antidepressants, Mirtazapine constitutes a class by itself.Mirtazapine is maincenter presynaptic membrane alpha-2 receptor
Antagonist, can strengthen the nerve conduction of adrenergic.It blocks 5-HT2 the and 5-HT3 acceptors of maincenter simultaneously, Mirtazapine
Two kinds of optical antipodes all have antidepressant activity, and levo form blocks α 2 and 5-HT2 acceptors, and d-isomer blocks 5-HT3 acceptors.Rice
Flat antihistaminicum acceptor (H1) characteristic of nitrogen plays sedation.The medicine has preferable tolerance, almost without anticholinergic effect,
On cardiovascular system without influence.Mirtazapine is applied to depression, to symptom such as anhedonia, and psychomotor activity suppresses, and sleep is owed
Good and weight loss is effective in cure.It can also be used for other symptoms such as：Interest, suicidal idea and mood ripple are lost to things
Dynamic, medication works after latter to two weeks, and its therapeutic dose is on cardiovascular system without influence.
After mirtazapine tablets are oral, its active component Mirtazapine is absorbed (bioavilability is about 50%) quickly, about 2 hours
Plasma concentration is peaked afterwards, and about 85% is combined with plasma protein, and mean half-life is 20~40 hours；It is accidental that to be up to 65 small
When.The size for removing half-life period is just being suitable for the mode of taking being set to once a day.Blood concentration reaches after taking medicine three to four days
, hereafter will be without building up phenomenon in vivo to steady will.In the dosage range recommended, " the pharmacokinetics form of Mirtazapine
It is linear ".Mirtazapine is metabolized and excreted after the tablet has been ingested in several days by urine and excrement mostly.Its main biochemical mode
It is that demethylation and oxidation reaction exist, is followed by association reaction.Metabolite after piptonychia still has pharmacology work as former compound
Property.Hepatic and renal function is bad to cause the reduction of Mirtazapine clearance rate.
Chinese patent CN101129341 discloses another preparation method of Mirtazapine oral disnitegration tablet, comprising Mirtazapine, collapses
Solve pharmaceutical formulation of agent, filler and other excipient and preparation method thereof.However, existing Mirtazapine preparation still has release
The problems such as uniformity is poor, dissolution rate is slow.
The content of the invention
The present invention proposes a kind of Mirtazapine tablet, and the Dissolution of Tablet has particle size dependence, and drug releasing rate is stable,
The problem of drug releasing rate fluctuation causes side effect can be avoided.
The technical proposal of the invention is realized in this way：
A kind of Mirtazapine tablet, is made up of label and coatings, in parts by weight, and it is auxiliary that label includes following original
Material：20~45 parts of Mirtazapine, 120~240 parts of lactose, 40~80 parts of sodium carboxymethyl starch, 30~60 parts of microcrystalline cellulose, low take
For 1~3 part of 15~30 parts of hydroxypropyl cellulose, 1~3 part of magnesium stearate and superfine silica gel powder；Coatings be containing titanium dioxide with
The polymer coating layer of polyethylene glycol.
Preferably, in some embodiments of the invention, the polymer is Hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxyl
Ethylmethylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methacrylate dimethylamino second
Ester-methyl acrylate copolymer, ethyl acrylate-methylmethacrylate copolymer, the one of methylcellulose and ethyl cellulose
Plant or more than one.
Preferably, in some embodiments of the invention, the coatings are the 1.8%~2.4% of label weight.
It is a further object to provide a kind of preparation method of Mirtazapine tablet, comprise the following steps：
1) by Mirtazapine, magnesium stearate, sodium carboxymethyl starch, superfine silica gel powder, low-substituted hydroxypropyl cellulose, microcrystalline cellulose
Element, lactose sieving for standby；
2) Mirtazapine, sodium carboxymethyl starch, lactose, purified water are taken, and is added to granulation in wet granulator, and will be made
Particle be put into drying machine dry；And dried particle is put into vibratory sieve carries out whole grain；
3) by step 2) the obtained particle of whole grain is put into Mixers with Multi-direction Movement, and add low-substituted hydroxypropyl cellulose,
Microcrystalline cellulose, superfine silica gel powder and magnesium stearate, mixing, compressing tablet, obtain label；
4) to step 3) Coating Solution is added in obtained label, it is coated, obtains Mirtazapine tablet.
Preferably, in some embodiments of the invention, step 2) described in the parts by weight of purified water be 20~30 parts.
Mirtazapine (1,2,3,4,10,14 β-hexahydro -2- methylpyrazoles simultaneously [2,1-a] pyrido [2,3-c] [2] benzo nitrogen
It is miscellaneous), refer to include compound in itself and its pharmaceutically acceptable salt.Can according to van der Burg United States Patent (USP) No.4,
062,848 prepares this compound.
Mirtazapine of the present invention include with substantially with the form of other stage enantiomer separations (enantiomer having it is pure
Degree is more than 95%, and more preferably greater than single (R) and (S) enantiomter and its salt of the Mirtazapine 99%) existed, and wrap
Include the mixture of the enantiomter of any ratio of racemic mixture.
Because solubility is relatively low in Mirtazapine water, its granularity directly affects the product quality of preparation, the lower gained rice of the present invention
The flat agent steady quality of nitrogen, preparation manipulation are simple, production cost is low, are suitable for industrialized large-scaled production.
Mirtazapine tablets not only have good therapeutic effect to depression in the present invention, and can reduce the bad of Mirtazapine
React incidence；And the Mirtazapine tablet that the present invention is provided uses sodium carboxymethyl starch, superfine silica gel powder and microcrystalline cellulose
As drug excipient, medicine stability is improved.Coatings are the polymer coating layer containing titanium dioxide and polyethylene glycol, are made
It has the sustained release performance that conventional tablet does not have, and Mirtazapine stable release in human body can be controlled to a certain extent, from
And it is long-lasting make it that mirtazapine tablets have, and traditional mirtazapine tablets can be avoided to make secondary caused by the fluctuation of human body rate of release
With.
Embodiment
Embodiment 1
A kind of Mirtazapine tablet, is made up of label and coatings, in parts by weight, and it is auxiliary that label includes following original
Material：30 parts of Mirtazapine, 200 parts of lactose, 60 parts of sodium carboxymethyl starch, 40 parts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose 20
2 parts of part, 2 parts of magnesium stearate and superfine silica gel powder；Coatings are the polymer coating layer containing titanium dioxide and polyethylene glycol.It is coated
Layer is the 2% of label weight.
Preparation method, comprises the following steps：
1) by Mirtazapine, magnesium stearate, sodium carboxymethyl starch, superfine silica gel powder, low-substituted hydroxypropyl cellulose, microcrystalline cellulose
Element, lactose sieving for standby；
2) Mirtazapine, sodium carboxymethyl starch, lactose, purified water are taken, and is added to granulation in wet granulator, and will be made
Particle be put into drying machine dry；And dried particle is put into vibratory sieve carries out whole grain；
3) by step 2) the obtained particle of whole grain is put into Mixers with Multi-direction Movement, and add low-substituted hydroxypropyl cellulose,
Microcrystalline cellulose, superfine silica gel powder and magnesium stearate, mixing, compressing tablet, obtain label；
4) preparation is coated using conventional coating equipment, using stomach dissolution type Opadry.
Embodiment 2
A kind of Mirtazapine tablet, is made up of label and coatings, in parts by weight, and it is auxiliary that label includes following original
Material：20 parts of Mirtazapine, 120 parts of lactose, 80 parts of sodium carboxymethyl starch, 30 parts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose 150
1 part of part, 1 part of magnesium stearate and superfine silica gel powder；Coatings are the polymer coating layer containing titanium dioxide and polyethylene glycol.It is coated
Layer is the 1.8% of label weight.
Preparation method, comprises the following steps：
1) by Mirtazapine, magnesium stearate, sodium carboxymethyl starch, superfine silica gel powder, low-substituted hydroxypropyl cellulose, microcrystalline cellulose
Element, lactose sieving for standby；
2) Mirtazapine, sodium carboxymethyl starch, lactose, purified water are taken, and is added to granulation in wet granulator, and will be made
Particle be put into drying machine dry；And dried particle is put into vibratory sieve carries out whole grain；
3) by step 2) the obtained particle of whole grain is put into Mixers with Multi-direction Movement, and add low-substituted hydroxypropyl cellulose,
Microcrystalline cellulose, superfine silica gel powder and magnesium stearate, mixing, compressing tablet, obtain label；
4) preparation is coated using conventional coating equipment, using stomach dissolution type Opadry.
Embodiment 3
A kind of Mirtazapine tablet, is made up of label and coatings, in parts by weight, and it is auxiliary that label includes following original
Material：45 parts of Mirtazapine, 240 parts of lactose, 40 parts of sodium carboxymethyl starch, 60 parts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose 30
3 parts of part, 3 parts of magnesium stearate and superfine silica gel powder；Coatings are the polymer coating layer containing titanium dioxide and polyethylene glycol.It is coated
Layer is the 2.4% of label weight.
Preparation method, comprises the following steps：
1) by Mirtazapine, magnesium stearate, sodium carboxymethyl starch, superfine silica gel powder, low-substituted hydroxypropyl cellulose, microcrystalline cellulose
Element, lactose sieving for standby；
2) Mirtazapine, sodium carboxymethyl starch, lactose, purified water are taken, and is added to granulation in wet granulator, and will be made
Particle be put into drying machine dry；And dried particle is put into vibratory sieve carries out whole grain；
3) by step 2) the obtained particle of whole grain is put into Mixers with Multi-direction Movement, and add low-substituted hydroxypropyl cellulose,
Microcrystalline cellulose, superfine silica gel powder and magnesium stearate, mixing, compressing tablet, obtain label；
4) preparation is coated using conventional coating equipment, using stomach dissolution type Opadry.
Test example
Release is tested
According to drug release determination method (two methods of annex XD first of Chinese Pharmacopoeia 2010 edition), using dissolution rate test method
One subtraction unit, using phosphate buffer as solvent, is operated in accordance with the law.Assay shines high performance liquid chromatography (Chinese Pharmacopoeia 2010
Two annex VD of year) determine.
The measurement result of the release of 1 embodiment of table 1~3
| Embodiment 1 | Embodiment 2 | Embodiment 3 | |
| 1h | 15.2 | 15.6 | 16.5 |
| 4h | 33.2 | 34.1 | 33.8 |
| 6h | 49.1 | 49.2 | 48.8 |
| 8h | 63.2 | 63.1 | 63.7 |
| 12h | 80.2 | 79.5 | 78.9 |
| 18h | 88.4 | 88.1 | 87.2 |
| 24h | 99.3 | 99.1 | 98.8 |
From the point of view of release experimental data, the insoluble drug release of Mirtazapine tablet of the invention can continue 24 hours, and release
Unwrapping wire is good.
Presently preferred embodiments of the present invention is the foregoing is only, is not intended to limit the invention, all essences in the present invention
God is with principle, and any modifications, equivalent substitutions and improvements made etc. should be included within the scope of the present invention.
Claims (5)
1. a kind of Mirtazapine tablet, it is characterised in that be made up of label and coatings, in parts by weight, label includes
Following supplementary material：20~45 parts of Mirtazapine, 120~240 parts of lactose, 40~80 parts of sodium carboxymethyl starch, microcrystalline cellulose 30~
1~3 part of 60 parts, 15~30 parts of low-substituted hydroxypropyl cellulose, 1~3 part of magnesium stearate and superfine silica gel powder；Coatings are to contain two
The polymer coating layer of titanium oxide and polyethylene glycol.
2. Mirtazapine tablet according to claim 1, it is characterised in that the polymer is Hydroxypropyl methylcellulose, hydroxyl second
Base cellulose, hydroxyethylmethylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methacrylate
Dimethylaminoethyl-methyl acrylate copolymer, ethyl acrylate-methylmethacrylate copolymer, methylcellulose and ethyl
The one or more of cellulose.
3. Mirtazapine tablet according to claim 1 or 2, it is characterised in that the coatings are the 1.8% of label weight
~2.4%.
4. the preparation method of Mirtazapine tablet as claimed in claim 1, it is characterised in that comprise the following steps：
1) by Mirtazapine, magnesium stearate, sodium carboxymethyl starch, superfine silica gel powder, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, breast
Sugared sieving for standby；
2) Mirtazapine, sodium carboxymethyl starch, lactose, purified water are taken, and is added to granulation in wet granulator, and will be obtained
Grain is put into drying machine and dried；And dried particle is put into vibratory sieve carries out whole grain；
3) by step 2) the obtained particle of whole grain is put into Mixers with Multi-direction Movement, and add low-substituted hydroxypropyl cellulose, crystallite
Cellulose, superfine silica gel powder and magnesium stearate, mixing, compressing tablet, obtain label；
4) to step 3) Coating Solution is added in obtained label, it is coated, obtains Mirtazapine tablet.
5. the preparation method of Mirtazapine tablet according to claim 4, it is characterised in that step 2) described in purified water
Parts by weight are 20~30 parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710188989.7A CN106943368A (en) | 2017-03-27 | 2017-03-27 | Mirtazapine tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710188989.7A CN106943368A (en) | 2017-03-27 | 2017-03-27 | Mirtazapine tablet and preparation method thereof |
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| CN106943368A true CN106943368A (en) | 2017-07-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710188989.7A Pending CN106943368A (en) | 2017-03-27 | 2017-03-27 | Mirtazapine tablet and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109793708A (en) * | 2019-02-22 | 2019-05-24 | 青岛农业大学 | Compound injection for badger and preparation method thereof |
| CN111714463A (en) * | 2020-08-14 | 2020-09-29 | 华农（肇庆）生物产业技术研究院有限公司 | Mirtazapine oral preparation and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103520169A (en) * | 2013-10-25 | 2014-01-22 | 山东鲁药制药有限公司 | Mirtazapine tablet and preparation method thereof |
-
2017
- 2017-03-27 CN CN201710188989.7A patent/CN106943368A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103520169A (en) * | 2013-10-25 | 2014-01-22 | 山东鲁药制药有限公司 | Mirtazapine tablet and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109793708A (en) * | 2019-02-22 | 2019-05-24 | 青岛农业大学 | Compound injection for badger and preparation method thereof |
| CN111714463A (en) * | 2020-08-14 | 2020-09-29 | 华农（肇庆）生物产业技术研究院有限公司 | Mirtazapine oral preparation and preparation method thereof |
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