CN103520169B - Mirtazapine tablet and preparation method thereof - Google Patents
Mirtazapine tablet and preparation method thereof Download PDFInfo
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- CN103520169B CN103520169B CN201310509567.7A CN201310509567A CN103520169B CN 103520169 B CN103520169 B CN 103520169B CN 201310509567 A CN201310509567 A CN 201310509567A CN 103520169 B CN103520169 B CN 103520169B
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Abstract
The invention relates to a mirtazapine tablet and a preparation method thereof. The mirtazapine tablet is prepared from a tablet core and a coating layer, wherein the tablet core contains 15-45mg of mirtazapine, 40-180mg of lactose, 70-200mg of starch, 8-25mg of hydroxy propyl cellulose, 0.75-3mg of magnesium stearate and 0.75-3mg of aerosol. The particle size range of the mirtazapine is 3.0-96.0 microns; the coating layer accounts for 2.0-3.0% of weight of the tablet core. The obtained mirtazapine tablet preparation disclosed by the invention is stable in quality, simple to prepare and operate, low in production cost, and applicable to industrial mass production. The mirtazapine tablet prepared by the invention simulates operation of the tablets in the stomach and intestines; an in vitro dissolution curve is determined; the mirtazapine tablet is good in consistency between batches, stable and controllable in quality, and consistent with the dissolution behaviors of an original development agent in four different mediums.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, more particularly, the present invention relates to a kind of mirtazapine tablets and preparation method thereof.
Background technology
Mirtazapine (Mirtazapine) is the well-known medicine being used for the treatment of depression, has tetracyclic structure, belongs to the tall and erect compounds 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 Adrenergic nerve conduction.It blocks 5-HT2 and the 5-HT3 receptor of maincenter simultaneously, and two kinds of optical antimers of mirtazapine all have antidepressant activity, and levo form blocks α 2 and 5-HT2 receptor, and d-isomer blocks 5-HT3 receptor.Antihistaminic receptor (H1) characteristic of mirtazapine plays sedation.This medicine has good toleration, almost without anticholinergic effect, on cardiovascular system without impact.Mirtazapine is applicable to depression, and to symptom as anhedonia, psychomotor activity suppresses, and sleeps not good enough and loses weight all effective in cure.Also can be used for other symptom as: to things lose interest, suicidal idea and anxious state of mind, after medication one to two week after onset, its therapeutic dose on cardiovascular system without impact.
After mirtazapine tablets is oral, its active component mirtazapine is absorbed (bioavailability is about 50%) very soon, and after about two hours, plasma concentration peaks.About 85% is combined with plasma protein.Mean half-life is 20-40 hour; Accidentally reach 65 hours; Also accidental shorter half-life in youngster.The size removing the half-life is just being suitable for the mode of taking to be decided to be once a day.Blood drug level reaches steady will after taking medicine three to four days, after this will occur without building up in body phenomenon.In recommended dosage range, " the pharmacokinetics form of mirtazapine is linear.Mirtazapine to be excreted by urine and feces in several days after the tablet has been ingested by metabolism mostly.Its main biochemical mode is that demethylation and oxidation reaction exist, and follows by association reaction.Metabolite after piptonychia is the same with former compound still has a pharmacologically active.The bad mirtazapine clearance rate that causes of hepatic and renal function reduces.
Authorized Chinese patent CN1173701C discloses and comprises mirtazapine or its pharmaceutically acceptable salt, pharmaceutically acceptable excipient and wrap by the pharmaceutical formulation of the coatings of mirtazapine and preparation method; the prescription of the mirtazapine oral cavity disintegration tablet under this patent requirements protection description entry and technique; mirtazapine crude drug is coated on celphere top layer by this technique as a solution; by bag by after ball core to mix homogeneously tabletting with other filleies, to reach the object discharged fast.Authorized Chinese patent CN101129341 discloses the another kind of preparation method of mirtazapine oral cavity disintegration tablet, comprises pharmaceutical formulation of mirtazapine, disintegrating agent, filler and other excipient and preparation method thereof.Pendent publication CN102078309A discloses the dosage form of mirtazapine dispersible tablet.
Summary of the invention
An object of the present invention is to provide one to comprise there is the deliquescent mirtazapine tablets of particle size dependence.Another object of the present invention is to provide a kind of preparation method of mirtazapine tablets.
Object of the present invention can be realized by following technical scheme:
A kind of mirtazapine tablets, it is characterized in that: be made up of label and coatings, containing containing 15 ~ 45mg mirtazapine, 40 ~ 180mg lactose, 70 ~ 200mg starch, 8 ~ 25mg hydroxypropyl cellulose, 0.75 ~ 3mg magnesium stearate and 0.75 ~ 3mg micropowder silica gel in every sheet of described label; The particle size range of described mirtazapine is 3.0 ~ 96.0 μm; Described coatings is 2.0% ~ 3.0% of label weight.
Preferably, its Core formulation is composed as follows:
Mirtazapine 15,30 or 45mg
Lactose 70 to 160mg
Starch 100 to 180mg
Hydroxypropyl cellulose 12 to 25mg
Magnesium stearate 0.9 to 2.4mg
Micropowder silica gel 0.9 to 2.4mg
Preferred, its Core formulation is composed as follows:
Mirtazapine 15,30 or 45mg
Lactose 120 to 160mg
Starch 130 to 170mg
Hydroxypropyl cellulose 19.5 to 25mg
Magnesium stearate 1.2 to 2.1mg
Micropowder silica gel 1.2 to 2.1mg
Preferably, granularity (unit: μm) distribution characteristics of described mirtazapine is: D
10∈ (6,10), D
50∈ (15,22), D
90∈ (33,41).
Preferably, described coatings is the polymer coating layer containing titanium dioxide and Polyethylene Glycol, and described polymer is one or more of hypromellose, hydroxyethyl-cellulose, methyl hydroxyethylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methacrylate dimethylaminoethyl-methyl acrylate copolymer, ethyl acrylate-methylmethacrylate copolymer, methylcellulose and ethyl cellulose; Described coatings is 2.3% ~ 2.8% of label weight.
The preparation method of described mirtazapine tablets, it is characterized in that: mirtazapine is crushed to regulation requirement, take after the mirtazapine of recipe quantity and lactose, starch mixes, add 8 ~ 10% hydroxypropyl cellulose aqueous solution appropriate, soft material processed, granulation, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, obtained label; Coating, to obtain final product.
The present invention compared with prior art has the following advantages: because in mirtazapine water, dissolubility is lower, its granularity directly affects the product quality of preparation, under this invention, the gained mirtazapine quality of the pharmaceutical preparations is stable, preparation manipulation is simple, production cost is low, is suitable for industrialized great production.Stripping curve is the important quality index evaluating gastrointestinal administration tablet, adopt the mirtazapine tablets that the present invention obtains, imitate the running of tablet in gastrointestinal, measure In Vitro Dissolution curve, each batch-to-batch consistency is good, stable and controllable for quality, consistent with the dissolved corrosion of former triturate in four kinds of different mediums.
Accompanying drawing explanation
Below in conjunction with accompanying drawing, the present invention is further illustrated.
Accompanying drawing 1 is prescription of the present invention (embodiment 1-7) and the stripping curve figure of former triturate in medium 0.1mol/LHCl;
Accompanying drawing 2 is prescription of the present invention (embodiment 1-7) and the stripping curve figure of former triturate in WATER AS FLOW MEDIUM;
Accompanying drawing 3 is prescription of the present invention (embodiment 1-7) and the stripping curve figure of former triturate in medium pH4.5 acetic acid-acetate buffer;
Accompanying drawing 4 is prescription of the present invention (embodiment 1-7) and the stripping curve figure of former triturate in medium pH6.8 sodium hydroxide-potassium phosphate buffer.
Detailed description of the invention
In order to the present invention is further illustrated, set forth with specific embodiment below, but the restriction to scope of the present invention can not be interpreted as.
embodiment 1:
Mirtazapine 30g
Lactose 40g
Starch 200g
10% hydroxypropyl cellulose aqueous solution 200ml
Magnesium stearate 0.75g
Micropowder silica gel 0.75g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=16.552, D after micronization processes
10=6.720 μm, D
50=15.221 μm, D
90=33.190 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 2:
Mirtazapine 30g
Lactose 180g
Starch 70g
10% hydroxypropyl cellulose aqueous solution 120ml
Magnesium stearate 1.5g
Micropowder silica gel 0.75g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=18.453, D after micronization processes
10=7.291 μm, D
50=17.195 μm, D
90=35.184 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 3:
Mirtazapine 30g
Lactose 160g
Starch 100g
8% hydroxypropyl cellulose aqueous solution 100ml
Magnesium stearate 1.2g
Micropowder silica gel 1.2g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=19.142, D after micronization processes
10=6.560 μm, D
50=18.814 μm, D
90=37.510 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 4:
Mirtazapine 30g
Lactose 180g
Starch 70g
8% hydroxypropyl cellulose aqueous solution 100ml
Magnesium stearate 0.75g
Micropowder silica gel 1.5g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=22.725, D after micronization processes
10=9.761 μm, D
50=21.335 μm, D
90=40.228 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 5:
Mirtazapine 30g
Lactose 130g
Starch 130g
8% hydroxypropyl cellulose aqueous solution 120ml
Magnesium stearate 1.5g
Micropowder silica gel 3.0g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=19.874, D after micronization processes
10=7.130 μm, D
50=18.720 μm, D
90=35.271 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 6:
Mirtazapine 30g
Lactose 90g
Starch 160g
8% hydroxypropyl cellulose aqueous solution 180ml
Magnesium stearate 3.0g
Micropowder silica gel 1.5g
Preparation method: lactose, starch cross 80 mesh sieves; By mirtazapine (granulometry: Dav=16.918, D10=6.088 μm, D after micronization processes
50=16.548 μm, D
90=35.469 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 7:
Mirtazapine 30g
Lactose 80g
Starch 170g
8% hydroxypropyl cellulose aqueous solution 220ml
Magnesium stearate 2.1g
Micropowder silica gel 2.1g
Preparation method: lactose, starch cross 80 mesh sieves; By the mirtazapine (granulometry: Dav=17.482, D after micronization processes
10=6.013 μm, D
50=16.314 μm, D
90=35.887 μm) mix homogeneously with lactose, starch by equal increments method; Add 10% hydroxypropyl cellulose aqueous solution soft material; 24 mesh sieves are granulated; 60 ± 5 DEG C of dryings 1.5 hours, seethe granule 2 to 3 times in dry run; 20 mesh sieve granulate; Magnesium stearate and the micropowder silica gel mix homogeneously of recipe quantity is added, tabletting in the granule after granulate.Adopt conventional coating equipment, use stomach dissolution type Opadry to carry out coating to preparation.
embodiment 8:
Get mirtazapine tablets prepared by above-described embodiment 1-7, stripping curve mensuration is carried out according to dissolution method (Chinese Pharmacopoeia 2010 editions two annex Ⅹ C slurry processes), rotating speed 50 revs/min, medium uses 0.1mol/LHCl, water, pH4.5 acetic acid-acetate buffer, pH6.8 sodium hydroxide-potassium phosphate buffer respectively, operate in accordance with the law, according to EP2013, adopt liquid chromatography to measure sample, comparison film is the mirtazapine tablets of former triturate, batch number: 817879; Date of manufacture: 20110107; Valid until: 2013.12; Manufacturing enterprise: N.V.Organon; Production address: Kloosterstraat6,5349AB, OSS, the Netherlands; Result is as table 1-4 and accompanying drawing 1-4:
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Claims (4)
1. a mirtazapine tablets, it is characterized in that: be made up of label and coatings, the label of every sheet consists of the following composition: 15 ~ 45mg mirtazapine, 40 ~ 180mg lactose, 40 ~ 180mg starch, 15 ~ 45mg hydroxypropyl cellulose, 0.75 ~ 3mg magnesium stearate and 0.75 ~ 3mg micropowder silica gel; The particle size range of described mirtazapine is 3.0 ~ 96.0 μm; Described coatings is 2.0% ~ 3.0% of label weight;
Coatings is the polymer coating layer containing titanium dioxide and Polyethylene Glycol, and described polymer is one or more of hypromellose, hydroxyethyl-cellulose, methyl hydroxyethylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methacrylate dimethylaminoethyl-methyl acrylate copolymer, ethyl acrylate-methylmethacrylate copolymer, methylcellulose and ethyl cellulose;
The preparation method of mirtazapine tablets is, mirtazapine is crushed to regulation requirement, take after the mirtazapine of recipe quantity and lactose, starch mixes, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulation, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, obtained label; Coating, to obtain final product.
2. mirtazapine tablets according to claim 1, is characterized in that described Core formulation is composed as follows: mirtazapine 15,30 or 45mg, lactose 120 to 160mg, starch 130 to 170mg, hydroxypropyl cellulose 19.5 to 25mg, magnesium stearate 1.2 to 2.1mg, micropowder silica gel 1.2 to 2.1mg.
3. mirtazapine tablets according to claim 1 and 2, is characterized in that described Core formulation is composed as follows: the particle size distribution characteristic of described mirtazapine is: D
10∈ (6,10), D
50∈ (15,22), D
90∈ (33,41), unit: μm.
4. mirtazapine tablets according to claim 1 and 2, is characterized in that described Core formulation is composed as follows: described coatings is 2.3% ~ 2.8% of label weight.
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| CN201310509567.7A CN103520169B (en) | 2013-10-25 | 2013-10-25 | Mirtazapine tablet and preparation method thereof |
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| CN103520169B true CN103520169B (en) | 2015-07-15 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105287418A (en) * | 2015-11-29 | 2016-02-03 | 南京多宝生物科技有限公司 | Simvastatin tablets with effect of reducing blood lipid |
| CN105412029A (en) * | 2015-12-03 | 2016-03-23 | 南京多宝生物科技有限公司 | Anti-hypertension benzene sulfonic acid levamlodipine besylate tablet |
| CN106822022A (en) * | 2017-03-01 | 2017-06-13 | 华益药业科技(安徽)有限公司 | Mirtazapine tablets and preparation method thereof |
| CN106943368A (en) * | 2017-03-27 | 2017-07-14 | 华益药业科技(安徽)有限公司 | Mirtazapine tablet and preparation method thereof |
| CN111714463B (en) * | 2020-08-14 | 2022-06-17 | 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 |
|---|---|---|---|---|
| CN102078309A (en) * | 2011-01-22 | 2011-06-01 | 王定豪 | Dispersible tablet containing antipsychotic medicines and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6019900A (en) * | 1999-11-24 | 2001-06-04 | Sumika Fine Chemicals Co., Ltd. | Anhydrous mirtazapine crystals and process for producing the same |
| EP1689371A2 (en) * | 2003-11-25 | 2006-08-16 | Aurobindo Pharma Limited | Pharmaceutical compositions of mirtazapine |
| IS7724A (en) * | 2005-03-02 | 2006-09-03 | Actavis Group | Composition of tablets with rapid decomposition containing heavy magnesium carbonate |
| CN101129341B (en) * | 2006-08-22 | 2011-06-01 | 上海医药工业研究院 | Intra-oral disintegration compositions and process for producing same |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102078309A (en) * | 2011-01-22 | 2011-06-01 | 王定豪 | Dispersible tablet containing antipsychotic medicines and application thereof |
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