CN104622826B - A kind of Mosapride Citrate Tablets agent and preparation method thereof - Google Patents
A kind of Mosapride Citrate Tablets agent and preparation method thereof Download PDFInfo
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- CN104622826B CN104622826B CN201510091634.7A CN201510091634A CN104622826B CN 104622826 B CN104622826 B CN 104622826B CN 201510091634 A CN201510091634 A CN 201510091634A CN 104622826 B CN104622826 B CN 104622826B
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Abstract
The invention discloses a kind of Mosapride Citrate Tablets agent and preparation method thereof, which is obtained using wet granulation and tabletting, and the adhesive in the wet granulation is the aqueous solution of mosapride citrate and 30 POVIDONE K 30 BP/USP 15.Compared with prior art, the drug-eluting of invention formulation is rapid, and stable quality, preparation process is simple, does not need complicated preparation equipment, is easy to industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of solid orally ingestible, more particularly to one kind
Tablet and preparation method thereof containing mosapride citrate.
Background technology
Mosapride citrate (Mosapride Citrate), entitled 4- amino -5- chloro-2-ethoxy-the N- [[4- of chemistry
(4- luorobenzyls) -2- morpholinyls] methyl] benzamide citrate, for white or off-white color crystalline powder, odorless, slight bitter.
143~145 DEG C of fusing point.Be soluble in dimethylformamide and pyridine, be slightly soluble in methanol, be insoluble in 95% ethyl alcohol, it is not soluble in water or
Ether.
Mosapride citrate is novel third generation medicine for stomach dynamic, is mainly used for functional dyspepsia FD and burns with stomach
The symptoms of digestive tract such as heat, belch, Nausea and vomiting, early satiety, big belly.The medicine can enhance gastrointestinal motility, but not influence hydrochloric acid in gastric juice point
It secretes, while without the side effects such as the extrapyramidal symptoms and diarrhea, and tolerance is good.
After oral solid formulation enters in vivo, it is both needed to by process in leaching, could be absorbed by organisms through biomembrane.But by
It is insoluble drug in mosapride citrate, water is practically insoluble in, in the reality of Mosapride citrate oral solid pharmaceutical preparation
Frequently encounter that dissolution rate is low or even underproof problem in production.In clinic, there is an urgent need to when quick-acting, high-efficiency preparation, solve
The problem that insoluble drug causes bioavilability low because solubility is small, dissolution is slow is always a great problem of pharmaceuticals industry.
CN101816639B discloses a kind of tablet and preparation method thereof containing mosapride citrate, and this method includes
Mosapride citrate is added in absolute ethyl alcohol, water-solubility carrier material is added to after being completely dissolved for 60 DEG C~65 DEG C heating water baths
Expect and stir to dissolve, then goes to solution in Rotary Evaporators, 60 DEG C remove ethyl alcohol under reduced pressure, and solid dispersions are made,
Then further processing piece agent is carried out, the process is more complicated.
CN101273973B discloses a kind of medicine group containing mosapride citrate prepared with direct powder compression
Close object and preparation method thereof.Tablet prepared by the patented technology can fater disintegration, but for insoluble drug, fater disintegration
Afterwards, drug, which also differs, is surely dissolved in dissolution medium.
104188927 A of CN disclose a kind of Mosapride Citrate Tablets agent and preparation method thereof, and this method includes by Chinese holly
Rafter acid dissolves in ethanol, and mosapride citrate raw material is added, is stirred to dissolve, and the dry solution obtains mixture；Then
This mixture is mixed with pharmaceutically acceptable auxiliary material, tabletting.The patented technology uses citric acid as solubilizer, but by
It is low in citric acid fusing point, sticking is easy in tableting processes.
Invention content
In view of the deficiencies in the prior art, the purpose of the present invention is to provide a kind of simple for process, dissolutions rapidly, stable quality
Mosapride Citrate Tablets agent.
In order to achieve the object of the present invention, inventor has carried out deep thinking：Mosapride citrate poor solubility, such as
Fruit can improve its solubility, can necessarily improve dissolution rate；Although acidic materials such as citric acid, which is added, can improve solubility,
But for the few patient of gastric acid secretion, after the acidic materials such as micro citric acid enter alimentary canal, it is not sufficient to ensure that entire digestion
The pH in road is acidity；If the acidic materials such as a large amount of citric acid are added in prescription, tabletting is caused because citric acid fusing point is low
Serious sticking in journey.Therefore, inventor considers, if improving mosapride citrate solubility by other approach, is not
Dependent on adjustment pH, the dissolution of mosapride citrate can be fundamentally solved the problems, such as.
Based on considerations above, inventor is by a large amount of experimental study it was unexpectedly observed that 30 POVIDONE K 30 BP/USP 15 is dissolved in water
In, mosapride citrate is then added, stirring can be such that mosapride citrate dissolves, and experiment shows that mosapride citrate exists
Solubility in water can be improved to 0.08-0.13g/ml.On the basis of this test result, inventor utilizes gathering containing drug
The viscosity of dimension ketone K15 aqueous solutions is pelletized using this solution as adhesive in blank auxiliary, dry, and whole grain, tabletting obtains
It is simple for process, dissolution is rapid, stable quality Mosapride Citrate Tablets agent.Specifically, the purpose of the present invention is by such as
What lower technical solution was realized：
A kind of Mosapride Citrate Tablets agent, which is obtained using wet granulation and tabletting, in the wet granulation
Adhesive is the aqueous solution of mosapride citrate and 30 POVIDONE K 30 BP/USP 15.
Preferably, Mosapride Citrate Tablets agent as described above, the wherein weight of mosapride citrate and 30 POVIDONE K 30 BP/USP 15
Amount is than being 1：(2~20).It is further preferred that the weight ratio of mosapride citrate and 30 POVIDONE K 30 BP/USP 15 is 1：(3~6).At this
In one most preferred embodiment of invention, the weight ratio of mosapride citrate and 30 POVIDONE K 30 BP/USP 15 is 1：4.
In addition, Mosapride Citrate Tablets agent of the present invention also contains disintegrant, filler and lubricant.Wherein,
The disintegrant is one or more of crospovidone, sodium carboxymethyl starch and croscarmellose sodium；It is described
Filler be lactose, microcrystalline cellulose and pregelatinized starch in it is one or more；The lubricant is magnesium stearate, firmly
One or more of resin acid fumaric acid sodium and talcum powder.
The present invention also provides the preparation methods of above-mentioned Mosapride Citrate Tablets agent, and this method comprises the following steps：It will
30 POVIDONE K 30 BP/USP 15 is dissolved in water, and mosapride citrate is added, is stirred to dissolve, then using this solution as adhesive, in medicine
It pelletizes on acceptable other auxiliary materials on, dry, lubricant is added in whole grain, is uniformly mixed, tabletting forms.
Compared with prior art, Mosapride Citrate Tablets agent of the present invention and preparation method thereof has the following advantages that
With marked improvement：
(1) drug-eluting is rapid, stable quality；
(2) preparation method is simple, and raw material does not need special crushing, and granularity requirements are not harsh, does not need complicated preparation
Equipment is easy to industrialized production.
Specific implementation mode
The preparation process and implementation result of the present invention, but the protection of the present invention are now further described by following embodiment
Range is not limited to following embodiment.
Embodiment 1
Preparation method：
The 30 POVIDONE K 30 BP/USP 15 of recipe quantity is dissolved in suitable quantity of water, the mosapride citrate of recipe quantity is added, stirring makes molten
Solution, then using this solution as adhesive, pelletizes on the mixed powder of lactose, microcrystalline cellulose and crospovidone, 60 DEG C of dryings,
Recipe quantity magnesium stearate is added in 14 mesh sieves, is uniformly mixed, tabletting forms.
Embodiment 2
Preparation method：
The 30 POVIDONE K 30 BP/USP 15 of recipe quantity is dissolved in suitable quantity of water, the mosapride citrate of recipe quantity is added, stirring makes molten
Solution, then using this solution as adhesive, pelletizes on the mixed powder of microcrystalline cellulose, pregelatinized starch and sodium carboxymethyl starch,
Recipe quantity sodium stearyl fumarate is added in 55 DEG C of dryings, 20 mesh sieves, is uniformly mixed, tabletting forms.
Embodiment 3
Preparation method：
The 30 POVIDONE K 30 BP/USP 15 of recipe quantity is dissolved in suitable quantity of water, the mosapride citrate of recipe quantity is added, stirring makes molten
Solution, then using this solution as adhesive, pelletizes on the mixed powder of lactose, microcrystalline cellulose and crospovidone, 60 DEG C of dryings,
Recipe quantity magnesium stearate is added in 18 mesh sieves, is uniformly mixed, tabletting forms.
Comparative example 1
Preparation method：
Recipe quantity weighs 30 POVIDONE K 30 BP/USP 15, mosapride citrate, microcrystalline cellulose and the crospovidone sieved with 100 mesh sieve
It is uniformly mixed, recipe quantity magnesium stearate is added, be uniformly mixed, tabletting forms.
Embodiment 4：The quality testing of Mosapride Citrate Tablets is tested
1. related substance-measuring method：Mosapride Citrate Tablets 10 prepared by each embodiment are extracted respectively, finely ground, essence
It is close to weigh in right amount, it is approximately equivalent to mosapride citrate 5mg, is set in 25ml volumetric flasks, mobile phase 15ml, shaking is added to make citric acid
Mosapride dissolves, and is diluted to scale with mobile phase, shakes up, and filters, and takes subsequent filtrate as test solution, and precision measures
2ml sets in 100ml volumetric flasks, mobile phase is added to be diluted to scale, shake up, as a contrast solution.It is surveyed according to high performance liquid chromatography
It is fixed, it uses octadecylsilane chemically bonded silica as filler, (is adjusted with sodium hydroxide test solution with 0.05mol/L citric acid solns
PH is to 4.0)-acetonitrile (70:30) it is mobile phase, Detection wavelength 274nm.10 microlitres of injection liquid chromatographs of contrast solution are taken, are adjusted
Sensitivity is saved, it is about the 20% of range to make principal component chromatographic peak peak height, then precision measures test solution and reference substance solution is each
10 microlitres, it is injected separately into liquid chromatograph.Single impurity must not cross 0.2%.
2. dissolution determination.Chromatographic condition is filler with octadecylsilane chemically bonded silica with system suitability；
It is stream with citric acid soln (adjusting pH value to 4.0 with the sodium hydroxide solution of 2mol/L)-acetonitrile (65: 35) of 0.05mol/L
Dynamic phase, Detection wavelength 274nm, number of theoretical plate is calculated by Mosapride peak is not less than 2000.
Mosapride Citrate Tablets 10 prepared by each embodiment are extracted respectively, according to dissolution method (Chinese Pharmacopoeia
Two annex of version in 2010, Ⅹ the second methods of C), using phosphate buffer (pH6.8) 900ml as dissolution medium, rotating speed is per minute
It 50 turns, operates in accordance with the law, when through 5min, takes solution appropriate respectively, filter, discard 10ml primary filtrates, take subsequent filtrate as test sample
Solution；Separately take mosapride citrate reference substance appropriate, it is accurately weighed, add methanol to dissolve and quantify dilution and is made in every 1ml about
Solution containing 0.28mg, precision measure 1ml, set in 50ml measuring bottles, be diluted to scale with dissolution medium, shake up, as a contrast product
Solution.Precision measures test solution and each 100 μ l of reference substance solution, is injected separately into liquid chromatograph, records chromatogram.By outer
Mark method takes mean value with the stripping quantity of calculated by peak area every, each group.Limit is the 70% of labelled amount, should meet regulation.
Acceleration environment：40 DEG C, 75%RH accelerates 6 months.
Table 1：The quality determination result of Mosapride Citrate Tablets prepared by each embodiment
According in the quality determination result of table 1 it is found that Mosapride Citrate Tablets prepared by 1-3 of the embodiment of the present invention,
Drug-eluting is rapid, and 5min is dissolved out completely, and related substance, the dissolution rate after accelerated experiment are basically unchanged；Comparative example 1 is not by Chinese holly
Rafter acid Mosapride is dissolved in 15 aqueous solution of 30 POVIDONE K 30 BP/USP, and as a result dissolution rate is low, and related substance increases apparent.
Claims (5)
1. a kind of preparation method of Mosapride Citrate Tablets agent, which is characterized in that this method comprises the following steps：By povidone
K15 is dissolved in water, addition mosapride citrate, and the weight ratio of mosapride citrate and 30 POVIDONE K 30 BP/USP 15 is 1：（2~20）,
It is stirred to dissolve, then using this solution as adhesive, pharmaceutically pelletizes on acceptable other auxiliary materials, dry, whole grain, then
Lubricant is added, is uniformly mixed, tabletting forms；Pharmaceutically acceptable other auxiliary materials are disintegrant and filler.
2. the preparation method of Mosapride Citrate Tablets agent according to claim 1, which is characterized in that citric acid Mo Shabi
Profit and the weight ratio of 30 POVIDONE K 30 BP/USP 15 are 1：（3~6）.
3. the preparation method of Mosapride Citrate Tablets agent according to claim 1, which is characterized in that the disintegrant
For one or more of crospovidone, sodium carboxymethyl starch and croscarmellose sodium.
4. the preparation method of Mosapride Citrate Tablets agent according to claim 1, which is characterized in that the filler
It is one or more in lactose, microcrystalline cellulose and pregelatinized starch.
5. the preparation method of Mosapride Citrate Tablets agent according to claim 1, which is characterized in that the lubricant
For one or more of magnesium stearate, sodium stearyl fumarate and talcum powder.
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| CN106913879B (en) * | 2015-12-28 | 2021-07-30 | 山东新时代药业有限公司 | Mosapride citrate tablet and preparation method thereof |
| CN109394711A (en) * | 2018-11-06 | 2019-03-01 | 威海贯标信息科技有限公司 | A kind of cinbitrate tartrate tablet composition |
| CN110354093B (en) * | 2019-07-31 | 2021-09-17 | 常州恒邦药业有限公司 | Mosapride citrate pharmaceutical composition |
| CN111505154B (en) * | 2020-05-07 | 2022-09-30 | 南京百思福医药科技有限公司 | Detection method for mosapride citrate and five key impurities in preparation thereof |
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| CN101816639A (en) * | 2010-01-15 | 2010-09-01 | 鲁南制药集团股份有限公司 | Tablets of mosapride citrate and preparation method thereof |
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| CN1150902C (en) * | 2001-12-26 | 2004-05-26 | 成都康弘科技实业（集团）有限公司 | Prescription of preparing moxapride citrate |
| TW200418486A (en) * | 2003-01-31 | 2004-10-01 | Takeda Chemical Industries Ltd | Solid preparation |
| JP2011246428A (en) * | 2010-05-26 | 2011-12-08 | Nisshin Seiyaku Kk | Orally disintegrating medicine and production method |
| CN104013595B (en) * | 2013-03-01 | 2016-08-24 | 安徽贝克生物制药有限公司 | A kind of SelegilineHydrochloride preparation and preparation technology thereof |
| CN104188927B (en) * | 2014-09-01 | 2019-04-05 | 鲁南制药集团股份有限公司 | A kind of Mosapride Citrate Tablets agent and preparation method thereof |
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| CN101816639A (en) * | 2010-01-15 | 2010-09-01 | 鲁南制药集团股份有限公司 | Tablets of mosapride citrate and preparation method thereof |
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| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20180626 Address after: No. 200, companion Kun Road, Minhang District, Shanghai Applicant after: Shanghai Pukang Pharmaceutical Co.,Ltd. Address before: 211200 Jintian pharmaceutical company, No. 1, economic development zone, Yong Yang Town, Lishui District, Nanjing, Jiangsu Applicant before: Sun Qiaoling |
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Denomination of invention: Mosapride citrate tablet and its preparation method Effective date of registration: 20230627 Granted publication date: 20180810 Pledgee: Bank of Hangzhou Limited by Share Ltd. Shanghai branch Pledgor: Shanghai Pukang Pharmaceutical Co.,Ltd. Registration number: Y2023310000315 |