CN105769872B - A kind of mosapride citrate composition of Fast Stripping - Google Patents
A kind of mosapride citrate composition of Fast Stripping Download PDFInfo
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Abstract
The present invention provides a kind of mosapride citrate compositions of Fast Stripping, including mosapride citrate and fumed silica, the mosapride citrate and the fumed silica common co-grinding in milling machinery, the two mass ratio is 1:0.2-1.2, partial size D50≤3.0 μm of the mosapride citrate；It also may include one of filler, disintegrating agent, adhesive, lubricant, glidant, corrigent or a variety of in the composition.Mosapride citrate composition of the present invention greatly improves dissolution rate of the mosapride citrate in the buffer solution (simulated intestinal fluid) of pH6.8, improve the validity of gastric anacidity type patient medication, its preparation process is easy, it is easily operated, without using any organic reagent, without damp and hot process is passed through, avoids mosapride citrate and wild effect occurs in hygrothermal environment, be suitable for industrialized large-scaled production application.
Description
Technical field
The present invention relates to field of medicaments, and in particular to a kind of mosapride citrate composition of Fast Stripping.
Background technique
Mosapride citrate is the third generation medicine for stomach dynamic of Nihon Pharmaceutical Co., Ltd.'s exploitation, and clinic is mainly used for function
Property indigestion is with symptoms of digestive tract persons such as heartburn, belch, Nausea and vomiting, early satiety, big bellies.Its chemical name is
(±) -4- amino -5- chloro-2-ethoxy-N- { [4- (4- luorobenzyl) -2- morphine base] methyl } toluamide citric acid monocalcium salt
Close object, molecular formula C21H25ClFN3O3·C6H8O7·2H2O, molecular weight 650.05, structural formula are
Mosapride Citrate Tablets were ratified to list in 1999 in China, and clinical use specification has 2.5mg and 5mg.Citron
Sour Mosapride is II class drug of BCS, and solubility in water is extremely low, for the solid pharmaceutical preparation of such drug, drug
The rate that ingredient is dissolved out from preparation is usually to influence the rate-limiting step of drug bioavailability.It is clearly advised in existing national standards
Mosapride Citrate Tablets are determined under the conditions of hydrochloric acid solution (simulate the gastric juice) of 0.1mol/L, and dissolution rate when 30min must not be low
In 75%, to guarantee that drug is effectively discharged and absorbed in patient's stomach.However, for the patient of certain gastric anaciditys
For, mosapride citrate preparation may will be greatly reduced in the dissolution of stomach, cause its vivo biodistribution availability to decline, no
Effective therapeutic purposes can be reached.For this some patients, duodenum is that mosapride citrate discharges in vivo
With the significant points of absorption.Therefore, mosapride citrate preparation is improved in the buffer solution medium (simulated intestinal fluid) of pH 6.8
In dissolution rate for guaranteeing that the safety of clinical application, validity have great significance.Existing country's import drugs standard
In also under the buffer conditions of pH6.8, dissolution rate when 45min must not be lower than clear stipulaties Mosapride Citrate Tablets
80%.The applicant by long-term experimental studies have found that, most of mosapride citrate preparations on domestic market
The dissolution rate bound requirements being all satisfied in the hydrochloric acid solution (simulate the gastric juice) of 0.1mol/L, but in the buffer solution of pH 6.8
Dissolution rate in medium (simulated intestinal fluid) is generally lower.Trouble may be faced in clinical application in view of mosapride citrate preparation
The problem of person's gastric anacidity, thus improve its dissolution rate in simulated intestinal fluid be very it is necessary to.
The currently used method of dissolution rate for improving insoluble drug mainly has: drug micronization, addition solubilizer or
Cosolvent, using cyclodextrin inclusion technique, prepare solid dispersions etc..But currently used solubilizer (or cosolvent) is big
There is irritation or serious adverse reaction strongly more, reduce the compliance of patient's Long-term taking medicine；Merely using micro-
Powdering techniques reduce that diameter of aspirin particle is different surely to reach ideal solubilizing effect, and use cyclodextrin inclusion technique or common
Often processing step is various, complicated for operation for solid dispersion technology, is unfavorable for amplification production.Such as: Chinese patent application
A kind of method for preparing mosapride citrate solid dispersions is disclosed in CN101816639A, comprising: citric acid is not husky
Must benefit be added to absolute ethanol, after heating for dissolving be added water soluble carrier material such as 30 POVIDONE K 30 BP/USP 15, PVP K30, polyethylene glycol
4000, Macrogol 6000 etc., is concentrated under reduced pressure after mixing, is dried under reduced pressure 3-6h again after volatilizing ethyl alcohol, is crushed, sieving
To obtain the final product.This method need to use organic reagent and be performed under heating conditions, and not only increase production cost, also bring certain peace
Full hidden danger, and mosapride citrate itself belongs to thermographic compound, is easy to happen wild effect under wet heat condition；And
And this method processing step is complicated, the Parameter Conditions for needing to control are more, are unfavorable for carrying out quality control in industrial mass production.
Summary of the invention
In view of drawbacks described above of the existing technology, the technical problem to be solved in the present invention is to provide it is a kind of can be in pH 6.8
Buffer solution (simulated intestinal fluid) in Fast Stripping mosapride citrate composition, to improve the biological utilisation of drug
Degree guarantees mosapride citrate preparation in clinical application to the validity of gastric anacidity patient.
The present invention is achieved by the following technical solutions:
A kind of mosapride citrate composition of Fast Stripping, including mosapride citrate and fumed silica,
The mosapride citrate and the fumed silica common co-grinding in milling machinery, the two mass ratio are 1:0.2-
1.2, preferably 1:0.3-0.9, more preferably 1:0.3-0.6；Partial size D50≤3.0 μm of the mosapride citrate, preferably
It is 1.0 μm -3.0 μm；
Preferably, revolving speed >=1000 turn/min of the milling machinery, preferably >=3000 turn/min；When co-grinding
Between be 15-40s, preferably 25s；
Further, the mosapride citrate composition further includes filler, disintegrating agent, adhesive, corrigent, lubrication
One of agent is a variety of；Wherein, the filler is selected from lactose, microcrystalline cellulose, mannitol, sucrose, pregelatinized starch, paste
One of essence, calcium sulfate are a variety of, preferably one of lactose, microcrystalline cellulose, pregelatinized starch or a variety of；The disintegration
Agent is in low-substituted hydroxypropyl cellulose, Crospovidone, sodium carboxymethyl starch, dried starch, alginic acid, sodium carboxymethylcellulose
One or more, preferably one of low-substituted hydroxypropyl cellulose, Crospovidone or a variety of；Described adhesive is selected from poly- dimension
One of ketone K30, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose are a variety of, preferably poly-
Tie up ketone K30, ethyl cellulose；The corrigent is selected from one of aspartame, honey element, fructose, Steviosin, xylose or more
Kind, preferably aspartame, honey element；The lubricant be selected from magnesium stearate, Stepanol MG, polyethylene glycol, stearic acid,
One of sldium lauryl sulfate is a variety of, preferably magnesium stearate, Stepanol MG；The glidant is selected from talcum powder；
Mosapride citrate dosage is 2%-6.9% in the composition, and fumed silica dosage is 1.9%-
2.6%, filler loading 57.8-91%, disintegrating agent dosage are 2.6%-18.5%, lubricant quantity 0-1%, adhesive
Dosage is 0-7.2%, and corrigent dosage is 0-2.6%, and glidant dosage is 0-21.6%；
Preferably, the mosapride citrate composition is made of the component of following mass percents: the Chinese holly of 2%-5%
Rafter acid Mosapride, the fumed silica of 2%-2.5%, the filler of 73%-88.3%, 7%-18.5% disintegrating agent and
The lubricant of 0.7%-1%, wherein filler is selected from lactose, microcrystalline cellulose, pregelatinized starch, and disintegrating agent is selected from low substitution hydroxyl
Propyl cellulose, Crospovidone or sodium carboxymethyl starch, the lubricant are selected from magnesium stearate, Stepanol MG；
The present invention further provides a kind of preferred mosapride citrate compositions, by the component of following mass percents
Be made: 3.3% mosapride citrate, 2% fumed silica, 82.9% filler, 11% disintegrating agent,
0.8% lubricant, wherein filler is selected from lactose, microcrystalline cellulose, and disintegrating agent is selected from low-substituted hydroxypropyl cellulose, hands over
Povidone, lubricant are selected from magnesium stearate.
Mosapride citrate composition of the present invention compared with prior art, has the advantage that
1, without using any organic reagent, production cost is low, highly-safe；
2, damp and hot process is needed not move through, mosapride citrate is avoided and wild effect occurs in hygrothermal environment；
3, preparation process is easy, easily operated, is suitable for industrialized large-scaled production application；
4, dissolution rate of the mosapride citrate in the buffer solution (simulated intestinal fluid) of pH 6.8 is greatly improved, is improved
The validity of gastric anacidity type patient medication.
Below by part Experiment content, the present invention is described further；Institute is experimentally and real in the present invention
It is as follows to test material:
1, dissolution determination method and evaluation
Dissolution determination method in 1.1 simulate the gastric juices (0.1mol/L hydrochloric acid solution)
Test sample is taken, according to dissolution method (two annex X C third methods of Chinese Pharmacopoeia version in 2010), with 0.1mol/L
Hydrochloric acid solution 250ml is solvent, and revolving speed is 50 turns per minute, operates according to methods, when through 30 minutes, takes solution appropriate, filters, take continuous
Filtrate shines spectrophotometry (two annex IVA of Chinese Pharmacopoeia version in 2010), and trap is measured at 274nm wavelength；It is another accurate
It is appropriate to weigh the mosapride citrate reference substance through determination of moisture, adds 0.1mol/L hydrochloric acid solution tepor ultrasonic treatment to make molten
Solution, and be made in every 1ml plus solvent is stated containing about the solution of 20 μ g, it is measured in the same method, calculates every the amount of dissolution.
Dissolution determination method in 1.2 simulated intestinal fluids (pH6.8 phosphate buffer)
Test sample is taken, according to dissolution method (two annex X C third methods of Chinese Pharmacopoeia version in 2010), with pH6.8 phosphorus
Phthalate buffer (takes potassium dihydrogen phosphate 1.70g and recasts hydrogen dipotassium 1.775g, add water 1000ml to make to dissolve, shake up) 900ml be
Solvent, revolving speed are 50 turns per minute, operate according to methods, when through 45 minutes, solution are taken to consider through filter membrane, and precision measures subsequent filtrate 5ml,
It sets in 10ml measuring bottle, solubilization goes out medium to scale, shakes up, as test solution.Precision is weighed through phosphorus pentoxide 60
It is appropriate DEG C to be dried under reduced pressure 4 hours mosapride citrate reference substances, with flowing phased soln and quantifies to dilute and every 1ml is made and contains
The solution of mosapride citrate 2.8ug, as contrast solution.According to high performance liquid chromatography (Chinese Pharmacopoeia 2010 version two
Annex VD) measurement.Used time octadecylsilane chemically bonded silica is filler, (takes Chinese holly with acetonitrile-methanol-citrate buffer
Rafter acid sodium 8.82g, adds water 800ml to make to dissolve, with salt acid for adjusting pH value to 3.3, adds water to 1000ml) (7:9:24) 2 be flowing
Phase, 40 DEG C of column temperature, Detection wavelength 274nm.Adjusting flow velocity makes the retention time of Mosapride be about 9 minutes, theoretical cam curve
4000 should be no less than by Mosapride calculating, the symmetrical factor at Mosapride peak should measure reference substance solution no more than 2.0. precision
It is injected separately into liquid chromatograph with each 50ul of test solution, by external standard method with calculated by peak area every the amount of dissolution.
1.3 evaluation criterion
In 0.1mol/L hydrochloric acid solution (simulate the gastric juice), the dissolution of mosapride citrate must not be lower than when 30min
75%；In pH6.8 phosphate buffer (simulated intestinal fluid), mosapride citrate dissolution should be not less than 80% when 45min.
2, experimental material
Mosapride citrate (Chengdu limited liability company, Kang Hong medicine company collective)；Lactose (German Mei Jile group,70)；Microcrystalline cellulose (U.S. FMC, PH102)；Crospovidone (U.S. ISP, XL-10), low-substituted hydroxypropyl fiber
Element (Anhui Shanhe Medical Accessary Material Co., Ltd., QB-11), pregelatinized starch (Anhui Shanhe Medical Accessary Material Co., Ltd.), corn
Starch (Zhejiang sea salt six and starch Co., Ltd), povidone (BASF Corp, K30), sodium carboxymethylcellulose (Huai Nanshan
River pharmaceutic adjuvant Co., Ltd), aspartame (Anhui Zhong Xu Biotechnology Co., Ltd), honey element (Xi'an Yuhua biology section
Skill Co., Ltd), mannitol (Co., Ltd, An Wei Double-Crane Pharmaceutical Co., Ltd), talcum powder (Anhui Shanhe Medical Accessary Material Co., Ltd.), second
Base cellulose (medical auxiliary materials factory, Luzhou Chemical Plant), fumed silica (CABOT company, the U.S.,M-5P)、
Magnesium stearate (Huzhou Zhanwang Pharmaceutical Co., Ltd.)；Single-punch tablet press (Beijing Gylongli Sci.&Tech. Co., Ltd.), efficient liquid phase
Chromatograph (Anjelen Sci. & Tech. Inc, 1200LC), (Tianda Tianfa Science and Technology Co. Ltd., ZRS-8G are intelligently dissolved out digestion instrument
Tester).
3, composition components are investigated
The preparation of 3.1 mosapride citrate compositions
Method one (physical mixed): taking each 2 parts of microcrystalline cellulose, lactose, Crospovidone, fumed silica, respectively with 5
Part mosapride citrate (D50=2.3um) hand mix is uniform, and it is spare；
Method two (co-grinding): taking each 2 parts of microcrystalline cellulose, lactose, Crospovidone, fumed silica, respectively with 5
Part mosapride citrate (D50=2.3um) the portable pulverizer that revolving speed is 2000 turns/min, co-grinding 25s are added jointly
Afterwards, spare.
8 parts of mosapride citrate mixture are taken made from method one, two respectively, and 91 parts of microcrystalline celluloses are added and mix,
Add 1 part of magnesium stearate, mix, tabletting to get.
The detection of 3.2 dissolution rates
The result of extraction of above-mentioned preparation is detected according to dissolution detection method described in " 1.1 ", " 1.2 ", as a result such as table 1-1
With shown in 1-2.
Table 1-1 dissolution rate (0.1mol/L hydrochloric acid) testing result
Table 1-2 dissolution rate (phosphate buffer of pH6.8) testing result
According to table 1-1 it is found that the composition that mosapride citrate is prepared from different auxiliary material using different hybrid modes
The equal > 75% of the dissolution rate of 30min in 0.1mol/L hydrochloric acid solution, meets the requirement (experimental example 1-8) of the related drug standards.
However, according to table 1-2 result it is found that in the phosphate buffer of pH6.8, not using different auxiliary material and citric acid
The composition dissolving out capability being prepared after Sha Bili mixing has bigger difference, uses mannitol, lactose and microcrystalline cellulose etc.
Manufactured composition has that dissolution is slow after auxiliary material and mosapride citrate carry out physical mixed or co-grinding,
Dissolution rate in 45min is below 80% (experimental example 10-12,14-16)；Applicant is found surprisingly that in an experiment, uses
Fumed silica can significantly improve the dissolving out capability of drug, but be different the mosapride citrate group that hybrid technique obtains
Closing object dissolving out capability also has obvious gap, is mixed mosapride citrate and fumed silica using General Physics hybrid mode
After conjunction, dissolution rate of the mosapride citrate in simulated intestinal fluid increases, but dissolution rate when 45min is only 78.7%
(experimental example 9) is unable to satisfy requirement (>=80%) of the related drug standards about dissolution rate；Using co-grinding mode preparation group
After closing object, dissolution rate of the mosapride citrate in simulated intestinal fluid is obviously accelerated, and the dissolution rate in 45min mentions significantly
Up to 85.9% (experimental example 13).
4, influence of the main ingredient partial size to dissolution rate
The preparation of 4.1 compositions
The mosapride citrate of different-grain diameter (being specifically shown in Table 2) is taken, is added jointly with appropriate fumed silica respectively
Revolving speed is the portable pulverizer of 2000 turns/min, spare after co-grinding 25s.
8 parts of aforementioned mosapride citrate mixture is taken, 91 parts of microcrystalline celluloses are added, mixes, is eventually adding 1 part of tristearin
Sour magnesium, mix, tabletting to get.
The detection of 4.2 dissolution rates
It is molten in the phosphate buffer of pH6.8 that above-mentioned preparation is detected according to dissolution detection method described in " 1.2 "
Effect out, the results are shown in Table 2.
2 mosapride citrate dissolution rate testing result of table
According to experimental result in table 2 it is found that before common co-grinding, the partial size of mosapride citrate (API) is big
The small dissolving out capability on composition has apparent influence, and when 3.0 μm of > of API partial size D50, mosapride citrate is in simulation intestines
The dissolution rate of 45min is lower than 80% in liquid, is unable to satisfy relevant criterion and requires (experimental example 21-23)；When API partial size D50≤3.0
μm when, up to 80% or more, and with the reduction of partial size, dissolution rate presentation is incremented by dissolution rate when 45min in simulated intestinal fluid
Gesture (experimental example 17-20).It can be seen that technology of the invention can be achieved when partial size D50≤3.0 μm of mosapride citrate
Effect, it is contemplated that the excessive reduction of partial size will lead to energy consumption in actual production and greatly increase, and operability reduces, therefore preferred Chinese holly
The partial size D50 of rafter acid Mosapride is 1.0-3.0 μm.
5, influence of the component ratio to dissolution rate in composition
The preparation of 5.1 compositions
The API (D50=2.3 μm) and fumed silica (being shown in Table 3) of different quality ratio are taken, the common revolving speed that is added is 2000
Turn/portable the pulverizer of min, it is spare after co-grinding 25s.
5 parts of aforementioned mixture are taken, is added in 91 parts of microcrystalline celluloses and mixes, adds 1 part of magnesium stearate, is mixed, tabletting,
To obtain the final product.
The detection of 5.2 dissolution rates
It is molten in the phosphate buffer of pH6.8 that above-mentioned preparation is detected according to dissolution detection method described in " 1.2 "
Effect out, the results are shown in Table 3.
3 mosapride citrate preparation dissolution rate testing result of table
As seen from the results in Table 3, the mass ratio of mosapride citrate and fumed silica to drug-eluting performance have compared with
It is big to influence, when mosapride citrate is 1.0:0.2-1.2 with fumed silica mass ratio, the 45min in simulated intestinal fluid
When dissolution rate be above 80.5% (experimental example 25-29), when mosapride citrate and fumed silica mass ratio are
When 1.0:0.3-0.9, the dissolution rate under the same terms is more excellent, up to 85.5% or more (experimental example 26-28), when citric acid is not husky
Must benefit with fumed silica mass ratio be 1.0:0.3-0.6 when, mosapride citrate dissolution rate can further improve to
87.4% or more (experimental example 26,27).
6, influence of the co-grinding condition to dissolution rate
The preparation of 6.1 compositions
5 parts and 3 parts of fumed silica of mosapride citrate (D50 2.3um) are taken, with the pulverizer of adjustable revolving speed
Carry out co-grinding, incorporation time 25s.
8 parts of aforementioned mixture are taken, 91 parts of microcrystalline celluloses are added and mix, are eventually adding 1 part of magnesium stearate, mix, tabletting,
To obtain the final product.
The detection of 6.2 dissolution rates
It is molten in the phosphate buffer of pH6.8 that above-mentioned preparation is detected according to dissolution detection method described in " 1.2 "
Effect out, the results are shown in Table 4.
4 mosapride citrate preparation dissolution rate testing result of table
As seen from the results in Table 4, the condition of co-grinding has the dissolution rate of mosapride citrate highly important
It influences, when carrying out co-grinding using the lower pulverizer of revolving speed, there is no apparent for the result of extraction of mosapride citrate
Improve (experimental example 32-34), when pulverizer revolving speed reaches 1000 turns/min or more, mosapride citrate dissolution rate mentions significantly
Height, and with the raising of revolving speed, (experimental example 35-39) is continuously improved in dissolution rate.Therefore, select pulverizer revolving speed >=1000 turn/
Min is advisable, preferably >=3000 turn/min.
Specific embodiment
Reference examples 1
Mosapride citrate, fumed silica are taken, after mixing, combination is made after ball mill grinding 3h is added
Object mixes composition obtained with low-substituted hydroxypropyl cellulose, adds starch, microcrystalline cellulose mixing, crosses 40 meshes
Dispersion 1 time, be added magnesium stearate total mix, mix, tabletting to get.According to the detection preparation dissolution of method described in " 1.1 ", " 1.2 "
It is as follows to investigate result for degree:
5 reference examples of table, 1 preparation dissolution rate investigates result
Reference examples 2
Mosapride Citrate Tablets are prepared referring to the technical solution of specification embodiment 8 in CN101816639A, according to
Method described in " 1.1 ", " 1.2 " detects preparation dissolution rate, and it is as follows to investigate result:
6 reference examples of table, 2 preparation dissolution rate investigates result
Embodiment 1
By above-mentioned prescription, take API that partial size D50 is 1.05um and fumed silica be added jointly revolving speed be 4500 turns/
The pulverizer of min is made composition after co-grinding 25s, composition obtained and mannitol, microcrystalline cellulose is mixed
Close, add sodium carboxymethyl starch mixing, cross 40 meshes disperse 1 time, be added magnesium stearate total mix, mix, tabletting to get.It presses
Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", it is as follows to investigate result:
7 embodiment of table, 1 preparation dissolution rate investigates result
Embodiment 2
By above-mentioned prescription, take API that partial size D50 is 1.7um and fumed silica be added jointly revolving speed be 2000 turns/
Composition is made after co-grinding 40s in the pulverizer of min, and composition obtained and sodium carboxymethyl starch, Crospovidone are carried out
Mixing adds microcrystalline cellulose, sucrose mixing, crosses 40 meshes and disperse 1 time, Stepanol MG total mix is added, mix, press
Piece to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", it is as follows to investigate result:
8 embodiment of table, 2 preparation dissolution rate investigates result
Embodiment 3
By above-mentioned prescription, take API that partial size D50 is 1.7um and fumed silica be added jointly revolving speed be 1500 turns/
The pulverizer of min is made composition after co-grinding 30s, composition obtained is mixed with aspartame, is added low
Replace hydroxypropylcellulose, microcrystalline cellulose, talcum powder, mixing, cross 40 meshes disperse 1 time, mix, tabletting to get.According to
Method described in " 1.1 ", " 1.2 " detects preparation dissolution rate, and it is as follows to investigate result:
9 embodiment of table, 3 preparation dissolution rate investigates result
Embodiment 4
By above-mentioned prescription, take API that partial size D50 is 2.3um and fumed silica be added jointly revolving speed be 3000 turns/
The pulverizer of min is made composition after co-grinding 20s, composition obtained is mixed with lactose, adds crystallite fibre
It ties up element, low-substituted hydroxypropyl cellulose, Crospovidone to mix, crosses 40 meshes and disperse 1 time, magnesium stearate total mix is added, mix, pressure
Piece to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", it is as follows to investigate result:
10 embodiment of table, 4 preparation dissolution rate investigates result
Embodiment 5
By above-mentioned prescription, take API that partial size D50 is 2.1um and fumed silica be added jointly revolving speed be 2000 turns/
Composition is made after co-grinding 15s in the pulverizer of min, and composition obtained is progressively increased with honey element equivalent, and it is primary to mix, and adds
Enter remaining composition to be mixed, it is mixed to add pregelatinized starch, microcrystalline cellulose, Crospovidone, PVP K30, talcum powder
It is even, cross 40 meshes disperse 1 time, mix, tabletting to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", is examined
It is as follows to examine result:
11 embodiment of table, 5 preparation dissolution rate investigates result
Embodiment 6
By above-mentioned prescription, take API that partial size D50 is 1.05um and fumed silica be added jointly revolving speed be 2000 turns/
The pulverizer of min is made composition after co-grinding 15s, composition obtained is mixed with lactose, adds crystallite fibre
It ties up element, low-substituted hydroxypropyl cellulose, Crospovidone to be uniformly mixed, crosses 40 meshes and disperse 1 time, be eventually adding magnesium stearate mixing,
Tabletting to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", it is as follows to investigate result:
12 embodiment of table, 6 preparation dissolution rate investigates result
Embodiment 7
By above-mentioned prescription, take API that partial size D50 is 2.1um and fumed silica be added jointly revolving speed be 1000 turns/
Composition is made after co-grinding 20s in the pulverizer of min, and composition obtained is progressively increased with aspartame equivalent, and it is primary to mix,
Remaining composition is added to be mixed, pregelatinized starch, microcrystalline cellulose, Crospovidone, ethyl cellulose, talcum powder are added
Mix, cross 40 meshes disperse 1 time, mix, tabletting to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ",
It is as follows to investigate result:
13 embodiment of table, 7 preparation dissolution rate investigates result
Embodiment 8
By above-mentioned prescription, take API that partial size D50 is 1.9um and fumed silica be added jointly revolving speed be 4000 turns/
Composition is made after co-grinding 35s in the pulverizer of min, and composition obtained is progressively increased with aspartame equivalent, and it is primary to mix,
Remaining composition is added to be mixed, adds lactose mixing, it is mixed to be eventually adding pregelatinized starch, Crospovidone, PVP K30
It is even, cross 40 meshes disperse 1 time, be added magnesium stearate total mix, mix, tabletting to get.According to method described in " 1.1 ", " 1.2 "
Preparation dissolution rate is detected, it is as follows to investigate result:
14 embodiment of table, 8 preparation dissolution rate investigates result
Embodiment 9
By above-mentioned prescription, take API that partial size D50 is 1.1um and fumed silica be added jointly revolving speed be 2000 turns/
The pulverizer of min is made composition after co-grinding 25s, composition obtained is mixed with sodium carboxymethylcellulose, is added
Lactose, microcrystalline cellulose mix, cross 40 meshes disperse 1 time, be added magnesium stearate total mix, mix, tabletting to get.According to
Method described in " 1.1 ", " 1.2 " detects preparation dissolution rate, and it is as follows to investigate result:
15 embodiment of table, 9 preparation dissolution rate investigates result
Embodiment 10
By above-mentioned prescription, take API that partial size D50 is 1.1um and fumed silica be added jointly revolving speed be 1500 turns/
The pulverizer of min is made composition after co-grinding 20s, composition obtained is mixed with Crospovidone, adds crystallite fibre
Dimension element mix, cross 40 meshes disperse 1 time, be added magnesium stearate total mix, mix, tabletting to get.According to institute in " 1.1 ", " 1.2 "
Method detection preparation dissolution rate is stated, it is as follows to investigate result:
16 embodiment of table, 10 preparation dissolution rate investigates result
Embodiment 11
By above-mentioned prescription, take API that partial size D50 is 1.9um and fumed silica be added jointly revolving speed be 1500 turns/
The pulverizer of min is made composition after co-grinding 15s, composition obtained is mixed with lactose, adds crystallite fibre
It ties up element, low-substituted hydroxypropyl cellulose, Crospovidone to be uniformly mixed, crosses 40 meshes and disperse 1 time, be eventually adding magnesium stearate mixing,
Tabletting to get.Preparation dissolution rate is detected according to method described in " 1.1 ", " 1.2 ", it is as follows to investigate result:
17 embodiment of table, 11 preparation dissolution rate investigates result
Claims (16)
1. a kind of mosapride citrate composition of Fast Stripping, including mosapride citrate and fumed silica, institute
Mosapride citrate and the fumed silica common co-grinding in milling machinery are stated, the two mass ratio is 1:0.2-
1.2, wherein partial size D50≤3.0 μm of the mosapride citrate, revolving speed >=1000 turn/min of the milling machinery, institute
Stating the co-grinding time is 15-40s, and the mosapride citrate composition is prepared using direct powder compression.
2. mosapride citrate composition according to claim 1, it is characterised in that mosapride citrate and gas phase
The mass ratio of silica is 1:0.3-0.9.
3. mosapride citrate composition according to claim 2, it is characterised in that mosapride citrate and gas phase
The mass ratio of silica is 1:0.3-0.6.
4. mosapride citrate composition according to claim 1, it is characterised in that the mosapride citrate
Partial size D50 is 1.0 μm -3.0 μm.
5. mosapride citrate composition according to claim 1, it is characterised in that the revolving speed of the milling machinery >=
3000 turns/min.
6. mosapride citrate composition according to claim 1, it is characterised in that the co-grinding time is
25s。
7. mosapride citrate composition according to claim 1 to 6, it is characterised in that the composition
In further include one of filler, disintegrating agent, adhesive, corrigent, lubricant or a variety of.
8. mosapride citrate composition according to claim 7, it is characterised in that the filler is selected from lactose, micro-
One of crystalline cellulose, mannitol, sucrose, pregelatinized starch, dextrin, calcium sulfate are a variety of；The disintegrating agent is selected from low take
For one of hydroxypropyl cellulose, Crospovidone, sodium carboxymethyl starch, dried starch, alginic acid, sodium carboxymethylcellulose or more
Kind；Described adhesive is selected from PVP K30, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose
One of or it is a variety of；The corrigent is selected from one of aspartame, honey element, fructose, Steviosin, xylose or a variety of；
The lubricant be selected from one of magnesium stearate, Stepanol MG, polyethylene glycol, stearic acid, sldium lauryl sulfate or
It is a variety of.
9. mosapride citrate composition according to claim 8, it is characterised in that the filler is selected from lactose, micro-
One of crystalline cellulose, pregelatinized starch are a variety of.
10. mosapride citrate composition according to claim 8, it is characterised in that the disintegrating agent is selected from low substitution
One of hydroxypropyl cellulose, Crospovidone are a variety of.
11. mosapride citrate composition according to claim 8, it is characterised in that described adhesive is selected from povidone
K30, ethyl cellulose.
12. mosapride citrate composition according to claim 8, it is characterised in that the corrigent is selected from aspa
Smooth, honey element.
13. mosapride citrate composition according to claim 8, it is characterised in that the lubricant is selected from stearic acid
Magnesium, Stepanol MG.
14. mosapride citrate composition according to claim 8, it is characterised in that citric acid is not in the composition
Sand must utilization be 2%-6.9%, fumed silica dosage is 1.9%-2.6%, and filler loading 57.8-91% collapses
Solution agent dosage is 2.6%-18.5%, lubricant quantity 0-1%, binder dosage 0-7.2%, and corrigent dosage is 0-
2.6%.
15. according to claim 1-6, mosapride citrate composition described in any one of 8-14, it is characterised in that described
Mosapride citrate composition is made of the component of following mass percents:
Wherein, filler is selected from lactose, microcrystalline cellulose, pregelatinized starch, and disintegrating agent is selected from low-substituted hydroxypropyl cellulose, hands over
Povidone or sodium carboxymethyl starch, the lubricant are selected from magnesium stearate, Stepanol MG.
16. mosapride citrate composition according to claim 15, it is characterised in that the mosapride citrate
Composition is made of the component of following mass percents:
Wherein, filler is selected from lactose, microcrystalline cellulose, and disintegrating agent is selected from low-substituted hydroxypropyl cellulose, Crospovidone, lubrication
Agent is selected from magnesium stearate.
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| CN201410819954.5A CN105769872B (en) | 2014-12-25 | 2014-12-25 | A kind of mosapride citrate composition of Fast Stripping |
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| CN105769872B true CN105769872B (en) | 2019-05-03 |
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| CN107661506B (en) * | 2016-07-26 | 2022-04-29 | 江苏豪森药业集团有限公司 | Mosapride citrate pharmaceutical preparation and preparation method thereof |
| CN108324697B (en) * | 2017-01-19 | 2021-03-19 | 科贝源(北京)生物医药科技有限公司 | Mosapride citrate-containing capsule and preparation method thereof |
| CN111529492A (en) * | 2020-05-25 | 2020-08-14 | 重庆方通动物药业有限公司 | Compound mosapride soluble powder and preparation method and application thereof |
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| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN101130432A (en) * | 2006-08-22 | 2008-02-27 | 德古萨股份公司 | Fumed silica for use as auxiliary in pharmaceutical and cosmetic compositions |
| CN101273973A (en) * | 2007-03-28 | 2008-10-01 | 成都康弘科技实业（集团）有限公司 | Pharmaceutical combination containing Mosapride citrate and method of preparing the same |
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| CN102885798A (en) * | 2011-07-21 | 2013-01-23 | 成都康弘药业集团股份有限公司 | Orally disintegrating tablet |
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| CN103705477A (en) * | 2013-12-26 | 2014-04-09 | 山东博迈康药物研究有限公司 | Tablets containing erlotinib hydrochloride and preparation method thereof |
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| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN101130432A (en) * | 2006-08-22 | 2008-02-27 | 德古萨股份公司 | Fumed silica for use as auxiliary in pharmaceutical and cosmetic compositions |
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| CN101352424A (en) * | 2008-09-16 | 2009-01-28 | 天津市中央药业有限公司 | Cefdinir dispersible tablet and preparation method thereof |
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| CN103142541A (en) * | 2012-09-05 | 2013-06-12 | 北京万全阳光医学技术有限公司 | Stable montelukast sodium capsule |
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