CN105769872A - Rapidly-dissolving mosapride citrate composition - Google Patents
Rapidly-dissolving mosapride citrate composition Download PDFInfo
- Publication number
- CN105769872A CN105769872A CN201410819954.5A CN201410819954A CN105769872A CN 105769872 A CN105769872 A CN 105769872A CN 201410819954 A CN201410819954 A CN 201410819954A CN 105769872 A CN105769872 A CN 105769872A
- Authority
- CN
- China
- Prior art keywords
- mosapride citrate
- dissolution
- mosapride
- cellulose
- compositions according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention provides a rapidly-dissolving mosapride citrate composition, which comprises mosapride citrate and fumed silica. Mosapride citrate and fumed silica are mixed and crushed in a crushing machine, wherein mass ratio of mosapride citrate to fumed silica is 1:0.2-1.2; and particle size D50 of the mosapride citrate is less than or equal to 3.0 microns. The composition also contains one or more ingredients selected from a filler, a disintegrating agent, an adhesive, a lubricant, a flow aid and a flavouring agent. By the use of the mosapride citrate composition, dissolution rate of mosapride citrate in a buffer solution (a simulated intestinal fluid) with pH 6.8 is greatly raised, and medication effectiveness is raised for achlorhydria patients. The preparation technology is simple and is easy to operate. Any organic reagents are not used, and hot and humid process is not required. Instability of mosapride citrate in a hot and humid environment is avoided. The composition of the invention is suitable for industrial production.
Description
Technical field
The present invention relates to field of medicaments, be specifically related to the mosapride citrate compositions of a kind of Fast Stripping.
Background technology
Mosapride citrate is the third generation medicine for stomach dynamic of Nihon Pharmaceutical Co., Ltd.'s exploitation, and clinic is mainly used in functional dyspepsia with symptom of digestive tract persons such as heartburn, belch, Nausea and vomiting, early satiety, big bellies.Its chemical name be (±)-4-amino-5-chloro-2-ethoxy-N-{ [4-(4-luorobenzyl)-2-morphine base] methyl toluamide citrate dihydrate, its molecular formula is C21H25ClFN3O3·C6H8O7·2H2O, molecular weight is 650.05, and structural formula is
Mosapride Citrate Tablets is in 1999 in China's approval listing, and Clinical practice specification has 2.5mg and 5mg.Mosapride citrate is BCS II class medicine, and its dissolubility in water is extremely low, and for the solid preparation of this type of medicine, ingredient speed of dissolution from preparation usually affects the rate-limiting step of drug bioavailability.In existing national standards, clear stipulaties Mosapride Citrate Tablets is under hydrochloric acid solution (simulated gastric fluid) condition of 0.1mol/L, dissolution during 30min must not lower than 75%, thus ensureing that medicine is effectively discharged in patient's stomach and absorbs.But, for the patient of some achlorhydria, mosapride citrate preparation may be substantially reduced in the dissolution of stomach, causes that its vivo biodistribution availability declines, it is impossible to reach effective therapeutic purposes.For this some patients, duodenum is the significant points that mosapride citrate discharges in vivo and absorbs.Therefore, mosapride citrate preparation dissolution in the buffer solution medium (simulated intestinal fluid) of pH6.8 is improved for ensureing that the safety of clinical application, effectiveness have great significance.In existing country import drugs standard, also clear stipulaties Mosapride Citrate Tablets is under the buffer conditions of pH6.8, and dissolution during 45min must not lower than 80%.The applicant experimental studies have found that through long-term, most of mosapride citrate preparations on domestic market are satisfied by the dissolution bound requirements in the hydrochloric acid solution (simulated gastric fluid) of 0.1mol/L, but the dissolution in the buffer solution medium (simulated intestinal fluid) of pH6.8 is generally relatively low.In view of mosapride citrate preparation is likely to face the anacid problem of Stomach in Patients in clinical practice, therefore improve its dissolution in simulated intestinal fluid and be extremely necessary.
The method of the at present conventional dissolution improving insoluble drug mainly has: drug micronization, adds solubilizing agent or cosolvent, employing cyclodextrin inclusion technique, prepare solid dispersion etc..But, solubilizing agent (or cosolvent) conventional at present has zest strongly or serious untoward reaction mostly, reduces the compliance of patient's Long-term taking medicine；Simple adopt micronization technology to reduce diameter of aspirin particle to differ and reach desirable solubilizing effect surely, and adopt cyclodextrin inclusion technique or common solid dispersion technology often processing step is various, complicated operation, be unfavorable for amplifying and produce.Such as: a kind of method preparing mosapride citrate solid dispersion disclosed in Chinese patent application CN101816639A, including: mosapride citrate is added in dehydrated alcohol, water soluble carrier material such as 30 POVIDONE K 30 BP/USP 15, PVP K30, Macrogol 4000, polyethylene glycol 6000 etc. are added after heating for dissolving, concentrating under reduced pressure is carried out after mix and blend, volatilize after ethanol drying under reduced pressure 3-6h again, pulverize, sieve and get final product.The method need to use organic reagent and carry out in a heated condition, not only increases production cost, also brings certain potential safety hazard, and mosapride citrate itself belongs to thermographic compound, is susceptible to wild effect under wet heat condition；Further, the method processing step is complicated, it is necessary to the Parameter Conditions of control is more, is unfavorable in the big production of industry and carries out quality control.
Summary of the invention
In view of the drawbacks described above that prior art exists, the technical problem to be solved in the present invention be to provide a kind of can in the buffer solution (simulated intestinal fluid) of pH6.8 the mosapride citrate compositions of Fast Stripping, thus improving the bioavailability of medicine, it is ensured that mosapride citrate preparation effectiveness to achlorhydria patient in clinical practice.
The present invention is achieved by the following technical solutions:
A kind of mosapride citrate compositions of Fast Stripping, including mosapride citrate and aerosil, described mosapride citrate and aerosil be common co-grinding in size reduction machinery, the two mass ratio is 1:0.2-1.2, it is preferably 1:0.3-0.9, more preferably 1:0.3-0.6；Particle diameter D50≤3.0 μm of described mosapride citrate, it is preferred to 1.0 μm-3.0 μm；
Preferably, the rotating speed >=1000 turn/min of described size reduction machinery, it is preferable that >=3000 turns/min；The co-grinding time is 15-40s, it is preferred to 25s；
Further, described mosapride citrate compositions also includes one or more in filler, disintegrating agent, binding agent, correctives, lubricant；Wherein, one or more in lactose, microcrystalline Cellulose, mannitol, sucrose, pregelatinized Starch, dextrin, the calcium sulfate of described filler, it is preferable that one or more in lactose, microcrystalline Cellulose, pregelatinized Starch；One or more in low-substituted hydroxypropyl cellulose, crospovidone, carboxymethyl starch sodium, dried starch, alginic acid, the sodium carboxymethyl cellulose of described disintegrating agent, it is preferable that one or more in low-substituted hydroxypropyl cellulose, crospovidone；Described binding agent is selected from one or more in PVP K30, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, it is preferable that PVP K30, ethyl cellulose；Described correctives is selected from one or more in Aspartane, cyclamate, fructose, steviosin, xylose, it is preferable that Aspartane, cyclamate；Described lubricant is selected from one or more in magnesium stearate, Stepanol MG, Polyethylene Glycol, stearic acid, sodium laurylsulfate, it is preferable that magnesium stearate, Stepanol MG；Described fluidizer is selected from Pulvis Talci；
In described compositions, mosapride citrate consumption is 2%-6.9%, aerosil consumption is 1.9%-2.6%, filler loading is 57.8-91%, disintegrating agent consumption is 2.6%-18.5%, lubricant quantity is 0-1%, binder dosage is 0-7.2%, and correctives consumption is 0-2.6%, and fluidizer consumption is 0-21.6%；
Preferably, described mosapride citrate compositions is made up of the component of following mass percent: the lubricant of the mosapride citrate of 2%-5%, the aerosil of 2%-2.5%, the filler of 73%-88.3%, the disintegrating agent of 7%-18.5% and 0.7%-1%, wherein filler is selected from lactose, microcrystalline Cellulose, pregelatinized Starch, disintegrating agent is selected from low-substituted hydroxypropyl cellulose, crospovidone or carboxymethyl starch sodium, and described lubricant is selected from magnesium stearate, Stepanol MG；
The present invention further provides a kind of preferred mosapride citrate compositions, be made up of the component of following mass percent: the mosapride citrate of 3.3%, the aerosil of 2%, 82.9% filler, 11% disintegrating agent, 0.8% lubricant, wherein, filler is selected from lactose, microcrystalline Cellulose, disintegrating agent is selected from low-substituted hydroxypropyl cellulose, crospovidone, and lubricant is selected from magnesium stearate.
Mosapride citrate compositions of the present invention compared with prior art, has the advantage that
1, without using any organic reagent, production cost is low, and safety is high；
2, damp and hot process is needed not move through, it is to avoid wild effect occurs mosapride citrate in hygrothermal environment；
3, preparation technology is easy, it is easy to operation, is suitable for industrialized large-scaled production application；
4, it is greatly improved mosapride citrate dissolution in the buffer solution (simulated intestinal fluid) of pH6.8, improves the effectiveness that achlorhydria type patient takes medicine.
Below by part Experiment content, the present invention is described further；In the present invention institute experimentally and experiment material as follows:
1, dissolution determination method and evaluation
Dissolution determination method in 1.1 simulated gastric fluid (0.1mol/L hydrochloric acid solution)
Take test sample, according to dissolution method (Chinese Pharmacopoeia two annex XC the 3rd methods of version in 2010), with 0.1mol/L hydrochloric acid solution 250ml for solvent, rotating speed is 50 turns per minute, operates in accordance with the law, through 30 minutes time, take solution appropriate, filter, take subsequent filtrate according to spectrophotography (Chinese Pharmacopoeia two annex IVA of version in 2010), measure trap at 274nm wavelength place；The mosapride citrate reference substance that another precision weighs through determination of water is appropriate, adds 0.1mol/L hydrochloric acid solution tepor supersound process and makes dissolving, and adds above-mentioned solvent and make in every 1ml the solution containing about 20 μ g, is measured in the same method, calculates the stripping quantity of every.
Dissolution determination method in 1.2 simulated intestinal fluids (pH6.8 phosphate buffer)
Take test sample, according to dissolution method (Chinese Pharmacopoeia two annex XC the 3rd methods of version in 2010), (take potassium dihydrogen phosphate 1.70g and the hydrogen dipotassium 1.775g that recasts with pH6.8 phosphate buffer, the 1000ml that adds water makes dissolving, shakes up) 900ml is solvent, rotating speed is 50 turns per minute, operate in accordance with the law, through 45 minutes time, taking solution and considered through filter membrane, precision measures subsequent filtrate 5ml, put in 10ml measuring bottle, add dissolution medium to scale, shake up, as need testing solution.Precision weighs through phosphorus pentoxide 60 DEG C of drying under reduced pressure mosapride citrate reference substance of 4 hours appropriate, dissolves with mobile phase and quantitatively dilutes and make every 1ml solution containing mosapride citrate 2.8ug, as contrast solution.Measure according to high performance liquid chromatography (Chinese Pharmacopoeia two annex VD of version in 2010).Used time octadecylsilane chemically bonded silica is filler, (sodium citrate 8.82g is taken with acetonitrile-methanol-citrate buffer, the 800ml that adds water makes dissolving, with salt acid for adjusting pH value to 3.3, add water to 1000ml) (7:9:24) 2 be mobile phase, column temperature 40 DEG C, detection wavelength is 274nm.Regulating flow velocity makes the retention time of mosapride be about 9 minutes, theoretical cam curve presses mosapride calculating should no less than 4000, the symmetrical factor at mosapride peak should be not more than 2.0. precision and measure reference substance solution and each 50ul of need testing solution is injected separately into chromatograph of liquid, by the external standard method stripping quantity with calculated by peak area every.
1.3 evaluation criterions
In 0.1mol/L hydrochloric acid solution (simulated gastric fluid), during 30min, the dissolution of mosapride citrate must not lower than 75%；In pH6.8 phosphate buffer (simulated intestinal fluid), during 45min, mosapride citrate dissolution should be not less than 80%.
2, experiment material
Mosapride citrate (Chengdu limited company of Kang Hong Pharmaceutical collective)；Lactose (Mei Jile group of Germany,70)；Microcrystalline Cellulose (U.S. FMC, PH102)；Crospovidone (American I SP, XL-10), low-substituted hydroxypropyl cellulose (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 company limited), polyvidone (BASF Corp, K30), sodium carboxymethyl cellulose (mountains and rivers, Huainan pharmaceutic adjuvant company limited), aspartame (Zhong Xu bio tech ltd, Anhui), cyclamate (Yuhua bio tech ltd, Xi'an), mannitol (company limited of An Wei Double-Crane Pharmaceutical Co., Ltd), Pulvis Talci (Anhui Shanhe Medical Accessary Material Co., Ltd.), ethyl cellulose (medical auxiliary materials factory of Luzhou Chemical Plant), aerosil (CABOT company of the U.S.,M-5P), magnesium stearate (Huzhou Zhanwang Pharmaceutical Co., Ltd.)；Single punch tablet machine (Beijing Gylongli Sci.&Tech. Co., Ltd.), high performance liquid chromatograph (Anjelen Sci. & Tech. Inc, 1200LC), digestion instrument (Tianda Tianfa Science and Technology Co. Ltd., ZRS-8G intelligence dissolving-out tester).
3, composition components is investigated
The preparation of 3.1 mosapride citrate compositionss
Method one (physical mixed): take microcrystalline Cellulose, lactose, crospovidone, each 2 parts of aerosil, respectively with 5 parts of mosapride citrate (D50=2.3um) hand mix is uniform, standby；
Method two (co-grinding): take microcrystalline Cellulose, lactose, crospovidone, each 2 parts of aerosil, respectively with 5 parts of mosapride citrate (D50=2.3um) jointly add the portable pulverizer that rotating speed is 2000 turns/min, after co-grinding 25s, standby.
8 parts of the mosapride citrate mixture that access method one, two prepares respectively, adds 91 parts of microcrystalline Cellulose mixings, adds 1 part of magnesium stearate, mixing, and tabletting to obtain final product.
3.2 dissolution detections
Described in " 1.1 ", " 1.2 ", dissolution detection method detects the result of extraction of above-mentioned preparation, and result is such as shown in table 1-1 and 1-2.
Table 1-1 dissolution (0.1mol/L hydrochloric acid) testing result
Table 1-2 dissolution (phosphate buffer of pH6.8) testing result
According to table 1-1, mosapride citrate adopts the compositions equal > 75% of the dissolution of 30min in 0.1mol/L hydrochloric acid solution prepared by different hybrid modes from different auxiliary material, meets the requirement (experimental example 1-8) of relevant drug standard.
But, according to table 1-2 result, in the phosphate buffer of pH6.8, the compositions dissolving out capability that different auxiliary material prepares after mixing with mosapride citrate is adopted to have bigger difference, using the compositions that the adjuvants such as mannitol, lactose and microcrystalline Cellulose and mosapride citrate are made after carrying out physical mixed or co-grinding all to there is dissolution problem slowly, the dissolution when 45min is below 80% (experimental example 10-12,14-16)；Applicant is found surprisingly that in an experiment, use aerosil can significantly improve the dissolving out capability of medicine, but the mosapride citrate compositions dissolving out capability that different hybrid techniques obtains also has obvious gap, after adopting General Physics hybrid mode to be mixed with aerosil by mosapride citrate, mosapride citrate dissolution rate in simulated intestinal fluid increases, but dissolution during 45min is only 78.7% (experimental example 9), it is impossible to meet the requirement (>=80%) about dissolution of the relevant drug standard；After adopting co-grinding mode to prepare compositions, mosapride citrate dissolution rate in simulated intestinal fluid is substantially accelerated, and the dissolution when 45min is greatly increased to 85.9% (experimental example 13).
4, the principal agent particle diameter impact on dissolution
The preparation of 4.1 compositionss
Take the mosapride citrate of different-grain diameter (being specifically shown in table 2), jointly add the portable pulverizer that rotating speed is 2000 turns/min respectively with appropriate aerosil, standby after co-grinding 25s.
Take 8 parts of aforementioned mosapride citrate mixture, add 91 parts of microcrystalline Cellulose, mixing, it is eventually adding 1 part of magnesium stearate, mixing, tabletting, to obtain final product.
4.2 dissolution detections
Dissolution detection method detection above-mentioned preparation result of extraction in the phosphate buffer of pH6.8 described in " 1.2 ", result is as shown in table 2.
Table 2 mosapride citrate dissolution testing result
According to experimental result in table 2, before common co-grinding, the dissolving out capability of compositions is had obvious impact by the size of mosapride citrate (API), as API particle diameter D50 > 3.0 μm, mosapride citrate in simulated intestinal fluid the dissolution of 45min lower than 80%, it is impossible to meet relevant criterion require (experimental example 21-23)；When API particle diameter D50≤3.0 μm, in simulated intestinal fluid, during 45min, dissolution is up to more than 80%, and along with the reduction of particle diameter, dissolution presents increasing trend (experimental example 17-20).As can be seen here, the technique effect of the present invention all can be realized during particle diameter D50≤3.0 μm of mosapride citrate, considering that the excessive reduction of particle diameter can cause that in actual production, energy consumption is greatly increased, operability reduces, it is thus preferred to the particle diameter D50 of mosapride citrate is 1.0-3.0 μm.
5, the component ratio impact on dissolution in compositions
The preparation of 5.1 compositionss
Taking API (D50=2.3 μm) and the aerosil (see table 3) of different quality ratio, common addition rotating speed is the portable pulverizer of 2000 turns/min, after co-grinding 25s, standby.
Take aforementioned mixture 5 parts, add in 91 parts of microcrystalline Cellulose and mix, add 1 part of magnesium stearate, mixing, tabletting, to obtain final product.
5.2 dissolution detections
Dissolution detection method detection above-mentioned preparation result of extraction in the phosphate buffer of pH6.8 described in " 1.2 ", result is as shown in table 3.
Table 3 mosapride citrate preparation dissolution testing result
As seen from the results in Table 3, drug-eluting performance is had considerable influence by the mass ratio of mosapride citrate and aerosil, when mosapride citrate and aerosil mass ratio are 1.0:0.2-1.2, in simulated intestinal fluid, dissolution during 45min is above 80.5% (experimental example 25-29), when mosapride citrate and aerosil mass ratio are 1.0:0.3-0.9, dissolution under the same terms is more excellent, up to more than 85.5% (experimental example 26-28), when mosapride citrate and aerosil mass ratio are 1.0:0.3-0.6, mosapride citrate dissolution can further improve to more than 87.4% (experimental example 26, 27).
6, the co-grinding condition impact on dissolution
The preparation of 6.1 compositionss
Taking mosapride citrate (D50 is 2.3um) 5 parts and aerosil 3 parts, carry out co-grinding with the pulverizer of scalable rotating speed, incorporation time is 25s.
Take aforementioned mixture 8 parts, add 91 parts of microcrystalline Cellulose mixings, be eventually adding 1 part of magnesium stearate, mixing, tabletting, to obtain final product.
6.2 dissolution detections
Dissolution detection method detection above-mentioned preparation result of extraction in the phosphate buffer of pH6.8 described in " 1.2 ", result is as shown in table 4.
Table 4 mosapride citrate preparation dissolution testing result
As seen from the results in Table 4, the condition of co-grinding has highly important impact for the dissolution of mosapride citrate, when the pulverizer adopting rotating speed relatively low carries out co-grinding, the result of extraction of mosapride citrate does not improve significantly (experimental example 32-34), when pulverizer rotating speed reaches 1000 turns/more than min, mosapride citrate dissolution is greatly improved, and along with the raising of rotating speed, dissolution improves constantly (experimental example 35-39).Therefore, pulverizer rotating speed >=1000 turn/min is selected to be advisable, it is preferable that >=3000 turns/min.
Detailed description of the invention
Reference examples 1
Take mosapride citrate, aerosil, after mix homogeneously, compositions is made after adding ball mill grinding 3h, prepared compositions is mixed with low-substituted hydroxypropyl cellulose, adds starch, microcrystalline Cellulose mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 5 reference examples 1 preparation dissolution investigates result
Reference examples 2
Mosapride Citrate Tablets is prepared with reference to the technical scheme of description embodiment 8 in CN101816639A, method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigate result as follows:
Table 6 reference examples 2 preparation dissolution investigates result
Embodiment 1
By above-mentioned prescription, take the API that particle diameter D50 is 1.05um and jointly add, with aerosil, the pulverizer that rotating speed is 4500 turns/min, compositions is made after co-grinding 25s, prepared compositions is mixed with mannitol, microcrystalline Cellulose, adds carboxymethyl starch sodium mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 7 embodiment 1 preparation dissolution investigates result
Embodiment 2
By above-mentioned prescription, take the API that particle diameter D50 is 1.7um and jointly add, with aerosil, the pulverizer that rotating speed is 2000 turns/min, compositions is made after co-grinding 40s, prepared compositions is mixed with carboxymethyl starch sodium, crospovidone, adds microcrystalline Cellulose, sucrose mixing, cross 40 mesh sieves and disperse 1 time, add Stepanol MG always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 8 embodiment 2 preparation dissolution investigates result
Embodiment 3
By above-mentioned prescription, take the API that particle diameter D50 is 1.7um and jointly add, with aerosil, the pulverizer that rotating speed is 1500 turns/min, compositions is made after co-grinding 30s, prepared compositions is mixed with aspartame, add low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, Pulvis Talci, mixing, cross 40 mesh sieves and disperse 1 time, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 9 embodiment 3 preparation dissolution investigates result
Embodiment 4
By above-mentioned prescription, take the API that particle diameter D50 is 2.3um and jointly add, with aerosil, the pulverizer that rotating speed is 3000 turns/min, compositions is made after co-grinding 20s, prepared compositions is mixed with lactose, adds microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crospovidone mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 10 embodiment 4 preparation dissolution investigates result
Embodiment 5
By above-mentioned prescription, take the API that particle diameter D50 is 2.1um and jointly add, with aerosil, the pulverizer that rotating speed is 2000 turns/min, compositions is made after co-grinding 15s, prepared compositions being progressively increased with cyclamate equivalent mixes once, adds remaining set compound and mixes, and adds pregelatinized Starch, microcrystalline Cellulose, crospovidone, PVP K30, Pulvis Talci mixing, cross 40 mesh sieves to disperse 1 time, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 11 embodiment 5 preparation dissolution investigates result
Embodiment 6
By above-mentioned prescription, take the API that particle diameter D50 is 1.05um and jointly add, with aerosil, the pulverizer that rotating speed is 2000 turns/min, compositions is made after co-grinding 15s, prepared compositions is mixed with lactose, add microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crospovidone mix homogeneously, cross 40 mesh sieves and disperse 1 time, be eventually adding magnesium stearate mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 12 embodiment 6 preparation dissolution investigates result
Embodiment 7
By above-mentioned prescription, take the API that particle diameter D50 is 2.1um and jointly add, with aerosil, the pulverizer that rotating speed is 1000 turns/min, compositions is made after co-grinding 20s, prepared compositions being progressively increased with aspartame equivalent mixes once, adds remaining set compound and mixes, and adds pregelatinized Starch, microcrystalline Cellulose, crospovidone, ethyl cellulose, Pulvis Talci mixing, cross 40 mesh sieves to disperse 1 time, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 13 embodiment 7 preparation dissolution investigates result
Embodiment 8
By above-mentioned prescription, taking the API that particle diameter D50 is 1.9um and jointly add, with aerosil, the pulverizer that rotating speed is 4000 turns/min, make compositions after co-grinding 35s, prepared compositions being progressively increased with aspartame equivalent mixes once, add remaining set compound to mix, add lactose mixing, be eventually adding pregelatinized Starch, crospovidone, PVP K30 mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 14 embodiment 8 preparation dissolution investigates result
Embodiment 9
By above-mentioned prescription, take the API that particle diameter D50 is 1.1um and jointly add, with aerosil, the pulverizer that rotating speed is 2000 turns/min, compositions is made after co-grinding 25s, prepared compositions is mixed with sodium carboxymethyl cellulose, adds lactose, microcrystalline Cellulose mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 15 embodiment 9 preparation dissolution investigates result
Embodiment 10
By above-mentioned prescription, take the API that particle diameter D50 is 1.1um and jointly add, with aerosil, the pulverizer that rotating speed is 1500 turns/min, compositions is made after co-grinding 20s, prepared compositions is mixed with crospovidone, adds microcrystalline Cellulose mixing, cross 40 mesh sieves and disperse 1 time, add magnesium stearate always to mix, mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 16 embodiment 10 preparation dissolution investigates result
Embodiment 11
By above-mentioned prescription, take the API that particle diameter D50 is 1.9um and jointly add, with aerosil, the pulverizer that rotating speed is 1500 turns/min, compositions is made after co-grinding 15s, prepared compositions is mixed with lactose, add microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crospovidone mix homogeneously, cross 40 mesh sieves and disperse 1 time, be eventually adding magnesium stearate mixing, tabletting, to obtain final product.Method detection preparation dissolution described in " 1.1 ", " 1.2 ", investigates result as follows:
Table 17 embodiment 11 preparation dissolution investigates result
Claims (9)
1. the mosapride citrate compositions of a Fast Stripping, including mosapride citrate and aerosil, described mosapride citrate and aerosil be common co-grinding in size reduction machinery, the two mass ratio is 1:0.2-1.2, it is preferably 1:0.3-0.9, more preferably 1:0.3-0.6.
2. mosapride citrate compositions according to claim 1, it is characterised in that particle diameter D50≤3.0 μm of described mosapride citrate, it is preferred to 1.0 μm-3.0 μm.
3. mosapride citrate compositions according to claim 1, it is characterised in that rotating speed >=1000 turn of described size reduction machinery/min, it is preferable that >=3000 turns/min.
4. mosapride citrate compositions according to claim 1, it is characterised in that the described co-grinding time is 15-40s, it is preferred to 25s.
5. the mosapride citrate compositions according to any one of claim 1-4, it is characterised in that described compositions also includes in filler, disintegrating agent, binding agent, correctives, lubricant one or more.
6. mosapride citrate compositions according to claim 5, it is characterized in that one or more in lactose, microcrystalline Cellulose, mannitol, sucrose, pregelatinized Starch, dextrin, the calcium sulfate of described filler, it is preferable that one or more in lactose, microcrystalline Cellulose, pregelatinized Starch；One or more in low-substituted hydroxypropyl cellulose, crospovidone, carboxymethyl starch sodium, dried starch, alginic acid, the sodium carboxymethyl cellulose of described disintegrating agent, it is preferable that one or more in low-substituted hydroxypropyl cellulose, crospovidone；Described binding agent is selected from one or more in PVP K30, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, it is preferable that PVP K30, ethyl cellulose；Described correctives is selected from one or more in Aspartane, cyclamate, fructose, steviosin, xylose, it is preferable that Aspartane, cyclamate；Described lubricant is selected from one or more in magnesium stearate, Stepanol MG, Polyethylene Glycol, stearic acid, sodium laurylsulfate, it is preferable that magnesium stearate, Stepanol MG；Described fluidizer is selected from Pulvis Talci.
7. mosapride citrate compositions according to claim 6, it is characterized in that in described compositions, mosapride citrate consumption is 2%-6.9%, aerosil consumption is 1.9%-2.6%, filler loading is 57.8-91%, disintegrating agent consumption is 2.6%-18.5%, and lubricant quantity is 0-1%, and binder dosage is 0-7.2%, correctives consumption is 0-2.6%, and fluidizer consumption is 0-21.6%.
8. the mosapride citrate compositions according to any one of claim 5-7, it is characterised in that described mosapride citrate compositions is made up of the component of following mass percent:
Wherein, filler is selected from lactose, microcrystalline Cellulose, pregelatinized Starch, and disintegrating agent is selected from low-substituted hydroxypropyl cellulose, crospovidone or carboxymethyl starch sodium, and described lubricant is selected from magnesium stearate, Stepanol MG.
9. mosapride citrate compositions according to claim 8, it is characterised in that described mosapride citrate compositions is made up of the component of following mass percent:
Wherein, filler is selected from lactose, microcrystalline Cellulose, and disintegrating agent is selected from low-substituted hydroxypropyl cellulose, crospovidone, and lubricant is selected from magnesium stearate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410819954.5A CN105769872B (en) | 2014-12-25 | 2014-12-25 | A kind of mosapride citrate composition of Fast Stripping |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410819954.5A CN105769872B (en) | 2014-12-25 | 2014-12-25 | A kind of mosapride citrate composition of Fast Stripping |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105769872A true CN105769872A (en) | 2016-07-20 |
| CN105769872B CN105769872B (en) | 2019-05-03 |
Family
ID=56378363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410819954.5A Active CN105769872B (en) | 2014-12-25 | 2014-12-25 | A kind of mosapride citrate composition of Fast Stripping |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105769872B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107661506A (en) * | 2016-07-26 | 2018-02-06 | 江苏豪森药业集团有限公司 | pharmaceutical preparation of mosapride citrate and preparation method thereof |
| CN108324697A (en) * | 2017-01-19 | 2018-07-27 | 科贝源(北京)生物医药科技有限公司 | A kind of capsule and preparation method thereof containing mosapride citrate |
| 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 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
-
2014
- 2014-12-25 CN CN201410819954.5A patent/CN105769872B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Non-Patent Citations (2)
| Title |
|---|
| 傅超美 等: "《药用辅料学》", 31 October 2008, 中国中医药出版社 * |
| 周建平: "《药剂学》", 31 March 2007, 东南大学出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107661506A (en) * | 2016-07-26 | 2018-02-06 | 江苏豪森药业集团有限公司 | pharmaceutical preparation of mosapride citrate and preparation method thereof |
| 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 |
| CN108324697A (en) * | 2017-01-19 | 2018-07-27 | 科贝源(北京)生物医药科技有限公司 | A kind of capsule and preparation method thereof containing mosapride citrate |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105769872B (en) | 2019-05-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104083328B (en) | Pharmaceutical Compositions Comprising 2-Oxo-1-Pyrrolidine Derivatives | |
| CN103006608A (en) | Drug composition containing gefitinib | |
| CN104546686B (en) | A kind of mosapride citrate is co-mulled and made into thing and preparation method thereof and containing its pharmaceutical composition | |
| CN105769872A (en) | Rapidly-dissolving mosapride citrate composition | |
| CN105640913A (en) | Olmesartan medoxomil tablet and preparation method thereof | |
| CN101991561B (en) | 3,4-dichlorophenyl-propenoyl-sec-butylamine composition | |
| CN101332191A (en) | Stable perindopril tert-butylamine salt tablets and preparation method thereof | |
| CN105496941A (en) | Folic acid solid preparation and preparation method thereof | |
| CN104940152A (en) | Pharmaceutical composition containing solifenacin succinate | |
| CN112569190B (en) | Oral administration preparation of pulsatilla chinensis saponin B4 and preparation method thereof | |
| CN102908377B (en) | Legalon dispersing tablet and preparation method thereof | |
| CN104666260B (en) | A kind of Ezetimibe tablet | |
| CN104971046B (en) | A kind of immediate-release granules and its quick releasing formulation containing Lurasidone HCl | |
| CN103284952A (en) | Medical composition containing fenofibrate | |
| CN102525967B (en) | Entecavir oral solid composition and preparation method thereof | |
| CN106913550B (en) | Preparation method of eslicarbazepine acetate tablets | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof | |
| CN104644601B (en) | Capecitabine tablet | |
| CN103610674A (en) | Solid preparation containing micronized prasugrel | |
| CN104523632B (en) | A kind of Azilsartan tablet | |
| CN109820828A (en) | Nilotinib liquid-solid compression tablet and preparation method thereof | |
| CN103372216B (en) | Solid medical composition containing celecoxib | |
| CN108186580A (en) | Huperzine-A-loaded microspheres and its preparation method and application | |
| CN110934872B (en) | Levohydroxyeugenol capsule and preparation method thereof | |
| CN115025104A (en) | Celecoxib preparation with high stability and preparation process thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |