CN111281875A - Composition containing mosapride citrate and preparation method thereof - Google Patents
Composition containing mosapride citrate and preparation method thereof Download PDFInfo
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Abstract
The invention provides a novel mosapride citrate composition, which is prepared by adopting a specially optimized fluidized bed granulation process, has better content uniformity, can keep the dissolution of a finished product not to be reduced for a long time, does not increase related substances, and ensures that the effectiveness and safety of a medicament after the mosapride citrate composition is placed for a long time are better guaranteed.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a mosapride citrate-containing composition and a preparation method thereof.
Background
Mosapride citrate is a selective 5-hydroxytryptamine 4 (5-HT)4) Receptor agonists, 5-HT by stimulation of cholinergic interneurons and the internuscular plexus of the gastrointestinal tract4The receptor promotes acetylcholine release to enhance upper gastrointestinal motility, and is a third-generation gastric motility promoting drug developed by japan pharmaceutical company. The clinical application is mainly usedFunctional dyspepsia is accompanied by digestive tract symptoms such as heartburn, belch, nausea, emesis, early satiety, epigastric distention, etc. The chemical name is (+/-) -4-amino-5-chloro-2-ethoxy-N- {4- (4-fluorobenzyl) -2-morphinyl]Methyl toluamide citrate dihydrate with molecular formula C21H25ClFN3O3·C6H8O7·2H2O, molecular weight 650.05, structural formula as follows:
mosapride citrate is a BCS class ii drug with very low solubility in water, and for solid formulations of this class of drugs, the rate of dissolution of the drug ingredient from the formulation is usually the rate-limiting step affecting the bioavailability of the drug. The existing national standard clearly stipulates that the dissolution rate of the mosapride citrate tablet in 0.1mol/L hydrochloric acid solution (simulated gastric juice) is not less than 75% at 30min, thereby ensuring that the drug can be effectively released and absorbed in the stomach of a patient. However, for some patients with achlorhydria, the dissolution of the mosapride citrate preparation in the stomach can be greatly reduced, so that the bioavailability in the body is reduced, and the effective treatment purpose cannot be achieved. Meanwhile, as the mosapride citrate belongs to a heat-sensitive compound, the industrially produced mosapride citrate preparation has serious stability problems if contacting a damp-heat environment in the long-term transportation and storage processes, so that related substances are increased, potential safety hazards are brought, and the clinical application is not facilitated, so that the control of the related substances in the preparation composition is a difficult problem to be continuously overcome in the field. In addition, the commonly used preparation specification of the mosapride citrate in clinical treatment is 5mg, such as Gaussun produced by Sumitomo pharmacy of original research company, so that the proportion of active ingredients in the preparation is lower, and the problem of unqualified content uniformity is easily generated, so that the curative effect is unstable in clinical application, and therefore, the requirement of meeting the content uniformity is very important for ensuring the stable curative effect of the mosapride citrate preparation.
Disclosure of Invention
In order to solve some key problems still existing in the prior art, the invention aims to provide a novel mosapride citrate-containing composition, which has better content uniformity, can keep the dissolution of a finished product not to be reduced and related substances not to be increased for a long time, and ensures that the effectiveness and safety of a drug of the mosapride citrate composition after being placed for a long time are better guaranteed.
The invention provides a composition containing mosapride citrate, which contains mosapride citrate, mannitol and hydroxypropyl methylcellulose (HPMC) and is prepared by adopting a fluidized bed granulation process.
The composition containing mosapride citrate, wherein the fluid bed granulation process comprises the following steps:
(1) preparing hydroxypropyl methylcellulose into a hydroxypropyl methylcellulose solution, adding mosapride citrate, and dispersing and dissolving to obtain an adhesive solution;
(2) the above binder was sprayed on mannitol to granulate.
Specifically, the hypromellose solution in step (1) is prepared by using an ethanol aqueous solution as a solvent;
the volume ratio concentration of the ethanol aqueous solution is 20-60% (v/v), preferably the volume ratio concentration of the ethanol aqueous solution is 30-40% (v/v), and more preferably the volume ratio concentration of the ethanol aqueous solution is 40% (v/v);
the mass/volume ratio concentration of the hypromellose solution is 2-10% (w/v), the mass/volume ratio concentration of the hypromellose solution is preferably 3-5% (w/v), and the mass/volume ratio concentration of the hypromellose solution is more preferably 3% (w/v).
The composition containing mosapride citrate further comprises other pharmaceutically acceptable auxiliary materials.
The composition containing the mosapride citrate comprises other pharmaceutically acceptable auxiliary materials including a filler, a disintegrant, a glidant and a lubricant.
Specifically, the composition containing mosapride citrate comprises the following preparation steps:
(1) dissolving hydroxypropyl methylcellulose in ethanol water solution to prepare hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to make it fully dispersed and dissolved to obtain adhesive solution;
(2) putting mannitol into a fluidized bed granulator, and spraying the adhesive on the mannitol to granulate;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
The composition containing the mosapride citrate comprises, by weight, 1.0-10.0 parts of the mosapride citrate, 10.0-100.0 parts of mannitol, 0.5-3.0 parts of hypromellose, 16.5-33.0 parts of a filler, 13.2-36.3 parts of a disintegrant, 0-1.65 parts of a glidant and 0-1.65 parts of a lubricant.
The composition containing mosapride citrate comprises one or more fillers selected from pregelatinized starch, corn starch, calcium hydrogen phosphate and microcrystalline cellulose, and is preferably microcrystalline cellulose.
The composition containing mosapride citrate comprises one or more disintegrating agents selected from crospovidone, low-substituted hypromellose, croscarmellose sodium and sodium carboxymethyl starch, and preferably a combination of low-substituted hypromellose and croscarmellose sodium.
The composition containing mosapride citrate comprises a glidant, a glidant and a lubricant, wherein the glidant is one or more selected from superfine silica gel powder and talcum powder, and superfine silica gel powder is preferred.
The composition containing mosapride citrate is characterized in that the lubricant is one or more selected from magnesium stearate, stearic acid, hydrogenated vegetable oil, polyethylene glycol and sodium lauryl sulfate, and magnesium stearate is preferred.
More specifically, the invention provides a composition containing mosapride citrate, which comprises the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 30-40% ethanol water solution to obtain 3-5% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 30-40 deg.C, spraying the above binder solution on mannitol for granulating, and drying;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
More specifically, the invention provides a composition containing mosapride citrate, which comprises the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 40% ethanol water solution to obtain 3% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 35 ℃, spraying the adhesive solution on the mannitol for granulation, and continuously drying after granulation;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
More specifically, the invention provides a composition containing mosapride citrate, which comprises the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 40% ethanol water solution to obtain 3% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 35 ℃, spraying the adhesive solution on the mannitol for granulation, and continuously drying after granulation;
(3) taking out the dry granules from the fluidized bed, granulating, adding microcrystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, aerosil and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The mosapride citrate composition provided by the invention has the following advantages:
(1) the wet granulation process is adopted to solve the problems that the dry granulation process has high requirements on the quality of raw and auxiliary materials or needs to carry out severe pretreatment in industrial production.
(2) The content uniformity of the finished product is obviously improved, the dissolution is fast, and the effect is fast.
(3) The finished product has better stability after being placed for a long time through accelerated simulation, and shows that the dissolution rate is not obviously reduced, and related substances are not obviously increased, so that the curative effect is kept, the safety is also ensured, and the quality is more stable.
Detailed Description
The following detailed description of specific embodiments of the present invention is provided to illustrate and explain the present invention and to be understood not to limit the present invention.
The measurement method of the indexes involved in the invention and the information of the original research products are as follows:
1. original research product information: mosapride citrate tablets (trade name:
) Specification 5mg, manufacturing enterprise: dainippon Sumitomo Pharma co. ltd., division packaging company: sumitomo pharmaceutical (Suzhou) Limited, product batch number: 2757 c.
2. The content uniformity is measured, 10 pieces of samples are taken, the relative content of each piece with the mark amount as 100 is measured, the average value X and the standard deviation S of the relative content and the absolute value A of the difference between the mark amount and the average value are calculated (namely A | -100-X |), and finally the value of A +1.80S is calculated, wherein the smaller the numerical value is, the higher the content uniformity is.
3. Dissolution rate measurement before and after acceleration, stability test under the limit acceleration condition: the temperature is 60 ℃, the humidity is 92.5%, and after the mixture is placed for 0 day and 10 days, the mixture is respectively sampled and analyzed. A dissolution measuring method comprises taking a sample, measuring by high performance liquid chromatography (second method of 0931 in the general rules of the national pharmacopoeia 2015), using 900ml of 0.1mol/L hydrochloric acid solution as solvent, rotating at 50 r/min, operating according to the method, taking appropriate amount of solution according to specified time, filtering, and taking the subsequent filtrate; octadecylsilane chemically bonded silica is used as a filling agent; and (3) adding the following components in percentage by weight of 7: 9: 24 acetonitrile-methanol-citrate buffer solution (taking 8.82g of sodium citrate dihydrate, adding 800ml of water for dissolving, adjusting the pH value to 3.3 by using dilute hydrochloric acid, and adding 1000ml of water) as a mobile phase; the detection wavelength is 274 nm; the column temperature is 40 ℃; the flow rate was adjusted so that the retention time of the mosapride peak was about 9 minutes, and the mosapride content was calculated by an external standard method using the peak area.
4. Determination of relevant substances before and after acceleration, stability test under extreme acceleration conditions: the temperature is 60 ℃, the humidity is 92.5%, and after the mixture is placed for 0 day and 10 days, the mixture is respectively sampled and analyzed. Taking a proper amount of fine powder (about 10mg equivalent to mosapride citrate), putting the fine powder into a 10ml measuring flask, adding a proper amount of diluent (citrate buffer solution), shaking for 20 minutes, diluting the fine powder to a scale with the diluent, shaking uniformly, filtering, and taking a subsequent filtrate as a test solution. Precisely measuring 1ml of the test solution, placing the test solution into a 200ml measuring flask, diluting the test solution to a scale with a diluent, and shaking up to obtain a control solution. And diluting a proper amount of mosapride citrate reference substance with a diluent to prepare a mixed solution containing about 2 mu g of mosapride citrate per 1ml as a system applicability solution. According to the test of high performance liquid chromatography (0512 in the four-department general regulation of 2015 edition in Chinese pharmacopoeia),octadecyl bonded silica gel as stationary phase (XSelect CSHTM C)185 μm, 4.6mm × 250 mm); using citric acid buffer salt solution (8.82 g sodium citrate is taken, 800ml water is added for dissolving, dilute hydrochloric acid is used for adjusting the pH value to 4.0, and water is added to 1000ml) as a mobile phase A, acetonitrile is used as a mobile phase B, and gradient elution is carried out according to the following table; the detection wavelength is 274 nm; the column temperature was 40 ℃; the flow rate was 1.0ml per minute.
Precisely measuring 10 μ l of system applicability solution, injecting into liquid chromatograph, and continuously sampling for 6 times, wherein the relative standard deviation of mosapride peak area is not more than 3.0%, and the theoretical plate number is not less than 4000 according to mosapride peak. Precisely measuring 10 mul of each of the test solution and the reference solution, respectively injecting into a liquid chromatograph, recording the chromatogram until 2 times of the retention time of the main component peak, and calculating the total content of related substances by the following calculation formula:
the total content of related substances [% ] (total peak area-main component peak area) × 100/self-control peak area × 200. The experimental materials and instruments used in the invention are as follows:
TABLE 1 Main test materials
TABLE 2 Main Equipment, Instrument List
Comparative example 1
The preparation process comprises the following steps:
1. weighing the filler and the disintegrant according to the prescription amount, and uniformly mixing by using a proper mixer.
2. Weighing the mosapride citrate raw material with the prescription amount, adding the mosapride citrate raw material into the mixed auxiliary materials by an equivalent progressive dilution method, and fully mixing and sieving by a 40-mesh sieve each time until the mosapride citrate raw material is completely and uniformly mixed.
3. Adding 3% HPMC ethanol water solution to prepare soft material, sieving with 18 mesh sieve, and making into wet granule.
4. Drying the obtained wet granules at 50 ℃ for 2h, taking out, and sieving with a 18-mesh sieve to obtain dry granules.
5. Weighing the silicon dioxide and the magnesium stearate with the prescription amount, fully and uniformly mixing the silicon dioxide and the magnesium stearate with the dry granules, and tabletting to obtain the tablet.
Comparative example 2
The preparation process comprises the following steps:
1. weighing the filler and the disintegrant according to the prescription amount, and uniformly mixing by using a proper mixer.
2. Weighing the mosapride citrate raw material with the prescription amount, adding the mosapride citrate raw material into the mixed auxiliary materials by an equivalent progressive dilution method, and fully mixing and sieving by a 40-mesh sieve each time until the mosapride citrate raw material is completely and uniformly mixed.
3. Adding 3% HPMC ethanol water solution to prepare soft material, sieving with 18 mesh sieve, and making into wet granule.
4. Drying the obtained wet granules at 50 ℃ for 2h, taking out, and sieving with a 18-mesh sieve to obtain dry granules.
5. Weighing the silicon dioxide and the magnesium stearate with the prescription amount, fully and uniformly mixing the silicon dioxide and the magnesium stearate with the dry granules, and tabletting to obtain the tablet.
Comparative example 3
The preparation process comprises the following steps:
1. dissolving HPMC in purified water, adding mosapride citrate, stirring for dispersing, and preparing into adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The content uniformity of the original ground product and the content uniformity of the comparative examples 1 to 3 were measured, an accelerated test was performed according to the accelerated test method, and the dissolution rate before and after acceleration and the content of the related substances were measured, and the results were as follows:
TABLE 3 results of measurements on samples of the original ground product and comparative examples 1 to 3
According to the results in the table, after the accelerated test, the dissolution rates of the compositions of the comparative examples 1 to 3 and the original ground product are remarkably reduced, the content of related substances is remarkably increased, and the compositions of the comparative examples 1 to 3 and the original ground product are remarkably reduced after being placed for a long time, so that the long-term transportation and storage are not facilitated.
Comparative testing of different excipients in granules in examples 1-6
The preparation process comprises the following steps:
1. dissolving HPMC in ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into adhesive solution.
2. Placing calcium hydrogen phosphate (or lactose, microcrystalline cellulose, starch, dextrin, and mannitol) in a fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the materials, atomizing the binder solution with a spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The content uniformity of the product is measured, an accelerated test is carried out according to the accelerated test method, the dissolution rate before and after acceleration and the content of related substances are measured, and the results are as follows:
TABLE 4 results of sample measurement for examples 1 to 6
Examples 7-10 comparative testing of different binders
The preparation process comprises the following steps:
1. dissolving CMC-Na (or PVP, HPC, HPMC) in ethanol water solution, adding mosapride citrate, stirring for dispersing, and making into adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The content uniformity of the product is measured, an accelerated test is carried out according to the accelerated test method, and the dissolution rate before and after acceleration is measured, and the result is as follows:
TABLE 5 results of sample measurements of examples 7 to 10
Examples 11-14 comparative testing of different ethanol concentrations of Binder solutions
The preparation process comprises the following steps:
1. dissolving HPMC in ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The content uniformity of the product is measured, an accelerated test is carried out according to the accelerated test method, and the dissolution rate before and after acceleration is measured, and the result is as follows:
TABLE 6 results of sample measurement for examples 11 to 14
EXAMPLES 15-18 comparative testing of different HPMC concentrations in Binder solutions
The preparation process comprises the following steps:
1. dissolving HPMC in ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into adhesive solution with corresponding concentration.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
The content uniformity of the product is measured, an accelerated test is carried out according to the accelerated test method, and the dissolution rate before and after acceleration is measured, and the result is as follows:
TABLE 7 results of sample measurements for examples 15-18
Example 19
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 20
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 21
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 22
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 23
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 24
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
Example 25
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding filler, disintegrant, silicon dioxide and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product. :
example 26
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 30 deg.C to boil the material, atomizing the binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant and the talcum powder according to the prescription amount, mixing uniformly, and tabletting to obtain the finished product.
Example 27
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 35 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the silicon dioxide and the sodium lauryl sulfate according to the prescription amount, uniformly mixing, and tabletting to obtain the tablet.
Example 28
The preparation process comprises the following steps:
1. dissolving HPMC in 40% ethanol water solution, adding mosapride citrate, stirring for dispersing, and preparing into 3% adhesive solution.
2. Placing mannitol in fluidized bed granulator, starting hot air, controlling temperature at 40 deg.C to boil the material, atomizing the above binder solution with spray gun, spraying onto mannitol, granulating, and drying with hot air.
3. Taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the silicon dioxide and the stearic acid according to the prescription amount, mixing uniformly, and tabletting to obtain the finished product.
The content uniformity of each of the test examples 19 to 28 was measured, and accelerated tests were carried out according to the accelerated test method described above to determine the dissolution rates before and after acceleration, and the results were as follows:
TABLE 8 results of sample measurements for examples 19-28
Claims (10)
1. A composition containing mosapride citrate is characterized by comprising mosapride citrate, mannitol and hydroxypropyl methylcellulose and being prepared by adopting a fluidized bed granulation process.
2. The mosapride citrate-containing composition according to claim 1, wherein the fluid bed granulation process comprises the steps of:
(1) preparing hydroxypropyl methylcellulose into a hydroxypropyl methylcellulose solution, adding mosapride citrate, and dispersing and dissolving to obtain an adhesive solution;
(2) the above binder was sprayed on mannitol to granulate.
3. The mosapride citrate-containing composition according to claim 2, wherein the hypromellose solution preparation in step (1) is performed by using an ethanol aqueous solution as a solvent, wherein the ethanol aqueous solution has a concentration of 20-60%, preferably the ethanol aqueous solution has a concentration of 30-40%, and more preferably the ethanol aqueous solution has a concentration of 40%; the concentration of the hypromellose solution is 2-10%, the concentration of the hypromellose solution is preferably 3-5%, and the concentration of the hypromellose solution is more preferably 3%.
4. The mosapride citrate-containing composition according to any one of claims 1-3, wherein the composition comprises other pharmaceutically acceptable excipients.
5. The mosapride citrate-containing composition according to claim 4, wherein the pharmaceutically acceptable other excipients comprise one or more of a filler, a disintegrant, a glidant and a lubricant.
6. The mosapride citrate-containing composition according to claim 5, wherein said composition is prepared by the steps comprising:
(1) dissolving hydroxypropyl methylcellulose in ethanol water solution to prepare hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to make it fully dispersed and dissolved to obtain adhesive solution;
(2) putting mannitol into a fluidized bed granulator, and spraying the adhesive on the mannitol to granulate;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
7. The mosapride citrate-containing composition according to claim 5, wherein the mosapride citrate is 1.0-10.0 parts, the mannitol is 10.0-100.0 parts, the hypromellose is 0.5-3.0 parts, the filler is 16.5-33.0 parts, the disintegrant is 13.2-36.3 parts, the glidant is 0-1.65 parts, and the lubricant is 0-1.65 parts.
8. The mosapride citrate-containing composition according to claim 5, wherein the filler is selected from one or more of pregelatinized starch, corn starch, calcium hydrogen phosphate and microcrystalline cellulose, preferably microcrystalline cellulose; the disintegrant is selected from one or more of crospovidone, low-substituted hypromellose, croscarmellose sodium and sodium carboxymethyl starch, preferably the combination of low-substituted hypromellose and croscarmellose sodium; the glidant is selected from one or more of superfine silica gel powder and talcum powder, and superfine silica gel powder is preferred; the lubricant is selected from one or more of magnesium stearate, stearic acid, hydrogenated vegetable oil, polyethylene glycol and sodium lauryl sulfate, and preferably magnesium stearate.
9. The mosapride citrate-containing composition according to any one of claims 5-8, comprising the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 30-40% ethanol water solution to obtain 3-5% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 30-40 deg.C, spraying the above binder solution on mannitol for granulating, and drying;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
10. The mosapride citrate-containing composition according to claim 9, comprising the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 40% ethanol water solution to obtain 3% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 35 ℃, spraying the adhesive solution on the mannitol for granulation, and continuously drying after granulation;
(3) taking out the dry granules from the fluidized bed, granulating, adding the filler, the disintegrant, the glidant and the lubricant according to the prescription amount, uniformly mixing, and tabletting to obtain the finished product.
Preferably, the composition containing the mosapride citrate is characterized by comprising the following components:
and is prepared by adopting the following fluidized bed granulation process:
(1) dissolving hydroxypropyl methylcellulose in 40% ethanol water solution to obtain 3% hydroxypropyl methylcellulose solution, adding mosapride citrate, stirring to disperse and dissolve completely to obtain adhesive solution;
(2) placing mannitol in a fluidized bed granulator, controlling the temperature at 35 ℃, spraying the adhesive solution on the mannitol for granulation, and continuously drying after granulation;
(3) taking out the dry granules from the fluidized bed, granulating, adding microcrystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, aerosil and magnesium stearate according to the prescription amount, mixing uniformly, and tabletting to obtain the final product.
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| CN115364063A (en) * | 2021-08-27 | 2022-11-22 | 成都硕德药业有限公司 | Potassium citrate sustained-release tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN105560249A (en) * | 2014-10-10 | 2016-05-11 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing mosapride citrate |
| CN106943369A (en) * | 2016-01-07 | 2017-07-14 | 江苏豪森药业集团有限公司 | pharmaceutical composition of mosapride citrate and preparation method thereof |
-
2018
- 2018-12-07 CN CN201811492138.2A patent/CN111281875A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN105560249A (en) * | 2014-10-10 | 2016-05-11 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing mosapride citrate |
| CN106943369A (en) * | 2016-01-07 | 2017-07-14 | 江苏豪森药业集团有限公司 | pharmaceutical composition of mosapride citrate and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 杨明，等: "《药剂学（第2版）》", 31 August 2018, 中国医药科技出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115364063A (en) * | 2021-08-27 | 2022-11-22 | 成都硕德药业有限公司 | Potassium citrate sustained-release tablet and preparation method thereof |
| CN115364063B (en) * | 2021-08-27 | 2024-03-29 | 成都硕德药业有限公司 | Potassium citrate sustained release tablet and preparation method thereof |
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