CN115089550A - Preparation method of mosapride citrate granules - Google Patents
Preparation method of mosapride citrate granules Download PDFInfo
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- CN115089550A CN115089550A CN202210933466.1A CN202210933466A CN115089550A CN 115089550 A CN115089550 A CN 115089550A CN 202210933466 A CN202210933466 A CN 202210933466A CN 115089550 A CN115089550 A CN 115089550A
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- mosapride citrate
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- mesh sieve
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- YPELFRMCRYSPKZ-UHFFFAOYSA-N 4-amino-5-chloro-2-ethoxy-N-({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)benzamide Chemical compound CCOC1=CC(N)=C(Cl)C=C1C(=O)NCC1OCCN(CC=2C=CC(F)=CC=2)C1 YPELFRMCRYSPKZ-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229960004085 mosapride Drugs 0.000 title claims abstract description 34
- 239000008187 granular material Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000002156 mixing Methods 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 18
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 14
- 229930195725 Mannitol Natural products 0.000 claims abstract description 14
- 239000000594 mannitol Substances 0.000 claims abstract description 14
- 235000010355 mannitol Nutrition 0.000 claims abstract description 14
- 239000002002 slurry Substances 0.000 claims abstract description 14
- 238000011049 filling Methods 0.000 claims abstract description 13
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 13
- 238000007873 sieving Methods 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 238000001035 drying Methods 0.000 claims abstract description 10
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 9
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 9
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 9
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 7
- 238000007599 discharging Methods 0.000 claims abstract description 6
- 238000007908 dry granulation Methods 0.000 claims abstract description 6
- 238000005550 wet granulation Methods 0.000 claims abstract description 5
- 238000005520 cutting process Methods 0.000 claims abstract description 4
- 239000008213 purified water Substances 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 3
- 238000012856 packing Methods 0.000 claims description 4
- 238000005070 sampling Methods 0.000 claims description 4
- 229910002012 Aerosil® Inorganic materials 0.000 claims description 3
- 238000012858 packaging process Methods 0.000 claims description 3
- 230000004580 weight loss Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000002245 particle Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 239000007919 dispersible tablet Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 230000000181 anti-adherent effect Effects 0.000 description 2
- 239000003911 antiadherent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 108091005482 5-HT4 receptors Proteins 0.000 description 1
- 102000008813 5-Hydroxytryptamine 4 receptors Human genes 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010059186 Early satiety Diseases 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000001288 gastroparesis Diseases 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention relates to the field of medicine production, and in particular relates to a preparation method of mosapride citrate granules. The invention relates to a preparation method of mosapride citrate granules, which comprises the following steps: (1) pretreating raw materials and auxiliary materials; (2) solvent preparation: taking ethanol, adding purified water, stirring uniformly, taking part of ethanol solution, adding the prescription dose of mosapride citrate, and starting a stirrer; (3) granulating, namely adding mannitol and hydroxypropyl cellulose in a formula amount into a wet mixing granulator, stirring and mixing, adding the slurry for granulating, finishing adding within 2min, rinsing a slurry barrel with the residual ethanol water solution, granulating for 4min in the total process from slurry pouring, cutting for granulating for 1min, and discharging; (4) and (3) wet granulation: sieving with 20 mesh sieve, and wet granulating; (5) drying; (6) dry granulation: sieving with 30 mesh sieve by rocking; (7) total mixing: adding magnesium stearate and silicon dioxide, and mixing; (8) and (6) filling.
Description
Technical Field
The invention relates to the field of medicine production, and in particular relates to a preparation method of mosapride citrate granules.
Background
The mosapride citrate is a prokinetic drug, is an agonist of a selective 5-hydroxytryptamine 4 receptor, can promote the release of acetylcholine so as to promote gastrointestinal tract movement, can improve functional dyspepsia symptoms, such as abdominal distension and constipation of patients, and has good effect when the mosapride citrate is taken. Has good treatment effect on gastroparesis caused by gastroesophageal reflux disease, diabetes and the like, nausea, early satiety, epigastric distending pain caused by dyspepsia and mosapride.
The existing mosapride citrate medicine is generally a tablet, for example, patents CN104188927A and CN107684548A are all tablets, and the tablet is not convenient for special people such as children to swallow.
The prior art CN104940148A discloses a mosapride citrate granule and a preparation method thereof, but the application needs to use polyethylene glycol and needs to melt the mosapride citrate and the polyethylene glycol. The crystal form of the raw materials of the scheme can be changed after the raw materials are melted. Different crystalline forms of the starting material have different chemical and physical properties and affect the stability, solubility and bioavailability of the formulation.
Disclosure of Invention
The invention hopes to provide a preparation method of mosapride citrate granules, and the specific scheme is as follows:
a preparation method of mosapride citrate granules comprises the following steps:
(1) pretreating raw materials and auxiliary materials: crushing mosapride citrate until D90 is less than 5um, respectively sieving mannitol and hydroxypropyl cellulose with a 40-mesh sieve, and respectively sieving magnesium stearate and aerosil with a 20-mesh sieve;
(2) solvent preparation: taking ethanol, adding purified water, stirring uniformly, taking part of ethanol solution, adding the prescription dose of mosapride citrate, and starting a stirrer;
(3) granulating, namely adding mannitol and hydroxypropyl cellulose in a formula amount into a wet mixing granulator, stirring and mixing, adding slurry for granulating, finishing adding within 2min (including 2min), rinsing a slurry barrel with the residual ethanol water solution, granulating for 4min in the total process from slurry pouring, cutting for granulating for 1min, and discharging;
(4) wet granulation: sieving with 20 mesh sieve, and grading;
(5) drying;
(6) dry granulation: sieving with 30 mesh sieve by rocking;
(7) total mixing: adding magnesium stearate and silicon dioxide, and mixing;
(8) and (6) filling.
The mass ratio of the mosapride citrate, the mannitol, the hydroxypropyl cellulose, the silicon dioxide and the magnesium stearate is 4:371.8:20:2: 2.
The mass fraction of the ethanol solution in the step (2) is 60-65%.
The mass ratio of the ethanol solution used in the steps (2) and (3) is 5-5.1: 1.5.
The air inlet temperature of the step (5) is 50 ℃, the drying time is more than or equal to 3min, and the drying weight loss is less than or equal to 1.0%.
The filling steps are as follows: before filling, the compressed air pipe is opened, the air pressure is checked to be 0.4-0.8 MPa, the front longitudinal temperature is 110-140 ℃, the rear longitudinal temperature is 110-140 ℃, the front transverse temperature is 110-140 ℃, the rear transverse temperature is 110-140 ℃, and the host speed is as follows: 100-300 bags/min, in the packaging process, the sampling frequency is 30 minutes/time, 10 bags are packaged each time, the average filling amount is controlled to be +/-2.0%, and the filling amount difference is controlled to be +/-7.0%.
In the invention, mannitol: mannitol can be used in direct compression processes and wet granulation processes. The mannitol-containing granules have the advantage of being easily dried and are suitable for heat-sensitive medicaments. Mannitol has sweetness and good taste because its heat of dissolution is negative, and is generally used as an excipient for chewable tablets and granules. Silicon dioxide: the product is white odorless hygroscopic fine amorphous powder, and is mainly used as disintegrant, antiadherent, and glidant in preparation. The product can greatly improve granule fluidity, increase bulk density, increase tablet hardness, shorten disintegration time, and increase drug dissolution rate; the product can also be used as internal desiccant to improve stability of hygroscopic medicine. Magnesium stearate: has lubricating, anti-sticking, and glidant effects. In tablets, capsules as lubricants, glidants or antiadherents. Magnesium stearate and silicon dioxide are prescribed primarily to improve the flowability of the granules.
And the raw and auxiliary materials of the invention are pretreated: in the prior art, the mosapride citrate dispersible tablet wastes time and labor for a mosapride citrate clathrate compound raw material freeze-drying treatment process, and has a complex process for a workshop and needs to be operated in a workshop-crossing manner. The mosapride citrate particle raw material only needs to be crushed to control the particle size D90 to be less than 5 mu m, and when the raw material is in the interval, the dissolution is fast dissolution. When the particle size of the raw material is increased beyond this range, the dissolution is reduced. Slurry preparation: the content of the API of the mosapride citrate particles (mosapride citrate) in the formula is about 1%, and the API has high risk of uneven mixing in the dry mixing stage, so that the API is added into the adhesive in the formula design stage to ensure the mixing uniformity of the materials. Total mixing and dry granulation: the mosapride citrate dispersible tablet in the prior art adopts total mixing and dry granulation, and the process is opposite to the process of the mosapride citrate granules. The total mixing and re-granulation of the dispersible tablets has an extrusion and gentle mixing of the granules with the additional excipients on the granulator, which may have an effect on the dissolution.
Detailed Description
Example 1
(1) Pretreating raw materials and auxiliary materials: API crushing until D90 is less than 5um (specifically 2.2um), respectively sieving mannitol and hydroxypropyl cellulose with 40 mesh sieve, and respectively sieving magnesium stearate and silica gel micropowder with 20 mesh sieve.
(2) Solvent preparation: taking 4.12kg of ethanol, adding purified water to 6.52kg, stirring uniformly, taking 5.02kg of ethanol solution, adding the prescription amount of mosapride citrate, starting a stirrer at 3500-4500rpm, stirring for 60min, and remaining 1.5kg of ethanol aqueous solution for later use.
(3) Granulating, namely adding the mannitol and the hydroxypropyl cellulose in the formula amount into a wet mixing granulator, stirring at 70rpm for 10 minutes, adding the slurry for granulating, finishing adding 2 minutes, rinsing a slurry barrel with the residual 1.50kg of ethanol aqueous solution, granulating for 4 minutes in the total process from slurry pouring, cutting at 900rpm for granulating for 1 minute, and discharging.
(4) Wet granulation: and (5) wet granulating by using a soft material with a 20-mesh sieve.
(5) And (3) drying: setting the air inlet temperature at 50 ℃, the drying time at least 3min, the drying weight loss at less than or equal to 1.0 percent and discharging.
(6) Dry granulation: and (4) swinging and sieving by a 30-mesh sieve.
(7) Total mixing: adding magnesium stearate and silicon dioxide, and mixing for 5min at a mixing speed: and (5) discharging at 40 Hz. Sampling and detecting the intermediate particles.
The effect is as follows: the fluidity of the particles becomes good, the filling and blanking of the particles are smooth, and the filling quantity difference is stable. Because the mannitol auxiliary material is too much and is easy to absorb moisture, the stability of the medicament with moisture absorption can be greatly improved by adding the magnesium stearate and the aerosil
(8) Filling: calculating the instruction loading according to the particle detection content, carrying out formal packaging, opening the compressed air pipe by an operator before filling, checking the air pressure of 0.4-0.8 MPa, the front longitudinal temperature of 110-140 ℃, the rear longitudinal temperature of 110-140 ℃, the front transverse temperature of 110-140 ℃, the rear transverse temperature of 110-140 ℃, and the host speed: 100-300 bags per minute, the sampling frequency is 30 minutes per time in the packaging process, 10 bags are packed each time, the average packing amount is controlled to be +/-2.0%, and the difference of the packing amounts is controlled to be +/-7.0%.
Examples 2 to 3 (the following examples are the same as example 1 except that the contents in the table are different, and the effects of using magnesium stearate and silicon dioxide in combination are illustrated)
Examples 4 to 5 (the following examples are otherwise the same as example 1 except that the contents in the table are different, and the effects of different concentrations of the aqueous ethanol solution used in step (2) were investigated)
Examples 6 to 8 (the following examples are the same as example 1 except that the contents in the table are different, and the influence of the particle size of the raw material used in step (2) was examined)
Examples 9 to 10 (the following examples are otherwise the same as example 1 except that the contents in the table are different, and the influence of the slurry addition time in step (3) was investigated)
The above-mentioned embodiments are only used for explaining the inventive concept of the present invention, and do not limit the protection of the claims of the present invention, and any insubstantial modifications of the present invention using this concept shall fall within the protection scope of the present invention.
Claims (6)
1. A preparation method of mosapride citrate granules is characterized by comprising the following steps:
(1) pretreating raw materials and auxiliary materials: crushing the mosapride citrate until D90 is less than 5um, respectively sieving mannitol and hydroxypropyl cellulose with a 40-mesh sieve, and respectively sieving magnesium stearate and aerosil with a 20-mesh sieve;
(2) solvent preparation: adding purified water into ethanol, stirring, adding mosapride citrate in a prescribed amount into part of the ethanol solution, and starting a stirrer;
(3) granulating, namely adding mannitol and hydroxypropyl cellulose in a formula amount into a wet mixing granulator, stirring and mixing, adding the slurry for granulating, finishing adding within 2min, rinsing a slurry barrel with the residual ethanol water solution, granulating for 4min in the total process from slurry pouring, cutting for granulating for 1min, and discharging;
(4) wet granulation: sieving with 20 mesh sieve, and grading;
(5) drying;
(6) dry granulation: sieving with 30 mesh sieve by rocking;
(7) total mixing: adding magnesium stearate and silicon dioxide, and mixing;
(8) and (6) filling.
2. The method for preparing mosapride citrate granules according to claim 1, wherein the method comprises the following steps: the mass ratio of the mosapride citrate, the mannitol, the hydroxypropyl cellulose, the silicon dioxide and the magnesium stearate is 4:371.8:20:2: 2.
3. The method for preparing mosapride citrate granules according to claim 1, wherein the method comprises the following steps: the mass fraction of the ethanol solution in the step (2) is 60-65%.
4. The method for preparing mosapride citrate granules according to claim 1, wherein the method comprises the following steps: the mass ratio of the ethanol solution used in the steps (2) and (3) is 5-5.1: 1.5.
5. The method for preparing mosapride citrate granules according to claim 1, wherein the method comprises the following steps: the air inlet temperature of the step (5) is 50 ℃, the drying time is more than or equal to 3min, and the drying weight loss is less than or equal to 1.0%.
6. The method for preparing mosapride citrate granules according to claim 1, wherein the filling step comprises: before filling, the compressed air pipe is opened, the air pressure is checked to be 0.4-0.8 MPa, the front longitudinal temperature is 110-140 ℃, the rear longitudinal temperature is 110-140 ℃, the front transverse temperature is 110-140 ℃, the rear transverse temperature is 110-140 ℃, and the host speed is as follows: 100-300 bags per minute, the sampling frequency is 30 minutes per time in the packaging process, 10 bags are packed each time, the average packing amount is controlled to be +/-2.0%, and the difference of the packing amounts is controlled to be +/-7.0%.
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| CN202210933466.1A CN115089550B (en) | 2022-08-04 | 2022-08-04 | Preparation method of mosapride citrate particles |
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| CN202210933466.1A CN115089550B (en) | 2022-08-04 | 2022-08-04 | Preparation method of mosapride citrate particles |
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| CN115089550B CN115089550B (en) | 2024-03-08 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070148230A1 (en) * | 2003-12-09 | 2007-06-28 | Keiichi Fujiwara | Medicament-containing particle and a solid preparation containing the particle |
| KR20150075959A (en) * | 2013-12-26 | 2015-07-06 | 한국유나이티드제약 주식회사 | Capsule containing mini-tablets comprising mosapride citrate for sustained-releasing formulation improving gastrointestinal disease and preparing the method thereof |
| CN104940148A (en) * | 2015-07-11 | 2015-09-30 | 鲁南制药集团股份有限公司 | Mosapride citrate granules and preparation method thereof |
| CN106913879A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Mosapride Citrate Tablets agent 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 |
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2022
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070148230A1 (en) * | 2003-12-09 | 2007-06-28 | Keiichi Fujiwara | Medicament-containing particle and a solid preparation containing the particle |
| KR20150075959A (en) * | 2013-12-26 | 2015-07-06 | 한국유나이티드제약 주식회사 | Capsule containing mini-tablets comprising mosapride citrate for sustained-releasing formulation improving gastrointestinal disease and preparing the method thereof |
| CN104940148A (en) * | 2015-07-11 | 2015-09-30 | 鲁南制药集团股份有限公司 | Mosapride citrate granules and preparation method thereof |
| CN106913879A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Mosapride Citrate Tablets agent 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 |
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| CN115089550B (en) | 2024-03-08 |
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