CN113307734A - Preparation method of calcium acetate raw material and preparation - Google Patents
Preparation method of calcium acetate raw material and preparation Download PDFInfo
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- CN113307734A CN113307734A CN202110413013.1A CN202110413013A CN113307734A CN 113307734 A CN113307734 A CN 113307734A CN 202110413013 A CN202110413013 A CN 202110413013A CN 113307734 A CN113307734 A CN 113307734A
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- calcium acetate
- preparation
- calcium
- raw material
- tablets
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- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 title claims abstract description 113
- 239000001639 calcium acetate Substances 0.000 title claims abstract description 113
- 229960005147 calcium acetate Drugs 0.000 title claims abstract description 113
- 235000011092 calcium acetate Nutrition 0.000 title claims abstract description 113
- 238000002360 preparation method Methods 0.000 title claims abstract description 66
- 239000002994 raw material Substances 0.000 title claims abstract description 41
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 31
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 24
- 229960000583 acetic acid Drugs 0.000 claims abstract description 20
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 20
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 230000008569 process Effects 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 11
- 239000008187 granular material Substances 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 235000019359 magnesium stearate Nutrition 0.000 claims description 15
- 239000004353 Polyethylene glycol 8000 Substances 0.000 claims description 13
- 229940085678 polyethylene glycol 8000 Drugs 0.000 claims description 13
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 238000007664 blowing Methods 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 239000013078 crystal Substances 0.000 abstract description 30
- 238000005469 granulation Methods 0.000 abstract description 5
- 230000003179 granulation Effects 0.000 abstract description 5
- 239000007921 spray Substances 0.000 abstract description 4
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 description 13
- 238000002441 X-ray diffraction Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 229910052573 porcelain Inorganic materials 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 208000018083 Bone metabolism disease Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 208000022458 calcium metabolism disease Diseases 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/08—Acetic acid
- C07C53/10—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and relates to a calcium acetate raw material and a preparation method of the preparation, which comprises the following steps: a calcium acetate material with crystal form consistent with that of original preparation and its preparation method are provided. The invention takes calcium carbonate and glacial acetic acid as starting raw materials, skillfully utilizes conventional production equipment in a raw material workshop and a preparation workshop, prepares raw material granules which can be obtained only by adopting a spray granulation process with high energy consumption and complex process, prepares tablets with the same crystal form as the original preparation through common mixing and tabletting processes, greatly simplifies the production operation period, saves the cost, and is a good preparation process.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a calcium acetate raw material with a crystal form consistent with that of an original preparation and a preparation method of the preparation.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
Calcium is an important component of organs such as bones, teeth and the like in a human body, plays an important role in physiological functions such as blood coagulation, neuromuscular excitation, cell membrane function maintenance, activation of enzyme reaction, rapid secretion and the like, and when calcium cannot meet the needs of the human body, calcium content, calcium balance and calcium concentration gradient in the human body change to cause calcium metabolism disorder, so that a plurality of diseases such as bone metabolism diseases, endocrine system diseases, nervous system diseases and the like are produced in the organism, and calcium supplement is one of important measures for improving the health level of the human body. Calcium acetate is easily dissolved in water and absorbed in small intestine to enter relevant parts of human body, thereby supplementing calcium. Calcium ions in calcium acetate are combined with phosphate ions or hydrogen phosphate ions in food to generate calcium phosphate or calcium hydrogen phosphate precipitates which are not easy to be absorbed by human bodies and are discharged out of the bodies, so the calcium acetate or the calcium hydrogen phosphate precipitates are also taken as the first choice medicine for treating hyperphosphatemia in recent years.
However, in the development process of the product, the crystal forms of a plurality of purchased approved CALCIUM ACETATE raw materials and a reference preparation (trade name: CALCIUM ACETATE) published by the central office are determined by an X-ray diffraction method, and the results show that the crystal forms are inconsistent. Different crystal forms of the same medicament may have obvious difference in aspects of appearance, solubility, melting point, dissolution rate, bioavailability and the like, so that the stability, bioavailability and curative effect of the medicament are influenced, and the phenomenon is particularly obvious in the aspect of oral solid preparations.
The calcium acetate raw material exists in various forms such as anhydrous, semi-hydrated and monohydrate, and the crystal form also exists in various forms. The CALCIUM ACETATE tablet raw material (trade name: CALCIUM ACETATE) is prepared from hemihydrate by spray granulation, and has stable crystal form. But the suitable crystal form and particle size cannot be directly purchased in China. The preparation method needs a more complex method, and wastes time and labor.
Disclosure of Invention
In order to overcome the problems, the invention aims to provide a CALCIUM ACETATE raw material with the same crystal form as the original preparation and a preparation method of the CALCIUM ACETATE raw material, so as to solve the problem of inconsistent crystal form with a reference preparation (trade name: CALCIUM ACETATE) and ensure the product quality.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
in a first aspect of the present invention, there is provided a method for preparing a calcium acetate raw material, comprising:
dissolving calcium carbonate and glacial acetic acid in a solvent, filtering, distilling under reduced pressure to remove part of the solvent, pouring the solution into a tray, and drying by air blowing until the weight is constant to obtain calcium acetate.
The invention takes calcium carbonate and glacial acetic acid as starting raw materials, skillfully utilizes conventional production equipment in a raw material workshop and a preparation workshop, prepares raw material granules which can be obtained only by adopting a spray granulation process with high energy consumption and complex process, and prepares tablets with the same crystal form as the original preparation through common mixing and tabletting processes, thereby greatly simplifying the production operation period and saving the cost.
In a second aspect of the invention, there is provided a calcium acetate material prepared by any of the above methods.
In a third aspect of the present invention, a method for preparing a calcium acetate tablet is provided, which comprises:
granulating the calcium acetate raw material by adopting a swing granulator or a quick dry method granulator to prepare calcium acetate particles;
mixing the calcium acetate granules with auxiliary materials, and tabletting to obtain the calcium acetate tablets.
The invention takes calcium carbonate and glacial acetic acid as starting raw materials, skillfully utilizes conventional production equipment in a raw material workshop and a preparation workshop, prepares raw material granules which can be obtained only by adopting a spray granulation process with high energy consumption and complex process, and prepares tablets with the same crystal form as the original preparation through common mixing and tabletting processes, thereby greatly simplifying the production operation period and saving the cost.
In a fourth aspect of the invention, there is provided a calcium acetate tablet prepared by any one of the above-described methods.
The CALCIUM ACETATE tablet prepared by the invention has the same water content and crystal form as the reference preparation, and ensures the consistency of the quality and curative effect of the product and the reference preparation (trade name: CALCIUM ACETATE).
The invention has the beneficial effects that:
(1) the invention skillfully utilizes the existing common equipment for synthesis and preparation, successfully solves the problem of the crystal form of the calcium acetate tablet, and avoids the difference of dissolution behavior, biological effectiveness and the like caused by inconsistent crystal forms, thereby ensuring the stability and biological equivalence of the medicine.
(2) The invention adopts the way of blowing and drying the solution in a porcelain plate to replace the prior filtering and crushing process, and the prepared CALCIUM ACETATE tablet has the moisture content and the crystal form consistent with those of a reference preparation, thereby ensuring the consistency of the quality and the curative effect of the product and the reference preparation (trade name: CALCIUM ACETATE).
(3) The operation method is simple, low in cost, universal and easy for large-scale production.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.
FIG. 1 shows the X-ray diffraction measurement results of the crystal form of the starting material in example 1.
FIG. 2 shows the X-ray diffraction measurement results of the crystal form of the preparation (tablet) in example 1.
FIG. 3 shows the results of X-ray diffraction-based crystal modification measurement in comparative example 1.
FIG. 4 shows the X-ray diffraction measurements of the CALCIUM ACETATE reference formulation.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
Calcium carbonate and glacial acetic acid are used as starting raw materials, a calcium acetate solution is prepared by a conventional method, then proper particles are prepared after drying and size stabilization treatment at proper temperature, and calcium acetate tablets with the crystal form consistent with that of the original preparation are prepared by mixing and tabletting with other auxiliary materials by the conventional method.
Water for preparing calcium acetate solution of the present invention: the ratio of calcium carbonate is 3-6: 1.
The drying temperature of the calcium acetate solution is 100-140 ℃.
The granule finishing requirement of the invention is that the granule density is 0.4-0.7 g/cm3。
The preferable prescription components and weight percentage of the calcium acetate pharmaceutical composition are respectively 90-99 percent of calcium acetate, 80000.5-5 percent of polyethylene glycol and 0.1-5 percent of magnesium stearate.
The invention relates to a preparation method of a calcium acetate raw material, which comprises the following operation steps:
(1) adding medicinal calcium carbonate and medicinal glacial acetic acid according to a molar ratio of 1: 2.0-2.4, wherein the solvent is water: the mass ratio of calcium carbonate is 3-6: 1, stirring and heating are carried out until the calcium carbonate is dissolved at 30-80 ℃, and insoluble substances are filtered;
(2) and (3) distilling the solution under reduced pressure to remove part of water, pouring the solution into a porcelain plate, and drying by blowing at 100-140 ℃ until the weight of the solution is constant, wherein the total weight of the rest is about 5 times of the weight of the added calcium carbonate, so as to obtain a white calcium acetate block and obtain the target crystal form raw material.
The preparation method of the calcium acetate pharmaceutical composition comprises the following operation steps:
(1) uses a swing granulator or a rapid dry granulator which are commonly used for the preparation to carry out granulation,the prepared density is 0.4-0.6 g/cm3The particles of (a);
(2) preferably, the components of the prescription and the weight percentages are respectively 90 percent to 99 percent of calcium acetate, 80000.5 percent to 5 percent of polyethylene glycol and 0.1 percent to 5 percent of magnesium stearate, and the components are added into a mixer to be mixed evenly;
(3) tabletting, and packaging to obtain tablet with crystal form consistent with that of original tablet (CALCIUM ACETATE).
The present invention is described in further detail below with reference to specific examples, which are intended to be illustrative of the invention and not limiting.
In THE following examples, THE fast dry granulator is a cone mill granulator type SLS-0104, available from THE FITTPATRICK COMPANY.
The rocking granulator was model LYK-90, available from pharmaceutical machinery, Inc., of the Dandong city.
Example 1:
1. preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 400 | 1 |
| Glacial acetic acid | 60 | 528 | 2.2 |
| Water (W) | 18 | 2000 | —— |
The preparation method comprises the following steps:
(1) putting 400g of calcium carbonate powder, 2000g of water and 528g of glacial acetic acid into a 3000ml three-necked bottle, stirring and heating to 60 ℃ for dissolution, and filtering insoluble substances;
(2) and distilling the solution under reduced pressure to remove part of water, pouring the solution into a porcelain dish after 1960g of the total weight of the solution is remained, and drying by blowing at 120 ℃ until the weight is constant to obtain 618g of a white calcium acetate block, wherein the crystal form determination result by an X-ray diffraction method is shown in figure 1.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (800 tablets) |
| Calcium acetate | 667 | 566 |
| Polyethylene glycol 8000 | 10 | 8 |
| Magnesium stearate | 3.5 | 2.8 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) taking 618g of calcium acetate raw material blocks, and sieving and granulating through a 1.143mm round hole screen mesh of a quick dry granulating machine;
(2) 563.5g of calcium acetate, 8g of polyethylene glycol 8000 and 2.8g of magnesium stearate are taken, added into a three-dimensional mixer and mixed for 5 minutes, and mixed evenly;
(3) tabletting, and packaging to obtain calcium acetate tablet, wherein the crystal form determination result by X-ray diffraction method is shown in figure 2.
Example 2
1. Preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 400 | 1 |
| Glacial acetic acid | 60 | 480 | 2.0 |
| Water (W) | 18 | 1200 | —— |
The preparation method comprises the following steps:
(1) putting 400g of calcium carbonate powder, 1200g of water and 480g of glacial acetic acid into a 3000ml three-necked bottle, stirring and heating to 80 ℃ for dissolution, and filtering insoluble substances;
(2) the solution was distilled under reduced pressure to remove a part of water, and after a total weight of the solution remained of 2030g, the solution was poured into a porcelain dish and dried by blowing at 120 ℃ until a constant weight was obtained, thereby obtaining 630g of a white calcium acetate cake.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (800 tablets) |
| Calcium acetate | 667 | 566 |
| Polyethylene glycol 8000 | 10 | 8 |
| Magnesium stearate | 3.5 | 2.8 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) taking 620g of calcium acetate raw material blocks, and sieving and granulating through a 1.143mm round hole screen mesh of a quick dry granulating machine;
(2) adding 566g of calcium acetate, 8g of polyethylene glycol 8000 and 2.8g of magnesium stearate into a three-dimensional mixer, mixing for 5 minutes, and uniformly mixing;
(3) tabletting and packaging to obtain the calcium acetate tablet.
Example 3
1. Preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 400 | 1 |
| Glacial acetic acid | 60 | 576 | 2.4 |
| Water (W) | 18 | 2400 | —— |
The preparation method comprises the following steps:
(1) putting 400g of calcium carbonate powder, 2400g of water and 576g of glacial acetic acid into a 5000ml three-necked bottle, stirring and heating to 70 ℃ for dissolution, and filtering insoluble substances;
(2) the solution was distilled under reduced pressure to remove part of the water, and 1965g of the total weight of the solution was poured into a porcelain dish, and forced air was applied thereto at 130 ℃ to dry the solution to a constant weight, to obtain 628g of a white cake of calcium acetate.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (800 tablets) |
| Calcium acetate | 667 | 566 |
| Polyethylene glycol 8000 | 10 | 8 |
| Magnesium stearate | 3.5 | 2.8 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) taking 620g of calcium acetate raw material blocks, and finishing the granules through a 20-mesh sieve of a swing granulator;
(2) adding 566g of calcium acetate, 8g of polyethylene glycol 8000 and 2.8g of magnesium stearate into a three-dimensional mixer, mixing for 5 minutes, and uniformly mixing;
(3) tabletting and packaging to obtain the calcium acetate tablet.
Example 4
1. Preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 400 | 1 |
| Glacial acetic acid | 60 | 504 | 2.1 |
| Water (W) | 18 | 2000 | —— |
The preparation method comprises the following steps:
(1) putting 400g of calcium carbonate powder, 2000g of water and 504g of glacial acetic acid into a 3000ml three-necked bottle, stirring and heating to 75 ℃ for dissolution, and filtering insoluble substances;
(2) the solution was distilled under reduced pressure to remove part of the water, and 1988g of the total weight of the residue was poured into a porcelain dish and dried by forced air at 100 ℃ until the weight was constant, to obtain 622g of a white calcium acetate block.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (800 tablets) |
| Calcium acetate | 667 | 566 |
| Polyethylene glycol 8000 | 10 | 8 |
| Magnesium stearate | 3.5 | 2.8 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) taking 618g of calcium acetate raw material blocks, and sieving and granulating the calcium acetate raw material blocks through a 20-mesh sieve of a swing granulator;
(2) adding 566g of calcium acetate, 8g of polyethylene glycol 8000 and 2.8g of magnesium stearate into a three-dimensional mixer, mixing for 5 minutes, and uniformly mixing;
(3) tabletting and packaging to obtain the calcium acetate tablet.
Example 5
1. Preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 600 | 1 |
| Glacial acetic acid | 60 | 792 | 2.2 |
| Water (W) | 18 | 2400 | —— |
The preparation method comprises the following steps:
(1) adding 600g calcium carbonate powder, 2400g water and 792g glacial acetic acid into 5000ml three-necked bottle, stirring and heating to 80 deg.C for dissolving, and filtering to remove insoluble substances;
(2) the solution was distilled under reduced pressure to remove a part of water, and 2945g of the total weight of the solution was poured into a porcelain dish and dried by forced air at 110 ℃ to a constant weight, to obtain 938g of a white calcium acetate block.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (1300 pieces) |
| Calcium acetate | 667 | 849 |
| Polyethylene glycol 8000 | 10 | 12 |
| Magnesium stearate | 3.5 | 4.2 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) sieving 938g of calcium acetate block material with a 1.143mm round hole screen of a rapid dry-process granulator;
(2) adding 849g of calcium acetate, 12g of polyethylene glycol 8000 and 4.2g of magnesium stearate into a three-dimensional mixer, mixing for 5 minutes, and uniformly mixing;
(3) tabletting and packaging to obtain the calcium acetate tablet.
Comparative example 1
1. Preparation of calcium acetate raw material
| Name (R) | Molecular weight | Batch (g) | Molar ratio of |
| |
100 | 400 | 1 |
| Glacial acetic acid | 60 | 528 | 2.2 |
| Water (W) | 18 | 2000 | —— |
The preparation method comprises the following steps:
(1) putting 400g of calcium carbonate powder, 2000g of water and 528g of glacial acetic acid into a 3000ml three-necked bottle, stirring and heating to 60 ℃ for dissolution, and filtering insoluble substances;
(2) distilling the solution under reduced pressure to remove most of water, cooling to below 20 deg.C, crystallizing for more than 2 hr, filtering, washing filter cake with small amount of cold water, and air drying at 80 deg.C to constant weight.
(3) Pulverizing with universal pulverizer to obtain white calcium acetate powder 529 g.
(4) The obtained raw material is monohydrate, and the crystal form is different from that of the original preparation.
2. Preparation of calcium acetate tablet
| Name (R) | Single dose of mg/tablet | g/actual batch (700 tablets) |
| Calcium acetate | 667 | 492.8 |
| Polyethylene glycol 8000 | 10 | 7 |
| Magnesium stearate | 3.5 | 2.45 |
Calcium acetate tablets: standard substance 667mg (in terms of C)4H6CaO4Meter)
The preparation method comprises the following steps:
(1) 492.8g of calcium acetate powder, 7.0g of polyethylene glycol 8000 and 2.45g of magnesium stearate are added into a three-dimensional mixer to be mixed for 5 minutes and uniformly mixed;
(2) and (3) tabletting, because the density is low, the filling weight can not reach the theoretical tablet weight, and the tabletting requirement can not be met.
TABLE 1 summary of test data for each of the examples and comparative examples
Comparison of example 1 with comparative example 1
And (3) comparing the moisture:
examples 1 to 5 the raw material contains 5.6 to 5.9% of water and is a hemihydrate; comparative example 1 the starting material had a water content of 10.2% and the comparative example was a monohydrate.
And (3) crystal form comparison: the samples of example 1 and comparative example 1, CALCIUM ACETATE as a raw material, and a reference preparation (trade name: CALCIUM ACETATE) were subjected to X-ray diffraction method (0451 on the national pharmacopoeia 2015 editions).
The results show that the crystal forms of the raw material and the calcium acetate tablet in the example 1 are consistent with those of the reference preparation; comparative example 1 the crystal form of the calcium acetate starting material is not in accordance with the reference formulation. The results are shown in FIGS. 1-4.
In conclusion, the invention provides a simple preparation method of a CALCIUM ACETATE raw material and a pharmaceutical composition, the existing filtering and crushing process is replaced by a way of blowing and drying a solution in a ceramic tray, the moisture content and the crystal form of the prepared CALCIUM ACETATE tablet are consistent with those of a reference preparation, and the consistency of the quality and the curative effect of the product and the reference preparation (trade name: CALCIUM ACETATE) is ensured.
It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and the present invention is not limited thereto, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications and equivalents can be made in the technical solutions described in the foregoing embodiments, or equivalents thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention. Although the present invention has been described with reference to the specific embodiments, it should be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
Claims (10)
1. A preparation method of a calcium acetate raw material is characterized by comprising the following steps:
dissolving calcium carbonate and glacial acetic acid in a solvent, filtering, distilling under reduced pressure to remove part of the solvent, pouring the solution into a tray, and drying by air blowing until the weight is constant to obtain calcium acetate.
2. The method for producing a calcium acetate material as claimed in claim 1, wherein the calcium acetate is a white lump powder.
3. The method of preparing a calcium acetate material of claim 1 wherein the calcium carbonate and glacial acetic acid are both pharmaceutical grade.
4. The method of preparing a calcium acetate material of claim 1 wherein the solvent is water.
5. A calcium acetate material produced by the process of any one of claims 1 to 4.
6. A preparation method of calcium acetate tablets is characterized by comprising the following steps:
granulating the calcium acetate raw material by adopting a swing granulator or a quick dry method granulator to prepare calcium acetate particles;
mixing the calcium acetate granules with auxiliary materials, and tabletting to obtain the calcium acetate tablets.
7. The method for preparing a calcium acetate tablet as claimed in claim 6, wherein the auxiliary materials comprise: polyethylene glycol 8000 and magnesium stearate.
8. The method for preparing calcium acetate tablets according to claim 6, wherein the density of the calcium acetate particles is 0.4-0.7 g/cm3。
9. The method for preparing calcium acetate tablets according to claim 6, wherein the mixing is performed using a three-dimensional mixer.
10. Calcium acetate tablets prepared by the method of any one of claims 6 to 9.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005154400A (en) * | 2003-11-26 | 2005-06-16 | Masaya Nagai | Calcium acetate for medicine/food additive |
| CN101322837A (en) * | 2008-07-14 | 2008-12-17 | 王冰 | Formulation for increasing bone density |
| CN101627973A (en) * | 2009-08-05 | 2010-01-20 | 王冰 | Calcium acetate tablet and preparation method thereof |
| CN102643187A (en) * | 2011-11-29 | 2012-08-22 | 昆明邦宇制药有限公司 | Production method of calcium acetate |
| CN106187742A (en) * | 2016-07-04 | 2016-12-07 | 华南协同创新研究院 | A kind of efficient calcium acetate preparation method |
| CN106588634A (en) * | 2016-11-28 | 2017-04-26 | 江苏润普食品科技股份有限公司 | Production process for food-grade calcium acetate |
| CN110279668A (en) * | 2019-08-07 | 2019-09-27 | 山东创新药物研发有限公司 | A kind of calcium acetate medications composition and its preparation method and application |
| CN210206819U (en) * | 2019-03-14 | 2020-03-31 | 昆明邦宇制药有限公司 | Special reaction unit of calcium acetate |
-
2021
- 2021-04-16 CN CN202110413013.1A patent/CN113307734A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005154400A (en) * | 2003-11-26 | 2005-06-16 | Masaya Nagai | Calcium acetate for medicine/food additive |
| CN101322837A (en) * | 2008-07-14 | 2008-12-17 | 王冰 | Formulation for increasing bone density |
| CN101627973A (en) * | 2009-08-05 | 2010-01-20 | 王冰 | Calcium acetate tablet and preparation method thereof |
| CN102643187A (en) * | 2011-11-29 | 2012-08-22 | 昆明邦宇制药有限公司 | Production method of calcium acetate |
| CN106187742A (en) * | 2016-07-04 | 2016-12-07 | 华南协同创新研究院 | A kind of efficient calcium acetate preparation method |
| CN106588634A (en) * | 2016-11-28 | 2017-04-26 | 江苏润普食品科技股份有限公司 | Production process for food-grade calcium acetate |
| CN210206819U (en) * | 2019-03-14 | 2020-03-31 | 昆明邦宇制药有限公司 | Special reaction unit of calcium acetate |
| CN110279668A (en) * | 2019-08-07 | 2019-09-27 | 山东创新药物研发有限公司 | A kind of calcium acetate medications composition and its preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| 钱如贵等: "乙酸钙的纯化工艺", 《中国医药工业杂志》 * |
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