CN113143882A - Preparation method of rosuvastatin calcium capsule and rosuvastatin calcium capsule - Google Patents
Preparation method of rosuvastatin calcium capsule and rosuvastatin calcium capsule Download PDFInfo
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- rosuvastatin calcium
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- 229960004796 rosuvastatin calcium Drugs 0.000 title claims abstract description 85
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 title claims abstract description 85
- 239000002775 capsule Substances 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 31
- 238000002156 mixing Methods 0.000 claims abstract description 25
- 238000001035 drying Methods 0.000 claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 19
- 238000007873 sieving Methods 0.000 claims abstract description 10
- 238000005469 granulation Methods 0.000 claims abstract description 4
- 230000003179 granulation Effects 0.000 claims abstract description 4
- 239000008187 granular material Substances 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000000945 filler Substances 0.000 claims description 19
- 239000000314 lubricant Substances 0.000 claims description 19
- 239000004094 surface-active agent Substances 0.000 claims description 19
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 16
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 16
- 239000008101 lactose Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229960000502 poloxamer Drugs 0.000 claims description 13
- 229920001983 poloxamer Polymers 0.000 claims description 13
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 12
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 12
- 239000007884 disintegrant Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 11
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 11
- 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 description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 9
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 9
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 9
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 9
- 229940057948 magnesium stearate Drugs 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000007779 soft material Substances 0.000 claims description 6
- 229910002012 Aerosil® Inorganic materials 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 229920001993 poloxamer 188 Polymers 0.000 claims description 5
- 229940044519 poloxamer 188 Drugs 0.000 claims description 5
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 238000007599 discharging Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000008188 pellet Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 9
- 238000005550 wet granulation Methods 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 19
- 238000012360 testing method Methods 0.000 description 17
- 230000000857 drug effect Effects 0.000 description 6
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000009507 drug disintegration testing Methods 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003741 agents affecting lipid metabolism Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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Images
Classifications
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- 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
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
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- 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
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- 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
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- A61K9/1629—Organic macromolecular compounds
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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Abstract
The preparation method comprises five steps of material preparation, mixing and wet granulation, drying and sieving, total mixing and granulation, capsule filling and the like, and the main material, namely rosuvastatin calcium, is micronized, so that rosuvastatin calcium can be dissolved out quickly; and the auxiliary materials are mixed and added, so that a good excipient effect can be achieved, the disintegration time limit of the medicine is effectively shortened, and the requirements of the rosuvastatin calcium capsule on the dissolution rate and the stability of the medicine effect are met. Therefore, the rosuvastatin calcium capsule prepared by the preparation method has fast medicine dissolution rate and good stability, and solves the technical problems of poor dissolution rate and poor medicine stability of the existing rosuvastatin calcium capsule.
Description
Technical Field
The application relates to the technical field of cardiovascular and cerebrovascular medicines, in particular to a preparation method of a rosuvastatin calcium capsule and the rosuvastatin calcium capsule.
Background
Cardiovascular and cerebrovascular diseases are one of common diseases harmful to human health, and dyslipidemia is an important risk factor of atherosclerosis, coronary heart disease and other cardiovascular and cerebrovascular diseases, so that the research and development and the use of lipid-regulating drugs have positive effects and profound influences on the prevention and treatment of the cardiovascular and cerebrovascular diseases. Wherein, the rosuvastatin calcium is used as a selective HMG-CoA reductase inhibitor, can be used for treating hyperlipidemia, regulating blood fat and has positive effects on preventing and treating atherosclerosis, coronary heart disease and the like; however, rosuvastatin calcium belongs to an insoluble drug, and only after the rosuvastatin calcium is well dissolved out, the drug effect can be effectively absorbed by a human body and a result of in vivo circulation is achieved, and rosuvastatin calcium is unstable in environments such as illumination, high temperature and the like, and easily generates degradation impurities such as illumination products, lactone products or oxidation products and the like, so that the drug effect is influenced. Therefore, aiming at the defects of poor dissolution rate and poor drug stability of the existing rosuvastatin calcium capsule, the invention provides a preparation method of the rosuvastatin calcium capsule and the rosuvastatin calcium capsule in order to effectively improve the drug action effect.
Disclosure of Invention
The application provides a preparation method of a rosuvastatin calcium capsule and the rosuvastatin calcium capsule, which are used for solving the technical problems of poor dissolution rate and poor drug stability of the existing rosuvastatin calcium capsule.
In view of the above, the first aspect of the present application provides a method for preparing rosuvastatin calcium capsule, comprising the following steps:
step 1, preparing materials: preparing rosuvastatin calcium, a disintegrant, a filler, a lubricant, a surfactant and a glidant according to a formula, wherein a solvent is an ethanol solution, the rosuvastatin calcium is micronized and then passes through a sieve of 140 meshes and 200 meshes, the disintegrant is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone, the filler is a mixture of lactose and maltose or mannitol, the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate, the surfactant is sodium lauryl sulfate or poloxamer, and the glidant is aerosil;
step 2, mixing and preparing wet granules: mixing rosuvastatin calcium, a disintegrant, a filler, a surfactant and a glidant, dissolving in an ethanol solution, uniformly mixing for 20-40 minutes to prepare a soft material, and placing the soft material into a wet granulator to prepare wet granules;
step 3, drying and sieving: drying the wet granules in a drying device at 45-70 deg.C for 2-3 hr to obtain dry granules, and sieving;
step 4, total mixing and granulation: putting the lubricant and the sieved dry granules into a mixer, mixing for 15-25 minutes, and discharging for finishing granules to obtain internal medicine granules;
step 5, filling into capsules: and (4) filling the inner medicine particles prepared in the step (4) into a capsule shell by adopting a capsule filling machine to prepare the rosuvastatin calcium capsule.
Optionally, the rosuvastatin calcium is micronized in a jet mill and sieved with a 140-200 mesh sieve.
Optionally, the drying device is a drying box;
the wet pellets were dried in a drying oven at a temperature of 58 ℃ for 2.5 hours.
Optionally, the ethanol solution has a mass concentration of 50-55%.
Optionally, in step 3, the dried dry granules have a water content of not more than 4%.
Optionally, in step 5, the filling speed of the capsule filling machine is 2100-.
Optionally, in step 3, the dried granules are sieved by a sieve with 15-20 meshes.
In a second aspect, the application provides a rosuvastatin calcium capsule, which is prepared according to the preparation method of the rosuvastatin calcium capsule;
the prescription comprises the following components in parts by weight: 3-15 parts of rosuvastatin calcium, 2-20 parts of disintegrant, 30-80 parts of filler, 0.3-1.5 parts of lubricant, 1-10 parts of surfactant and 0.5-4 parts of glidant;
the disintegrating agent is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone;
the filler is a mixture of lactose and maltose or mannitol;
the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate;
the surfactant is sodium dodecyl sulfate or poloxamer;
the glidant is micropowder silica gel.
Optionally, the weight ratio of lactose to maltose in the mixture of lactose and maltose is 1 (0.8-1.3).
Optionally, the type of poloxamer employed is poloxamer 188.
According to the technical scheme, the method has the following advantages:
the preparation method of the rosuvastatin calcium capsule provided by the application comprises five steps of material preparation, mixing and wet granulation, drying and sieving, total mixing and granule finishing, capsule filling and the like, and the main material, namely rosuvastatin calcium, is subjected to micronization treatment, so that rosuvastatin calcium can be dissolved out quickly; auxiliary materials such as a disintegrating agent, a filling agent, a surfactant and a flow aid are mixed and added, so that a good forming effect can be formed on the capsule, the disintegration time limit of the rosuvastatin calcium capsule can be effectively shortened, and the requirements of the rosuvastatin calcium capsule on the dissolution rate and the stability of the drug effect are met; in the total mixing process, the addition of the lubricant can further improve the compressibility, the medicine flowability and the like between the main material and the auxiliary material, prevent the material sticking phenomenon in the process of granulating or filling into capsules and improve the qualification rate of products. In order to effectively improve the dissolution rate and the drug effect of the capsule, according to the experience of the inventor for many years, the medicinal components in the formula are selected as follows: the disintegrating agent is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone, the filler is a mixture of lactose and maltose or mannitol, the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate, the surfactant is sodium lauryl sulfate or poloxamer, and the glidant is aerosil; the addition of the sodium dodecyl sulfate or the poloxamer is beneficial to obviously improving the hydrophilicity of the rosuvastatin calcium and other medicinal components and promoting the dissolution of the capsule. By the preparation method of the rosuvastatin calcium capsule, the prepared rosuvastatin calcium capsule has the advantages of high drug disintegration speed, good drug dissolution effect and good stability of drug ingredients, and the technical problems of poor dissolution rate and poor drug stability of the existing rosuvastatin calcium capsule are solved.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments described in the present application, and other drawings can be obtained by those skilled in the art according to the drawings.
Fig. 1 is a schematic flow chart of a preparation method of rosuvastatin calcium capsule provided in the present application embodiment.
Detailed Description
In order to make the technical solutions of the present application better understood, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
Example 1
For ease of understanding, referring to fig. 1, the present application provides an embodiment of a method for preparing rosuvastatin calcium capsule, comprising the steps of:
step 1, preparing materials: preparing rosuvastatin calcium, a disintegrant, a filler, a lubricant, a surfactant and a glidant according to a formula, wherein a solvent is an ethanol solution, the rosuvastatin calcium is micronized and then passes through a sieve of 140 meshes and 200 meshes, the disintegrant is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone, the filler is a mixture of lactose and maltose or mannitol, the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate, the surfactant is sodium lauryl sulfate or poloxamer, and the glidant is aerosil;
step 2, mixing and preparing wet granules: mixing rosuvastatin calcium, a disintegrant, a filler, a surfactant and a glidant, dissolving in an ethanol solution, uniformly mixing for 20-40 minutes to prepare a soft material, and placing the soft material into a wet granulator to prepare wet granules;
step 3, drying and sieving: drying the wet granules in a drying device at 45-70 deg.C for 2-3 hr to obtain dry granules, and sieving;
step 4, total mixing and granulation: putting the lubricant and the sieved dry granules into a mixer, mixing for 15-25 minutes, and discharging for finishing granules to obtain internal medicine granules;
step 5, filling into capsules: and (4) filling the inner medicine particles prepared in the step (4) into a capsule shell by adopting a capsule filling machine to prepare the rosuvastatin calcium capsule.
In the present application, the mass concentration of the ethanol solution is 50-55%, and the water content of the dried granules is not more than 4%, considering that the wettability affects the dissolution rate or the deliquescence of the drug.
The preparation method of the rosuvastatin calcium capsule provided by the application comprises five steps of material preparation, mixing and wet granulation, drying and sieving, total mixing and granule finishing, capsule filling and the like, and the main material, namely rosuvastatin calcium, is subjected to micronization treatment, so that rosuvastatin calcium can be dissolved out quickly; auxiliary materials such as a disintegrating agent, a filling agent, a surfactant and a flow aid are mixed and added, so that a good forming effect can be formed on the capsule, the disintegration time limit of the rosuvastatin calcium capsule can be effectively shortened, and the requirements of the rosuvastatin calcium capsule on the dissolution rate and the stability of the drug effect are met; in the total mixing process, the addition of the lubricant can further improve the compressibility, the medicine flowability and the like between the main material and the auxiliary material, prevent the material sticking phenomenon in the process of granulating or filling into capsules and improve the qualification rate of products. In order to effectively improve the dissolution rate and the drug effect of the capsule, according to the experience of the inventor for many years, the medicinal components in the formula are selected as follows: the disintegrating agent is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone, the filler is a mixture of lactose and maltose or mannitol, the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate, the surfactant is sodium lauryl sulfate or poloxamer, and the glidant is aerosil; the addition of the sodium dodecyl sulfate or the poloxamer is beneficial to obviously improving the hydrophilicity of the rosuvastatin calcium and other medicinal components and promoting the dissolution of the capsule. By the preparation method of the rosuvastatin calcium capsule, the prepared rosuvastatin calcium capsule has the advantages of high drug disintegration speed, good drug dissolution effect and good stability of drug ingredients, and the technical problems of poor dissolution rate and poor drug stability of the existing rosuvastatin calcium capsule are solved.
Example 2
For ease of understanding, the present application provides one example of a rosuvastatin calcium capsule, prepared according to the aforementioned method of preparing a rosuvastatin calcium capsule; the prescription comprises the following components in parts by weight: 3-15 parts of rosuvastatin calcium, 2-20 parts of disintegrant, 30-80 parts of filler, 0.3-1.5 parts of lubricant, 1-10 parts of surfactant and 0.5-4 parts of glidant; the disintegrating agent is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone; the filler is a mixture of lactose and maltose or mannitol; the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate; the surfactant is sodium dodecyl sulfate or poloxamer; the glidant is micropowder silica gel. Optionally, the weight ratio of lactose to maltose in the mixture of lactose and maltose is 1 (0.8-1.3). Optionally, the type of poloxamer employed is poloxamer 188.
The poloxamer 188 has strong surface activity and gelling effect, can improve the stability of the preparation and the bioavailability of the insoluble drug, and promotes the release and dissolution of the drug.
In one embodiment, the preparation method of rosuvastatin calcium capsule provided by the present application comprises five steps of preparing materials, mixing and preparing wet granules, drying and sieving, totally mixing and granulating, and filling into capsules, so as to prepare a group of rosuvastatin calcium capsules, which are labeled as test article a, wherein the test article a has a formula comprising, in parts by weight: 10 parts of rosuvastatin calcium, 12 parts of microcrystalline cellulose, 55 parts of a mixture of lactose and maltose, 1.0 part of magnesium stearate, 5 parts of sodium dodecyl sulfate and 2 parts of superfine silica gel powder, wherein the weight ratio of lactose to maltose is 1:1, the selected rosuvastatin calcium is micronized and then sieved by a 170-mesh sieve, the mass concentration of an ethanol solution is 50%, the drying temperature of wet granules in a drying oven is 58 ℃, the drying time is 2.5 hours, the filling speed of a capsule filling machine is 2250 granule/minute, and the dried granules are sieved by a 18-mesh sieve.
The preparation method of the test article A is the same as that of the test article A, and two other groups of rosuvastatin calcium capsules are prepared and marked as a test article B and a test article C, wherein the test articles B and C are different from the test article A only in the components or the component contents of the prescription, and the other aspects in the preparation process are the same as those of the test article A; the difference is that the prescription of the test article B comprises the following components in parts by weight: 12 parts of croscarmellose sodium, 55 parts of mannitol, 1.0 part of magnesium lauryl sulfate and 5 parts of poloxamer 188; the prescription of test sample C includes 12 parts of polyvinylpyrrolidone, 55 parts of mannitol, and 1.0 part of sodium stearyl fumarate.
Selecting capsules of the test products A-C as test examples, selecting two commercially available rosuvastatin calcium capsules as reference examples (marked as reference products D and E), placing five medicines under accelerated test conditions (the temperature is 45 +/-3 ℃, and the relative humidity is 80 +/-2%), performing accelerated stability tests for 0 month, 3 months and 6 months, sampling at 5min to determine the dissolution rate and the total impurity content, and observing the appearances of the medicines, wherein the test results are shown in Table 1.
TABLE 1 test results Table
And (4) conclusion: as can be seen from table 1, the rosuvastatin calcium capsule prepared by the preparation method provided by the present application has good drug stability, and the dissolution rate after accelerating for 6 months is still good, and the drug dissolution behavior is significantly faster than that of the reference substance; compared with the impurity content and appearance performance of a reference substance, the rosuvastatin calcium capsule prepared by the application has better contrast advantages; in addition, the test pieces A to C were also acceptable in all other respects. Therefore, the preparation method of the rosuvastatin calcium capsule and the rosuvastatin calcium capsule provided by the application solve the technical problems of poor dissolution rate and poor drug stability of the existing rosuvastatin calcium capsule.
The above embodiments are only used for illustrating the technical solutions of the present application, and not for limiting the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions in the embodiments of the present application.
Claims (10)
1. A preparation method of rosuvastatin calcium capsule is characterized by comprising the following steps:
step 1, preparing materials: preparing rosuvastatin calcium, a disintegrant, a filler, a lubricant, a surfactant and a glidant according to a formula, wherein a solvent is an ethanol solution, the rosuvastatin calcium is micronized and then passes through a sieve of 140 meshes and 200 meshes, the disintegrant is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone, the filler is a mixture of lactose and maltose or mannitol, the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate, the surfactant is sodium lauryl sulfate or poloxamer, and the glidant is aerosil;
step 2, mixing and preparing wet granules: mixing rosuvastatin calcium, a disintegrant, a filler, a surfactant and a glidant, dissolving in an ethanol solution, uniformly mixing for 20-40 minutes to prepare a soft material, and placing the soft material into a wet granulator to prepare wet granules;
step 3, drying and sieving: drying the wet granules in a drying device at 45-70 deg.C for 2-3 hr to obtain dry granules, and sieving;
step 4, total mixing and granulation: putting the lubricant and the sieved dry granules into a mixer, mixing for 15-25 minutes, and discharging for finishing granules to obtain internal medicine granules;
step 5, filling into capsules: and (4) filling the inner medicine particles prepared in the step (4) into a capsule shell by adopting a capsule filling machine to prepare the rosuvastatin calcium capsule.
2. The method for preparing rosuvastatin calcium capsule according to claim 1, wherein the rosuvastatin calcium is micronized in a jet mill and sieved with 140-200 mesh sieve.
3. The process for the preparation of rosuvastatin calcium capsule according to claim 1, wherein the drying device is a drying oven;
the wet pellets were dried in a drying oven at a temperature of 58 ℃ for 2.5 hours.
4. The process for the preparation of rosuvastatin calcium capsule according to claim 1, wherein the ethanol solution has a mass concentration of 50 to 55%.
5. The process for the preparation of rosuvastatin calcium capsule according to claim 1, wherein the dried particles in step 3 have a water content of not more than 4%.
6. The process for the preparation of rosuvastatin calcium capsule according to claim 1, wherein the filling speed of the capsule filling machine in step 5 is 2100 particles/min.
7. The process for the preparation of rosuvastatin calcium capsule according to claim 1, wherein in step 3, the dried granules are sieved with 15-20 mesh sieve.
8. Rosuvastatin calcium capsule, characterized in that it is prepared according to the method of preparation of rosuvastatin calcium capsule according to any of claims 1 to 7;
the prescription comprises the following components in parts by weight: 3-15 parts of rosuvastatin calcium, 2-20 parts of disintegrant, 30-80 parts of filler, 0.3-1.5 parts of lubricant, 1-10 parts of surfactant and 0.5-4 parts of glidant;
the disintegrating agent is one of microcrystalline cellulose, croscarmellose sodium and polyvinylpyrrolidone;
the filler is a mixture of lactose and maltose or mannitol;
the lubricant is one of magnesium stearate, magnesium lauryl sulfate and sodium stearyl fumarate;
the surfactant is sodium dodecyl sulfate or poloxamer;
the glidant is micropowder silica gel.
9. Rosuvastatin calcium capsule according to claim 8, characterized in that the weight ratio of lactose to maltose in the mixture of lactose and maltose is 1 (0.8-1.3).
10. Rosuvastatin calcium capsule according to claim 8, characterized in that the type of poloxamer used is poloxamer 188.
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