CN115282123B - Preparation method of stable nicorandil preparation - Google Patents

Preparation method of stable nicorandil preparation Download PDF

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CN115282123B
CN115282123B CN202211109086.2A CN202211109086A CN115282123B CN 115282123 B CN115282123 B CN 115282123B CN 202211109086 A CN202211109086 A CN 202211109086A CN 115282123 B CN115282123 B CN 115282123B
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nicorandil
preparation
mixture
prepare
higher alcohol
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CN115282123A (en
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方硕
刘倩
高丽雯
欧阳城真
孙晓丽
周悦
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Nanjing Bison Pharmaceutical Technology Co ltd
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Nanjing Bison Pharmaceutical Technology Co ltd
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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

A method of preparing a stable nicorandil formulation, the method comprising: grinding higher alcohol into higher alcohol mixed powder, and preparing the nicorandil, the disintegrating agent, the lubricant, the filler and the higher alcohol mixed powder into a nicorandil preparation by a direct tabletting method; the filler comprises at least one of anhydrous lactose, microcrystalline fiber and corn starch, and the particle size of the filler is 20-400 μm, so that the active medicine is more uniformly distributed in other auxiliary materials; the higher alcohols include stearyl alcohol, which is used to improve the stability of the nicorandil formulation. The invention aims to improve the stability of the nicorandil while the preparation of the nicorandil preparation is convenient, so that the nicorandil can keep the pharmaceutical activity in wet and hot environments, reduce toxic and side effects and ensure the safety and effectiveness of the medication of patients.

Description

Preparation method of stable nicorandil preparation
Technical Field
The invention belongs to the technical field of nicorandil preparations, and particularly relates to a preparation method of a stable nicorandil preparation.
Background
The nicorandil chemical name is oxynicotinamide nitrate, belongs to nitrate compounds, is a potassium ion channel opener which is clinically used for ATP sensitivity at the earliest, has obvious effects on unique angina pectoris such as spasticity, labor force and the like, can effectively reduce the occurrence rate of cardiovascular events, and can also play an obvious role in improving prognosis of patients with coronary heart disease; at present, the medicine is the first medicine for treating coronary heart disease, so the preparation of the medicine is widely concerned.
For example: the patent application publication No. CN87100285A discloses a method for improving the stability of a nicorandil tablet by adding a saturated higher fatty acid or a saturated higher fatty alcohol which is solid at normal temperature to a proper dosage form, but the preparation is prepared by adopting a wet granulation process, the process is complex, and the stability of the preparation still needs to be improved.
The patent application publication No. CN1980644A discloses a preparation method for adding a lubricant into a composition, wherein the lubricant is solid non-micronized higher saturated aliphatic acid, salt thereof and/or saturated higher alcohol at normal temperature, and the preparation method adopts direct tabletting to prepare a preparation, and has simple process, but the stability of the preparation is slightly poor and needs to be stored at the temperature lower than 25 ℃.
Patent application publication No. CN85109190A discloses a method for improving the stability of a nicorandil tablet by using finely pulverized sugar and a powdery organic acid as an excipient, but this method requires that the sugar as an excipient must be subjected to air-jet pulverization to an average particle diameter of less than 10 μm, and uniformity and stability of the active ingredient of the resulting tablet are not fully satisfactory.
Patent application publication No. CN1839836A discloses a method for producing a nicorandil tablet by directly pressing or dry granulating and tabletting powder or blank granulating method, which can avoid degradation of nicorandil caused by the influence of humidity and heat, but the preparation prepared by the method is only placed for 4 weeks under the condition of 40 ℃ and 75% RH, so that the content of active ingredients is reduced to 85% -87%, and the problem of poor stability of the nicorandil preparation cannot be completely solved by the method.
The patent application publication No. CN203075205U discloses a packaging combination of nicorandil preparation, which aims to improve the stability of nicorandil in the processes of storage, transportation and use, but the packaging combination is complex, has high cost and is not suitable for commercial use.
Therefore, the preparation of the Nicotiana preparation is not convenient enough, the chemical property of the Nicotiana preparation is very unstable in the preparation process, and the Nicotiana preparation is easily influenced by a tabletting process and a damp-heat environment, so that the activity of the medicine is reduced, the toxic and side effects are increased, and the safety of the medicine application of a patient and the preparation effectiveness are not ensured.
Disclosure of Invention
The invention aims to provide a stable preparation method of a nicorandil preparation, so that the preparation is convenient and fast, the stability of nicorandil is improved, the nicorandil can maintain the pharmaceutical activity in wet and hot environments, the toxic and side effects are reduced, and the safety and the effectiveness of the medication of patients are ensured.
A method of preparing a stable nicorandil formulation, the method comprising: grinding higher alcohol into higher alcohol mixed powder, and making nicorandil, disintegrating agent, lubricant, filler and higher alcohol mixed powder into nicorandil preparation by direct tabletting method.
By adopting the technical scheme, the direct tabletting process is simpler, granulation and drying are not needed, and the influence of humidity and heat on the stability of nicorandil in the production process is avoided.
Preferably, the filler comprises at least one of lactose anhydrous, microcrystalline cellulose, and corn starch.
Preferably, the particle size of the filler ranges from 20 μm to 400 μm.
By adopting the technical scheme, the active medicine is likely to be unevenly distributed in the auxiliary materials by adopting a direct tabletting method, so that the quality of a product is affected, the active medicine is more evenly distributed in other auxiliary materials by controlling the particle size range of the filling agent, the active medicine comprises nicorandil, and the other auxiliary materials comprise disintegrating agent, lubricant, filling agent and higher alcohol mixed powder.
Preferably, the higher alcohol comprises stearyl alcohol, which is used to improve the stability of the nicorandil formulation.
By adopting the technical scheme, in order to make the nicorandil preparation more stable, the octadecanol is added into the prescription to inhibit the degradation of the nicorandil, so that the nicorandil can maintain the pharmaceutical activity in wet and hot environments, reduce toxic and side effects, and ensure the safety and effectiveness of the medication of patients.
Preferably, the disintegrant comprises calcium carboxymethyl cellulose.
Preferably, the lubricant comprises calcium stearate.
Preferably, the higher alcohol is present in an amount of at least 0.5% of the total amount of the nicorandil formulation.
Preferably, the higher alcohol is put into a mortar for grinding, and the higher alcohol mixed powder is obtained after filtering by a 40-mesh screen, and the step of the direct compression method is to mix the nicorandil, the disintegrating agent, the lubricant, the filler and the higher alcohol mixed powder to prepare a mixture, and the mixture is compressed and molded into the nicorandil preparation by a tablet press.
Preferably, the nicorandil mass percent is 10%, the disintegrant mass percent is 5%, the lubricant mass percent is 1.5-4%, the filler mass percent is 79-82%, and the higher alcohol mixed powder mass percent is 1.5%.
The beneficial effects of the invention are as follows:
firstly, the invention uses a direct tabletting method, is convenient to prepare, does not need to granulate and dry, and avoids the influence of humidity and heat on the stability of nicorandil in the production process;
secondly, the particle size range of the filler is 20-400 mu m, and the active medicine is unevenly distributed in the auxiliary materials by adopting a direct tabletting method, so that the active medicine is more evenly distributed in other auxiliary materials by controlling the particle size range of the filler, the active medicine comprises nicorandil, and the other auxiliary materials comprise disintegrating agent, lubricant, filler and higher alcohol mixed powder;
thirdly, the octadecanol is added to inhibit the degradation of the nicorandil, so that the nicorandil preparation is more stable, the nicorandil can maintain the pharmaceutical activity in wet and hot environments, the toxic and side effects are reduced, and the safety and the effectiveness of the administration of patients are further ensured;
in conclusion, the three points combined action ensures that the preparation of the nicorandil preparation is convenient and fast, and simultaneously, the stability of the nicorandil can be improved, so that the nicorandil can maintain the drug activity in wet and hot environments, the toxic and side effects are reduced, and the safety and the effectiveness of the drug administration of patients are ensured.
Detailed Description
Example 1
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 1 below:
TABLE 1
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 20-160 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 1, placed in a self-sealing bag and mixed to prepare a mixture, the content uniformity of the mixture was checked, the content uniformity results were referred to in Table 11, and the mixture was then tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 2
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 2 below:
TABLE 2
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 100-250 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 2, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was then tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 3
A method for preparing a stable nicorandil preparation, the formulation of which is shown in table 3 below:
TABLE 3 Table 3
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 50-200 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 3, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was then tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 4
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 4 below:
TABLE 4 Table 4
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 200-400 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 4, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was then tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 5
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 5 below:
TABLE 5
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 100-400 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 5, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was then tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 6
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 6 below:
TABLE 6
The preparation method comprises the following steps: (1) Anhydrous lactose with particle size of 20-400 μm, preferably 20-250 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 6, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Example 7
A process for preparing a stable nicorandil formulation, the formulation of which is shown in table 7 below:
TABLE 7
The preparation method comprises the following steps: (1) Microcrystalline cellulose having a particle size of 20 μm to 400 μm, preferably 20 μm to 250 μm; (2) Grinding stearyl alcohol in a mortar, filtering with a 40-mesh screen to obtain higher alcohol mixed powder, (3) weighing the components according to the above table 7, mixing in a hopper mixer to obtain a mixture, detecting the content uniformity of the mixture, referring to table 11 for the content uniformity result, tabletting the mixture by a tablet press to obtain nicorandil preparations, wherein each nicorandil preparation weighs 50mg, and each nicorandil preparation contains 5mg of nicorandil.
Example 8
A method for preparing a stable nicorandil formulation, the formulation of which is shown in table 8 below:
TABLE 8
The preparation method comprises the following steps: (1) Microcrystalline cellulose having a particle size of 20 μm to 400 μm, preferably 200 μm to 400 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 8, placed in a hopper mixer and mixed to prepare a mixture, the content uniformity of the mixture was examined, the content uniformity results were referred to in Table 11, and the mixture was tabletted by a tablet press to prepare nicorandil formulations each having a weight of 50mg and each having a content of 5mg.
Comparative example 1
A preparation method of a commercially available nicorandil preparation comprises the following steps of:
TABLE 9
The preparation method comprises the following steps: (1) Jet milling mannitol for 5min to an average particle size of less than 10 μm, preferably a particle size D90 of 9.5 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components were weighed according to the above Table 9, mixed in a hopper mixer to prepare a mixture, the content uniformity of the mixture was checked, the content uniformity results were referred to in Table 11, and the mixture was tabletted by a tablet press to prepare a nicorandil preparation.
Comparative example 2
A preparation method of a Nicotiana preparation on the market comprises the following steps of:
table 10
The preparation method comprises the following steps: (1) Pulverizing D-mannitol for 5min, weighing 50g of pulverized D-mannitol, adding 10g of purified water, mixing, sieving with 40 mesh sieve, drying at 50deg.C for 30min, and sieving with 40 mesh sieve to obtain D-mannitol granule; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) Nicotil, corn starch, D-mannitol particles, stearyl alcohol, carboxymethylcellulose calcium and calcium stearate are weighed according to the table 10, placed in a self-sealing bag, mixed to prepare a mixture, the content uniformity of the mixture is detected, the content uniformity results are shown in table 11, and then the mixture is tabletted and formed by a tablet press to prepare the Nicotil preparation.
The content uniformity of the mixtures of examples 1 to 8 and comparative examples 1 to 2 was characterized by the average content and RSD, and the detection results are shown in the following table 11:
TABLE 11
Numbering device Average content (%) RSD(％)
Example 1 102.89 2.3
Example 2 96.60 1.1
Example 3 97.66 1.7
Example 4 97.02 2.1
Example 5 98.45 2.6
Example 6 97.1 2.9
Example 7 96.98 1.3
Example 8 101.68 2.1
Comparative example 1 107.94 8.7
Comparative example 2 95.61 24.3
The RSD values of the nicorandil preparation prepared by the invention are less than 3%, the mixing is more uniform, and the preparation is beneficial to adopting a simple powder direct tabletting process which can avoid the influence of humidity and heat.
Samples were prepared by taking examples 1 to 8, reference preparations and commercially available nicorandil preparations as comparative examples 3 to 7, and the samples were exposed and left at 40℃under 75% RH for 30 days to measure the active ingredient content and total impurity content of the samples, and the specifications of the reference preparations and comparative examples 3 to 7 are shown in Table 12, and the measurement results are shown in Table 13 below:
table 12
Numbering device Specification of specification
Reference formulation 5mg
Comparative example 3 5mg
Comparative example 4 5mg
Comparative example 5 5mg
Comparative example 6 5mg
Comparative example 7 5mg
TABLE 13
After being exposed and placed for 30 days under the conditions of 40 ℃ and 75% RH, the content of active ingredients of the nicorandil preparation prepared by the invention can reach more than 60%, and the total impurity content is lower than 30% and can reach 17.26%; compared with the traditional Chinese medicine preparation, the content of the active ingredients in comparative examples 3-7 is lower than 50%, and the total impurity content is higher than 40%, which proves that the prepared nicorandil preparation is more stable, the nicorandil can maintain the pharmaceutical activity in wet and hot environments, the toxic and side effects are reduced, and the safety and the effectiveness of the medication of patients are ensured.
Samples were prepared by taking examples 1 to 8, reference formulations, and commercially available nicorandil formulations as comparative examples 3 to 7, and the samples were packaged at 40 ℃ and 75% rh for 6 months, and then the contents of the active ingredients and the total impurities of the samples were measured, and the specifications of the reference formulations and comparative examples 3 to 7 are shown in table 12, and the packaging materials of examples 1 to 8 comprise: the packaging materials of the PVC/PE/PVDC composite hard sheet, aluminum foil, desiccant, moisture-proof bag, reference preparation and comparative examples 3-7 comprise: aluminum plastic plate, desiccant, moisture-proof bag, the detection results are shown in table 14 below:
TABLE 14
The content of the active ingredients of the nicorandil preparation prepared by the invention can reach more than 90 percent after the preparation is packaged and placed for 6 months under the conditions of 40 ℃ and 75 percent RH, and the total impurity content is lower than 2 percent and can reach 0.56 percent; compared with the traditional Chinese medicine preparation, the content of the active ingredients in the comparative examples 3-7 is lower than 77%, the total impurity content exceeds 19%, and the content can reach 35.69%, which proves that the prepared nicorandil preparation is more stable, the nicorandil can maintain the pharmaceutical activity in wet and hot environments, the toxic and side effects are reduced, and the safety and the effectiveness of the medication of patients are ensured.
The foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (4)

1. A method for preparing a stable nicorandil preparation, which is characterized in that the nicorandil preparation comprises the following formula:
the preparation method comprises the following steps: (1) The filler is anhydrous lactose with the particle size ranging from 20 mu m to 160 mu m; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) Weighing the components according to the table, mixing in a self-sealing bag to prepare a mixture, detecting the content uniformity of the mixture, and tabletting the mixture by a tablet press to prepare the nicorandil preparation, wherein each nicorandil preparation weighs 50mg, and each nicorandil preparation contains 5mg of nicorandil.
2. A method for preparing a stable nicorandil preparation, which is characterized in that the nicorandil preparation comprises the following formula:
the preparation method comprises the following steps: (1) The filler is anhydrous lactose with the particle size ranging from 100 μm to 250 μm; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components are weighed according to the table, placed in a hopper mixer to be mixed to prepare a mixture, the content uniformity of the mixture is detected, and then the mixture is pressed into tablets by a tablet press to prepare the nicorandil preparation, wherein each tablet of the nicorandil preparation has the weight of 50mg, and each tablet of the nicorandil preparation contains 5mg of nicorandil.
3. A method for preparing a stable nicorandil preparation, which is characterized in that the nicorandil preparation comprises the following formula:
the preparation method comprises the following steps: (1) The filler is anhydrous lactose with the particle size ranging from 50 mu m to 200 mu m; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components are weighed according to the table, placed in a hopper mixer to be mixed to prepare a mixture, the content uniformity of the mixture is detected, and then the mixture is pressed into tablets by a tablet press to prepare the nicorandil preparation, wherein each tablet of the nicorandil preparation has the weight of 50mg, and each tablet of the nicorandil preparation contains 5mg of nicorandil.
4. A method for preparing a stable nicorandil preparation, which is characterized in that the nicorandil preparation comprises the following formula:
the preparation method comprises the following steps: (1) The filler is anhydrous lactose with the particle size ranging from 200 mu m to 400 mu m; (2) Grinding stearyl alcohol in a mortar, and filtering with a 40 mesh screen to obtain higher alcohol mixed powder; (3) The components are weighed according to the table, placed in a hopper mixer to be mixed to prepare a mixture, the content uniformity of the mixture is detected, and then the mixture is pressed into tablets by a tablet press to prepare the nicorandil preparation, wherein each tablet of the nicorandil preparation has the weight of 50mg, and each tablet of the nicorandil preparation contains 5mg of nicorandil.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85109190A (en) * 1984-12-17 1986-07-16 中外制药株式会社 Produce the method for stable nicorandil preparation
CN87100285A (en) * 1986-01-17 1987-08-19 中外制药株式会社 Produce the method for stable nicorandil preparation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85109190A (en) * 1984-12-17 1986-07-16 中外制药株式会社 Produce the method for stable nicorandil preparation
CN87100285A (en) * 1986-01-17 1987-08-19 中外制药株式会社 Produce the method for stable nicorandil preparation

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