CN106860415A - Simvastatin tablet and preparation method thereof - Google Patents
Simvastatin tablet and preparation method thereof Download PDFInfo
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- CN106860415A CN106860415A CN201710118539.0A CN201710118539A CN106860415A CN 106860415 A CN106860415 A CN 106860415A CN 201710118539 A CN201710118539 A CN 201710118539A CN 106860415 A CN106860415 A CN 106860415A
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- simvastatin
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- thin film
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- lubricant
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/2004—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
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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
- A61K9/2004—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
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract
The present invention proposes a kind of simvastatin tablet and preparation method thereof, including following supplementary material：Simvastatin, microcrystalline cellulose, dextrin, lactose, antioxidant, lubricant and thin film coating material；Wherein, the lubricant is the mixture of Compritol 888 ATO and magnesium stearate.Preparation method, comprises the following steps：1) it is pre-mixed：Weigh Simvastatin, microcrystalline cellulose, antioxidant, dextrin and lactose to be pre-mixed, the time is 25~30min；2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 20~30 mesh sieves, obtains particle；3) by lubricant and step 2) particle be well mixed, then carry out compressing tablet；4) it is coated：By thin film coating material and step 3) label be coated.The simvastatin tablet is improved by auxiliary material, possesses controllability in scale large-scale production process, and Simvastatin Tablets keep quality stability in 48 months.
Description
Technical field
The invention belongs to simvastatin composition technical field, and in particular to a kind of simvastatin tablet and its preparation
Method.
Background technology
In recent years, with eating habit change, living standard raising, operating pressure increase, hyperlipidemia and hyperproteinemia
Disease patient is more and more, and, patient population increasingly rejuvenation.With continuing to develop for medical science, it was recognized that courage is solid
The too high Basic disease cause for being to occur angiocardiopathy of alcohol, fatty equal size, high fat of blood is coronary heart disease and hypertension occur main
Hazards.Therefore, people start the emphasis as prevention and cure of cardiovascular disease using the exploitation of regulating plasma lipid medicine.Fat is exchanged by the world of medicine
Effect of the medicine in terms of prevention and cure of cardiovascular disease is filled with unbounded confidence, and adjusts fat therapy to turn into the main of 21 century prevention of cardiovascular disease
Method.
Simvastatin (simvastatin) is a kind of semi-synthetic lipid-regulation medicine of novel potent, by suppressing endogenous courage
The synthesis of sterol and reduce low-density lipoprotein (LDL) and VLDL (VLDL), moderate increasing high density fat
Albumen (HDLC), reduces triglycerides, so as to reduce cholesterol, has obvious curative effect to high cholesterol, coronary heart disease etc., is treatment
One of choice drug of high fat of blood.
There is incompatibility in Simvastatin, be susceptible to hydrolyze and aoxidize with various pharmaceutic adjuvants, interior under conditions of high humidity
Ester linkage breaking open loop generates its active metabolite Simvastatin carboxylic acid, and the ethylene linkage of intramolecule two occurs slow under the high temperature conditions
Oxidation copolymerization reaction generation dimer or polymer.Li Yan, Zhao Li just etc. delivered on Chinese journal of Practical Pharmacy within 2009
Entitled " influence of the different auxiliary material to simvastatin tablet stability ", acidizer citric acid makes Simvastatin under conditions of high humidity
The relevant content of material of tablet increases；Magnesium stearate lubricant and stearic acid make the medicine of simvastatin tablet under the high temperature conditions
Content declines, and relevant content of material is dramatically increased；Antioxidant BHA makes Simvastatin Tablets under the conditions of hot and humid
The relevant content of material of agent increases；Lubricant Compritol 888 ATO makes simvastatin tablet stablize relatively.But, if do not used
Magnesium stearate and stearic acid can not only bring the problem of cost increase using other lubricants as lubricant, it is also possible to
Bring the problem of stability.
The content of the invention
The present invention proposes a kind of simvastatin tablet, and the simvastatin tablet is improved by auxiliary material, in scale
Possesses controllability in large-scale production process, Simvastatin Tablets keep quality stability in 48 months.
The technical proposal of the invention is realized in this way：
A kind of simvastatin tablet, including following supplementary material：
Simvastatin, microcrystalline cellulose, dextrin, lactose, antioxidant, lubricant and thin film coating material；Wherein, it is described
Lubricant is the mixture of Compritol 888 ATO and magnesium stearate.
Preferably, in some embodiments of the present invention, in parts by weight, including following supplementary material：
28~30 parts of Simvastatin, 14~16 parts of microcrystalline cellulose, 28~30 parts of dextrin, 200~210 parts of lactose, antioxygen
8~10 parts of 0.05~0.06 part of agent, 4~5 parts of lubricant and thin film coating material；Wherein, the lubricant is that behenic acid is sweet
The mixture of grease and magnesium stearate.
Preferably, in some embodiments of the present invention, the antioxidant is butylhydroxy anisole.
Preferably, in some embodiments of the present invention, the thin film coating material includes that Hydroxypropyl methylcellulose, hydroxypropyl are fine
Dimension element, talcum powder and titanium dioxide.
It is a further object to provide a kind of preparation method of simvastatin tablet, comprise the following steps：
1) it is pre-mixed：Weigh Simvastatin, microcrystalline cellulose, antioxidant, dextrin and lactose to be pre-mixed, the time is
25~30min；
2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 20~30 mesh sieves, obtains particle；
3) by lubricant and step 2) particle be well mixed, then carry out compressing tablet；
4) it is coated：By thin film coating material and step 3) label be coated.
Preferably, in some embodiments of the present invention, the antioxidant is butylhydroxy anisole.
Preferably, in some embodiments of the present invention, the thin film coating material includes that Hydroxypropyl methylcellulose, hydroxypropyl are fine
Dimension element, talcum powder and titanium dioxide.
Beneficial effects of the present invention：
1st, dextrin：It is nontoxic, nonirritant under the dosage of auxiliary material application.Although significant amount intake may be harmful to,
Larger dose has no adverse reaction, LD50 (mouse, IV) for nutritional supplementation：0.35g/kg；GRAS , Shou Load have been taken in FDA
《Inactive ingredients guide》.
2nd, with the presence of document report magnesium stearate and Simvastatin Tablets incompatibility, the stability of Simvastatin is influenceed,
In this research, because Simvastatin is subject to Compritol 888 ATO, dextrin mixing parcel, the influence of magnesium stearate is not affected by, used
Magnesium stearate in the big production of scale, shows superior compressing tablet depanning efficiency as the prescription of lubricant.
Specific embodiment
Embodiment 1
28 parts of Simvastatin, 14 parts of microcrystalline cellulose, 28 parts of dextrin, 200 parts of lactose, butylhydroxy anisole 0.05
Part, 2 parts of Compritol 888 ATO and 2 parts of magnesium stearate and thin film coating material 8.
Thin film coating material includes Hydroxypropyl methylcellulose, hydroxypropylcellulose, talcum powder and titanium dioxide.
Preparation method：
Comprise the following steps：
1) it is pre-mixed：Simvastatin, microcrystalline cellulose, butylhydroxy anisole, dextrin and lactose is weighed to be premixed
Close, the time is 20min；
2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 20 mesh sieves, obtains particle；
3) by Compritol 888 ATO and magnesium stearate and step 2) particle be well mixed, then carry out compressing tablet；
4) it is coated：Thin film coating material purified water is mixed to get suspension, even spraying is coated until label is complete
By uniform fold last layer film.
Embodiment 2
29 parts of Simvastatin, 16 parts of microcrystalline cellulose, 30 parts of dextrin, 206 parts of lactose, butylhydroxy anisole 0.056
9 parts of part, 2 parts of Compritol 888 ATO, 3 parts of magnesium stearate and thin film coating material.
Thin film coating material includes Hydroxypropyl methylcellulose, hydroxypropylcellulose, talcum powder and titanium dioxide.
Preparation method：
Comprise the following steps：
1) it is pre-mixed：Weigh a small amount of microcrystalline cellulose and butylhydroxy anisole and cross 20 mesh sieves, mix 15 minutes, then
Simvastatin, remaining microcrystalline cellulose, lactose and dextrin lactose is added to be pre-mixed, the time is 30min；
2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 26 mesh sieves, obtains particle；
3) by Compritol 888 ATO and magnesium stearate and step 2) particle be well mixed, then carry out compressing tablet；
4) it is coated：Thin film coating material purified water is mixed to get suspension, even spraying is coated until label is complete
By uniform fold last layer film.
Embodiment 3
30 parts of Simvastatin, 15 parts of microcrystalline cellulose, 29 parts of dextrin, 210 parts of lactose, butylhydroxy anisole 0.06
10 parts of part, 2 parts of Compritol 888 ATO, 2.5 parts of magnesium stearate and thin film coating material.
Thin film coating material includes Hydroxypropyl methylcellulose, hydroxypropylcellulose, talcum powder and titanium dioxide.
Preparation method：
Comprise the following steps：
1) it is pre-mixed：Weigh a small amount of microcrystalline cellulose and butylhydroxy anisole and cross 20 mesh sieves, mix 15 minutes, then
Simvastatin, remaining microcrystalline cellulose, lactose and dextrin lactose is added to be pre-mixed, the time is 30min；
2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 30 mesh sieves, obtains particle；
3) by Compritol 888 ATO and magnesium stearate and step 2) particle be well mixed, then carry out compressing tablet；
4) it is coated：Thin film coating material purified water is mixed to get suspension, even spraying is coated until label is complete
By uniform fold last layer film.
By embodiment 1-3 tablets, according to《Chinese Pharmacopoeia》Version two in 2010 records the lower detection outward appearance of Simvastatin, hard
Degree and disintegration time limited, content, relevant material, every Testing index meet standard requirement.
The quality index of the embodiment 1-3 tablets of table 1
| Embodiment 1 | Embodiment 2 | Embodiment 3 | |
| Disintegration time limited (min) | 8 | 7.5 | 7 |
| Content (%) | 100.1% | 100.0% | 100.2% |
| Total impurities | 0.4 | 0.45 | 0.42 |
| Dissolution rate | 86.8% | 87.2% | 86.3% |
By embodiment 1-3 tablets, under the conditions of 40 DEG C of+75%RH, proterties, content, relevant is carried out after placing 6 months
Material, dissolution rate detection, judge mass change trend.
The embodiment 1-3 tablet stability experimental results of table 2
Presently preferred embodiments of the present invention is the foregoing is only, is not intended to limit the invention, it is all in essence of the invention
Within god and principle, any modification, equivalent substitution and improvements made etc. should be included within the scope of the present invention.
Claims (7)
1. a kind of simvastatin tablet, it is characterised in that including following supplementary material：
Simvastatin, microcrystalline cellulose, dextrin, lactose, antioxidant, lubricant and thin film coating material；Wherein, the lubrication
Agent is the mixture of Compritol 888 ATO and magnesium stearate.
2. simvastatin tablet according to claim 1, it is characterised in that in parts by weight, including following original
Auxiliary material：
28~30 parts of Simvastatin, 14~16 parts of microcrystalline cellulose, 28~30 parts of dextrin, 200~210 parts of lactose, antioxidant
8~10 parts of 0.05~0.06 part, 4~5 parts of lubricant and thin film coating material；Wherein, the lubricant is Compritol 888 ATO
With the mixture of magnesium stearate.
3. simvastatin tablet according to claim 1 and 2, it is characterised in that the antioxidant is tert-butyl hydroxy
Anisole.
4. simvastatin tablet according to claim 1 and 2, it is characterised in that the thin film coating material includes hydroxypropyl
Methylcellulose, hydroxypropylcellulose, talcum powder and titanium dioxide.
5. the preparation method of simvastatin tablet as claimed in claim 1, it is characterised in that comprise the following steps：
1) it is pre-mixed：Simvastatin, microcrystalline cellulose, antioxidant, dextrin and lactose is weighed to be pre-mixed, the time be 25~
30min；
2) by step 1) the mixing supplementary material that obtains carries out dry granulation, crosses 20~30 mesh sieves, obtains particle；
3) by lubricant and step 2) particle be well mixed, then carry out compressing tablet；
4) it is coated：By thin film coating material and step 3) label be coated.
6. the preparation method of simvastatin tablet according to claim 5, it is characterised in that the antioxidant is tertiary fourth
Base BHA.
7. the preparation method of simvastatin tablet according to claim 5, it is characterised in that the thin film coating material bag
Include Hydroxypropyl methylcellulose, hydroxypropylcellulose, talcum powder and titanium dioxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710118539.0A CN106860415A (en) | 2017-03-01 | 2017-03-01 | Simvastatin tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710118539.0A CN106860415A (en) | 2017-03-01 | 2017-03-01 | Simvastatin tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106860415A true CN106860415A (en) | 2017-06-20 |
Family
ID=59169163
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710118539.0A Pending CN106860415A (en) | 2017-03-01 | 2017-03-01 | Simvastatin tablet and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114588121A (en) * | 2021-05-05 | 2022-06-07 | 鲁南贝特制药有限公司 | Simvastatin tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1977841A (en) * | 2005-12-08 | 2007-06-13 | 上海信谊万象药业股份有限公司 | Method for preparing simvastatin tablet |
| CN102106835A (en) * | 2009-12-29 | 2011-06-29 | 张凤文 | Method for preparing simvastatin tablet by employing micronizing and power direct compressing technologies |
| CN106265555A (en) * | 2015-05-19 | 2017-01-04 | 上海信谊天平药业有限公司 | A kind of Simvastatin Tablets and preparation method thereof |
-
2017
- 2017-03-01 CN CN201710118539.0A patent/CN106860415A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1977841A (en) * | 2005-12-08 | 2007-06-13 | 上海信谊万象药业股份有限公司 | Method for preparing simvastatin tablet |
| CN102106835A (en) * | 2009-12-29 | 2011-06-29 | 张凤文 | Method for preparing simvastatin tablet by employing micronizing and power direct compressing technologies |
| CN106265555A (en) * | 2015-05-19 | 2017-01-04 | 上海信谊天平药业有限公司 | A kind of Simvastatin Tablets and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 吕文辉: "不同辅料对辛伐他汀片剂稳定性的影响", 《中国保健营养》 * |
| 李燕等: "不同辅料对辛伐他汀片剂稳定性的影响", 《中国药剂学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114588121A (en) * | 2021-05-05 | 2022-06-07 | 鲁南贝特制药有限公司 | Simvastatin tablet and preparation method thereof |
| CN114588121B (en) * | 2021-05-05 | 2024-01-26 | 鲁南贝特制药有限公司 | Simvastatin tablet and preparation method thereof |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170620 |
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