CN104546788A - Preparation method of simvastatin tablets - Google Patents
Preparation method of simvastatin tablets Download PDFInfo
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- CN104546788A CN104546788A CN201510015479.0A CN201510015479A CN104546788A CN 104546788 A CN104546788 A CN 104546788A CN 201510015479 A CN201510015479 A CN 201510015479A CN 104546788 A CN104546788 A CN 104546788A
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Abstract
The invention discloses a preparation method of simvastatin tablets. The preparation method comprises the following steps: preparing a solid dispersion from a simvastatin raw material by using a spray-drying technology, and mixing the solid dispersion with auxiliary materials and dry-pressing, so that the slow quick-release feature of the simvastatin tablets in in-vitro dissolution is better, and the dissolution curve of simvastatin is closer to an S shape, and the stability thereof is higher. The purpose of such a release feature can much meet clinic needs, and has a great blood-fat reducing effect.
Description
Technical field
The present invention relates to technical field of medicine, particularly a kind of preparation method of Simvastatin Tablets.
Background technology
Simvastatin (simvastatin) belongs to HMG-CoA reductase inhibitor, clinical research proves, simvastatin can significantly reduce serum TC, LDL-C, and moderate reduces serum levels of triglyceride TG, increasing serum HDL-C (HDL-C) in various degree.Simvastatin comes across late 1980s, and now in many countries, simvastatin has become a non-proprietary preparation, is widely used in clinical practice as the first-selection in statins.
The preparation method of existing simvastatin, have plenty of and regulate the pH value of Statins mixture to prepare (as US20030153617, CN200610029655.7, CN99814403.7), have plenty of the ratio changing water-soluble filler and water-insoluble filler to prepare (as US20050186270), the feed postition having plenty of open stabilizing agent (as is dissolved in fountain solution, spraying dry, except desolventizing, US20070202159, the preparation of simvastatin in WO2008006715 and Handbook of pharmaceutical manufacturingformulations:compressed solid description CN 103230376A43/5 page 5products), and the invention of the relevant simvastatin of the applicant's application is (as CN 103356494B, CN 1977841A etc.), these patents mainly solve the stability of simvastatin.
The present invention adopts spray drying technology that simvastatin raw material is prepared into solid dispersion, remixes adjuvant dry-pressing, makes the In Vitro Dissolution of product present the feature of S type stripping curve, meets clinical slow rapid release demand, reaches better lipid-lowering effect.The dissolved corrosion of what the present invention mainly solved is simvastatin.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of Simvastatin Tablets, in order to overcome above-mentioned weak point, what make Simvastatin Tablets presents better slow immediate release profile at stripping ectosome, improves simvastatin tablet stability, meet the clinical needs of modern medicine, reach better lipid-lowering effect.
The present invention solves the main technical schemes that its technical problem adopts: a kind of preparation method of Simvastatin Tablets, first simvastatin raw material and carrier material are dissolved in anhydrous ethanol solvent, adopt spray drying method removing dehydrated alcohol, prepare simvastatin solid dispersion; Obtained Simvastatin Tablets after tableting aid tabletting and coating solution coating again; The proportioning by weight of described simvastatin and carrier material is: simvastatin 95 ~ 105 parts, carrier material 570 ~ 630 parts.
Described spray drying method, adopts spray dryer to carry out drying, and described spray dryer adopts BILON-6000Y type small-sized spray drier.
Preferred described carrier material be selected from PVP K30 or poloxamer one or both.
Described tableting aid comprises filler, antioxidant and lubricant.
Preferred described filler is one or more in microcrystalline Cellulose, pregelatinized Starch, lactose.
Preferred described antioxidant is Butylated hydroxyanisole or Butylated hydroxyanisole and vitamin C.
Preferred described lubricant is magnesium stearate.
A preparation method for Simvastatin Tablets, composed of the following components by weight:
Simvastatin solid dispersion
Simvastatin 95 ~ 105 parts
PVP-K30 570 ~ 630 parts
Dehydrated alcohol 1900 ~ 2100 parts
Tableting aid
Coating solution
Opadry 57 ~ 63 parts
80% ethanol 893 ~ 987 parts
Described Simvastatin Tablets is prepared especially by following steps:
Step 1) prepare simvastatin solid dispersion
Step 101, mixs homogeneously recipe quantity simvastatin raw material with PVP-K30, is melted in 60 DEG C of recipe quantity dehydrated alcohol, is made into mixed solution;
Step 102, adopts spray drying method dry, operating temperature 45 DEG C, liquid feeding pump 30rpm, and dehydrated alcohol in removing mixed solution, obtains simvastatin solid dispersion.
Step 2) tabletting
Step 201, pulverizes recipe quantity lactose and BHA, crosses 30 mesh sieves for subsequent use.
Step 202, by step 1) microcrystalline Cellulose of the simvastatin solid dispersion prepared and recipe quantity, pregelatinized Starch, lactose, BHA, magnesium stearate mix homogeneously, tabletting, obtained simvastatin element sheet.
Step 3) coating
Step 301, is placed in agitator by recipe quantity 80% ethanol, under stirring, slowly adds recipe quantity Opadry, and stirs half an hour more than, prepare Opadry coating solution.
Step 302, by step 202) obtained simvastatin element sheet is placed in coating pan, when coating pan inlet temperature is between 50 ~ 80 DEG C, be preheated to leaving air temp 42 DEG C time, the Opadry coating solution that access above-mentioned steps 301 is obtained, can coating be carried out, to terminating, barrelling, to be checked.
The coated rear weightening finish 2 ~ 4% of described simvastatin element sheet.
The invention has the beneficial effects as follows: the preparation method providing a kind of Simvastatin Tablets, the preparation method that this patent provides makes the slow immediate release profile of Simvastatin Tablets stripping in vitro better, and make the stripping curve of simvastatin more level off to S type, stability is higher.The object of this release characteristic more can meet clinical needs, and has extraordinary lipid-lowering effect.
Accompanying drawing explanation
Fig. 1 is from film-making stripping curve figure in PH1.2 medium;
Fig. 2 is from film-making stripping curve figure in PH4.0 medium;
Fig. 3 is from film-making stripping curve figure in PH6.8 medium;
Fig. 4 is from film-making stripping curve figure in aqueous medium;
Detailed description of the invention
Further illustrate the present invention below by specific embodiment and comparative example, but should be understood to, these embodiments and contrast are only used for the use specifically described more in detail, and should not be construed as limiting the present invention in any form.It will be apparent to those skilled in the art that hereinafter, if not specified, material therefor of the present invention and operational approach are well known in the art.
Embodiment 1
Be prepared from by following component by weight:
Simvastatin solid dispersion
Simvastatin 100g
PVP-K30 600g
Dehydrated alcohol 2000g
Tableting aid
Coating solution
Opadry 60g
80% ethanol 940g
Prepare especially by following steps:
Step 1) prepare simvastatin solid dispersion (10000):
Step 101, mixs homogeneously recipe quantity simvastatin raw material with PVP-K30, is melted in 60 DEG C of recipe quantity dehydrated alcohol, is made into mixed solution;
Step 102, adopts spray drying method dry, operating temperature 45 DEG C, liquid feeding pump 30rpm, and dehydrated alcohol in removing mixed solution, obtains simvastatin solid dispersion.
Step 2) tabletting
Step 201, pulverizes recipe quantity lactose and BHA, crosses 30 mesh sieves for subsequent use.
Step 202, by step 1) microcrystalline Cellulose of the simvastatin solid dispersion prepared and recipe quantity, pregelatinized Starch, lactose, BHA, magnesium stearate mix homogeneously, tabletting, obtained 10000 simvastatins element sheets.
Step 3) coating
Recipe quantity 80% ethanol is placed in agitator by step 301, under stirring, slowly adds recipe quantity Opadry, and stirs half an hour more than, prepare Opadry coating solution.
Step 302, by step 2) obtained simvastatin element sheet is placed in coating pan, when coating pan inlet temperature is between 50 ~ 80 DEG C, be preheated to leaving air temp 42 DEG C time, the Opadry coating solution that access above-mentioned steps 301 is obtained, can coating be carried out, to terminating, barrelling, to be checked.Obtaining this batch experiment sample lot number is X131201.
Embodiment 2
Be prepared from by following component by weight:
Simvastatin solid dispersion
Simvastatin 95g
PVP-K30 570g
Dehydrated alcohol 1900g
Tableting aid
Coating solution
Opadry 63g
80% ethanol 890g
Concrete preparation process is identical with embodiment 1, and obtaining this batch experiment sample lot number is X131202.
Embodiment 3
Be prepared from by following component by weight:
Simvastatin solid dispersion
Simvastatin 105g
PVP-K30 622g
Dehydrated alcohol 2050g
Tableting aid
Coating solution
Opadry 58g
80% ethanol 980g
Concrete preparation process is identical with embodiment 1, and obtaining this batch experiment sample lot number is X131203.
Simvastatin Tablets stripping curve is investigated:
Simvastatin Tablets (X131201, X131202, X131203) stripping curve in different dissolution medium that above-described embodiment 1, embodiment 2, embodiment 3 are obtained:
Take from film-making X131201, X131202, X131203 respectively, according to dissolution method (annex XC second method) [2], (sodium chloride 2.0g is got respectively with the PH1.2 solution containing 0.3% tween 80, add water and make dissolving in right amount, add hydrochloric acid 7ml, be diluted with water to 1000ml again, mixing, to obtain final product.); PH4.0 phosphate buffer containing 0.3% tween 80 (is got disodium hydrogen phosphate dodecahydrate 17.90g, is dissolved in water and is diluted to 1000ml, obtain the sodium dihydrogen phosphate of 0.05mol/L; Separately get monohydrate potassium (also known as citric acid) 5.25g, be dissolved in water and be diluted to 1000ml, obtain the citric acid solution of 0.025mol/L.Then regulate sodium dihydrogen phosphate with citric acid solution, make final pH value to 4.0, to obtain final product); Containing the PH6.8 phosphate buffer (get potassium dihydrogen phosphate 1.7g and disodium hydrogen phosphate,anhydrous 1.775g, add water after making dissolving in right amount, be settled to 1000ml, to obtain final product) of 0.3% tween 80; Containing solution in the purified water 4 of 0.3% tween 80 as dissolution medium.
Respectively in 5min, 10min, 15min, 30min, 45min, 60min, 90min, 120min, sampling, every sub-sampling 3ml (simultaneously supplementing equality of temperature same media 3ml), filters through 0.45 μm of microporous filter membrane, gets subsequent filtrate as need testing solution; Shrewdness takes simvastatin reference substance, is mixed with 5.5 μ g/ml, in contrast product with mobile phase dilution; Detect according to chromatographic condition, its dissolved corrosion is as follows:
From film-making stripping curve in PH1.2 medium---as shown in Figure 1:
From film-making stripping curve in PH4.0 medium---as shown in Figure 2:
From film-making stripping curve in PH6.8 medium---as shown in Figure 3:
From film-making stripping curve in aqueous medium---as shown in Figure 4:
Can find out from stripping curve shown in above-mentioned stripping curve Fig. 1 to Fig. 4 and adopt compared with the Simvastatin Tablets prepared of the present invention adopts existing technique with comparative example, in the identical time, there is better result of extraction, ease up and release at a slow speed, it should be noted that this is best to the slow release effect of ten minutes from film-making the first five minute in different dissolution mediums especially, meet clinical needs; This preparation technology simply, while guarantee simvastatin stability is easy to industrialized mass production simultaneously.
Obviously, those skilled in the art can carry out various change and modification to the present invention and not depart from the spirit and scope of the present invention.Like this, if these amendments of the present invention and modification belong within the scope of the claims in the present invention and equivalent technologies thereof, then the present invention is also intended to comprise these change and modification.
Claims (10)
1. a preparation method for Simvastatin Tablets, is characterized in that, comprises the following steps:
1) simvastatin raw material and carrier material are dissolved in anhydrous ethanol solvent, adopt spray drying method removing dehydrated alcohol, prepare simvastatin solid dispersion;
2) solid dispersion and adjuvant tabletting are obtained simvastatin element sheet;
3) by obtained Simvastatin Tablets after the coated liquid coating of simvastatin element sheet;
The proportioning by weight of described simvastatin and carrier material is: simvastatin 95 ~ 105 parts, carrier material 570 ~ 630 parts.
2. the preparation method of a kind of Simvastatin Tablets according to claim 1, is characterized in that, described carrier material be selected from PVP K30 or poloxamer one or both.
3. the preparation method of a kind of Simvastatin Tablets according to claim 1, is characterized in that, described tableting aid comprises filler, antioxidant and lubricant.
4. the preparation method of a kind of Simvastatin Tablets according to claim 3, is characterized in that, described filler is one or more in microcrystalline Cellulose, pregelatinized Starch, lactose.
5. the preparation method of a kind of Simvastatin Tablets according to claim 3, is characterized in that, described antioxidant is Butylated hydroxyanisole, or Butylated hydroxyanisole and vitamin C.
6. the preparation method of a kind of Simvastatin Tablets according to claim 3, is characterized in that, described lubricant is magnesium stearate.
7. the preparation method of a kind of Simvastatin Tablets according to claim 1, is characterized in that, composed of the following components by weight:
Simvastatin solid dispersion
Simvastatin 95 ~ 105 parts
PVP-K30 570 ~ 630 parts
Dehydrated alcohol 1900 ~ 2100 parts
Tableting aid
Coating solution
Opadry 57 ~ 63 parts
80% ethanol 893 ~ 987 parts.
8. the preparation method of a kind of Simvastatin Tablets according to claim 7, is characterized in that, step 1) specifically comprise the following steps:
Step 101, mixs homogeneously recipe quantity simvastatin raw material with PVP-K30, is melted in 60 DEG C of recipe quantity dehydrated alcohol, is made into mixed solution;
Step 102, adopts spray drying method dry, operating temperature 45 DEG C, liquid feeding pump 30rpm, and dehydrated alcohol in removing mixed solution, obtains simvastatin solid dispersion.
9. the preparation method of a kind of Simvastatin Tablets according to claim 7, is characterized in that, step 2) specifically comprise the following steps:
Step 201, pulverizes recipe quantity lactose and BHA, crosses 30 mesh sieves for subsequent use.
Step 202, by step 1) microcrystalline Cellulose of the simvastatin solid dispersion prepared and recipe quantity,
Pregelatinized Starch, lactose, BHA, magnesium stearate mix homogeneously, tabletting, obtained simvastatin element sheet.
10. the preparation method of a kind of Simvastatin Tablets according to claim 7, is characterized in that, step 3) specifically comprise the following steps:
Step 301, is placed in agitator by recipe quantity 80% ethanol, under stirring, slowly adds recipe quantity Opadry, and stirs half an hour more than, prepare Opadry coating solution.
Step 302, by step 2) obtained simvastatin label is placed in coating pan, when coating pan inlet temperature is between 50 ~ 80 DEG C, be preheated to leaving air temp 42 DEG C time, the Opadry coating solution that access above-mentioned steps 301 is obtained, can coating be carried out, to terminating, barrelling, to be checked.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107569461A (en) * | 2017-06-26 | 2018-01-12 | 安徽永生堂药业有限责任公司 | A kind of Simvastatin Tablets and preparation method thereof |
Citations (4)
| 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 |
| WO2010133611A1 (en) * | 2009-05-18 | 2010-11-25 | Royal College Of Surgeons In Ireland | Solid drug dispersions |
| CN101951891A (en) * | 2008-01-11 | 2011-01-19 | 希普拉有限公司 | Solid pharmaceutical dosage form |
| CN103230376A (en) * | 2012-12-24 | 2013-08-07 | 山东新华制药股份有限公司 | Simvastatin tablet preparation method |
-
2015
- 2015-01-13 CN CN201510015479.0A patent/CN104546788B/en active Active
Patent Citations (4)
| 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 |
| CN101951891A (en) * | 2008-01-11 | 2011-01-19 | 希普拉有限公司 | Solid pharmaceutical dosage form |
| WO2010133611A1 (en) * | 2009-05-18 | 2010-11-25 | Royal College Of Surgeons In Ireland | Solid drug dispersions |
| CN103230376A (en) * | 2012-12-24 | 2013-08-07 | 山东新华制药股份有限公司 | Simvastatin tablet preparation method |
Non-Patent Citations (3)
| Title |
|---|
| ANSHUMAN A. AMBIKE ET.AL: "Spray-Dried Amorphous Solid Dispersions of Simvastatin,a Low Tg Drug: In Vitro and in Vivo Evaluations", 《PHARMACEUTICAL RESEARCH》 * |
| 彭霞: "辛伐他汀固体分散体的研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
| 顾珽等: "辛伐他汀片处方工艺筛选及溶出度一致性评价", 《上海医药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107569461A (en) * | 2017-06-26 | 2018-01-12 | 安徽永生堂药业有限责任公司 | A kind of Simvastatin Tablets and preparation method thereof |
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