CN100411612C - Quick-disintegration tablets of calcium atovastatine, and its prepn. method - Google Patents
Quick-disintegration tablets of calcium atovastatine, and its prepn. method Download PDFInfo
- Publication number
- CN100411612C CN100411612C CNB2006100481882A CN200610048188A CN100411612C CN 100411612 C CN100411612 C CN 100411612C CN B2006100481882 A CNB2006100481882 A CN B2006100481882A CN 200610048188 A CN200610048188 A CN 200610048188A CN 100411612 C CN100411612 C CN 100411612C
- Authority
- CN
- China
- Prior art keywords
- atorvastatin calcium
- disintegrating agent
- filler
- lubricant
- correctives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
A fast disintegrated atorvastin calcium tablet is prepared from atorvastin calcium, disintegrant, flavouring, filler and lubricant proportionally. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and preparation method, especially quick-disintegration tablets of calcium atovastatine, and its preparation method belongs to medical technical field.
Background technology
Atorvastatin (Atorvastatin Calcium) is a kind of selectivity, the competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, the HMG-CoA reductase is a rate-limiting enzyme, and this enzyme is converted into mevalonic acid (comprising the precursor of cholesterol at interior sterin) with 3-hydroxy-3-methyl-glutaryl coenzyme A.Triglyceride and cholesterol are merged into C-VLDL (VLDL) and are discharged in the blood plasma with further conveying surrounding tissue in liver.Low-density lipoprotein cholesterol (LDL) is formed by C-VLDL (VLDL) and main low-density lipoprotein cholesterol (LDL) receptor catabolism by high-affinity.
Thereby HMG-CoA reductase and the synthetic of cholesterol that atorvastatin passes through to suppress in the liver reduce cholesterol and lipoprotein levels in the blood plasma, and pass through to increase liver low-density lipoprotein cholesterol (LDL) receptor of cell surface to strengthen picked-up and the metabolism of LDL.
Atorvastatin can reduce total plasma cholesterol (TC), LDL-C and the apolipoprotein B (ApoB) of homozygote and heterozygote familial hypercholesterolemia, non-familial hypercholesterolemia and Combination lipid metabolism impaired patients, the level of C-VLDL (VLDL-C) and triacylglycerol (TG) can also be reduced, and plasma hdl cholesterol (HDL-C) and ApoA can be improved to some extent
1(ApoA
1) level.
The clinical use determined curative effect of Atorvastatin calcium, effect are remarkable, but because Atorvastatin calcium has bitter in the mouth, soluble,very slightly in water, it is all extremely sensitive to heat, moist, low PH environment and light, particularly under acid environment, Atorvastatin calcium can be degraded into corresponding lactone, and its conventional tablet exists problems such as disintegrate delay, stripping be slow, directly affects its clinical drug effect.In addition, in clinical practice, the Atorvastatin calcium initial dose is 10mg () on the one, later passing along with treatment time, the dosage scope is 10-60mg (a 1-6 grain), and so heavy dose of is oral, has brought inconvenience also for the patient of child, old man or dysphagia.
Summary of the invention
The present invention is used to overcome the defective of prior art and provides that a kind of disintegrate is rapid, dissolution is high, be easy to oral atorvastatin calcium tablet and preparation method.
The alleged problem of the present invention is to solve like this:
A kind of can quickly disintegrated atorvastatin calcium tablet, make by principal agent Atorvastatin calcium and pharmaceutical carrier, its special feature is: described pharmaceutical carrier mainly is made up of disintegrating agent, correctives, lubricant, filler, principal agent and pharmaceutical carrier proportioning by weight percentage are as follows: Atorvastatin calcium 5-25%, disintegrating agent 28-55%, correctives 1-5%, filler 25-50%, lubricant 1-5%.
Above-mentioned can quickly disintegrated atorvastatin calcium tablet, described disintegrating agent is microcrystalline Cellulose, sodium lauryl sulphate and three kinds of component couplings of crospolyvinylpyrrolidone, wherein, sodium lauryl sulphate is for adding disintegrating agent; Microcrystalline Cellulose is inside and outside with disintegrating agent, and the inside and outside part by weight that adds is 2: 1; Crospolyvinylpyrrolidone (PVPP) is for inside and outside with disintegrating agent, in the part by weight that adds be 3: 1.
Above-mentioned can quickly disintegrated atorvastatin calcium tablet, described correctives is selected from one or more in Fructus Citri sinensis powdered flavor, aspartame, cyclamate, glycyrrhizin, stevioside, the glucide; Lubricant is selected from one or more in magnesium stearate, silicon dioxide, Pulvis Talci, the Polyethylene Glycol; Filler is selected from one or more in pregelatinized Starch, lactose, Icing Sugar, starch, the mannitol.
Above-mentioned can quickly disintegrated atorvastatin calcium tablet, described correctives is selected from the Fructus Citri sinensis powdered flavor; Lubricant is selected from Pulvis Talci; Filler is selected from pregelatinized Starch.
Above-mentioned preparation method that can quickly disintegrated atorvastatin calcium tablet, it carries out as follows:
A. take by weighing Atorvastatin calcium, filler, correctives by said ratio, behind three's mix homogeneously, pulverized 100 mesh sieves;
B. with disintegrating agent, put into the mixer mixing jointly in taking by weighing by said ratio with three in a step;
C. it is an amount of to add binding agent, stirs 5～10 minutes, granulate with 32 mesh sieves, and 40 ℃ ± 5 ℃ aeration-dryings, dried granule is crossed 24 mesh sieve granulate;
D. after adding adds disintegrating agent, lubricant and the abundant mix homogeneously of dried granule, sample examination, qualified tabletting, the two aluminum packings in the qualified back of product inspection are the dress box also.
Above-mentioned can the preparation method of quickly disintegrated atorvastatin calcium tablet in, described binding agent is selected from 5% polyvinylpyrrolidone, i.e. 5% PVP aqueous solution.Described binding agent is meant in right amount is enough to make material moistening that is obtained among the step b and the amount that can granulate.
The problems such as common Atorvastatin calcium disintegrate delay, stripping are slow, mouthfeel bitterness that the present invention is directed to are improved, by a large amount of experiments, selection, usage and consumption to disintegrating agent are explored, determine that the inside and outside ratio that adds of PVPP is 3: 1, the inside and outside ratio that adds of microcrystalline Cellulose is that 2: 1 o'clock finely dispersed time is the shortest; If add a small amount of sodium lauryl sulphate again effect will further be optimized.By testing result as can be known, the disintegration of tablet of the present invention, dissolution have all obtained significant raising or improvement, compare with conventional tablet, have that good dispersing state, disintegration time are short, the medicine stripping rapidly, absorb fast, characteristics such as bioavailability is high, untoward reaction is few, taking convenience.Can swallow, chew to contain and suck, or in water, disperse back and fruit juice, milk and clothes.The present invention has not only reduced production cost, and has solved the problem that the Atorvastatin calcium medicine is occurred in clinical practice and pharmacy practice.
The specific embodiment
The present invention for solve common Atorvastatin calcium disintegrate delay, stripping slowly problem done a large amount of experiments, selection, usage and consumption to disintegrating agent are explored, find to adopt microcrystalline Cellulose, crospolyvinylpyrrolidone (PVPP), sodium lauryl sulphate to make disintegrating agent separately, the dispersing uniformity of tablet all can not meet the demands.Dispersing uniformity had clear improvement when PVPP and microcrystalline Cellulose share.When PVPP adopts inside and outside adding, microcrystalline Cellulose adopts the inside and outside added-time, and effect is further obviously improved.On this basis, inside and outside ratio that adds of PVPP and the inside and outside ratio that adds of microcrystalline Cellulose have been carried out further research, found that the inside and outside ratio that adds of PVPP is 3: 1, the inside and outside ratio that adds of microcrystalline Cellulose is that 2: 1 o'clock dispersing uniformity time is the shortest; Adding a small amount of sodium lauryl sulphate again is optimized the present invention.
Below, compare, the superiority of effect of the present invention can be described with commercially available atorvastatin calcium tablet by the cumulative in vitro determination of dissolution rate of five batch samples (lot number is respectively 060301,060302,060303,060304,060305).
Dissolution determination method is as follows:
Getting this product, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2005), is solvent with water 900ml water, rotating speed is that per minute 50 changes, and operation in accordance with the law is in the time of 5,10,15,20,30 minutes, it is an amount of to get solution, filters, and gets subsequent filtrate as need testing solution; Other gets Atorvastatin calcium reference substance an amount of (being equivalent to atorvastatin 25mg approximately), and accurate the title decides, and puts in the 25ml measuring bottle, add dissolve with methanol and be diluted to scale, shake up, precision is measured 1ml, put in the 100ml measuring bottle, thin up shakes up to scale, in contrast solution, get above-mentioned two kinds of solution, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2005), measure trap respectively at the wavelength place of 241nm, calculate every stripping quantity with the ratio meter of the two trap.
The above method of average dissolution of a test agent and a commercially available sample time point is checked result such as following table in each batch:
Below, compare, further specify superiority of the present invention with commercially available atorvastatin calcium tablet by mensuration to the dispersing uniformity of calcium tablet five batch samples of the present invention (lot number is respectively 060301,060302,060303,060304,060305).
" inspection method of Chinese pharmacopoeia version appendix in 2005 dispersing uniformity is as follows:
Get two of test samples, place 20 ℃ ± 1 ℃ 100ml water, jolting three minutes, all disintegrate is also by No. two sieves.
Concrete operations are as follows:
Get 060301 batch of (test sample) 20 of sample of the present invention, be divided into 10 groups and numbering; Get 20 of commercially available atorvastatin calcium tablets (reference product), be divided into 10 groups and numbering, and will be above two groups by numbering correspondence one by one, become 10 groups of matched groups.With the test sample in each matched group and reference product according to " inspection method of Chinese pharmacopoeia version appendix in 2005 dispersing uniformity is checked, write down test sample and reference product disintegration time separately in each matched group, and calculate 10 groups of average disintegration times.4 batches of in the sample all the other, also method is measured according to this.
Testing result is as follows:
By above-mentioned testing result as can be known, tablet of the present invention is compared with conventional tablet, and good dispersing state, disintegration time weak point, medicine stripping are rapidly, absorption is fast, bioavailability is high.In addition, the reasonable interpolation by correctives can improve mouthfeel, be easy to take, and can swallow, and chews to contain and suckes, or disperse back and fruit juice, milk clothes together in water.Tablet of the present invention has several specifications of different content, is fit to different patients and uses.Tablet of the present invention single dose is at any time taken, and all can when feed or non-feed.Initial dose is 10mgd-1, and dosage range is 10～80mgd-1.Take the individualized treatment scheme according to therapeutic goal and therapeutic response.To the renal insufficiency patient, needn't adjust dosage.Therefore, the present invention can effectively solve the problem that the Atorvastatin calcium medicine is occurred in clinical practice and pharmacy practice.
Several specific embodiments below are provided:
Embodiment one, prepares 1000 atorvastatin calcium tablets that specification is the 10mg/ sheet, and each amounts of components is as follows:
Atorvastatin calcium (in atorvastatin) 10.0g
Microcrystalline Cellulose (in add) 50g
Microcrystalline Cellulose (adding) 25g
Pregelatinized Starch 80g
PVPP (in add) 15g
PVPP (adding) 5g
Sodium lauryl sulphate 2g
Fructus Citri sinensis powdered flavor 2g
Pulvis Talci 3g
The 5%pvp aqueous solution is an amount of
Embodiment two, prepare the atorvastatin calcium tablet of the present invention that 1000 specifications are the 20mg/ sheet, and each amounts of components is as follows:
Atorvastatin calcium (in atorvastatin) 20.0g
Microcrystalline Cellulose (in add) 40g
Microcrystalline Cellulose (adding) 20g
Lactose 50g
PVPP (in add) 30g
PVPP (adding) 10g
Sodium lauryl sulphate 10g
Cyclamate 10g
Magnesium stearate 10g
The 5%pvp aqueous solution is an amount of
Embodiment three, prepare 1000 atorvastatin calcium tablets that specification is the 40mg/ sheet, and each amounts of components is as follows:
Atorvastatin calcium (in atorvastatin) 40.0g
Microcrystalline Cellulose (in add) 36.5g
Microcrystalline Cellulose (adding) 18.2g
Icing Sugar 93.1g
PVPP (in add) 45g
PVPP (adding) 15g
Sodium lauryl sulphate 5g
Glycyrrhizin 5.32g
Silicon dioxide 7.98g
The 5%pvp aqueous solution is an amount of
Embodiment four, prepare 1000 atorvastatin calcium tablets that specification is the 60mg/ sheet, and each amounts of components is as follows:
Atorvastatin calcium (in atorvastatin) 60.0g
Microcrystalline Cellulose (in add) 40g
Microcrystalline Cellulose (adding) 20g
Starch 150g
PVPP (in add) 15g
PVPP (adding) 5g
Sodium lauryl sulphate 4g
Stevioside 3g
Polyethylene Glycol 3g
The 5%pvp aqueous solution is an amount of
Embodiment five, prepare 1000 atorvastatin calcium tablets that specification is the 80mg/ sheet, and each amounts of components is as follows:
Atorvastatin calcium (in atorvastatin) 80.0g
Microcrystalline Cellulose (in add) 46.7g
Microcrystalline Cellulose (adding) 23.3g
Mannitol 128g
PVPP (in add) 15g
PVPP (adding) 5g
Sodium lauryl sulphate 6g
Glucide 6.4g
Pulvis Talci 9.6g
The 5%pvp aqueous solution is an amount of
Preparation method is as follows:
(a) take by weighing Atorvastatin calcium, filler, correctives by the foregoing description, behind three's mix homogeneously, pulverized 100 mesh sieves;
(b) by embodiment take by weighing in put into the mixer mixing jointly with three in disintegrating agent and (a) step;
(c) add the 5%pvp aqueous solution in right amount as binding agent, stirred 5 minutes, granulate with 32 mesh sieves, 40 ℃ ± 5 ℃ aeration-dryings, dried granule is crossed 24 mesh sieve granulate;
(d) again according to proportioning add add disintegrating agent, lubricant and the abundant mix homogeneously of dried granule after, sample examination, qualified tabletting, the two aluminum packings in the qualified back of product inspection are also adorned box.
Claims (5)
- One kind can quickly disintegrated atorvastatin calcium tablet, make by principal agent Atorvastatin calcium and pharmaceutical carrier, it is characterized in that: described pharmaceutical carrier mainly is made up of disintegrating agent, correctives, lubricant, filler, principal agent and pharmaceutical carrier proportioning by weight percentage are as follows: Atorvastatin calcium 5-25%, disintegrating agent 28-55%, correctives 1-5%, filler 25-50%, lubricant 1-5%; Described disintegrating agent is microcrystalline Cellulose, sodium lauryl sulphate and three kinds of component couplings of crospolyvinylpyrrolidone, and wherein, sodium lauryl sulphate is for adding disintegrating agent; Microcrystalline Cellulose is inside and outside with disintegrating agent, and the inside and outside part by weight that adds is 2: 1; Crospolyvinylpyrrolidone is inside and outside with disintegrating agent, in the part by weight that adds be 3: 1.
- 2. according to claim 1 can quickly disintegrated atorvastatin calcium tablet, it is characterized in that: described correctives is selected from one or more in Fructus Citri sinensis powdered flavor, aspartame, cyclamate, glycyrrhizin, stevioside, the glucide; Lubricant is selected from one or more in magnesium stearate, silicon dioxide, Pulvis Talci, the Polyethylene Glycol; Filler is selected from one or more in pregelatinized Starch, lactose, Icing Sugar, starch, the mannitol.
- 3. according to claim 2 can quickly disintegrated atorvastatin calcium tablet, it is characterized in that: described correctives is selected the Fructus Citri sinensis powdered flavor for use; Lubricant is selected Pulvis Talci for use; Filler is selected pregelatinized Starch for use.
- 4. one kind as preparation method that can quickly disintegrated atorvastatin calcium tablet as described in the claim 1,2 or 3, and it is characterized in that: it carries out as follows:A. take by weighing place's Atorvastatin calcium, filler, correctives by proportioning, behind three's mix homogeneously, pulverized 100 mesh sieves;B. with disintegrating agent, put into the mixer mixing jointly in taking by weighing by proportioning with three in a step;C. it is an amount of to add binding agent, stirs 5～10 minutes, granulate with 32 mesh sieves, and 40 ℃ ± 5 ℃ aeration-dryings, dried granule is crossed 24 mesh sieve granulate;D. after adding adds disintegrating agent, lubricant and the abundant mix homogeneously of dried granule, sample examination, qualified tabletting, the two aluminum packings in the qualified back of product inspection are the dress box also.
- 5. preparation method that can quickly disintegrated atorvastatin calcium tablet according to claim 4 is characterized in that binding agent is selected from 5% polyvinylpyrrolidone aqueous solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100481882A CN100411612C (en) | 2006-08-25 | 2006-08-25 | Quick-disintegration tablets of calcium atovastatine, and its prepn. method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100481882A CN100411612C (en) | 2006-08-25 | 2006-08-25 | Quick-disintegration tablets of calcium atovastatine, and its prepn. method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1911209A CN1911209A (en) | 2007-02-14 |
| CN100411612C true CN100411612C (en) | 2008-08-20 |
Family
ID=37720376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100481882A Active CN100411612C (en) | 2006-08-25 | 2006-08-25 | Quick-disintegration tablets of calcium atovastatine, and its prepn. method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100411612C (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101637452B (en) * | 2008-07-28 | 2011-05-25 | 佛山达意科技有限公司 | Atorvastatin calcium dried suspension and preparation method thereof |
| CN101791297B (en) * | 2010-02-10 | 2012-03-28 | 中国药科大学 | Atorvastatin calcium oral disintegrating tablet and preparation method thereof |
| WO2012042951A1 (en) * | 2010-09-30 | 2012-04-05 | アステラス製薬株式会社 | Atorbastatin-containing medicinal tablet |
| CN102309462B (en) * | 2011-07-16 | 2012-12-12 | 南京正宽医药科技有限公司 | Atorvastatin calcium tablet |
| CN104069078B (en) * | 2014-05-22 | 2019-06-11 | 西藏九瑞健康股份有限公司 | Atorvastatin calcium medicine compound and preparation method thereof |
| CN105168162A (en) * | 2015-09-06 | 2015-12-23 | 合肥华方医药科技有限公司 | Atorvastatin calcium rapidly disintegrating oral tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030162827A1 (en) * | 2002-01-30 | 2003-08-28 | Suresh Venkataram | HMG CoA reductase inhibiting composition, method of preparation thereof and method for competitively inhibiting HMG CoA reductase using such composition |
| WO2006054308A2 (en) * | 2004-11-22 | 2006-05-26 | Dexcel Pharma Technologies Ltd. | Stable atorvastatin formulations |
-
2006
- 2006-08-25 CN CNB2006100481882A patent/CN100411612C/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030162827A1 (en) * | 2002-01-30 | 2003-08-28 | Suresh Venkataram | HMG CoA reductase inhibiting composition, method of preparation thereof and method for competitively inhibiting HMG CoA reductase using such composition |
| WO2006054308A2 (en) * | 2004-11-22 | 2006-05-26 | Dexcel Pharma Technologies Ltd. | Stable atorvastatin formulations |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1911209A (en) | 2007-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100411612C (en) | Quick-disintegration tablets of calcium atovastatine, and its prepn. method | |
| SA517390473B1 (en) | Solid dosage forms of palbociclib | |
| CN101327213B (en) | Irbesartan and hydrochlorothiazide pharmaceutical composition and preparation method thereof | |
| CA2751313C (en) | Process for the preparation of a pharmaceutical composition comprising ezetimibe | |
| MXPA02004389A (en) | Pharmaceutical compositions. | |
| EP4026539A1 (en) | Coated granule, solid dispersion, and preparation containing vortioxetine hydrobromide for oral taste masking | |
| CN103655481A (en) | Preparation method of ezetimibe orally-taken preparation | |
| CN101816637B (en) | Leflunomide tablet preparation and preparation method thereof | |
| CN109662949A (en) | A kind of fludrocortisone acetate oral disnitegration tablet and preparation method thereof | |
| CN103566373B (en) | Comprise pharmaceutical composition of cholesterol absorption inhibitor and HMG-CoA reductase inhibitor and its production and use | |
| CN105412026B (en) | Acotiamide hydrochloride hydrate piece and preparation method thereof | |
| CN104546686B (en) | A kind of mosapride citrate is co-mulled and made into thing and preparation method thereof and containing its pharmaceutical composition | |
| EP2612659A1 (en) | Panaxatriol saponins enteric pellet, capsule comprising same and method for preparing same | |
| CN103524533A (en) | Cefprozil compound, and dispersible tablets, dry suspension and preparation method thereof | |
| CN104940152B (en) | A kind of pharmaceutical composition containing butanedioic acid Solifenacin | |
| CN102309462B (en) | Atorvastatin calcium tablet | |
| CN105560199A (en) | Infantile domperidone orally disintegrating tablet and preparation method thereof | |
| CN110063944A (en) | A kind of Levamlodipine besylate atorvastatin and preparation method thereof | |
| CN106018618A (en) | Escitalopram oxalate tablet composition and quality control method | |
| CN1927301A (en) | Tongmai Jiangzhi dispersant tablet and method for making same | |
| CN103536577B (en) | Tenofovir dipivoxil fumarate capsule and preparation method thereof | |
| CN101249119B (en) | Compound compound paracetamol and zincgluconate dispersible tablet and method of preparing the same | |
| CN104983702A (en) | Atorvastatin calcium composition tablet for treating hypercholesterolemia | |
| CN103893185B (en) | A kind of valsartan and Hydrochlorothiade dispersible tablet and preparation method thereof | |
| CN102309461B (en) | Pyridostigmine bromide odor masking dispersible tablets and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |