CN101219121A - Pitavastatin calcium tablet and method for preparing the same - Google Patents
Pitavastatin calcium tablet and method for preparing the same Download PDFInfo
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- CN101219121A CN101219121A CNA2007101734322A CN200710173432A CN101219121A CN 101219121 A CN101219121 A CN 101219121A CN A2007101734322 A CNA2007101734322 A CN A2007101734322A CN 200710173432 A CN200710173432 A CN 200710173432A CN 101219121 A CN101219121 A CN 101219121A
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- pitavastatin calcium
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Abstract
The invention relates to a pitavastatin calcium tablet and a preparation method thereof. The pitavastatin calcium tablet comprises a tablet core and a coating. The tablet core comprises components that (by weight percent): pitavastatin 1-5, sodium bicarbonate 5-16, lactose 75-85, croscarmellose sodium 3-6, bonding agent 0.1-0.4, silicon dioxide 1.5-3.0, magnesium stearate plus French chalk 0.5-4.0. The preparation method comprises that (in sequence): raw materials are weighed according to a prescription and screened by a 100-mesh or 80-mesh sieve; the pitavastatin, part of the croscarmellose sodium and the sodium bicarbonate are added gradually with equal quantity and well mixed to obtain a powder mixture; the powder mixture is added with the bonding agent, and well mixed and made into soft material; the soft material is squeezed through a 18-20-mesh sieve to obtain wet granules which are dried under the temperature of 50-70 DEG C; the dry granules are finished with a 20-mesh sieve and added with magnesium stearate, French chalk, silicon dioxide and the rest croscarmellose sodium and then well mixed; the mixture is squashed to obtain the tablet cores, which are coated to obtain the finished products.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of medicine and preparation method thereof, especially a kind of pitavastatin calcium tablet and preparation method thereof.
Background technology
Pitavastatin Calcium is by the third generation statins of the common exploitation of Japanese Nissan chemical industry Co., Ltd. and Kowa company Ltd, goes on the market at Japan registration in July, 2003.Mainly be applicable to the treatment of hyperlipidemia and familial hypercholesterolemia.
Pitavastatin Calcium is by hindering the synthetic rate-limiting enzyme of cholesterol---it is synthetic that the effect of HMG-CoA reductase hinders the cholesterol of liver, thereby thereby promote liver L DL receptor active, promote liver absorb LDL from blood to make the total plasma cholesterol reduction.And the obstruction cholesterol of persistence is synthetic in liver, makes excretory VLDL minimizing in blood, reduces the triglyceride level in the blood plasma.
The chemistry of Pitavastatin is called (E)-3,5-dihydroxy-7-[4 '-4 '-fluorophenyl-2 '-cyclopropyl-quinoline-3 '-yl]-the 6-heptenoic acid, Pitavastatin and calcium salt thereof need to adopt alkaline matter make the pH value of its aqueous solution or suspension remain on certain level in acidity less stable to the neutrallty condition.
Application number 200510057110.2 discloses a kind of Pitavastatin pharmaceutical composition, point out not contain the pH regulator agent of alkalescence, pH value is greater than 6 less than 7, and this pharmaceutical composition also contains filler, disintegrating agent etc. in addition, wherein, disintegrating agent comprises microcrystalline Cellulose, sodium carboxymethyl cellulose etc.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of pitavastatin calcium tablet, adopts the better disintegrating agent of stripping property, and the medicine stripping is rapid, and comprises alkaline matter as stabilizing agent, and drug quality is stable, is fit to long term storage, and clinical efficacy is good.
The present invention solves the problems of the technologies described above the technical scheme of being taked: a kind of pitavastatin calcium tablet, comprise label and coating, and wherein each compositions in weight percentage of label (%) meter comprises:
Pitavastatin Calcium 1～5
Sodium bicarbonate 5～16
Lactose 75～85
Cross-linking sodium carboxymethyl cellulose 3～6
Binding agent 0.1～0.4
Silica 1 .5～3.0%
Magnesium stearate+Pulvis Talci 0.5～4.0%.
The present invention adds sodium bicarbonate in the preparation process of pitavastatin calcium tablet be stabilizing agent, and limit its consumption in certain limit, and the calcium salt of Pitavastatin is in the weakly alkaline stable environment in addition, has improved the stability of Pitavastatin in the preparation, is fit to long term storage.
In addition, in the preparation process of pitavastatin calcium tablet, adopt special disintegrating agent: cross-linking sodium carboxymethyl cellulose (Croscarmellose sodium), it is the carboxymethyl cellulose ether (nearly 70% carboxyl is a sodium-salt type) of crosslinkedization, because the existence of cross-bond, so it is water insoluble, but can absorb about 10 times to the water of weight own and expand, a small amount of interpolation promptly demonstrates very strong disintegrative, stripping property, has fabulous stability simultaneously, and the disintegrating property of cross-linking sodium carboxymethyl cellulose is subjected to the influence of hardness and tabletting pressure hardly, is not subjected to the influence of pH value and viscosity.In the contrast experiment, use the sample strip of cross-linking sodium carboxymethyl cellulose, just disintegrate fully in about 5 minutes, dissolution reached 95% in 15 minutes.And when disintegrating agent uses pregelatinized Starch, the complete disintegrate of ability in about 12 minutes of same sample.
Wherein, the consumption of Pitavastatin Calcium specifically can be by weight percentage: 1,1.2,1.5,1.8,2,2.3,2.5,2.7,3.0,3.2,3.5,3.8,4.0,4.3,4.5,4.7,5.0%.
The consumption of sodium bicarbonate specifically can be by weight percentage: 5,5.5,6,6.5,6.8,7,7.2,7.5,7.8,8,8.3,8.5,8.7,9,9.2,9.5,9.8,10,10.2,10.5,10.8,11,11.3,11.5,11.8,12,12.2,12.5,13,13.5,14,14.5,15,15.5,16%.
The consumption of lactose specifically can be by weight percentage: 75,75.5,76,76.5,77,77.5,80,80.5,81,81.5,82,82.5,83,83.5,84,85%.
The consumption of cross-linking sodium carboxymethyl cellulose specifically can be by weight percentage: 3,3.3,3.5,3.8,4,4.2,4.5,4.8,5,5.2,5.5,5.7,6%.
On the basis of such scheme, the consumption of cross-linking sodium carboxymethyl cellulose is preferably 4～5%.
The consumption of silicon dioxide specifically can be by weight percentage: 1.5,1.6,1.7,1.8,1.9,2.0,2.1,2.15,2.2,2.25,2.3,2.35,2.4,2.5,2.6,2.7,2.8,2.9,3.0%.
Magnesium stearate+talcous consumption specifically can be by weight percentage: 0.5,0.8,1.0,1.2,1.5,1.8,2.0,2.2,2.5,2.8,3.0,3.1,3.3,3.5,3.8,4.0%.
On the basis of such scheme, described Pitavastatin Calcium coating tablets is the Ka Lekang coating powder, and consumption is 3～5% of a label gross weight.
On the basis of such scheme, the water of described hydroxypropyl methylcellulose or alcoholic solution are as the binding agent of pitavastatin calcium tablet.The consumption of hydroxypropyl methylcellulose specifically can be by weight percentage: 0.1,0.12,0.15,0.18,0.2,0.22,0.25,0.28,0.3,0.32,0.35,0.38,0.4%.
Preparation method at above-mentioned pitavastatin calcium tablet comprises the steps:
(1) take by weighing raw material by prescription, Pitavastatin Calcium and adjuvant are crossed 100 or 80 mesh sieves respectively, and standby, adjuvant comprises: sodium bicarbonate, lactose, cross-linking sodium carboxymethyl cellulose;
(2) with cross-linking sodium carboxymethyl cellulose, the sodium bicarbonate of Pitavastatin Calcium and lactose, part, with the equivalent method mix homogeneously that progressively increases, obtain mixed-powder, wherein, the equivalent method of progressively increasing is taken out a part and the about mixed in equal amounts of the little medicine of amount for measuring big medicine, so doubly measures the big medicine of recruitment until whole mixings;
(3) add binding agent in the mixed-powder, i.e. the water of hydroxypropyl methylcellulose or alcoholic solution, mix homogeneously is made soft material;
(4) soft material pushed 18～20 mesh sieves, made wet granular;
(5) granule is in 50～70 ℃ of following air blast oven dry;
(6) dried granule 20 mesh sieve granulate add magnesium stearate and Pulvis Talci, silicon dioxide and rest parts cross-linking sodium carboxymethyl cellulose, mix homogeneously;
(7) tabletting is made label;
(8) the label coating is made finished product.
Being incorporated as of described cross-linking sodium carboxymethyl cellulose adds 1/2 of total consumption in the step (2), add remaining 1/2 in the step (6).
Comprise the granule check in the described step (6), particulate loss on drying is less than 6%.
The label coating of described step (7) comprises that coating material is added ethanol makes coating solution, in coating pan coating solution is sprayed on the label, simultaneously hot air drying.
Described baking temperature is 40～50 ℃, coating weightening finish 2～4%, and the rotary speed of coating pan is 50 rev/mins.
The invention has the beneficial effects as follows: Pitavastatin Calcium is added the tablet that appropriate amount of auxiliary materials is made, the employing sodium bicarbonate is a stabilizing agent, cross-linking sodium carboxymethyl cellulose is a disintegrating agent, the medicine stripping rapidly fully, steady quality, be fit to long term storage, through check, indexs such as its content, character, discriminating, stripping, content uniformity all meet " Chinese pharmacopoeia and pertinent regulations.
The specific embodiment
Embodiment 1
A kind of 1mg pitavastatin calcium tablet, label % by weight percentage comprise following component:
Pitavastatin Calcium 10g 1.1%
Lactose 705g 77.8%
Cross-linking sodium carboxymethyl cellulose 40g 4.5%
Sodium bicarbonate 100g 11.0%
Hypromellose 2.6g 0.3%
Silicon dioxide 20g 2.2%
Pulvis Talci 20g 2.2%
Magnesium stearate 8g 0.9%
The Pitavastatin Calcium piece preparation method comprises the steps:
(1) take by weighing raw material by prescription, Pitavastatin Calcium, sodium bicarbonate, lactose, cross-linking sodium carboxymethyl cellulose are crossed 100 mesh sieves respectively, and be standby;
(2),, obtain mixed-powder with the equivalent method mix homogeneously that progressively increases with cross-linking sodium carboxymethyl cellulose, the sodium bicarbonate of Pitavastatin Calcium and lactose, 1/2 amount;
(3) add binding agent in the mixed-powder, mix homogeneously is made soft material, and wherein binding agent is 50% alcoholic solution of hydroxypropyl cellulose;
(4) soft material pushed 18 mesh sieves, made wet granular;
(5) granule places drying baker, 60 ℃ of air blast oven dry;
(6) dried granule 20 mesh sieve granulate, the cross-linking sodium carboxymethyl cellulose that adds prescription consumption magnesium stearate, Pulvis Talci, silicon dioxide and remain 1/2 amount, mix homogeneously;
(7) check particle drying weightlessness, drug content, loss on drying should be less than 6%, and calculating answers tabletting heavy according to granule content, and tabletting is made label;
(8) label coating, with the label of want coating, put into coating pan, open coating pan, spray into coating solution, electrical heating simultaneously and be blown into hot blast and carry out drying, wherein, coating solution is that 40g Ka Lekang coating powder adds 80% alcoholic solution and is made into 500ml solution, wrap 10000 of labels approximately, the coating pan rotating speed is 50 rev/mins, and baking temperature is 40 ℃～50 ℃, coating weightening finish 2～4%.
Examine entirely through finished product at last, make finished product, the packing warehouse-in.
Embodiment 2
A kind of 2mg pitavastatin calcium tablet, label % by weight percentage comprise following component:
Pitavastatin Calcium 20g 1.5%
Lactose 1041g 79.9%
Cross-linking sodium carboxymethyl cellulose 62g 4.8%
Sodium bicarbonate 110g 8.4%
Hypromellose 2.9g 0.2%
Silicon dioxide 32g 2.5%
Pulvis Talci 32g 2.5%
Magnesium stearate 13g 1.0%.
Other preparation methoies are identical with embodiment 1, coating solution difference just, and coating solution is that 50g Ka Lekang coating powder adds 80% alcoholic solution and is made into 625ml solution, wraps 10000 of labels approximately.
Embodiment 3
A kind of 3mg pitavastatin calcium tablet, label % by weight percentage comprise following component:
The 3mg pitavastatin calcium tablet, 10000 sheet core components are as follows:
Pitavastatin Calcium 30g 1.8%
Lactose 1300g 79.4%
Cross-linking sodium carboxymethyl cellulose 80g 4.9%
Sodium bicarbonate 150g 9.2%
Hypromellose 3.3g 0.2%
Silicon dioxide 36g 2.2%
Pulvis Talci 36g 2.2%
Magnesium stearate 1.8g 1.1%.
Other preparation methoies are identical with embodiment 1, coating solution difference just, and coating solution is that 60g Ka Lekang coating powder adds 80% alcoholic solution and is made into 750ml solution, wraps 10000 of labels approximately.
Claims (9)
1. a pitavastatin calcium tablet comprises coating and label, and its label is (%) meter by weight percentage, comprises following component:
Pitavastatin Calcium 1～5%
Sodium bicarbonate 5～16%
Lactose 75～85%
Cross-linking sodium carboxymethyl cellulose 3～6%
Binding agent 0.1～0.4%
Silica 1 .5～3.0%
Magnesium stearate+Pulvis Talci 0.5～4.0%.
2. pitavastatin calcium tablet according to claim 1 is characterized in that: the consumption of described cross-linking sodium carboxymethyl cellulose is 3～5% by weight percentage.
3. pitavastatin calcium tablet according to claim 1 is characterized in that: described pitavastatin calcium tablet coats coating outward by label and constitutes, and this coating is the Ka Lekang coating powder, and consumption is 3～5% of a label gross weight.
4. pitavastatin calcium tablet according to claim 1 is characterized in that: described binding agent is the aqueous solution or the alcoholic solution of hydroxypropyl methylcellulose.
5. at the preparation method of the described pitavastatin calcium tablet of one of claim 1 to 4, comprise the steps:
(1) take by weighing raw material by prescription, Pitavastatin Calcium and adjuvant are crossed 100 or 80 mesh sieves respectively, and be standby;
(2),, obtain mixed-powder with the equivalent method mix homogeneously that progressively increases with cross-linking sodium carboxymethyl cellulose, the sodium bicarbonate of Pitavastatin Calcium and lactose, part;
(3) add binding agent in the mixed-powder, mix homogeneously is made soft material;
(4) soft material is squeezed into wet granular;
(5) granule places drying baker, 50～70 ℃ of air blast oven dry;
(6) add magnesium stearate, Pulvis Talci, silicon dioxide and rest parts cross-linking sodium carboxymethyl cellulose, mix homogeneously in the dried granule;
(7) tabletting is made label;
(8) the label coating is made finished product.
6. the preparation method of pitavastatin calcium tablet according to claim 5 is characterized in that, the adding method of described cross-linking sodium carboxymethyl cellulose is: add 1/2 of total consumption in the step (2), add remaining 1/2 in the step (6).
7. the preparation method of pitavastatin calcium tablet according to claim 5 is characterized in that: comprise the granule check in the described step (6), its particulate loss on drying is less than 6%.
8. the preparation method of pitavastatin calcium tablet according to claim 5, it is characterized in that: the label coating of described step (7) comprises that coating material is added ethanol makes coating solution, coating solution is sprayed on the label, simultaneously hot air drying.
9. the preparation method of pitavastatin calcium tablet according to claim 8, it is characterized in that: described baking temperature is 40～50 ℃, coating weightening finish 2～4%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101734322A CN101219121A (en) | 2007-12-27 | 2007-12-27 | Pitavastatin calcium tablet and method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101734322A CN101219121A (en) | 2007-12-27 | 2007-12-27 | Pitavastatin calcium tablet and method for preparing the same |
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| Publication Number | Publication Date |
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| CN101219121A true CN101219121A (en) | 2008-07-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007101734322A Pending CN101219121A (en) | 2007-12-27 | 2007-12-27 | Pitavastatin calcium tablet and method for preparing the same |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102688206A (en) * | 2012-05-29 | 2012-09-26 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
| CN102861018A (en) * | 2011-07-05 | 2013-01-09 | 南京长澳医药科技有限公司 | Pitavastatin calcium preparation and preparation technology |
-
2007
- 2007-12-27 CN CNA2007101734322A patent/CN101219121A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102861018A (en) * | 2011-07-05 | 2013-01-09 | 南京长澳医药科技有限公司 | Pitavastatin calcium preparation and preparation technology |
| CN102688206A (en) * | 2012-05-29 | 2012-09-26 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
| CN102688206B (en) * | 2012-05-29 | 2014-08-20 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
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Open date: 20080716 |