CN102008477A - Method for preparing tablet drug composition containing Rosuvastatin calcium - Google Patents
Method for preparing tablet drug composition containing Rosuvastatin calcium Download PDFInfo
- Publication number
- CN102008477A CN102008477A CN2010105614637A CN201010561463A CN102008477A CN 102008477 A CN102008477 A CN 102008477A CN 2010105614637 A CN2010105614637 A CN 2010105614637A CN 201010561463 A CN201010561463 A CN 201010561463A CN 102008477 A CN102008477 A CN 102008477A
- Authority
- CN
- China
- Prior art keywords
- coating
- standby
- rosuvastatin calcium
- drug composition
- calcium
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for preparing a tablet drug composition containing Rosuvastatin calcium. The preparation forms of the drug composition can be administered to the patients safely and the stability of Rosuvastatin calcium and the absorbability in gastrointestinal tract can be improved. Specifically, the invention relates to a method for preparing the drug composition containing amorphous Rosuvastatin calcium and beta-cyclodextrin. The method is characterized by grinding Rosuvastatin calcium and beta-cyclodextrin under alkaline condition, drying and crashing to obtain (80-100)-mesh fine powder, mixing the fine powder with appropriate auxiliary materials, preparing granules, carrying out tabletting and carrying out coating, thus preparing the drug composition. The in vitro release of the composition is improved to a greater degree, thus improving the bioavailability; and the composition can effectively treat hyperlipidemia, is convenient to take orally, covers the bad taste and is fast to disintegrate and absorb and convenient to carry.
Description
Technical field
The present invention relates to its preparation method of Rosuvastatin calcium medicine compound a kind of.Rosuvastain calcium is scattered in the betacyclodextrin, can improves the release in vitro degree largely, thereby improve bioavailability.
Background technology
Rosuvastain calcium (Rosuvastatin Calcium); chemistry is by name: two-[(E)-the fluorine-based phenyl of 7-[4-(4-)-6-isopropyl-2-[methyl (mesyl) amino]-pyrimidine-5-yl] (3R; 5R)-3,5-dihydroxy heptyl-6-olefin(e) acid] calcium salt (2:1).
Its structural formula is:
Molecular formula: (C
22H
27FN
3O
6S)
2Ca
Molecular weight: 1001.13
The pharmacology type:Rosuvastatin is 3-hydroxyl-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, and cholesterol levels descends in the blood plasma so can make.
Mechanism of action:Rosuvastatin can suppress the synthetic rate-limiting enzyme HMG-CoA of cholesterol reductase in the liver by selectivity, liver albumen is generated reduce, and low-density lipoprotein cholesterol (LDL-C) expression of receptor increases, so blood plasma cholesterol level descends.
Indication:This product is applicable to primary hypercholesterolemia (the Iia type comprises the heterozygote familial hypercholesterolemia) or the mixed type lipidemia unusual (Iib type) that still can not suitably control dyslipidemia through diet control and other non-drug therapy (as: exercise therapy, lose weight).
This product also is applicable to the patient of homozygote familial hypercholesterolemia, as the auxiliary treatment of diet control and other blood fat reducing measure (removing therapy as LDL), or uses when these methods are inapplicable.
Usage and dosage:Before the treatment beginning, should give the cholesterol reducing diet control of patient's standard, and during treating, keep diet control.The use of this product should be followed principle of individuation, takes all factors into consideration the cholesterol levels of individual patients, the cardiovascular risk of expection and the potential danger that untoward reaction takes place.Oral this product initial dose commonly used is 5 mg, 1 time on the 1st.The selection of initial dose should be taken all factors into consideration the cholesterol levels of individual patients, the cardiovascular risk of expection and the potential danger that untoward reaction takes place.Need the patient who reduces LDL-C can consider 10 mg for those, 1 time on the 1st this dosage can be controlled the blood lipid level of Most patients as initial dose more potently.If necessary, can adjust the dosage level of the paramount one-level of dosage in 4 week of treatment back.This product maximal dose every day is 20 mg.This product can be in one day administration whenever, can take on the feed or on an empty stomach.
Along with the raising of people's living standard, the change of custom, the sickness rate of hyperlipemia increases year by year, patient's age trend rejuvenation.According to statistics, the normal population sickness rate is 20%～40%, and China has hyperlipemia patient 8,000 ten thousand people approximately, and every day is still with ten thousand people's speed increase.And hyperlipemia is the principal element of incidence of atherosclerosis, can cause serious cardiovascular and cerebrovascular disease, influences people's healthy and quality of life.Therefore, in recent years, people are for the more and more attention of hyperlipemia.
Hyperlipemia (hyperlipidemia) is meant body fat mass in human body metabolism or running unusually, the content of the T-CHOL in the blood plasma (TC), triacylglycerol (TG), LDL-C, C-VLDL (VLDL-C) surpasses arm's length standard, the content of HDL-C (HDL-C) in blood plasma is low excessively in addition, also belongs to the category of dyslipidemia.Hyperlipemia is produced too much by VLDL or removing obstacles and VLDL be transformed into LDL too much due to.Obesity, diabetes, ethanol are excessive, nephrotic syndrome or genetic flaw can cause that liver VLDL produces too much.The removing obstacles of LDL is relevant with the fault of construction of apolipoprotein B (ApoB).In addition, removing obstacles also may be because ldl receptor quantity reduces or dysfunction (vigor reduction), and this may be for due to gene or the dietary factor.
General hyperlipemia can be classified by following characteristics: can be divided into six types by clinical manifestation.The I type: TG significantly increases, and cholesterol is normal, and mainly due to the congenital deficiency lipoproteinesterase, exogenous triacylglycerol can not be decomposed and accumulate in the blood plasma, so claim exogenous high triglyceride mass formed by blood stasis, this kind of is rare; II a type: TC significantly increases, and TG is normal, is the inborn errors of metabolism of familial, so claim familial hypercholesterolemia again, this kind of is more sees; II b type: TC significantly increases, and TG is high slightly, for familial or hypercholesterolemia hyperphagia cause, morely sees; III type: TC and TG all obviously increase, and are heritability, thus claim familial hyperlipidemia again, rare; The IV type: TG significantly increases, and TC is normal or high slightly, and how unusual carbohydrate tolerance test is, is to cause owing to liver is converted into triacylglycerol with sugar too much, so also claim sugar hyperlipemia or endogenous high triglyceride mass formed by blood stasis, morely sees; V type: TG is very high, and TC is high slightly, is exogenous and endogenic, has the feature of I type, IV amphitypy concurrently, thus claim Combination high triglyceride mass formed by blood stasis again, rare.Can be divided into constitutional and Secondary cases by cause of disease branch hyperlipemia.Wherein Primary hyperlipemia belongs to hereditary disorders of lipid metabolism disease.
Hyperlipemia is high morbidity in mid-aged population, and along with the raising of people's living standard, the change of living habit, the sickness rate of hyperlipemia increases year by year, and patient's age is tending towards rejuvenation.There is hyperlipemia 8,000 ten thousand in China, and increases with ten thousand people's quantity every day, and hyperlipidemia is threatening people's health at any time just as time bomb.The most direct infringement of hyperlipidemia is the arteriosclerosis that causes whole body, and then causes the disease of being correlated with, and can cause diseases such as coronary heart disease, angina pectoris, myocardial infarction and cerebrovascular accident as the arteriosclerosis of heart and brain.Clinical the most common hyperlipemia is hypercholesterolemia (Iia type) and combined hyperlipidemia familial (Iib type).Cholic acid chelating agent class medicine is difficult for tolerance in the existing curative commonly used, and the special class of shellfish reduces TC and LDL poor effect, and nicotinic acid badness reaction ambassador uses limited, so the most frequently used curative is a statins.In the existing statins, Time To Markets such as lovastatin, pravastatin, simvastatin, fluvastatin are longer, problem such as untoward reaction and unsatisfactory curative effect manifests gradually, eliminates for market gradually, uses maximum be atorvastatin and Rosuvastatins now clinically.
The main site of action of Rosuvastatin is efficient selective HMG-CoA reductase inhibitor at liver, the liver lipoprotein is generated reduce, and the LDL-C expression of receptor increases, and blood plasma cholesterol level is descended.It can also make VLDL and TG significantly descend, and increases antiatherogenic HDL.By the reduction blood plasma lipide, thereby suppress accumulating and interior pachyhymenia of lipid.
Existing clinical research data shows, atorvastatin is compared with Rosuvastatin, safety is suitable, compliance is good, but the 10th European annual meeting announces that two relate to 470,000 and take statins and transfer the large-scale investigation of fat effect studies show that according to International Pharmaceutical economics and clinical final result research association, and Rosuvastatin transfers the fat effect the strongest, the consumption minimum reduces the cardiovascular event effect and also is better than other statinses.STELLAR research is extensive a, multicenter, parallel grouping, open trial, the curative effect that has compared simvastatin, pravastatin, atorvastatin and each dosage range of Rosuvastatin, patient's 2431 examples that are selected in hypercholesterolemia altogether, use Rosuvastatin 10,20 or 40mg/d respectively, atorvastatin 10,20,40 or 80 mg/d, simvastatin 10,20,40 or 80 mg/d, pravastatin 10,20 or 40 mg/d.Result of study shows, the curative effect that LDL-C totally falls in Rosuvastatin after 6 weeks obviously is better than other his spit of fland.The Rosuvastatin of 10mg can make patient LDL-C descend 46%～55%.By comparison, accept only have 72% to reach this target among the patient of atorvastatin 80mg treatment.This shows that more low dose of Rosuvastatin can reach than the better therapeutic effect of atorvastatin.
A shortcoming of rosuvastain calcium is: in some cases, in the hot and humid photoenvironment, it is easy to degraded, the primary product that forms is the lactone catabolite, oxidative breakdown product and illumination degrading product, thereby cause the configuring product operating difficulties, and the pharmaceutical composition for preparing does not reach the requirement of storage life, this unstability is determined by itself, β in the rosuvastain calcium molecule on the heptenoic acid chain, δ-hydroxyl is highly stable, and wherein, the hydroxyl that carbon-to-carbon double bond is adjacent is easy to be oxidized to ketone, also molecule inner ring condensation can take place, generate lactone.
A kind of stabilization medicines compositions that contains statin compound is disclosed among the Chinese patent CN93100650, said composition is to remain on 8 alkaline medium (for example carbonate or bicarbonate) at least by the pH value that adds a kind of aqueous solution that can make said composition or dispersion liquid to reach Stabilization.Yet the inventor repeatedly finding in the experiment, and the pH value of control combination thing separately also is not enough to solve the stability problem of Rosuvastatin calcium composition.
Disclose a kind of stabilizing pharmaceutical composition that contains Rosuvastatin or its officinal salt among the Chinese patent CN00122484, said composition is to be that three alkali valency phosphate (for example three alkali valency calcium phosphate) reach and stablize purpose by the cation that adds as stabilizing agent.Yet, the disclosed prescription that contains three alkali valency calcium phosphate during the inventor all finds according to patent CN00122484 in repeatedly testing, adopt domestic wet granulation technique commonly used to granulate, in 40 ℃ of heated-air circulation oven dry runs, composition grain gradually becomes faint yellow even yellowish-brown by pure white.Especially in the industrialized great production process, wet granular output is big, and drying time is longer, and this variable color can't be avoided.This significant variation can directly cause the failure of producing.According to the compositions that disclosed method among the patent CN00122484 prepares, be placed on 30 ℃, under relative humidity 75% condition, the obvious flavescence of compositions after seven days illustrates to have generated other foreign pigment.
Chinese patent CN00122484 adopts dry method direct compression or fluid-bed drying to reduce the open-assembly time of described compositions under wet condition, though these two kinds of methods have been evaded the phenomenon of Rosuvastatin calcium composition flavescence in preparation process, show no sign of the fact that changes said composition storage meeting flavescence under super-humid conditions.
Chinese patent ZL200710024860.9 discloses a kind of stable combination of oral medication, relates to particularly containing rosuvastain calcium, micropowder silica gel and the pharmaceutical composition of proper supplementary material pharmaceutically, with and its production and use.The defective of this patent is, the domestic micropowder silica gel of still not having medicinal registration permission causes this Pharmaceutical composition not implement, and can't realize industrialization.Adopt the compositions of this patent preparation, though the storage color does not change under super-humid conditions, placed 10 days under illumination and hot conditions, its oxidative breakdown product and light degradation product all rise appreciably.Also be not enough to solve the stability problem of Rosuvastatin calcium composition.
Chinese patent 200780034516.6 discloses a kind of new pharmaceutical composition, it comprises amorphous rosuvastatin calcium and as magnesium hydroxide and/or calcium acetate or calcium gluconate or the calcium glycerophosphate or the aluminium hydroxide of stabilization additives, and one or more medicinal acceptable excipient.Adopt the compositions of this patent preparation, though the storage color does not change under super-humid conditions, placed 10 days under illumination and hot conditions, its light degradation product all rises appreciably.Also be not enough to solve the stability problem of Rosuvastatin calcium composition.
According to above-mentioned prior art, the stabilizing pharmaceutical composition that comprises rosuvastain calcium that needs preparation to be easy to prepare.
In order to address the above problem, the inventor gropes by long-term a large amount of test, the astonishing pharmaceutical composition of having found a kind of new rosuvastain calcium, said composition is under preparation, storage, super-humid conditions, its lactone degradation product, oxidative degradation thing, illumination degrading thing all no longer increase, can guarantee the stability of long term store, thereby solve the problem that always perplexs the rosuvastain calcium preparation stability.The present invention after 36 months time, measures its related substance at ambient temperature, basic not degraded.Has more good quality stability.By being carried out PROCESS FOR TREATMENT, it has improved said preparation quality and stability thereof greatly.Simultaneously, said composition has prescription, technology is simple, need not special handling production equipment, advantage such as with low cost, thereby is the extensive popularization of this medicine in clinical, has played more positive effect.
Summary of the invention
According to existing adjuvant and working condition, guaranteeing to have lower production cost and simple preparation technology, be suitable under the prerequisite of large-scale industrial production, be necessary to work out the preparation technology that a kind of stable prescription is formed, make rosuvastain calcium have good stability of drug products.
Purpose of the present invention provides a kind of Rosuvastatin calcium tablet and preparation method thereof, and the prescription that it is characterized in that making 1000 is composed as follows:
Form 1
Rosuvastain calcium 10-20g
Betacyclodextrin 40-80g
Sodium hydroxide 0.01-0.02g
Form 2
Cross-linking sodium carboxymethyl cellulose 30-60g
Microcrystalline Cellulose 100-200g
Lactose 100-240g
Pregelatinized Starch 20-40g
Pulvis Talci 1-2g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 90-180g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Be preferably:
Form 1
Rosuvastain calcium 20g
Betacyclodextrin 80g
Sodium hydroxide 0.02g
Form 2
Cross-linking sodium carboxymethyl cellulose 60g
Microcrystalline Cellulose 200g
Lactose 240g
Pregelatinized Starch 40g
Pulvis Talci 2g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 180g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Below by test data beneficial effect of the present invention is described.
Carried out constant temperature accelerated stability test and the room temperature stability test that keeps sample with the product of prior art embodiment 1 of the present invention and embodiment 2,3, the result is as follows:
Constant temperature accelerated stability test result
Above result of the test explanation, embodiment 1 is in quickening put procedure, and the sample related substance is not significantly increased, and dissolution reduces, the quality instability; Adopt the embodiment 2 of preparation technology of the present invention preparation and embodiment 3 in quickening put procedure, each monitoring index of sample is all qualified.
Advantage of the present invention is technical maturity, and is simple to operate, is fit to industrial large-scale production.
Advantage of the present invention also is to adopt rosuvastain calcium is scattered in the betacyclodextrin, obviously overcome and adopt conventional preparation method in the production technology, low and the mobile difference of release such as is difficult for making at shortcoming, and this method has improved its dissolution in vitro greatly, and then improves its bioavailability.
Cyclodextrin is a starch derivatives, mainly as oral and injection medicine preparation, and the most frequently used is α-, β-, gamma-cyclodextrin has 6,7,8 glucose units respectively.Cyclodextrin is the ring molecule of the cavity by rigid structure and center thereof " tubbiness " or " coniform " that constitute, and its size is according to the type of cyclodextrin
Difference and difference, the cavity inner surface is a hydrophobicity, and the outside of ring is a hydrophilic, this is by due to the arrangement in the polyhydroxylated molecule, this arrangement makes cyclodextrin hold enclosed molecule in the cavity again, forms clathrate.Cyclodextrin can be used to prepare the clathrate of multiple drug molecule, mainly plays and improves the effect that improves release and bioavailability, and this is attributable to the increase of dissolubility, and the raising of chemistry and physical stability.The clathrate of cyclodextrin also is used for covering the disagreeable taste of active substance and liquid substance is converted into solid material.
It is oral nontoxic that beta-schardinger dextrin-is considered to, so safety when using in solid preparation.
Below prescription design and optimization Test are used to illustrate the present invention.
Prescription screening mainly is the screening by rosuvastain calcium and betacyclodextrin consumption and different alkaline diluent, further the screening prescription:
| Prescription is formed | 1 | 2 | 3 | 4 |
| Rosuvastain calcium (g) | 20 | 20 | 20 | 20 |
| HYDROXYPROPYL BETA-CYCLODEXTRIN (g) | 40 | 80 | 40 | 80 |
| Sodium hydroxide (g) | 0.01 | 0.02 | 0 | 0 |
| Dipotassium hydrogen phosphate (g) | 0 | 0 | 5 | 10 |
| Crosslinked carboxyl and sodium cellulosate (g) | 60 | 60 | 60 | 60 |
| Microcrystalline Cellulose (g) | 200 | 200 | 200 | 200 |
| Lactose (g) | 240 | 240 | 240 | 240 |
| Pregelatinized Starch (g) | 40 | 40 | 40 | 40 |
| Pulvis Talci (g) | 2 | 2 | 2 | 2 |
| 5% polyvidone ethanol solution | In right amount | In right amount | In right amount | In right amount |
Technology:
1) rosuvastain calcium, betacyclodextrin, alkaline diluent are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Result of the test shows
| The prescription number | 1 | 2 | 3 | 4 |
| Compressibility | Good, no sticking | Good, no sticking | Good, no sticking | Good, no sticking |
| Unilateral | Bright and clean | Bright and clean | Bright and clean | Bright and clean |
| Hardness (kg) | 6.4 | 5.2 | 6.2 | 6.8 |
| Dissolution | 97.8% | 96.9% | 98.0% | 97.9% |
| Oxidation lactone catabolite | 0.16 | 0.08 | 0.36 | 0.68 |
Adopt the prescription of clathrate process preparation, obtain good surface appearance and hardness, dissolution is also all qualified, and 2 related substances of writing out a prescription are owing to other prescriptions, and we are further screening art for coating on prescription 2 bases.
1, coating fluid prescription:
Coating powder 180g
80% ethanol adds to 100ml
Make 1000
2, operating procedure: according to the product operation rules of enteric coating powder producer, 30 ℃ of coating inlet temperature, coating solution sprays fast 2g/min, and the product behind the coating descended dry 1 hour at 30 ℃, promptly.
Coating prescription 2 is at dissolution determination
| Time | 5 | 30 | 45 | 60 |
| Prescription 2 | 83% | 99% | 100% | 99% |
The final optimised process of determining prescription
Form 1
Rosuvastain calcium 10-20g
Betacyclodextrin 40-80g
Sodium hydroxide 0.01-0.02g
Form 2
Cross-linking sodium carboxymethyl cellulose 30-60g
Microcrystalline Cellulose 100-200g
Lactose 100-240g
Pregelatinized Starch 20-40g
Pulvis Talci 1-2g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 90-180g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail, but should understands the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1(comparative example)
Rosuvastain calcium 10-20g
Cross-linking sodium carboxymethyl cellulose 30-60g
Microcrystalline Cellulose 100-200g
Lactose 100-240g
Pregelatinized Starch 20-40g
Pulvis Talci 1-2g
5% polyvidone ethanol solution is an amount of
Coating powder 90-180g
Make 1000
Preparation method process following steps:
1) with rosuvastain calcium, microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
2) with the supplementary material mix homogeneously, standby;
3) get 2) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
4) with 3) sample that makes puts in the coating pan, coating, promptly.
Embodiment 2
Form 1
Rosuvastain calcium 20g
Betacyclodextrin 80g
Sodium hydroxide 0.02g
Form 2
Cross-linking sodium carboxymethyl cellulose 60g
Microcrystalline Cellulose 200g
Lactose 240g
Pregelatinized Starch 40g
Pulvis Talci 2g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 180g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Embodiment 2
Form 1
Rosuvastain calcium 10g
Betacyclodextrin 40g
Sodium hydroxide 0.01g
Form 2
Cross-linking sodium carboxymethyl cellulose 30g
Microcrystalline Cellulose 100g
Lactose 100g
Pregelatinized Starch 20g
Pulvis Talci 1g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 90g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Claims (1)
1. rosuvastain calcium preparation of drug combination method is characterized in that: each component is formed and proportioning is:
Form 1
Rosuvastain calcium 10-20g
Betacyclodextrin 40-80g
Sodium hydroxide 0.01-0.02g
Form 2
Cross-linking sodium carboxymethyl cellulose 30-60g
Microcrystalline Cellulose 100-200g
Lactose 100-240g
Pregelatinized Starch 20-40g
Pulvis Talci 1-2g
5% polyvidone ethanol solution is an amount of
Coating is formed
Coating powder 90-180g
Make 1000
Preparation method process following steps:
1) rosuvastain calcium, betacyclodextrin, sodium hydroxide are put in the mortar, added low amounts of water and grind to form pastel, dry below 50 ℃, be ground into 80-100 order fine powder, standby;
2) with microcrystalline Cellulose, lactose, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, Pulvis Talci sieves respectively, and is standby;
3) with the adjuvant 2 of recipe quantity) add 1) in, mix homogeneously, standby;
4) get 3) the middle 5% polyvidone ethanol solution that adopts, mixing is made 30-40 order granule, and dry below 50 ℃, granulate adds lubricant, mix homogeneously, tabletting;
5) with 4) sample that makes puts in the coating pan, coating, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105614637A CN102008477B (en) | 2010-11-28 | 2010-11-28 | Method for preparing tablet drug composition containing Rosuvastatin calcium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105614637A CN102008477B (en) | 2010-11-28 | 2010-11-28 | Method for preparing tablet drug composition containing Rosuvastatin calcium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102008477A true CN102008477A (en) | 2011-04-13 |
| CN102008477B CN102008477B (en) | 2012-11-07 |
Family
ID=43838948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105614637A Expired - Fee Related CN102008477B (en) | 2010-11-28 | 2010-11-28 | Method for preparing tablet drug composition containing Rosuvastatin calcium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102008477B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102860994A (en) * | 2011-07-04 | 2013-01-09 | 石药集团中奇制药技术（石家庄）有限公司 | Rosuvastatin calcium tablet and preparation method |
| CN102908335A (en) * | 2012-11-19 | 2013-02-06 | 山东罗欣药业股份有限公司 | Rosuvastatain calcium composition and preparation method thereof |
| CN104523650A (en) * | 2014-12-20 | 2015-04-22 | 山东新时代药业有限公司 | Capsule containing rosuvastatin calcium |
| CN104644592A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Perampanel pharmaceutical composition and preparation method thereof |
| CN104644591A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Saxagliptin medicinal composition and preparation method thereof |
| CN107811989A (en) * | 2016-09-14 | 2018-03-20 | 南京先声东元制药有限公司 | A kind of Rosuvastatin calcium medicine compound and preparation method thereof |
| CN110732037A (en) * | 2018-07-20 | 2020-01-31 | 广州倍绣生物技术有限公司 | Hemostatic paste and preparation method thereof |
| CN110974793A (en) * | 2019-12-26 | 2020-04-10 | 鲁南制药集团股份有限公司 | Rosuvastatin calcium tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101559228A (en) * | 2009-06-01 | 2009-10-21 | 石药集团欧意药业有限公司 | Pharmaceutical composition for treating chronic stable angina pectoris with hyperlipemia |
| CN101766578A (en) * | 2010-02-09 | 2010-07-07 | 鲁南贝特制药有限公司 | Tablet containing Rosuvastatin calcium and preparation process thereof |
-
2010
- 2010-11-28 CN CN2010105614637A patent/CN102008477B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101559228A (en) * | 2009-06-01 | 2009-10-21 | 石药集团欧意药业有限公司 | Pharmaceutical composition for treating chronic stable angina pectoris with hyperlipemia |
| CN101766578A (en) * | 2010-02-09 | 2010-07-07 | 鲁南贝特制药有限公司 | Tablet containing Rosuvastatin calcium and preparation process thereof |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102860994A (en) * | 2011-07-04 | 2013-01-09 | 石药集团中奇制药技术（石家庄）有限公司 | Rosuvastatin calcium tablet and preparation method |
| CN102908335A (en) * | 2012-11-19 | 2013-02-06 | 山东罗欣药业股份有限公司 | Rosuvastatain calcium composition and preparation method thereof |
| CN102908335B (en) * | 2012-11-19 | 2015-04-08 | 山东罗欣药业集团股份有限公司 | Rosuvastatain calcium composition and preparation method thereof |
| CN104644592A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Perampanel pharmaceutical composition and preparation method thereof |
| CN104644591A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Saxagliptin medicinal composition and preparation method thereof |
| CN104523650A (en) * | 2014-12-20 | 2015-04-22 | 山东新时代药业有限公司 | Capsule containing rosuvastatin calcium |
| CN104523650B (en) * | 2014-12-20 | 2017-04-12 | 山东新时代药业有限公司 | Capsule containing rosuvastatin calcium |
| CN107811989A (en) * | 2016-09-14 | 2018-03-20 | 南京先声东元制药有限公司 | A kind of Rosuvastatin calcium medicine compound and preparation method thereof |
| WO2018049989A1 (en) * | 2016-09-14 | 2018-03-22 | 南京先声东元制药有限公司 | Rosuvastatin calcium pharmaceutical composition and preparation method therefor |
| CN110732037A (en) * | 2018-07-20 | 2020-01-31 | 广州倍绣生物技术有限公司 | Hemostatic paste and preparation method thereof |
| CN110732037B (en) * | 2018-07-20 | 2023-05-26 | 广州倍绣生物技术有限公司 | Hemostatic paste and preparation method thereof |
| CN110974793A (en) * | 2019-12-26 | 2020-04-10 | 鲁南制药集团股份有限公司 | Rosuvastatin calcium tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102008477B (en) | 2012-11-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102008477B (en) | Method for preparing tablet drug composition containing Rosuvastatin calcium | |
| CN103800322B (en) | Fluvastatin composition of sodium | |
| AU2010210123B2 (en) | Process for the preparation of a pharmaceutical composition comprising ezetimibe | |
| CN105792813B (en) | A kind of medicine composition containing Amlodipine, Losartan and rosuvastatin | |
| CN101972260B (en) | Rosuvastatin calcium oral drug composition | |
| KR20050083827A (en) | Sustained release l-arginine formulations and methods of manufacture and use | |
| CN103239725A (en) | Compound preparation for treating cardiovascular and cerebrovascular diseases | |
| US20150037414A1 (en) | Stable controlled release pharmaceutical compositions containing fenofibrate and pravastatin | |
| EP1651194B1 (en) | Stable controlled release pharmaceutical compositions containing fenofibrate and pravastatin | |
| CN102258459B (en) | Rosuvastatin calcium oral solid preparation and applications thereof | |
| CN1778391A (en) | Safety and high-efficient compound hypolipidemic medicine | |
| ES2387913T3 (en) | Combination preparations of salts of O-acetylsalicylic acid | |
| CA2534660A1 (en) | Single unit pharmaceutical composition comprising a mixture of a fibrate and an homocysteine reducing agent | |
| WO2010087150A1 (en) | Gastric acid secretion inhibitor, and potassium channel inhibitor | |
| CN107811989B (en) | Rosuvastatin calcium pharmaceutical composition and preparation method thereof | |
| WO2020020317A1 (en) | Metformin compound composition and use thereof | |
| WO2019101151A1 (en) | Pharmaceutical composition of hs-25 and hmg-coa reductase inhibitor | |
| CN113134086B (en) | Pharmaceutical composition for reducing blood fat | |
| CN101411697A (en) | Medicinal composition for treating angiocardiopathy | |
| JPWO2009044548A1 (en) | Anti-diarrhea composition, contents thereof and method for preventing diarrhea | |
| AU2003254428B2 (en) | Stable controlled release pharmaceutical compositions containing Fenofibrate and Pravastatin | |
| CN1309376C (en) | Musk slow-controlled release preparation and preparation method thereof | |
| CN110974793A (en) | Rosuvastatin calcium tablet and preparation method thereof | |
| CN109999004A (en) | A kind of comprehensive Simvastatin Tablets for adjusting rouge | |
| CN104546854A (en) | Rosuvastatin calcium choline fenofibrate sustained-release 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 | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181010 Address after: 300409 88 Huashi Road, Beichen science and Technology Park, Tianjin Patentee after: TIANJIN HANRUI PHARMACEUTICAL CO., LTD. Address before: 300203 Tianjin Hexi District Dagu South Road 4, 3 Patentee before: Tianjin Hankang Pharmaceutical Biotechnology Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121107 Termination date: 20181128 |