CN101766578B - Tablet containing Rosuvastatin calcium and preparation process thereof - Google Patents
Tablet containing Rosuvastatin calcium and preparation process thereof Download PDFInfo
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Abstract
The invention belongs to the filed of medicine, in particular to a tablet containing Rosuvastatin calcium and a preparation process thereof. As for the tablet containing the Rosuvastatin calcium of the invention, lactose and hydroxypropyl cyclodextrin with the ratio ranging from 1:1 to 2.5:1 are selected to serve as fillers, and opacifier medicinal iron oxide red is added in production process. In the invention, a direct powder tabletting method is utilized for taletting, and the prepared tablet containing the Rosuvastatin calcium has the characteristics of stable long-term preservation, rapid disintegration rate, high dissolution and high bioavailability.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of tablet and preparation technology thereof of rosuvastain calcium, the Rosuvastatin calcium tablet adopts the direct powder compression tabletting, has that disintegrate is fast, dissolution is high, the characteristics that bioavailability is high are efficient, safe blood lipid regulation medicines.
Background technology
In recent years, along with dietary habit change, growth in the living standard and operating pressure increase, hyperlipemia and hyperproteinemia patient are more and more, and patient group is rejuvenation more and more.Epidemiological study shows that increasing of blood plasma low density lipoprotein, LDL (LDL) and very low density lipoprotein (VLDL) (VLDL) level is the key factor of early starting pulse atherosclerosis and coronary heart disease.Statistical analysis shows, the every reduction by 1% of serum cholesterol, and the pathogenetic risk of coronary disease will reduce by 2%.Therefore, logical diet, motion and Drug therapy are very important to hyperlipemia and hyperlipoproteinemia patient.
Rosuvastatin is the statins antilipemic drugs of new generation of synthetic, alternative 3 hydroxy-3-methyl glutaryl coenzyme As (HMG-CoA) reductase that suppresses.Wherein, the HMG-CoA reductase is the biosynthetic rate-limiting enzyme of cholesterol, but catalysis HMG-CoA transforms to mevalonic acid (precursor of cholesterol).Can cause TC content attenuating in the hepatocyte after the HMG-CoA reductase is suppressed, thereby cell cultured supernatant Surface L DL expression of receptor increases, promote LDL precursor and LDL from circulation, to remove, make the decline of LDL level.In addition, rosuvastain calcium also can suppress the synthetic and secretion that the lipoprotein of TG is rich in the synthetic and minimizing of VLDL, ApoB-100 in the liver.Generally speaking, but rosuvastain calcium hypercholesterolemia reducing (total-C), low-density lipoprotein cholesterol (LDL-C), C-VLDL (VLDL-C), ApoB, non-HDL-C (nonHDL-C) and TG level, raising HDL-C level.Its main site of action is liver (liver cell is had high selectivity), secondly is spleen and adrenal gland, does not see that it has inhibitory action to the TC in testis, kidney, muscle and the brain.Its cardiovascular morbidity and mortality rate are not done detection.A large amount of clinical trials show, other statins that the effect of rosuvastain calcium reduction LDL-C, rising HDL-C is better than having gone on the market.
WO 01/54669 discloses a kind of tablet of the HMGCoA of containing digestive enzyme inhibitor, and the feature of this tablet is to contain Rosuvastatin and pharmaceutically acceptable salt and inorganic multivalent salts.This disclosure of the Invention by improving the stability of principal agent in the tablets in tablet, adding multivalent salts such as Mg salt, Zn salt, Al salt.But it only still increases comparatively fast by the method impurity content that adds inorganic multivalent salts raising stability, and does not have long-acting study on the stability.
CN1557319A discloses a kind of Rosuvastatin dispersible tablet and preparation method thereof.This dispersible tablet is made up of rosuvastain calcium and pharmaceutic adjuvant, adopts the wet granule compression tablet preparation.This dispersible tablet has that drug release rate is fast, taking convenience, can improve the onset speed and the bioavailability of oral Rosuvastatin.But its preparation technology is relatively loaded down with trivial details.
CN200610000665.8 discloses a kind of Rosuvastatin soft capsule and preparation method thereof.This soft capsule has improved the stripping quantity of Rosuvastatin, has improved curative effect of medication.But its technology is more complicated also.
The rosuvastain calcium dosage form of listing is mainly capsule and tablet at present.Tablet is mainly ordinary tablet and dispersible tablet, because the rosuvastain calcium raw material is insoluble in water, conventional tablet exists dissolution low, the problem that bioavailability is low, the present invention is mainly by adjuvant in the preferred tablet production technology, adopt the direct powder compression tabletting, make the quick disintegrate of tablet, the quick stripping of principal agent.In addition, the present invention has improved the quality stability of preparation by preferred adjuvant, has overcome the rosuvastain calcium raw material and has seen the labile shortcoming of light.
Summary of the invention
Because rosuvastain calcium is insoluble in water, the Rosuvastatin calcium tablet for preparing according to commonsense method all exists stripping slow, the interior lower defective of bioavailability of external and body.For dissolution and the bioavailability that improves rosuvastain calcium, first purpose of the present invention provides a kind of novel tablet that contains rosuvastain calcium.
The optimization prescription of Rosuvastatin calcium tablet provided by the invention, its composition is by weight percentage:
Rosuvastatin 5～35%
Filler 50～90%
Crospolyvinylpyrrolidone 8-10%
Magnesium stearate 1-3%
Medicinal iron oxide 0.1%
Filler is solubility and solubilizing auxiliary materials in the preparation of the present invention, and wherein the solubility adjuvant is a lactose, and solubilizing auxiliary materials is a hydroxypropyl cyclodextrin.
Tablet dissolution in vitro by effect embodiment rosuvastain calcium as can be seen, the embodiment of the invention is made the rosuvastain calcium conventional tablet that tablet all is better than the prior art report, especially the external dissolution rate of making by embodiment 2 prescriptions of tablet is fast, and stripping difference is little.The Rosuvastatin calcium tablet of the relative prior art of the tablet bioavailability that the embodiment of the invention is made report improves greatly, and the relative bioavailability of the relative rosuvastain calcium conventional tablet of making according to embodiment 2 prescriptions of Rosuvastatin calcium tablet is 118.95 ± 22.32%.
Preparation of the present invention can use conventional tablet manufacturing device fabrication, and concrete preparation technology is as follows: preparation method adopts direct powder compression, comprises the steps: that (1) is with opacifier medicinal iron oxide red and principal agent mistake 80 mesh sieves respectively.Take by weighing respectively according to quantity, mix homogeneously is made the homogeneous mixture.(2) filler is crossed 80 mesh sieves,, crossed 60 mesh sieves by equivalent progressively increase method and mixture mix homogeneously.(3) add crospolyvinylpyrrolidone and magnesium stearate in the mixture, mixing, tabletting are promptly.
Below by contrast test technical solution of the present invention is described further:
(1) selection of filler
The present invention adopts the direct powder compression film-making, therefore the selection of filler is extremely important, and filler mainly solves the disintegrate problem of tablet in prescription, and the selectable filler of preparation ordinary tablet is more, take raw material properties and the object of the invention into consideration, select solvable and the hydrotropy adjuvant.Solvable and hydrotropy filler mainly contains lactose, dextrin, mannitol, hydroxypropyl cyclodextrin and microcrystalline Cellulose etc.
The present invention is further described by following concrete experiment, and the Rosuvastatin calcium tablet that adopts above different filler combination to make sees Table 1.The disintegrative of the Rosuvastatin calcium tablet tablet that different filleies are pressed into and dissolution and relevant nature relatively see Table 2.
Tablet filler kind and component ratio in table 1 experiment
| Component/different proportionings | 1 | 2 | 3 | 4 | 5 | 6 |
| Rosuvastatin | 10 | 10 | 10 | 10 | 10 | 10 |
| Microcrystalline Cellulose | 52.9. | 52.9 | 52.9 | - | - | - |
| Lactose | - | - | 28 | 52.9 | 52.9 | 52.9 |
| Dextrin | - | 28 | - | - | - | 28 |
| Mannitol | 28 | - | - | - | 28 | - |
| Hydroxypropyl cyclodextrin | - | - | - | 28 | - | - |
| Crospolyvinylpyrrolidone | 8 | 8 | 8 | 8 | 8 | 8 |
| Magnesium stearate | 1 | 1 | 1 | 1 | 1 | 1 |
| Medicinal iron oxide red | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
The disintegrative of the compressed tablet of the different filleies of table 2 and dissolution and relevant nature are relatively
| Project/prescription | 1 | 2 | 3 | 4 | 5 | 6 |
| Mobile | Qualified | Defective | Qualified | Qualified | Qualified | Defective |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Defective | Qualified | Qualified | Defective | Defective |
| Disintegrate | Qualified | Qualified | Qualified | Qualified | Defective | Defective |
| Dissolution % | 72.6 | 80.3 | 71.8 | 100.2 | 76.5 | 70.2 |
| Overall merit | Defective | Defective | Defective | Qualified | Defective | Defective |
As seen the 4 tablet appearance stable homogeneous that are pressed into of writing out a prescription, and disintegration of tablet is rapid, and dissolution is higher.Therefore, be chosen as lactose and hydroxypropyl cyclodextrin as filler in the prescription of the present invention, its content is 50～90% of total formulation weight.
(2) selection of the consumption of the ratio of filler and disintegrating agent
The selection of filler ratio is very crucial in technical scheme, in the method that adopts direct powder compression, filler as proper ratio in the present invention prescription is: account for total formulation weight 35-55% lactose and account for the two the mixture of 20-35% hydroxypropyl cyclodextrin of total formulation weight, and the ratio between lactose and the hydroxypropyl cyclodextrin is 1: 1～2.5: 1, and disintegrating agent is the 8-10% of gross weight.The slice, thin piece hardness and the outward appearance that adopt this ratio to make are good, and disintegration rate is fast.
Characteristics of the present invention are: adopt direct powder compression, select that compressibility is strong, the adjuvant of good fluidity is as filler, adds the stronger disintegrating agent of disintegrating property again, thereby make tablet at short notice molten the loosing of disintegrate improve dissolution rate.The present invention has also improved the quality stability of preparation by the adding medicinal iron oxide red, solved the deficiencies in the prior art preferably.Preparation technology of the present invention is simple, is easy to promote.
Specific embodiment
First: example of formulations part
This part embodiment comprises embodiment 1-5, and Rosuvastatin calcium tablet provided by the invention is not limited only to the embodiment of this part.
Embodiment 1: the preparation of Rosuvastatin calcium tablet
Rosuvastatin 5%
Lactose 52.9%
Hydroxypropyl cyclodextrin 33%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide 0.1%
Concrete preparation method is as follows: medicinal iron oxide red and raw material are crossed 80 mesh sieves respectively, take by weighing by recipe quantity, mix homogeneously, then with hydroxypropyl cyclodextrin by the equivalent method mix homogeneously that progressively increases, cross 60 mesh sieves, again with all the other adjuvant mix homogeneously of recipe quantity, survey semi-finished product content, the calculating sheet is heavy, tabletting, promptly.The slice, thin piece outward appearance and the hardness of system are fine, and stripping 99.35% ± 0.8% when dissolution was 45min.
The preparation of embodiment 2 Rosuvastatin calcium tablets
Rosuvastatin 10%
Lactose 50.9%
Hydroxypropyl cyclodextrin 30%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide red 0.1%
Concrete preparation method is as follows: medicinal iron oxide red and raw material are crossed 80 mesh sieves respectively, take by weighing by recipe quantity, mix homogeneously, then with hydroxypropyl cyclodextrin by the equivalent method mix homogeneously that progressively increases, cross 60 mesh sieves, again with all the other adjuvant mix homogeneously of recipe quantity, survey semi-finished product content, the calculating sheet is heavy, tabletting, promptly.The slice, thin piece outward appearance and the hardness of system are fine, and stripping 101.23% ± 0.5% when dissolution was 45min.
The preparation of embodiment 3 Rosuvastatin calcium tablets
Rosuvastatin 5%
Lactose 44%
Hydroxypropyl cyclodextrin 43.9%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide red 0.1%
Concrete preparation method is as follows: medicinal iron oxide red and raw material are crossed 80 mesh sieves respectively, take by weighing by recipe quantity, mix homogeneously, then with hydroxypropyl cyclodextrin by the equivalent method mix homogeneously that progressively increases, cross 60 mesh sieves, again with all the other adjuvant mix homogeneously of recipe quantity, survey semi-finished product content, the calculating sheet is heavy, tabletting, promptly.The slice, thin piece outward appearance and the hardness of system are fine, and stripping 99.35% ± 0.8% when dissolution was 45min.
The preparation of embodiment 4 Rosuvastatin calcium tablets
Rosuvastatin 35%
Lactose 35%
Hydroxypropyl cyclodextrin 20.9%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide 0.1%
Concrete preparation method is as follows: medicinal iron oxide red and raw material are crossed 80 mesh sieves respectively, take by weighing by recipe quantity, mix homogeneously, then with hydroxypropyl cyclodextrin by the equivalent method mix homogeneously that progressively increases, cross 60 mesh sieves, again with all the other adjuvant mix homogeneously of recipe quantity, survey semi-finished product content, the calculating sheet is heavy, tabletting, promptly.The slice, thin piece outward appearance and the hardness of system are fine, and stripping 99.05% ± 0.96% when dissolution was 45min.
The preparation of embodiment 5 Rosuvastatin calcium tablets
Rosuvastatin 20%
Lactose 50.7%
Hydroxypropyl cyclodextrin 20.2%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide red 0.1%
Concrete preparation method is as follows: medicinal iron oxide red and raw material are crossed 80 mesh sieves respectively, take by weighing by recipe quantity, mix homogeneously, then with hydroxypropyl cyclodextrin by the equivalent method mix homogeneously that progressively increases, cross 60 mesh sieves, again with all the other adjuvant mix homogeneously of recipe quantity, survey semi-finished product content, the calculating sheet is heavy, tabletting, promptly.The slice, thin piece outward appearance and the hardness of system are fine, and stripping 98.37% ± 0.6% when dissolution was 45min.
Reference embodiment: according to disclosed prescription of prior art and prepared Rosuvastatin calcium tablet (reference substance).
Rosuvastain calcium 2.5mg
Povidone 2.5mg
Tricalcium orthophosphate 20.0mg
Microcrystalline Cellulose 34.5mg
One Lactose hydrate 34.0mg
Carboxymethyl starch sodium 6.0mg
Magnesium stearate 1.0mg
Dibenzylatiooluene 0.05mg
Preparation technology: dibenzylatiooluene and part tricalcium orthophosphate be contained in mix 30s in the bag.Rosuvastain calcium, povidone, microcrystalline Cellulose, a Lactose hydrate, remaining tricalcium orthophosphate, the dibenzylatiooluene that mixes and tricalcium orthophosphate mixture and part of sodium carboxymethyl starch are mixed 30s in granulator.Adding speed interpolation pure water with 70mg/ sheet/min granulates to mixture of powders.Making granule is dried to moisture and is lower than 2% (w/w) on 50 ℃ fluid bed.Dry good granule is milled by one.Particle that grinds and carboxymethyl starch sodium mixing 5 minutes.Sieve with No. 40 apertures filters magnesium stearate, adds to then in the mixture and with mixture and mixes at least three minutes.The homogeneous mixture that obtains is pressed into tablet.Second portion effect embodiment part
The test of embodiment 6 rosuvastain calcium tablet stabilities
(1) influence factor of Rosuvastatin calcium tablet test
Get sample and reference substance (2.5mg/ sheet that the foregoing description 1,2,3,4,5 makes, embodiment makes by reference), place respectively under 60 ℃ of high temperature, high humidity 92.5%, the illumination 4500LX condition and placed 10 days, investigate appearance character, content, disintegration time and the dissolution of sample.The results are shown in Table 3.
Influence factor's result of the test of table 3 Rosuvastatin calcium tablet
Tablet influence factor test shows: according to the prescription of embodiment of the invention 1-5, adopt the Rosuvastatin calcium tablet of direct powder compression compacting, the outward appearance stable homogeneous, within storage under high temperature, high humidity or the high light 10 days, it is constant that content of medicines, disintegration time and dissolution keep substantially.And reference substance content and dissolution all decrease with the increase of storage time, and disintegration time increases, and change color also clearly.The prepared tablet of the present invention significantly is better than reference substance, the particularly tablet of making by embodiment 2 in these areas, and not only each parameter keeps constant, and at short notice can the more medicine of stripping.
(2) accelerated test of Rosuvastatin calcium tablet
In order to investigate the stability of Rosuvastatin calcium tablet, sample and reference substance (2.5mg/ sheet that embodiment 1,2,3,4,5 is made, embodiment makes by reference) place the climatic chamber of 30 ℃/RH60% to store 6 months, detect respectively at the 1st, 2,3,6 sampling at the end of month, investigate appearance character, content, disintegration time and the dissolution of sample.Accelerated test the results are shown in Table 4.
The accelerated test result of table 4 Rosuvastatin calcium tablet
(3) the long-term stability test of rosuvastain calcium sheet
Sample and reference substance (2.5mg/ sheet that embodiment 1,2,3,4,5 is made, embodiment makes by reference) 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% is stored, respectively at the one-time detection of taking a sample 3rd month, 6 months, 9 months, 12 the end of month, investigate appearance character, content, disintegration time and the dissolution of sample.The results are shown in Table 5.
The long-term stability test result of table 5 rosuvastain calcium sheet
Accelerated test and long-time stability are investigated test and are shown, the Rosuvastatin calcium tablet Long-term Storage of making by the present invention or in accelerated test steady quality, it is constant that dissolution and medicament contg keep, every index all is better than reference substance.Reference substance long-term storage its related substances rises to some extent.
By the rosuvastain calcium tablet appearance homogeneous that the present invention makes, impurity content does not increase in long-term storage and the accelerated test, and it is constant that dissolution and medicament contg keep.
The Study on relative bioavailability of embodiment 7 Rosuvastatin calcium tablets
1 materials and methods
1.1 medicine and reagent
Test preparation: Rosuvastatin calcium tablet I, according to the embodiment of the invention 2 preparations, specification 10mg/ sheet and 5mg/ sheet; Reference preparation (reference substance): Rosuvastatin calcium tablet II (2.5mg/ sheet, embodiment makes by reference); Methanol (chromatographically pure), Merck company produces; Perchloric acid (analytical pure), chemical reagent factory in Nanjing produces; Experimental water is a distilled water.
1.2 instrument and high performance liquid chromatography (HPLC) condition
LC-MS-2010A liquid chromatograph one GC-MS, day island proper Tianjin company product; The high speed microcentrifuge, Beijing Medical Centrifugal Machine Factory; The BT25S electronic balance, Sartorius produces.
Chromatograph chromatographic column: Shim-pack C
18(150mm * 2.0mm, 5 μ m); With following gradient elution mode and program: mobile phase: the aqueous solution-methanol (60: 40) of 0.002% triethylamine aqueous solution and 0.5m molL ammonium acetate; Flow is 0.2mLmin
-1, the methanol (%) of different time (min) is respectively 0.2-4.5: 40%-98%; 4.5-6.0: 98%; 6.0-6.5: 98%-40%; 6.5-11.0: 40%; Column temperature: 35 ℃.
Mass spectrum electron-spray ionizing (ESI); Selected ion monitoring (selected-ion monitoring, SIM); 250 ℃ of bent type Desolventizing apparatus (CDL) temperature; 200 ℃ of heat block (block) temperature; CDL voltage: 25V; Detect voltage :+1.60kV; Detect ion: Rosuvastatin ([M-H]
-, m/z): 480.00, interior mark ([M-H]
-, m/z): 364.00; Atomization gas flow 1.5Lmin
-1Dry gas flow 2.0Lmin
-1
1.3 experimental subject and dosage regimen
1.3.1 experimental subject is selected
12 male dogs of healthy Beagle, body weight 10 ± 1kg; 6 monthly ages of age.Complete physical examination is all normal, comprising auscultation of lung, liver palpation of spleen, electrocardiogram, heart rate, blood pressure, hepatic and renal function, routine blood test, routine urinalysis etc.
1.3.2 dosage regimen
12 healthy Beagle dogs are divided into 2 groups at random, adopt single dose binary cycle trial design at random, and twice intertrial interval phase was 1 week; The phase dosage is 10mg weekly; Begin fasting 12h preceding 1 day evening in test day, begins test the 2nd day 7: 30 morning.Single dose gives rosuvastain calcium on an empty stomach and is subjected to test preparation or reference preparation.Before administration and administration after 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,24h venous blood collection 3ml.Blood sample is through centrifuging and taking serum, put preserve in-20 ℃ of refrigerators to be measured.Take medicine and freely intake behind the 2h, unified feed behind the 4h.The tight observation tried the dog adverse events.Tried dog and after taking medicine, avoided aggravating activities.
1.4 sample process
Get blood plasma 1.0mL, mark (5.0gmL in adding
-1Hydrochlorothiazide) 10 μ l and 0.1molL
-1Glacial acetic acid 200 μ l, behind the mixing and the 6mL that adds diethyl ether again, centrifugal (4500rmin vibrates
-1) each 5min; Get supernatant 4.5mL, put 40 ℃ of water bath with thermostatic control N
2Dry up; With methanol 100 μ l dissolved residues, again through 18000rmin
-1Behind the centrifugal 10min, sample introduction 10 μ l get peak area and carry out quantitative analysis.
1.5 the foundation of rosuvastain calcium standard curve
1.5.1 standard curve preparation
Contain rosuvastain calcium 0.1,0.2,0.5,1.0,2.5,5.0,10.0,25.0 and 50.0ngmL
-1, measure and calculate regression equation: R=8.210
-3C+1 * 10
-6, γ=0.9999 (P＜0.01, n=5).Range of linearity 0.1-50.0ngmL
-1Minimal detectable concentration is 0.1ngmL
-1
1.5.2 precision and extraction recovery are measured
Accurate preparation rosuvastain calcium makes its concentration be respectively 0.2,2.5 and 25.0ngmL
-1Each 5 parts of plasma samples, according to aforementioned blood sample disposal methods and mensuration, sample peak area/interior mark peak area is updated to the regression equation of known standard product, obtain corresponding concentration, thereby try to achieve its method response rate, the precision of evaluation methodology and accuracy.Basic, normal, high concentration plasma sample in a few days, measurement result sees Table 6 in the daytime.
The precision and the determination of recovery rates of Rosuvastatin calcium in the table 7Beagle dog plasma
1.6 the stability of rosuvastain calcium plasma sample
Prepare high and low 2 concentration (50,0.05ng/mL) QC sample respectively by the standard curve preparation method, each concentration is carried out 3 sample analyses.Experimental result shows that the rosuvastain calcium plasma sample at room temperature places 7h, and freeze thawing 2 times has good stability under freezing 3,6 all conditions.
1.7 date processing and statistical method
According to survey rosuvastain calcium blood drug level-time data, adopt DAS2.0 pharmacokinetics program, calculate main pharmacokinetic parameter (Cmax, Tmax measured value, the AUC of rosuvastain calcium test preparation and reference preparation
0-∞Adopt trapezoidal method to calculate), Tmax adopts rank test, Cmax and AUC
0-∞Go respectively to adopt the t check behind the ln logarithm, and carry out (1～2 α) confidence interval and analyze, and estimate the bioavailability of Rosuvastatin calcium tablet I Rosuvastatin calcium tablet II.
2 results
2.1 the specificity of method
Get the blank plasma 0.2ml of 6 Beagle dogs respectively, except that not adding interior mark, other are by 1.4 operations down, and sample introduction 20 μ l get chromatogram; Certain density standard solution and inner mark solution are added in the blank plasma,, get chromatogram according to the method operation.Contrast two chromatograms and learn that the retention time of Rosuvastatin and interior mark hydrochlorothiazide is respectively 2.35,2.64min.Get the plasma sample after the experimenter takes medicine, under 1.4, operate, get chromatogram.The result shows that the endogenous material in the blank plasma is not disturbed the mensuration of Rosuvastatin and interior mark hydrochlorothiazide.
2.2 pharmacokinetic parameter
According to survey rosuvastain calcium serum-concentration-time data, utilize DAS2.0 pharmacokinetics program to calculate main pharmacokinetic parameters Tmax, Cmax, AUC
0-∞With relative bioavailability F (%) (seeing Table 8).
The pharmacokinetic parameter of table 8 Rosuvastatin calcium tablet I and Rosuvastatin calcium tablet II
T
MaxThrough rank test difference not statistically significant (P＞0.05); Rosuvastatin calcium tablet Tmax, Cmax, AUC
0-∞The numerical value warp is to number conversion, and The results of analysis of variance shows that Rosuvastatin calcium tablet I compares ln (AUC with Rosuvastatin calcium tablet II
0- ∞), lnCmax has statistical significance (P＜0.05) at the medicament differences, Rosuvastatin calcium tablet I is 118.95 ± 22.32% to the relative bioavailability of Rosuvastatin calcium tablet II, this explanation Rosuvastatin calcium tablet I compares with Rosuvastatin calcium tablet II, and bioavailability obviously improves.Rosuvastatin calcium tablet I compares ln (AUC with Rosuvastatin calcium tablet II
0-∞), lnCmax is smaller at interindividual variation, and has statistical significance (P＜0.05).
Claims (1)
1. Rosuvastatin calcium tablet is characterized in that containing the component of following percetage by weight:
Rosuvastain calcium 5～35%
Filler 50～90%
Crospolyvinylpyrrolidone 3～10%
Magnesium stearate 1～5%
Medicinal iron oxide red 0.1%
Described filler is solvable and solubilizing auxiliary materials, and wherein the solubility adjuvant is a lactose, and solubilizing auxiliary materials is a hydroxypropyl cyclodextrin, and the weight ratio of lactose and hydroxypropyl cyclodextrin is 1:1 ~ 2.5:1.
2. Rosuvastatin calcium tablet as claimed in claim 1 is characterized in that being made up of the component of following percetage by weight:
Rosuvastatin 10%
Lactose 50.9%
Hydroxypropyl cyclodextrin 30%
Crospolyvinylpyrrolidone 8%
Magnesium stearate 1%
Medicinal iron oxide red 0.1%.
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| CN101972260B (en) * | 2010-11-24 | 2012-05-02 | 天津市汉康医药生物技术有限公司 | Rosuvastatin calcium oral drug composition |
| CN102008477B (en) * | 2010-11-28 | 2012-11-07 | 天津市汉康医药生物技术有限公司 | Method for preparing tablet drug composition containing Rosuvastatin calcium |
| CN102860994B (en) * | 2011-07-04 | 2016-01-20 | 石药集团中奇制药技术（石家庄）有限公司 | A kind of rosuvastatin calcium tablets and preparation method thereof |
| CN103877042A (en) * | 2014-03-18 | 2014-06-25 | 孙常成 | Rosuvastatin calcium oral composition for increasing dissolution rate and preparation method of composition |
| JP6243265B2 (en) * | 2014-03-20 | 2017-12-06 | 日医工株式会社 | Pharmaceutical preparation containing rosuvastatin |
| CN106963738A (en) * | 2017-03-31 | 2017-07-21 | 华益药业科技(安徽)有限公司 | A kind of enalapril maleate piece of stabilization and preparation method thereof |
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| CN1149997C (en) * | 2000-01-26 | 2004-05-19 | 阿斯特拉曾尼卡有限公司 | Medicine composition |
| CN1557319A (en) * | 2004-02-09 | 2004-12-29 | 杨喜鸿 | Rosuvastatin dispersion tablet and its preparation method |
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| CN1149997C (en) * | 2000-01-26 | 2004-05-19 | 阿斯特拉曾尼卡有限公司 | Medicine composition |
| CN1557319A (en) * | 2004-02-09 | 2004-12-29 | 杨喜鸿 | Rosuvastatin dispersion tablet and its preparation method |
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