CN103018190B - A kind of pharmaceutical preparation and dissolution determination method thereof - Google Patents
A kind of pharmaceutical preparation and dissolution determination method thereof Download PDFInfo
- Publication number
- CN103018190B CN103018190B CN201110283448.5A CN201110283448A CN103018190B CN 103018190 B CN103018190 B CN 103018190B CN 201110283448 A CN201110283448 A CN 201110283448A CN 103018190 B CN103018190 B CN 103018190B
- Authority
- CN
- China
- Prior art keywords
- dissolution
- determination method
- pharmaceutical preparation
- tablet
- dissolution determination
- 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.)
- Expired - Fee Related
Links
Abstract
The invention belongs to medical art, the invention discloses a kind of containing active component (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2, the pharmaceutical preparation of 3-dihydroindene-5 acid amides sesquisulfates and dissolution method thereof, this dissolution method, determined by scientific experiment, take water as dissolution medium, rotating speed is 75 rpms, adopt ultraviolet spectrophotometry, measure absorbance log at 257nm.Said preparation composition is determined by dissolution method.
Description
Technical field
The invention belongs to medical art, be specifically related to one and there is the inhibiting pharmaceutical preparation of tyrosine protein kinase and dissolution determination method thereof.
Background technology
Medicine is for human body, and medicine in vivo emission and absorption is the key of drug effect.And every a collection of product all can not carry out in vivo studies, therefore create in vitro test means-Dissolution Rate Testing, it is more simple and easy to do than discharging analytical approach in medicine body.Be used for the treatment of the medicine of human diseases, solid pharmaceutical preparation accounts for sizable ratio.Solid pharmaceutical preparation only has stripping could be absorbed by body, and the number of stripping quantity, then one of reference index that can be used as drug effect.Therefore, pharmacopoeia of each country all defines dissolution determination project to many pharmaceutical preparations.In recent years, the quality standard of pharmaceutical solid preparation that China newly gives an written reply has formulated dissolution test project all as much as possible.
Patent WO2010072166 discloses the tyrosine protein kinase inhibitor of all new generation: dihydroindene amides compound, instructions embodiment 16 discloses (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, this patent to quality of preparation, preparation etc. without any research.
Summary of the invention
For these reasons, the applicant has determined containing active component (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2, the pharmaceutical preparation of 3-dihydroindene-5 acid amides sesquisulfates and measure the dissolution method of this pharmaceutical preparation, the method is determined by scientific experiment, take water as dissolution medium, rotating speed is 75 rpms, adopt ultraviolet spectrophotometry, measure absorbance log at 257nm.
The present invention is achieved through the following technical solutions.
A dissolution determination method for pharmaceutical preparation containing type I compound,
（Ⅰ）
Be dissolution medium with water in its dissolution determination method.
Wherein 75 turns per minute of dissolution determination method medium speed.
Dissolution determination method described above is: according to Chinese Pharmacopoeia version in 2010 two annex
c second method dissolution method, with 1000ml distilled water for dissolution medium, rotating speed is 75 turns per minute, through 30 minutes time, get solution, filter, getting subsequent filtrate is that need testing solution or precision measure subsequent filtrate distilled water and quantitatively dilute that to make in every 1ml containing the solution of type I compound 2-20 μ g be need testing solution, according to Chinese Pharmacopoeia version in 2010 two annex
a UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 257nm; Another modus ponens I compound control product are appropriate, accurately weighed, dissolve and quantitatively dilute the solution made containing 2-20 μ g in every 1ml, being measured in the same method, calculate the stripping quantity of preparation with distilled water.
Pharmaceutical preparation described above comprises tablet or capsule.
During tablet described above or capsule 30 minutes, dissolution rate is more than or equal to 80% and is less than or equal to 100%.
During tablet described above or capsule 30 minutes, dissolution rate is more than or equal to 90% and is less than or equal to 100%.
Tablet described above consists of wherein tablet and consists of (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 1-5 weight portions, filling agent 6-30 weight portion, disintegrant 0.3-2 weight portion, adds or does not add lubricant 0.07-0.5 weight portion.
In tablet described above, filling agent is one or more in lactose, microcrystalline cellulose, cornstarch, pregelatinized starch, sweet mellow wine, sorbierite, calcium monohydrogen phosphate, calcium sulphate.
In tablet described above, disintegrant is one or more in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, Ac-Di-Sol, sodium carboxymethyl starch, calcium carboxymethylcellulose.
In tablet described above, lubricant is one or more in dolomol, talcum powder, superfine silica gel powder, Macrogol 4000, Macrogol 6000.
The preparation method of tablet described above is: get (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2, the disintegrant of 3-dihydroindene-5 acid amides sesquisulfates, filling agent, 80%-90% weight mixes, with water softwood, granulate, add residue disintegrant, add lubricant, mix, compressing tablet, to obtain final product.
One, dissolution method research
1, the selection of dissolution medium
Test method: respectively with the water of 1000ml, 0.1M aqueous hydrochloric acid solution, pH6.8 phosphate buffer for dissolution medium, be 75rpm according to dissolution method (Chinese Pharmacopoeia 2010 editions annex XC second methods) rotating speed, operate in accordance with the law, respectively at 5,10,15,20,30,45,60min gets solution 10ml, 0.45 μm of filtering with microporous membrane, and supplement the fresh dissolution medium of equal-volume simultaneously, (40mg specification piece measures in 2.5ml to 10ml measuring bottle respectively to get subsequent filtrate, distilled water is settled to scale, shakes up) be need testing solution; Another accurate Weigh Compound I reference substance is about 10mg, accurately weighed, and put in 100ml measuring bottle, be settled to scale with water, precision measures in 5ml to 50ml measuring bottle, is settled to scale with distilled water, is reference substance solution.According to ultraviolet-visible spectrophotometry, measure the absorbance log of need testing solution and reference substance solution in 257nm place, external standard method calculates the stripping quantity of different time points, draws accumulation stripping curve.
Table 1 stripping curve result (0.1M aqueous hydrochloric acid solution is medium)
Table 2 stripping curve result (pH6.8 phosphate buffer is medium)
Table 3 stripping curve result (water is dissolution medium)
Experimental result: same batch sample (preparation embodiment 1 tablet) adopts different dissolution mediums to measure its cumulative leaching rate.Result shows that the dissolution rate of tablet in three kinds of dissolution mediums prepared by chemical compounds I is suitable, therefore selects water as dissolution medium.
2, the selection of rotating speed
Select slurry processes to carry out dissolution determination, and investigate the impact of different rotating speeds on compound stripping.
Test method: rotating speed selects 100rpm, 75rpm and 50rpm respectively, with 1000ml water for dissolution medium, respectively at 5,10,15,20,30,45,60min sampling, measure in accordance with the law, obtain stripping result.
The comparison of dissolution rate under table 4 different rotating speeds condition
Test findings: what measure under same batch sample (preparation embodiment 1 tablet) three kinds of speed conditions the results are shown in Table 4.Under result 50rpm, 75rpm and 100rpm speed conditions, sample is about 97.18%, 92.23%, 95.58% respectively through 30min stripping quantity, stripping is complete, but result can be found out, under 50rpm condition, the homogeneity otherness of each sample is larger, 75rpm and 100rpm condition stripping curve is substantially similar, for ensureing that sample stripping is complete, selection of speed 75rpm.
3, the Method validation of dissolution determination
(1) determination of determined wavelength
Respectively accurate Weigh Compound reference substance is appropriate, respectively with water, 0.1mol/l hydrochloric acid solution, pH6.8 phosphate buffered saline into about the solution of 0.01mg/ml; Scan respectively in 200 ~ 400nm wavelength coverage, select maximum absorption wavelength, the maximum absorption wavelength that preferred 230nm is later, sample solution should between 0.5 ~ 0.7 in the absorbance log of maximum absorption wave strong point.The ultraviolet absorpting spectrum of result display main ingredient compound in water, pH6.8 phosphate buffer is basically identical, and maximum absorption wavelength is respectively 257nm, maximum absorption wavelength slightly violet shift in 256nm, 0.1M hydrochloric acid solution.Because this product dissolution determination is dissolution medium with water, therefore, select 257nm wavelength as the determined wavelength of dissolution determination.
(2) linear
The solution into about 0.3mg/ml prepared in right amount by Weigh Compound reference substance, and as mother liquor, the accurate 0.25ml that draws puts in 25ml measuring bottle, is diluted with water to scale, is designated as solution a(3 μ g/ml); The accurate mother liquor 0.5ml that draws puts in 25ml measuring bottle, is diluted with water to scale, is designated as solution b(6 μ g/ml); The accurate mother liquor 0.75ml that draws puts in 25ml measuring bottle, is diluted with water to scale, is designated as solution c(9 μ g/ml); The accurate mother liquor 1ml that draws puts 25ml measuring bottle, is diluted with water to scale, is designated as solution d(12 μ g/ml); In accurate absorption mother liquor 1.25ml to 25ml measuring bottle, be diluted with water to scale, be designated as solution e(15 μ g/ml); In accurate absorption mother liquor 1.5ml to 25ml measuring bottle, be diluted with water to scale, be designated as solution f(18 μ g/ml).
By the sequential determination absorbance log of a, b, c, d, e, f, the results are shown in Table 5.Record absorbance log and linear regression is carried out to concentration, ask regression curve and related coefficient.Visible, compound of the present invention is in the scope of 3.00-18.00ug/ml in concentration, and linearly well, regression curve is Y=0.0499X+0.0055, r2=0.9999.
The absorbance log of compound solution under 257nm of table 5 variable concentrations
| Concentration (μ g/mL) | 3 | 6 | 9 | 12 | 15 | 18 |
| A | 0.154 | 0.308 | 0.457 | 0.601 | 0.753 | 0.908 |
(3) precision
Weigh Compound reference substance 10mg, in 100ml volumetric flask, is dissolved in water and is settled to scale, shaking up; In accurate absorption 1ml to 10ml volumetric flask, distilled water is settled to scale, shakes up, and obtains the solution (100% concentration level) that concentration is 10 μ g/ml.METHOD FOR CONTINUOUS DETERMINATION 6 its absorbances.The results are shown in Table 6, RSD is 0.20%, shows that precision is good.
Table 6 withinday precision (n=6)
| No | 1 | 2 | 3 | 4 | 5 | 6 | RSD% |
| A | 0.452 | 0.451 | 0.452 | 0.451 | 0.450 | 0.450 | 0.20 |
(4) stability
To get under precision item solution respectively at 0,2,4,6,8,12,24, measure absorbance log in 36h, investigate the RSD% of absorbance log.The results are shown in Table 7, result shows that sample solution is good at 36 hours internal stabilities.
The stability of table 7 compound solution
(5) recovery
Take blank prescription 75mg, nominal gets 12 parts, put in 50ml measuring bottle, numbering is designated as 1 ~ No. 12 bottle, adds bulk drug be about 5mg(50% respectively at 1 ~ 3 bottle of precision), add bulk drug in 4 ~ No. 6 bottle precisions and be about 8mg(80%), add bulk drug in 7 ~ No. 9 bottle precisions and be about 10mg(100%), in 10-12 bottle, precision adds bulk drug and is about 12mg(120%).Add water appropriate, shake well, adds water and is settled to scale, as need testing solution.Separately get reference substance appropriate, be configured to the solution solution in contrast of 10 μ g/ml.According to UV-VIS spectrophotometry, measure the absorbance of need testing solution and reference substance solution respectively, external standard method calculates content and the recovery, the results are shown in Table 8.Visible, the average recovery rate of each level is respectively 99.55%, 99.71%, 99.60% and 101.7%, meets dissolution determination requirement.
The table 8 compound sheet dissolution determination method recovery investigates result
Through the Method validation of system, linear, precision, the recovery, the stability of solution of the method meet the requirement of dissolution determination, may be used for the dissolution determination of compound tablet.
4, criticize in and batch between stripping homogeneity investigate
(1) embodiment sample stripping curve criticizes the investigation of interior homogeneity
Method through system is screened, and has carried out the Method validation of system to quantivative approach, determines that the dissolution determination method of this product is as follows:
With 1000ml water for dissolution medium, according to dissolution method (Chinese Pharmacopoeia 2010 editions annex
c second method) rotating speed is 75rpm, operate in accordance with the law, respectively at 5,10,15,20,30,45,60min gets solution 10ml, 0.45 μm of filtering with microporous membrane, and supplement isopyknic fresh dissolution medium simultaneously, getting subsequent filtrate (40mg specification piece measures in 2.5ml to 10ml measuring bottle respectively, and distilled water is settled to scale, shakes up) is need testing solution; Another accurate Weigh Compound reference substance is about 10mg, accurately weighed, and put in 100ml measuring bottle, add water and make dissolving, add water to scale, shake up, precision measures in 5ml to 50ml measuring bottle, is settled to scale with water, is reference substance solution.According to ultraviolet-visible spectrophotometry, measure the absorbance log of need testing solution and reference substance solution in 257nm place, external standard method calculates the stripping quantity of different time points, draws the curve of accumulation stripping quantity.In table 9 ~ 14.
Table 9 embodiment 2 tablet cumulative leaching rate
Table 10 embodiment 3 tablet cumulative leaching rate
Table 11 embodiment 4 tablet cumulative leaching rate
Table 12 embodiment 5 cumulative leaching rates
Table 13 embodiment 6 tablet cumulative leaching rate
Table 14 embodiment 7 tablet cumulative leaching rate
Each three batch samples batch between stripping homogeneity investigate
Calculate the average dissolution profiles of each three batch samples of two specifications respectively, and more each batch sample criticize between stripping homogeneity, the results are shown in Table and see 15.
The stripping of table 15 three batch sample batch between homogeneity investigate result
The dissolution determination of six batch samples
Through the optimization of above condition, finally determine the dissolution determination method of this product:
With 1000ml water for dissolution medium, according to dissolution method (Chinese Pharmacopoeia 2010 editions annex
c second method) rotating speed is 75rpm, operate in accordance with the law, get solution with 0.45 μm of filtering with microporous membrane after 30min, getting subsequent filtrate (40mg specification piece measures in 12ml to 50ml measuring bottle, and distilled water is settled to scale, shakes up) is need testing solution; Another accurate Weigh Compound reference substance is about 10mg, accurately weighed, and put in 100ml measuring bottle, add water and make dissolving, add water to scale, shake up, precision measures in 5ml to 50ml measuring bottle, is settled to scale with water, is reference substance solution.According to ultraviolet-visible spectrophotometry, measure the absorbance log of need testing solution and reference substance solution in 257nm place, external standard method calculates the stripping quantity of every sheet.
Test findings: the dissolution determination of six batch samples the results are shown in Table 16, and result shows, the dissolution rate of each three batch sample 30min of different embodiment is about 89% ~ 96%, all more than 80%, therefore is ordered by standard limits as 30min stripping quantity is not less than 80% of labelled amount.
The dissolution test result of table 16 six batches of compound tablet
| Sample lot number | Dissolution rate |
| Embodiment 2 | 99.87±1.74 |
| Embodiment 3 | 94.14±1.48 |
| Embodiment 4 | 100.93±1.17 |
| Embodiment 5 | 96.32±4.16 |
| Embodiment 6 | 98.12±4.04 |
| Embodiment 7 | 96.59±4.43 |
Two, embodiment is prepared
Embodiment 1
Tablet formulation (1000 preparation unit amount): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 10g, filling agent pregelatinized starch 25g, microcrystalline cellulose 35g, Ac-Di-Sol 3.5g, lubricant talcum powder 0.75g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, pregelatinized starch, microcrystalline celluloses, 2.8g Ac-Di-Sol, with water softwood, granulate, add 0.7g Ac-Di-Sol, add lubricant talcum powder, mix, compressing tablet, to obtain final product.
Embodiment 2
Tablet formulation (1000 preparation unit amount): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 45g, filling agent pregelatinized starch 150g, microcrystalline cellulose 140g, low-substituted hydroxypropyl cellulose 19g, lubricant Macrogol 6000 4.77g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, pregelatinized starch, microcrystalline celluloses, 17.1g low-substituted hydroxypropyl cellulose mixes, with water softwood, granulate, add 1.9g low-substituted hydroxypropyl cellulose, add lubricant Macrogol 6000, mix, compressing tablet, to obtain final product.
Embodiment 3
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 25g, filling agent lactose 50g, microcrystalline cellulose 100g, disintegrant polyvinylpolypyrrolidone 12.5g, lubricant superfine silica gel powder 2.3g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline celluloses, 10.6g polyvinylpolypyrrolidone mixes, with water softwood, granulate, add 1.9g polyvinylpolypyrrolidone, add lubricant superfine silica gel powder, mix, compressing tablet, to obtain final product.
Embodiment 4
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 10g, filling agent lactose 17g, microcrystalline cellulose 41g, pregelatinized starch 3.7g, disintegrating agent carboxymethyl base sodium starch 3.4g, magnesium stearate lubricant 0.75g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 3g sodium carboxymethyl starch mixes, with water softwood, granulate, add 0.4g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 5
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 40g, filling agent lactose 68g, microcrystalline cellulose 163g, pregelatinized starch 15g, disintegrating agent carboxymethyl base sodium starch 13.5g, magnesium stearate lubricant 4.4g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 12g sodium carboxymethyl starch mixes, with water softwood, granulate, add 1.5g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 6
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 20g, filling agent lactose 35g, microcrystalline cellulose 80g, pregelatinized starch 7.5g, disintegrating agent carboxymethyl base sodium starch 7g, magnesium stearate lubricant 1.6g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 6g sodium carboxymethyl starch mixes, with water softwood, granulate, add 1g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 7
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 30g, filling agent lactose 50g, microcrystalline cellulose 125g, pregelatinized starch 12g, disintegrating agent carboxymethyl base sodium starch 10.5g, magnesium stearate lubricant 2.30g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 9g sodium carboxymethyl starch mixes, with water softwood, granulate, add 1.5g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 8
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 25g, filling agent lactose 42g, microcrystalline cellulose 103g, pregelatinized starch 10g, disintegrating agent carboxymethyl base sodium starch 8.7g, magnesium stearate lubricant 1.9g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 7.4g sodium carboxymethyl starch mixes, with water softwood, granulate, add 1.3g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 9
Tablet formulation (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 50g, filling agent lactose 75g, microcrystalline cellulose 205g, pregelatinized starch 18g, disintegrating agent carboxymethyl base sodium starch 19.4g, magnesium stearate lubricant 4.90g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, pregelatinized starch, 16.7g sodium carboxymethyl starch mixes, with water softwood, granulate, add 2.7g sodium carboxymethyl starch, add magnesium stearate lubricant, mix, compressing tablet, to obtain final product.
Embodiment 10
Capsule prescription (1000 preparation unit amount): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 40g, filling agent pregelatinized starch 248g, disintegrant low-substituted hydroxypropyl cellulose 13.3g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, pregelatinized starch, low-substituted hydroxypropyl celluloses mix, with water softwood, granulate, incapsulate, to obtain final product.
Embodiment 11
Capsule prescription (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 80g, filling agent lactose 211g, microcrystalline cellulose 358g, disintegrant low-substituted hydroxypropyl cellulose 34.7g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, low-substituted hydroxypropyl celluloses mix, with water softwood, granulate, incapsulate, to obtain final product.
Embodiment 12
Capsule prescription (1000 preparation unit): (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 80g, filling agent lactose 208g, microcrystalline cellulose 370g, disintegrant Ac-Di-Sol 39g.
Preparation method:
Get recipe quantity (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfates, lactose, microcrystalline cellulose, Ac-Di-Sols mix, with water softwood, granulate, incapsulate, to obtain final product.
Described embodiment includes but not limited to above-mentioned.
Claims (9)
1. a dissolution determination method for the pharmaceutical preparation containing type I compound,
It is characterized in that dissolution determination method is: according to Chinese Pharmacopoeia version in 2010 two annex XC second method dissolution methods, with 1000ml distilled water for dissolution medium, rotating speed is 75 turns per minute, through 30 minutes time, get solution, filter, getting subsequent filtrate is that need testing solution or precision measure subsequent filtrate distilled water and quantitatively dilute that to make in every 1ml containing the solution of type I compound 2-20 μ g be need testing solution, according to Chinese Pharmacopoeia version in 2010 two annex IVA UV-VIS spectrophotometry, measure absorbance log at the wavelength place of 257nm; Another modus ponens I compound control product are appropriate, accurately weighed, dissolve and quantitatively dilute the solution made containing 2-20 μ g in every 1ml, being measured in the same method, calculate the stripping quantity of preparation with distilled water.
2. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 1, its pharmaceutical formulations comprises tablet or capsule.
3. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 2, during wherein tablet or capsule 30 minutes, dissolution rate is more than or equal to 80% and is less than or equal to 100%.
4. the dissolution determination method of a kind of pharmaceutical preparation containing formula I according to right 2, during wherein tablet or capsule 30 minutes, dissolution rate is more than or equal to 90% and is less than or equal to 100%.
5. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 2, wherein tablet consists of (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2,3-dihydroindene-5 acid amides sesquisulfate 1-5 weight portions, filling agent 6-30 weight portion, disintegrant 0.3-2 weight portion, adds or does not add lubricant 0.07-0.5 weight portion.
6. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 5, wherein filling agent is one or more in lactose, microcrystalline cellulose, cornstarch, pregelatinized starch, sweet mellow wine, sorbierite, calcium monohydrogen phosphate, calcium sulphate.
7. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 5, wherein disintegrant is one or more in low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, Ac-Di-Sol, sodium carboxymethyl starch, calcium carboxymethylcellulose.
8. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 5, wherein lubricant is one or more in dolomol, talcum powder, superfine silica gel powder, Macrogol 4000, Macrogol 6000.
9. the dissolution determination method of a kind of pharmaceutical preparation containing type I compound according to claim 5, wherein the preparation method of tablet is: get (1S)-1-(4-methylpiperazine-1-yl)-N-(4-methyl-3-[(4-pyridin-3-yl pyrimidine-2-base) is amino] phenyl)-2, the disintegrant of 3-dihydroindene-5 acid amides sesquisulfates, filling agent, 80%-90% weight mixes, with water softwood, granulate, add residue disintegrant, add lubricant, mix, compressing tablet, both.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110283448.5A CN103018190B (en) | 2011-09-22 | 2011-09-22 | A kind of pharmaceutical preparation and dissolution determination method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110283448.5A CN103018190B (en) | 2011-09-22 | 2011-09-22 | A kind of pharmaceutical preparation and dissolution determination method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103018190A CN103018190A (en) | 2013-04-03 |
| CN103018190B true CN103018190B (en) | 2016-02-10 |
Family
ID=47967043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110283448.5A Expired - Fee Related CN103018190B (en) | 2011-09-22 | 2011-09-22 | A kind of pharmaceutical preparation and dissolution determination method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103018190B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108414466A (en) * | 2018-03-09 | 2018-08-17 | 浙江美华鼎昌医药科技有限公司 | A kind of minocycline hydrochloride sustained release tablet In Vitro Dissolution assay method |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403083A (en) * | 2002-08-05 | 2003-03-19 | 南昌弘益医药研究所 | Fast disintegrated and stripped oral cilostazol table and its prepn process |
| CN1562018A (en) * | 2004-03-15 | 2005-01-12 | 深圳海王药业有限公司 | Cilostazol solid dispersion and its method for preparing tablet |
| CN1634479A (en) * | 2004-03-12 | 2005-07-06 | 诺氏制药（吉林）有限公司 | Medicine composition for treating cold and upper respiratory tract infection, preparation method and purpose thereof |
| CN1723901A (en) * | 2005-07-04 | 2006-01-25 | 广州固志医药科技有限公司 | Fleroxacin lactate dispersion tablet, and its prepn. method |
| CN1919185A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Compound ammonium glycyrrhizinato S dispersed tablet and its preparing process |
| CN101759683A (en) * | 2008-12-25 | 2010-06-30 | 北京美迪赛医药技术有限公司 | Preparation method of hydrindene amide compound, medical composition comprising hydrindene amide compound and application thereof as protein kinase inhibitor |
-
2011
- 2011-09-22 CN CN201110283448.5A patent/CN103018190B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403083A (en) * | 2002-08-05 | 2003-03-19 | 南昌弘益医药研究所 | Fast disintegrated and stripped oral cilostazol table and its prepn process |
| CN1634479A (en) * | 2004-03-12 | 2005-07-06 | 诺氏制药（吉林）有限公司 | Medicine composition for treating cold and upper respiratory tract infection, preparation method and purpose thereof |
| CN1562018A (en) * | 2004-03-15 | 2005-01-12 | 深圳海王药业有限公司 | Cilostazol solid dispersion and its method for preparing tablet |
| CN1723901A (en) * | 2005-07-04 | 2006-01-25 | 广州固志医药科技有限公司 | Fleroxacin lactate dispersion tablet, and its prepn. method |
| CN1919185A (en) * | 2006-09-18 | 2007-02-28 | 黄本东 | Compound ammonium glycyrrhizinato S dispersed tablet and its preparing process |
| CN101759683A (en) * | 2008-12-25 | 2010-06-30 | 北京美迪赛医药技术有限公司 | Preparation method of hydrindene amide compound, medical composition comprising hydrindene amide compound and application thereof as protein kinase inhibitor |
| WO2010072166A1 (en) * | 2008-12-25 | 2010-07-01 | 北京美迪赛医药技术有限公司 | Preparation method of dihydroindene amide compounds,their pharmaceutical compositions containg compounds thereof and use as protein kinases inhibitor |
Non-Patent Citations (3)
| Title |
|---|
| 《X C 溶出度测定法》;国家药典委员会编;《中华人民民共和国药典2010年版》;中国医药科技出版社;20101231;390 * |
| 《浅谈溶出度检查方法的研究》;王亚敏;《药物分析杂志》;20071231;第27卷(第10期);1667-1670 * |
| 《药物溶出度试验的应用和进展》;翁水旺等;《中国医院药学杂质》;20030428;第23卷(第4期);240-242 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103018190A (en) | 2013-04-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101984960B (en) | Rizatriptan benzoate capsule and preparation method thereof | |
| CN100370984C (en) | Telmisartan dispersible tablet and its preparation method | |
| CN109662950A (en) | A kind of pharmaceutical composition containing dapoxetine hydrochloride | |
| CN104510719A (en) | Acotiamide tablet and preparation method thereof | |
| CN103018190B (en) | A kind of pharmaceutical preparation and dissolution determination method thereof | |
| CN109908104B (en) | Amoxicillin capsule and preparation method thereof | |
| CN104337811A (en) | Repaglinide-metformin hydrochloride tablet and preparing method thereof | |
| CN104706655B (en) | Meglumine cyclic adenosine for injecta powder-injection pharmaceutical composition and preparation method | |
| CN101836981B (en) | Compound valsartan benzenesulfonic acid amlodipine medicament composition and new preparation method thereof | |
| CN111297800B (en) | Ion exchange fiber chloroquine suspension and preparation method thereof | |
| CN104523628A (en) | Succinic acid solifenacin tablet capable of achieving direct powder compression and preparation method of succinic acid solifenacin tablet | |
| CN110960501B (en) | Norfloxacin capsule and preparation method thereof | |
| CN107496369A (en) | A kind of Citicoline sodium tablets and its direct powder compression preparation method | |
| CN108379235B (en) | Tacrolimus sustained-release tablet composition capable of rapidly disintegrating | |
| CN106932506A (en) | A kind of slow controlled-release solid formulations detection pre-treating method of hydrogel matrix type | |
| CN102552210B (en) | Entecavir capsule and preparation method thereof | |
| CN108125919B (en) | A kind of glycine chelated calcium tablet composition and preparation method thereof | |
| CN103768068B (en) | A kind of Bosentan pharmaceutical composition | |
| CN100402030C (en) | Pharmaceutical composition containing amoxicillin and preparation method thereof | |
| CN103893185B (en) | A kind of valsartan and Hydrochlorothiade dispersible tablet and preparation method thereof | |
| CN112691084A (en) | Pharmaceutical composition and preparation method thereof | |
| CN103432090A (en) | Cyclovirobuxine D sublingual tablet as well as preparation method and application thereof | |
| CN110251471A (en) | A kind of difenidol hydrochloride piece and preparation method thereof | |
| CN109893509A (en) | A kind of pellet tablet and preparation method thereof containing rosuvastain calcium | |
| CN108653224A (en) | A kind of Amoxicillin Tablet In Normal Subjects 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 |
Effective date of registration: 20170808 Address after: 150025, 29 Beijing Road, Limin economic and Technological Development Zone, Heilongjiang, Harbin Patentee after: HARBIN GLORIA PHARMACEUTICALS Co.,Ltd. Address before: 100016 B87, G 21, Jiuxianqiao, Beijing, Chaoyang District Co-patentee before: HARBIN GLORIA PHARMACEUTICALS Co.,Ltd. Patentee before: BEIJING MEDCONXIN PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160210 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |