CN108524462A - A kind of Sarpogrelate hydrochloride tablets agent preparation process - Google Patents
A kind of Sarpogrelate hydrochloride tablets agent preparation process Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology fields, and in particular to a kind of Sarpogrelate hydrochloride tablets agent preparation process.The preparation process, in order to improve influence of the wet granulation to sarpogrelate hydrochloride stability, have adjusted preparation process, the same sarpogrelate hydrochloride of light anhydrous silicic acid, avicel cellulose and carboxymethyl cellulose are mixed into together and a step is completely pelletized, improve light anhydrous silicic acid helps stream to act in pelletization, raw material mixing is more uniform, and convenient for molding, granulation efficiency is high；Change based on preparation process, the preparation raw material dosage of Sarpogrelate hydrochloride tablets agent accordingly adjusts, reduce the dosage of filler, increase the dosage of stabilizer, glidant and disintegrant, with the combination that preparation process and raw material components dosage adjust, stability, stripping property and the better Sarpogrelate hydrochloride tablets agent of compressibility have been obtained.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of Sarpogrelate hydrochloride tablets agent preparation process.
Background technology
Sarpogrelate hydrochloride is used pharmaceutically in ulcer, pain and the creeping chill etc. improved caused by chronic arterial occlusion and lacks
Courageous and upright symptom, to the 5-HT of blood platelet and vascular smooth muscle2Antibody has specific antagonistic action.
The listing preparation of sarpogrelate hydrochloride is the hydrochloric acid sand Gray of Japanese Tanabe Mitsubishi Pharmaceutical Co's production at present
Ester piece, supplementary material include sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, light anhydrous silicon
Acid, citric acid, magnesium stearate and coating powder, but its preparation process is that sarpogrelate hydrochloride and avicel cellulose, carboxymethyl are fine
Dimension element after mixing be added carboxy-propyl cellulose and citric acid dissolving after prepare adhesive granulation, add silicic acid anhydride and
It is coated and is made after magnesium stearate mixed pressuring plate.Due to sarpogrelate hydrochloride in wet-granulation process facile hydrolysis, hydrochloric acid obtained
Sarpogrelate stability is not easy to ensure, i.e., can influence the use drug effect of Sarpogrelate hydrochloride tablets agent clinically.
Invention content
Based on problem above, the object of the present invention is to provide a kind of Sarpogrelate hydrochloride tablets agent preparation processes, improve original
Harmful effect of the tablet wet granulation to sarpogrelate hydrochloride stability, and hydrochloric acid sand is had adjusted on the basis of process reform
The dosage of auxiliary material in Gray's ester tablet.
The technical scheme is that：
The present invention provides a kind of Sarpogrelate hydrochloride tablets agent preparation process,
In parts by weight, the raw material for preparing of the Sarpogrelate hydrochloride tablets agent includes 100 parts of sarpogrelate hydrochlorides, 20-50
Part avicel cellulose, 10-50 parts of carboxymethyl celluloses, 1-5 parts of light anhydrous silicic acids, 0.5-3 parts of citron acid hydrates, 2-7 parts
Hydroxypropyl cellulose, 2-10 part magnesium stearate, 2-10 parts of hypromellose, 0.5-3 parts of titanium oxide, 0.5-3 parts of poly- second two
Alcohol 6000 and 0.5-3 parts of talcum powder；
The preparation process includes the following steps：
(1) bonding agent is prepared：After carboxy-propyl cellulose is dissolved in the water, citron acid hydrate mixed dissolution is added, obtains
It is spare in conjunction with agent solution；
(2) preliminary granulation：Sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and light anhydrous silicic acid are carried out
After mixing, the combination agent solution of step (1) is added, continues to stir, completes preliminary granulation；
(3) dry：The particle for completing to obtain after preliminary granulation is dried, drying to particle temperature reaches 32-35 DEG C
Stop heating afterwards, completes drying；
(4) secondary granulation：After particle of the completion after dry is mixed with magnesium stearate, secondary granulation is completed；
(5) tabletting：Particle progress after secondary granulation is tabletted, obtain sarpogrelate hydrochloride plain piece；
(6) coating solution is prepared：Macrogol 6000 mixed dissolution is added in the third methylcellulose of carboxylic after being dissolved in the water, then adds
Enter titanium oxide and talcum powder, it is made to be uniformly dispersed, coating solution is made；
(7) the sarpogrelate hydrochloride plain piece is coated using the coating solution, that is, completes to prepare.
The preparation process of the Sarpogrelate hydrochloride tablets agent of the present invention stablizes sarpogrelate hydrochloride for wet granulation is improved
Property influence consider, by light anhydrous silicic acid in preliminary pelletization with sarpogrelate hydrochloride, avicel cellulose and carboxymethyl
Mixing is added in cellulose together, while also playing raising and stream is helped to act on, and easily facilitates pelletizing forming, and former preparation process is by lightweight
Silicic acid anhydride is added together with magnesium stearate in secondary granulation, and light anhydrous silicic acid helps stream effect that cannot obviously be played
Come, each component is susceptible to mixing unevenness, the bad phenomenon of result of extraction in human body in obtained Sarpogrelate hydrochloride tablets agent.
Due to the adjustment of preparation process, adaptively, the dosage of filler avicel cellulose is reduced, increase stabilizer citron
The dosage of acid hydrate, glidant light anhydrous silicic acid and disintegrating agent carboxymethyl base cellulose, has obtained the sarpogrelate hydrochloride
The raw material for preparing of tablet forms, more preferable with the stability of this obtained Sarpogrelate hydrochloride tablets agent, stripping property and compressibility.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, hydrochloric acid is husky in Sarpogrelate hydrochloride tablets agent obtained
Gray's ester content is 100mg/ pieces.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, in step (1), first with 50-70 DEG C of water-bath ring
Carboxy-propyl cellulose is dispersed in water in border, then after being cooled to 30-40 DEG C, waits for that carboxy-propyl cellulose completely dissolves in water
Afterwards, citron acid hydrate is added.Hot water is not dissolved in since carboxy-propyl cellulose is dissolved in cold water, will appear if direct plungeing into cold water
Swelling, which makes to combine, to be also layered, therefore in hot bath now that carboxy-propyl cellulose is evenly dispersed in water, then is gradually cooled down, it is made
It is slowly dissolved in the water, dispersing and dissolving can be obtained and uniformly combine agent solution.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, in step (2), by sarpogrelate hydrochloride, knot
After crystalline cellulose, carboxymethyl cellulose and light anhydrous silicic acid carry out mixing 5-6min, the bonding agent that step (1) is added is molten
Liquid continues to stir 1-2min.In preliminary pelletization, batch mixing and one step of granulation step are realized, and is stirred in very short mixing
The production efficiency that material mixing is substantially increased to sarpogrelate hydrochloride can be achieved the effect that by mixing in the time.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, in step (2), with efficient mixer-granulator into
The preliminary granulation of row, the side wall and binder solution entrance of the efficient mixer-granulator are provided with cutter, efficiently to mix
The cutter of granulator side wall are in pelletization constantly by the sarpogrelate hydrochloride in preliminary pelletization, crystalline fibers
Element, carboxymethyl cellulose and light anhydrous silicic acid mixture carry out cutting and grinding, will with the cutter of binder solution entrance
The combination agent solution carries out cutting dispersion, ensures that granulation material is uniformly mixed.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention will obtain in step (3) after completing preliminary granulation
The particle arrived carries out fluidized bed drying, and dry inlet air temperature is 75-85 DEG C, and particle temperature stops heating after reaching 32-35 DEG C,
When temperature of outgoing air is down to 35-40 DEG C, particle is taken out.With fluidized bed drying, suitable inlet air temperature and air quantity are controlled, is made
Particle reaches suitable boiling height, and particle had both been made to reach good drying effect, will not be excessive thin because of generation of acutely boiling
Powder, particle temperature, which reaches to stop heating after 32-35 DEG C, can make particle water content control in suitable range, convenient for further
With magnesium stearate mixing granulation.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention further includes before it is dried, inciting somebody to action in step (3)
Particle after preliminary granulation crushes and crosses the herringbone sieve of 1cm, and operation is dried in the lower particle of sieve.It crushed through herringbone sieve
Particle after sieve, grain size comply with standard, uniform convenient for drying, and granule fines content will not be excessive, cause excessive material wave
Take.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, in step (4), by particle of the completion after dry
It carries out crushing and crossing 1.5mm circular hole sieves again, the lower particle of sieve is mixed with magnesium stearate, carries out secondary granulation.Through 1.5mm's
Sieve crushes and particle easily mixes completion granulation with magnesium stearate under the sieve that is sieved.
The preparation process of Sarpogrelate hydrochloride tablets agent according to the present invention, in step (6), first with 50-70 DEG C of water-bath ring
The third methylcellulose of carboxylic is dispersed in water in border, then after being cooled to 30-40 DEG C, Macrogol 6000 mixed dissolution is added.By
In the third methylcellulose of carboxylic be dissolved in cold water do not dissolve in hot water, if direct plunge into cold water will appear swelling make combine also be layered, because
It is in this present hot bath that the third methylcellulose of carboxylic is evenly dispersed in water, then gradually cool down, so that it is slowly dissolved in the water, it can
To obtain the uniform coating solution of dispersing and dissolving.
Beneficial effects of the present invention are：
The preparation process of the Sarpogrelate hydrochloride tablets agent of the present invention stablizes sarpogrelate hydrochloride to improve wet granulation
The influence of property, has adjusted preparation process, by the same sarpogrelate hydrochloride of light anhydrous silicic acid, avicel cellulose and carboxymethyl cellulose
It is mixed into together and a step is completely pelletized, improve light anhydrous silicic acid and help stream to act in pelletization, raw material mixes more
Uniformly, it is convenient for molding, granulation efficiency high；Change based on preparation process, the preparation raw material dosage phase of Sarpogrelate hydrochloride tablets agent
It should adjust, reduce the dosage of filler, the dosage of stabilizer, glidant and disintegrant be increased, with preparation process and raw material
The combination of amounts of components adjustment, has obtained stability, stripping property and the better Sarpogrelate hydrochloride tablets agent of compressibility.
Specific implementation mode
To make the object, technical solutions and advantages of the present invention clearer, technical scheme of the present invention will be carried out below
Detailed description.Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Base
Embodiment in the present invention, those of ordinary skill in the art are obtained all without making creative work
Other embodiment belongs to the range that the present invention is protected.
Following embodiment is with 1 part for 1kg.
Embodiment 1
The present invention provides a kind of Sarpogrelate hydrochloride tablets agent preparation process,
In parts by weight, the raw material for preparing of the Sarpogrelate hydrochloride tablets agent includes 100 parts of sarpogrelate hydrochlorides, 20 parts of knots
Crystalline cellulose, 50 parts of carboxymethyl celluloses, 1 part of light anhydrous silicic acid, 3 parts of citron acid hydrates, 2 parts of hydroxypropyl celluloses, 10
Part magnesium stearate, 2 parts of hypromellose, 3 parts of titanium oxide, 0.5 part of Macrogol 6000 and 3 parts of talcum powder；
The preparation process includes the following steps：
(1) bonding agent is prepared：First to be dispersed in water carboxy-propyl cellulose in 50 DEG C of water baths, then it is cooled to 40 DEG C
Afterwards, after carboxy-propyl cellulose completely dissolves in water, citron acid hydrate mixed dissolution is added, obtains combining agent solution, it is standby
With；
(2) preliminary granulation：Sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and light anhydrous silicic acid are carried out
5min is stirred to after mixing, the combination agent solution of step (1) is added, continues to stir 2min, completes preliminary granulation；
(3) dry：The particle for completing to obtain after preliminary granulation is subjected to fluidized bed drying, dry inlet air temperature is 75
DEG C, particle temperature stops heating after reaching 35 DEG C, and when temperature of outgoing air is down to 35 DEG C, particle is taken out, and completes drying；
(4) secondary granulation：The circular hole sieve for carrying out particle of the completion after dry to crush and cross specification again as 1.5mm,
The lower particle of sieve is mixed with magnesium stearate, completes secondary granulation；
(5) tabletting：Particle progress after secondary granulation is tabletted, obtain sarpogrelate hydrochloride plain piece；
(6) coating solution is prepared：First to be dispersed in water the third methylcellulose of carboxylic in 70 DEG C of water baths, then it is cooled to 30
After DEG C, Macrogol 6000 mixed dissolution is added, adds titanium oxide and talcum powder, it is made to be uniformly dispersed, coating solution is made；
(7) the sarpogrelate hydrochloride plain piece is coated using the coating solution, that is, completes to prepare, the hydrochloric acid of gained
In Sarpogrelate tablet, sarpogrelate hydrochloride content is 100mg/ pieces.
Embodiment 2
The present invention provides a kind of Sarpogrelate hydrochloride tablets agent preparation process,
In parts by weight, the raw material for preparing of the Sarpogrelate hydrochloride tablets agent includes 100 parts of sarpogrelate hydrochlorides, 50 parts of knots
Crystalline cellulose, 10 parts of carboxymethyl celluloses, 5 parts of light anhydrous silicic acids, 0.5 part of citron acid hydrate, 7 parts of hydroxypropyl celluloses, 2
Part magnesium stearate, 10 parts of hypromellose, 0.5 part of titanium oxide, 3 parts of Macrogol 6000s and 0.5 part of talcum powder；
The preparation process includes the following steps：
(1) bonding agent is prepared：First to be dispersed in water carboxy-propyl cellulose in 70 DEG C of water baths, then it is cooled to 30 DEG C
Afterwards, after carboxy-propyl cellulose completely dissolves in water, citron acid hydrate mixed dissolution is added, obtains combining agent solution, it is standby
With；
(2) preliminary granulation：It is tentatively pelletized with efficient mixer-granulator, the side wall of the efficient mixer-granulator and viscous
Knot agent solution entrance is provided with cutter；By sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and light anhydrous silicon
Acid is stirred 6min, in mixed process the cutter of side wall in pelletization constantly by the hydrochloric acid in preliminary pelletization
Sarpogrelate, avicel cellulose, carboxymethyl cellulose and light anhydrous silicic acid mixture carry out cutting and grinding, until being uniformly mixed
Afterwards, the combination agent solution of step (1) is added, in adition process, with the cutter of binder solution entrance by the bonding agent
Solution carries out cutting dispersion, and guarantee is uniformly mixed in conjunction with agent solution with the mixture of the above raw material；It is added completely into and combines agent solution
Afterwards, continue to stir 1min, complete preliminary granulation；
(3) dry：Particle after preliminary granulation is crushed and hole specification of being sieved is the herringbone sieve of 1cm, it will the lower particle of sieve
Fluidized bed drying is carried out, dry inlet air temperature is 85 DEG C, and particle temperature stops heating after reaching 32 DEG C, waits for that temperature of outgoing air is down to
At 40 DEG C, particle is taken out, completes drying；
(4) secondary granulation：The circular hole sieve for carrying out particle of the completion after dry to crush and cross specification again as 1.5mm,
The lower particle of sieve is mixed with magnesium stearate, completes secondary granulation；
(5) tabletting：Particle progress after secondary granulation is tabletted, obtain sarpogrelate hydrochloride plain piece；
(6) coating solution is prepared：First to be dispersed in water the third methylcellulose of carboxylic in 50 DEG C of water baths, then it is cooled to 40
After DEG C, Macrogol 6000 mixed dissolution is added, adds titanium oxide and talcum powder, it is made to be uniformly dispersed, coating solution is made；
(7) the sarpogrelate hydrochloride plain piece is coated using the coating solution, that is, completes to prepare, the hydrochloric acid of gained
In Sarpogrelate tablet, sarpogrelate hydrochloride content is 100mg/ pieces.
Embodiment 3
The present invention provides a kind of Sarpogrelate hydrochloride tablets agent preparation process,
In parts by weight, the raw material for preparing of the Sarpogrelate hydrochloride tablets agent includes 100 parts of sarpogrelate hydrochlorides, 30 parts of knots
Crystalline cellulose, 20 parts of carboxymethyl celluloses, 3 parts of light anhydrous silicic acids, 2 parts of citron acid hydrates, 5 parts of hydroxypropyl celluloses, 5 parts
Magnesium stearate, 8 parts of hypromellose, 1 part of titanium oxide, 2 parts of Macrogol 6000s and 1 part of talcum powder；
The preparation process includes the following steps：
(1) bonding agent is prepared：First to be dispersed in water carboxy-propyl cellulose in 60 DEG C of water baths, then it is cooled to 38 DEG C
Afterwards, after carboxy-propyl cellulose completely dissolves in water, citron acid hydrate mixed dissolution is added, obtains combining agent solution, it is standby
With；
(2) preliminary granulation：It is tentatively pelletized with efficient mixer-granulator, the side wall of the efficient mixer-granulator and viscous
Knot agent solution entrance is provided with cutter；By sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and light anhydrous silicon
Acid is stirred 6min, in mixed process the cutter of side wall in pelletization constantly by the hydrochloric acid in preliminary pelletization
Sarpogrelate, avicel cellulose, carboxymethyl cellulose and light anhydrous silicic acid mixture carry out cutting and grinding, until being uniformly mixed
Afterwards, the combination agent solution of step (1) is added, in adition process, with the cutter of binder solution entrance by the bonding agent
Solution carries out cutting dispersion, and guarantee is uniformly mixed in conjunction with agent solution with the mixture of the above raw material；It is added completely into and combines agent solution
Afterwards, continue to stir 2min, complete preliminary granulation；
(3) dry：Particle after preliminary granulation is crushed and hole specification of being sieved is the herringbone sieve of 1cm, it will the lower particle of sieve
Fluidized bed drying is carried out, dry inlet air temperature is 80 DEG C, and particle temperature stops heating after reaching 33 DEG C, waits for that temperature of outgoing air is down to
At 38 DEG C, particle is taken out, completes drying；
(4) secondary granulation：The circular hole sieve for carrying out particle of the completion after dry to crush and cross specification again as 1.5mm,
The lower particle of sieve is mixed with magnesium stearate, completes secondary granulation；
(5) tabletting：Particle progress after secondary granulation is tabletted, obtain sarpogrelate hydrochloride plain piece；
(6) coating solution is prepared：First to be dispersed in water the third methylcellulose of carboxylic in 60 DEG C of water baths, then it is cooled to 35
After DEG C, Macrogol 6000 mixed dissolution is added, adds titanium oxide and talcum powder, it is made to be uniformly dispersed, coating solution is made；
(7) the sarpogrelate hydrochloride plain piece is coated with the coating solution using high-efficiency coating machine, that is, completes system
Standby, in the Sarpogrelate hydrochloride tablets agent of gained, sarpogrelate hydrochloride content is 100mg/ pieces.
Experimental example
By the hydrochloric acid sand lattice of the trade name Anplag of existing commercially available Japanese Tanabe Mitsubishi Pharmaceutical Co's production
Thunder ester piece be the Sarpogrelate hydrochloride tablets that comparative example and 1-3 of the embodiment of the present invention are obtained under equal conditions carry out its stability,
Dissolution rate and compressibility experiment.
1, Dissolution Rate Testing：It is measured under same test conditions with Japanese Pharmacopoeia dissolution test method, it is specific to test
Condition is experiment liquid measure 900mL, plate slurry rotation number is 50/min, and temperature is 37.5 DEG C.It tests liquid and uses pH6.8 (Japan respectively
The second liquid of pharmacopeia disintegration experiment liquid).The results are shown in Table 1 for the dissolution rate (%) of different time points.
Table 1
| 5min | 10min | 15min | 20min | 30min | |
| Embodiment 1 | 37 | 93 | 100 | 101 | 101 |
| Embodiment 2 | 35 | 90 | 100 | 101 | 102 |
| Embodiment 3 | 27 | 91 | 101 | 102 | 102 |
| Comparative example | 20 | 71 | 101 | 102 | 104 |
Table 1 shows that the dissolution rate in Sarpogrelate hydrochloride tablets agent of the invention in 10min has had reached 93%, is more than
The dissolution rate of comparative example 71%, shows more excellent dissolution rate.
2, stability experiment：Tablet to be tested is put into the plastic containers equipped with drier, in 40 ± 1 DEG C of temperature, wet
It is preserved under conditions of 75 ± 5%RH of degree.Since preservation, preparation was taken out at 1 month, 3 months, 6 months, carried out purity examination
It tests, records the amount for the sarpogrelate hydrochloride similar substance being detected, be averaged, as a result such as table 2.
Table 2
| 1 month | 3 months | 6 months | |
| Embodiment 1 | 0.05 | 0.13 | 0.16 |
| Embodiment 2 | 0.06 | 0.13 | 0.15 |
| Embodiment 3 | 0.05 | 0.10 | 0.13 |
| Comparative example | 0.08 | 0.16 | 0.18 |
Table 2 shows that existing comparative example preparation is compared in the Sarpogrelate hydrochloride tablets agent of the present invention, shows better production
Product stability.
3, compressibility indicates that the results are shown in Table 3 with hardness tester measurement.
Table 3
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Comparative example | |
| Hardness/N | 70 | 68 | 68 | 60 |
Table 3 shows that the hardness of the Sarpogrelate hydrochloride tablets agent of the present invention is excellent, and compressibility is better than the existing hydrochloric acid of comparative example
Sarpogrelate tablet, meets product requirement.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any
Those familiar with the art in the technical scope disclosed by the present invention, can easily think of the change or the replacement, and should all contain
Lid is within protection scope of the present invention.Therefore, protection scope of the present invention should be based on the protection scope of the described claims.
Claims (10)
1. a kind of Sarpogrelate hydrochloride tablets agent preparation process, which is characterized in that
In parts by weight, the raw material for preparing of the Sarpogrelate hydrochloride tablets agent includes 100 parts of sarpogrelate hydrochlorides, 20-50 parts of knots
Crystalline cellulose, 10-50 part carboxymethyl cellulose, 1-5 parts of light anhydrous silicic acids, 0.5-3 parts of citron acid hydrates, 2-7 parts of hydroxypropyls
Base cellulose, 2-10 part magnesium stearate, 2-10 parts of hypromellose, 0.5-3 parts of titanium oxide, 0.5-3 parts of polyethylene glycol
6000 and 0.5-3 parts of talcum powder；
The preparation process includes the following steps：
(1) bonding agent is prepared：After carboxy-propyl cellulose is dissolved in the water, citron acid hydrate mixed dissolution is added, is tied
Mixture solution, it is spare；
(2) preliminary granulation：Sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and light anhydrous silicic acid are mixed
After uniformly, the combination agent solution of step (1) is added, continues to stir, completes preliminary granulation；
(3) dry：The particle for completing to obtain after preliminary granulation is dried, drying stops after reaching 32-35 DEG C to particle temperature
It only heats, completes drying；
(4) secondary granulation：After particle of the completion after dry is mixed with magnesium stearate, secondary granulation is completed；
(5) tabletting：Particle progress after secondary granulation is tabletted, obtain sarpogrelate hydrochloride plain piece；
(6) coating solution is prepared：Macrogol 6000 mixed dissolution is added after being dissolved in the water in the third methylcellulose of carboxylic, adds oxygen
Change titanium and talcum powder, it is made to be uniformly dispersed, coating solution is made；
(7) the sarpogrelate hydrochloride plain piece is coated using the coating solution, that is, completes to prepare.
2. preparation process according to claim 1, which is characterized in that hydrochloric acid sand lattice in Sarpogrelate hydrochloride tablets agent obtained
Thunder ester content is 100mg/ pieces.
3. preparation process according to claim 1, which is characterized in that in step (1), first with 50-70 DEG C of water bath
It is middle to be dispersed in water carboxy-propyl cellulose, then after being cooled to 30-40 DEG C, after carboxy-propyl cellulose completely dissolves in water,
Citron acid hydrate is added.
4. preparation process according to claim 1, which is characterized in that in step (2), by sarpogrelate hydrochloride, crystallization
After cellulose, carboxymethyl cellulose and light anhydrous silicic acid carry out mixing 5-6min, the bonding agent that step (1) is added is molten
Liquid continues to stir 1-2min.
5. preparation process according to claim 1, which is characterized in that in step (2), in pelletization, constantly
By sarpogrelate hydrochloride, avicel cellulose, carboxymethyl cellulose and the light anhydrous silicic acid mixture in preliminary pelletization into
The combination agent solution is carried out cutting dispersion by row cutting and grinding in conjunction with agent solution addition.
6. preparation process according to claim 1, which is characterized in that in step (3), obtained after preliminary granulation will be completed
Particle carry out fluidized bed drying, dry inlet air temperature be 75-85 DEG C, particle temperature reach 32-35 DEG C after stop heating, wait for
When temperature of outgoing air is down to 35-40 DEG C, particle is taken out.
7. preparation process according to claim 1, which is characterized in that in step (3), further include, it before it is dried, will be first
Particle after step granulation crushes and crosses 1cm sieves, and operation is dried in the lower particle of sieve.
8. preparation process according to claim 1, which is characterized in that the sieve is herringbone sieve.
9. preparation process according to claim 1, which is characterized in that in step (4), will complete it is dry after particle into
Row crushes and crosses 1.5mm sieves again, and the lower particle of sieve is mixed with magnesium stearate, carries out secondary granulation.
10. preparation process according to claim 1, which is characterized in that in step (6), first with 50-70 DEG C of water bath
It is middle to be dispersed in water the third methylcellulose of carboxylic, then after being cooled to 30-40 DEG C, Macrogol 6000 mixed dissolution is added.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903182A (en) * | 2005-07-29 | 2007-01-31 | 三菱制药株式会社 | Miniaturization sarpogrelate hydrochloride oral drug-giving preparation |
| JP2009209137A (en) * | 2008-02-07 | 2009-09-17 | Nipro Corp | Tablet improved in palatability |
| JP2009269858A (en) * | 2008-05-08 | 2009-11-19 | Takada Seiyaku Kk | Orally administrable preparation of sarpogrelate |
| JP4934314B2 (en) * | 2005-11-25 | 2012-05-16 | 大原薬品工業株式会社 | Method for producing stable sarpogrelate hydrochloride-containing tablets |
| KR20120060983A (en) * | 2010-10-04 | 2012-06-12 | 근화제약주식회사 | Sustained release dosage form and manufacturing procedure of Sarpogrelate HCl |
| CN103040749A (en) * | 2012-12-18 | 2013-04-17 | 海南百思特医药科技有限公司 | Sarpogrelate hydrochloride lipidosome solid preparation |
| KR20130135493A (en) * | 2012-06-01 | 2013-12-11 | 씨제이제일제당 (주) | Oral sustained-release matrix formulation comprising stabilized sarpogrelate hydrochloride and process for the preparation thereof |
| CN105769800A (en) * | 2014-12-22 | 2016-07-20 | 山东金诃药物研究开发有限公司 | Sarpogrelate hydrochloride tablet and preparation method thereof |
| CN106580909A (en) * | 2016-12-21 | 2017-04-26 | 天津红日药业股份有限公司 | Solid drug composition containing sarpogrelate hydrochloride |
-
2018
- 2018-06-15 CN CN201810616354.7A patent/CN108524462A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903182A (en) * | 2005-07-29 | 2007-01-31 | 三菱制药株式会社 | Miniaturization sarpogrelate hydrochloride oral drug-giving preparation |
| JP4934314B2 (en) * | 2005-11-25 | 2012-05-16 | 大原薬品工業株式会社 | Method for producing stable sarpogrelate hydrochloride-containing tablets |
| JP2009209137A (en) * | 2008-02-07 | 2009-09-17 | Nipro Corp | Tablet improved in palatability |
| JP2009269858A (en) * | 2008-05-08 | 2009-11-19 | Takada Seiyaku Kk | Orally administrable preparation of sarpogrelate |
| KR20120060983A (en) * | 2010-10-04 | 2012-06-12 | 근화제약주식회사 | Sustained release dosage form and manufacturing procedure of Sarpogrelate HCl |
| KR20130135493A (en) * | 2012-06-01 | 2013-12-11 | 씨제이제일제당 (주) | Oral sustained-release matrix formulation comprising stabilized sarpogrelate hydrochloride and process for the preparation thereof |
| CN103040749A (en) * | 2012-12-18 | 2013-04-17 | 海南百思特医药科技有限公司 | Sarpogrelate hydrochloride lipidosome solid preparation |
| CN105769800A (en) * | 2014-12-22 | 2016-07-20 | 山东金诃药物研究开发有限公司 | Sarpogrelate hydrochloride tablet and preparation method thereof |
| CN106580909A (en) * | 2016-12-21 | 2017-04-26 | 天津红日药业股份有限公司 | Solid drug composition containing sarpogrelate hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| 方亮: "《药剂学》", 31 March 2016, 中国医药科技出版社 * |
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