CN102516338A - Capecitabine compound, its pharmaceutical composition and preparation method thereof - Google Patents
Capecitabine compound, its pharmaceutical composition and preparation method thereof Download PDFInfo
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Abstract
Belonging to the technical field of medicines, the invention specifically relates to capecitabine, which is a crystal. Cu-K alpha ray measurement of the capecitabine crystal can obtain X-ray powder diffraction, which shows a characteristic peak at positions where 2theta is 8.3 degrees, 13.2 degrees, 16.5 degrees, 22.2 degrees, 23.3 degrees, 26.1 degrees, 27.2 degrees, 31.1 degrees, 31.9 degrees, 35.6 degrees, and 36.7 degrees. The invention also relates to a capecitabine pharmaceutical composition, which is a capecitabine oral tablet composed of 100-600 parts of capecitabine, 30-150 parts of compressible starch, 20-160 parts of microcrystalline cellulose, 25-90 parts of sodium carboxymethylcellulose, 50-200 parts of low-substituted hydroxypropyl cellulose, 15-105 parts of cross-linked polyvinylpyrrolidone, and 3-8 parts of magnesium stearate.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of capecitabine compound, its pharmaceutical composition and preparation method thereof.
Background technology
Capecitabine (capecitabine, CAP), chemistry 5-deoxidation by name-5-fluoro-N-[(amyl group) carbonyl]-cytidine(C, (molecular formula is: C for thymidylate synthase, TS) Depressant to belong to thymidylate synthase
15H
22FN
3O
6, molecular weight: 359.35, fusing point: 110-121 ℃, water-soluble, solubleness 26mg/ml (20 ℃).Capecitabine is that (fluorouracil FU) does the chemical structure transformation and forms prodrug (prodrug), and it can be absorbed rapidly by intestinal mucosa with complete molecular form because of containing the mephenesin Carbamate structure with Fluracil with chemical process.Capecitabine is a kind of oral fluoropyrimidine nucleoside analogue with good target effect, can be in tumor tissues selectivity be activated and produce the active cells poisonous substance matter of high density, thereby improve the tolerance of tumour patient, and make the antitumour activity maximization.But the capecitabine poor stability is prone to degraded, and lucifuge protection against the tide close drying storage that its preparation needs (to be generally 2-8 ℃) at low temperatures requires harsh to storage condition, and then its its related substances is higher in long-time storage.
CN102260309A discloses a kind of preparation method of high purity capecitabine; Comprise the capecitabine bullion is dissolved in and be selected from least a organic solvent in ethers or the haloalkane hydro carbons; In the solution that obtains, add the alkanes organic solvent; Thereby separate out white solid is capecitabine, and fusing point is 112.5-113.5 ℃.The process for purification of this capecitabine obviously improves capecitabine purity, and yield significantly improves, and compares with process for refining in the past, has that the impurity of removing is effective, yield is high, simple and safe operation, is easy to advantages such as large-scale industrial production.
CN101433546A discloses oral controlled release agent of a kind of capecitabine and preparation method thereof, and this oral controlled release agent contains following composition by weight percentage: (1) capecitabine, or its pharmacy acceptable salt, or the amount of its ester derivative is 50-90%; (2) acceptable accessories of 10-50% is comprising the auxiliary material of pharmaceutically acceptable slow-releasing and controlled-releasing action of 4-44%.This patent adopts the pharmaceutical excipient that has gone on the market, and active constituents of medicine content high (weight percent＞50%) can delay controlled release 12 to 24 hours.
CN101522168A discloses a kind of capecitabine pediatric tablets; Be the film coating pharmaceutical composition, said compsn comprises capecitabine and at least a disintegrating agent, and said disintegrating agent is selected from and comprises following group: Sodium Croscarmellose; Primojel; Low-substituted hydroxypropyl cellulose, Pharmaburst C or these arbitrary combination form rapid disintegration tablet together with other pharmaceutical excipient.Said compsn is being less than disintegration in 2 minutes in 37 ℃ of water in USP disintegration device, and said compsn has the hardness of 8-13scu.
In order to find better capecitabine of a kind of stability and pharmaceutical composition thereof, special proposition the present invention.
Summary of the invention
First purpose of the present invention provides the better capecitabine compound of a kind of stability.
Second purpose of the present invention provides a kind of pharmaceutical composition that contains above-mentioned capecitabine, and this pharmaceutical composition disintegration is faster, and extended storage stability is better.
The 3rd purpose of the present invention provides the preparation of drug combination method of above-mentioned capecitabine.
In order to realize the foregoing invention purpose, the present invention takes following technical scheme:
A kind of capecitabine; Said capecitabine is a crystal, and the X-ray powder diffraction that said capecitabine crystal uses the Cu-K alpha-ray to measure is 8.3 °, 13.2 °, 16.5 °, 22.2 °, 23.3 °, 26.1 °, 27.2 °, 31.1 °, 31.9 °, 35.6 °, 36.7 ° at 2 θ and locates to show characteristic peak.
According to foregoing capecitabine, the fusing point of said capecitabine is 131-133 ℃.
Capecitabine provided by the present invention; The X-ray powder diffraction shows that its crystalline structure is different from the capecitabine of prior art; The stability of the capecitabine of new crystal provided by the invention is more good, stores for a long time that the capecitabine content is little, its related substances is few.
The preparation method of above-mentioned capecitabine provided by the invention comprises: get the capecitabine bulk drug, be dissolved in methyl alcohol and acetonitrile by 1～2: in the mixed solvent that 1 volume ratio is made into, regulate pH to 8-9 with triethylamine, be heated to 60～65 ℃ and process saturated solution; Continue to be heated to 65-70 ℃, add the medical active carbon decoloring, stir; Filter, agitation condition drips normal heptane down and is cooled to 0-5 ℃ with the speed of 1-1.5 ℃/min, filters; Get the white micro-crystals powder, use methanol wash, drying under reduced pressure.
With a kind of compound, different crystal formations causes inner solid-state structure different, causes its lattice energy different, and the high more then constraint to compound molecule of lattice energy is big more, and crystalline structure is stable more, and promptly this compound is stable more.The present invention is a raw material with commercially available capecitabine bullion; Through experiment repeatedly, finally under change comprises solvent types and crystallization conditions such as proportioning, pH and the alkaline matter of adjusting pH, anti-solvent types, temperature, crystallization rate, prepare a kind of capecitabine with new crystal formation; The fusing point of the capecitabine of this crystal formation is 131-133 ℃; Compared with prior art, capecitabine lattice energy of the present invention is higher relatively, and crystalline structure is more stable.
Among the preparation method of above-mentioned capecitabine, the mixed solvent that methyl alcohol and acetonitrile preferably are made into by 2: 1 volume ratio.
Among the preparation method of above-mentioned capecitabine, process saturated solution after, preferably continue to be heated to 70 ℃.
Among the preparation method of above-mentioned capecitabine, agitation condition drips normal heptane down and lowers the temperature with the speed of 1.5 ℃/min.
Among the preparation method of above-mentioned capecitabine, the consumption of normal heptane be mixed solvent volume 3-5 doubly.
Among the preparation method of above-mentioned capecitabine; Adding decolorizing with activated carbon is this area common technology means; Can handle referring to any decolouring; Those skilled in the art need not to pay any creative work, can carry out appropriate selection according to the prior art of himself grasping, and realize the object of the invention.
In order further to improve the formulation products quality, the present invention also can be preferably be filtered into the use ultrafiltration membrance filter after decolouring.
The capecitabine crystalline particle diameter that the preparation method of above-mentioned capecitabine obtains is 150-250 μ m.
The present invention also provides a kind of pharmaceutical composition that contains foregoing capecitabine.
According to foregoing pharmaceutical composition, said pharmaceutical composition is the capecitabine oral tablet.
According to foregoing pharmaceutical composition; By weight, said capecitabine oral tablet comprises 100～600 parts of capecitabines, 30～150 parts of amylum pregelatinisatums, 20～160 parts of Microcrystalline Celluloses, 25～90 parts of Xylo-Mucines, 50～200 parts of low-substituted hydroxypropyl celluloses, 15～105 parts of cross-linked polyvinylpyrrolidones, 3～8 parts of Magnesium Stearates.
According to foregoing pharmaceutical composition; By weight, said capecitabine oral tablet comprises 100 parts of capecitabines, 30 parts of amylum pregelatinisatums, 40 parts of Microcrystalline Celluloses, 25 parts of Xylo-Mucines, 50 parts of low-substituted hydroxypropyl celluloses, 25 parts of cross-linked polyvinylpyrrolidones, 3 parts of Magnesium Stearates.
According to foregoing pharmaceutical composition; By weight, said capecitabine oral tablet comprises 125 parts of capecitabines, 45 parts of amylum pregelatinisatums, 38 parts of Microcrystalline Celluloses, 29 parts of Xylo-Mucines, 60 parts of low-substituted hydroxypropyl celluloses, 30 parts of cross-linked polyvinylpyrrolidones, 3 parts of Magnesium Stearates.
According to foregoing pharmaceutical composition; By weight, said capecitabine oral tablet comprises 150 parts of capecitabines, 50 parts of amylum pregelatinisatums, 40 parts of Microcrystalline Celluloses, 35 parts of Xylo-Mucines, 65 parts of low-substituted hydroxypropyl celluloses, 35 parts of cross-linked polyvinylpyrrolidones, 4 parts of Magnesium Stearates.
According to foregoing pharmaceutical composition; By weight, said capecitabine oral tablet comprises 175 parts of capecitabines, 60 parts of amylum pregelatinisatums, 45 parts of Microcrystalline Celluloses, 40 parts of Xylo-Mucines, 75 parts of low-substituted hydroxypropyl celluloses, 40 parts of cross-linked polyvinylpyrrolidones, 4 parts of Magnesium Stearates.
The contriver has done a series of stability experiments that contain the pharmaceutical composition of foregoing capecitabine; Its result shows; The good stability of the capecitabine in the pharmaceutical composition, this pharmaceutical composition has extraordinary stability in storage, and it is low to place its related substances for a long time; Be convenient to very much transportation, store, improved patient's drug safety greatly.
The present invention also provides the preparation method of above-mentioned capecitabine oral tablet, and said preparation method may further comprise the steps:
(1) capecitabine and amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, Magnesium Stearate are sieved respectively, subsequent use;
(2) Microcrystalline Cellulose, amylum pregelatinisatum, Sodium Croscarmellose and Magnesium Stearate were dried by the fire 1～2 hour under 60～80 ℃ of conditions respectively, cross 60～80 mesh sieves, subsequent use;
(3) take by weighing above-mentioned subsequent use pharmaceutical excipient by recipe quantity; With capecitabine, amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone; Adopt the equivalent method of progressively increasing to carry out mixing, add the Magnesium Stearate of recipe quantity again, mixing; And the control mixing time obtains mixed powder again in the 5min;
(4) after sampling detects, open tabletting machine, mixed powder is carried out direct pressed powder, dressing, promptly get.Capecitabine provided by the invention and pharmaceutical composition thereof have following advantage:
(1) capecitabine good stability of the present invention is placed with related substance for a long time and changes little;
(2) capecitabine pharmaceutical composition of the present invention has extraordinary stability in storage, and is stronger to the tolerance of storage environment, and it is low to place its related substances for a long time, is convenient to very much transportation, stores, and improved patient's drug safety greatly.
Description of drawings
Fig. 1 is the capecitabine crystalline X-RD spectrogram of embodiment 1 preparation.
Embodiment
Practical implementation method of the present invention only limits to further explain and explanation the present invention, content of the present invention is not constituted restriction.
Embodiment 1
Capecitabine crystalline preparation: the mixed solvent that methyl alcohol and acetonitrile are made into by 2: 1 volume ratio, and be heated to 65 ℃, and get capecitabine bulk drug 100g and place Agitation Tank, add also stirring of mixed solvent; Until processing saturated solution, regulate pH to 8 with triethylamine, continue to be heated to 70 ℃, add medicinal carbon 10g decolouring; Stir, filter, agitation condition drips normal heptane down and is cooled to 0 ℃ with the speed of 1.5 ℃/min, and the consumption of normal heptane is 5 times of volume of mixed solvent; Filter, the white micro-crystals powder, with methanol wash 3 times; Drying under reduced pressure 3h obtains described capecitabine crystal, and particle diameter is 150-250 μ m.Yield 81.9%, HPLC content 99.66%, mp131～133 ℃.
The X-ray powder diffraction that the capecitabine crystal that obtains uses the Cu-K alpha-ray to measure is 8.3 °, 13.2 °, 16.5 °, 22.2 °, 23.3 °, 26.1 °, 27.2 °, 31.1 °, 31.9 °, 35.6 °, 36.7 ° at 2 θ and locates to show characteristic peak.
Embodiment 2
Capecitabine crystalline preparation: the mixed solvent that methyl alcohol and acetonitrile are made into by 1: 1 volume ratio, and be heated to 60 ℃, and get capecitabine bulk drug 100g and place Agitation Tank, add also stirring of mixed solvent; Until processing saturated solution, regulate pH to 9 with triethylamine, continue to be heated to 65 ℃, add medicinal carbon 10g decolouring; Stir, filter, agitation condition drips normal heptane down and is cooled to 5 ℃ with the speed of 1 ℃/min, and the consumption of normal heptane is 3 times of volume of mixed solvent; Filter, the white micro-crystals powder, with methanol wash 3 times; Drying under reduced pressure 4h obtains described capecitabine crystal, and particle diameter is 150-250 μ m.Yield 79.5%, HPLC content 99.58%, mp131～133 ℃.
The X-ray powder diffraction collection of illustrative plates of capecitabine crystal that obtains and embodiment 1 product has identical parameters.
Embodiment 3
Capecitabine crystalline preparation: the mixed solvent that methyl alcohol and acetonitrile are made into by 1.5: 1 volume ratio, and be heated to 65 ℃, and get capecitabine bulk drug 100g and place Agitation Tank, add also stirring of mixed solvent; Until processing saturated solution, regulate pH to 8 with triethylamine, continue to be heated to 70 ℃, add medicinal carbon 10g decolouring; Stir, filter, agitation condition drips normal heptane down and is cooled to 0 ℃ with the speed of 1.5 ℃/min, and the consumption of normal heptane is 4 times of volume of mixed solvent; Filter, the white micro-crystals powder, with methanol wash 3 times; Drying under reduced pressure 4h obtains described capecitabine crystal, and particle diameter is 150-250 μ m.Yield 80.7%, HPLC content 99.69%, mp131～133 ℃.
The X-ray powder diffraction collection of illustrative plates of capecitabine crystal that obtains and embodiment 1 product has identical parameters.
Embodiment 4
Prescription:
Table 1
| First group | Second group | The 3rd group | The 4th group | The 5th group | The 6th group | |
| Capecitabine | 100g | 125g | 150g | 175g | 100g | 600g |
| Amylum pregelatinisatum | ?30g | 45g | 50g | 60g | 30g | 150g |
| Microcrystalline Cellulose | ?40g | 38g | 40g | 45g | 20g | 160g |
| Xylo-Mucine | ?25g | 29g | 35g | 40g | 25g | 90g |
| Low-substituted hydroxypropyl cellulose | ?50g | 60g | 65g | 75g | 60g | 200g |
| Cross-linked polyvinylpyrrolidone | ?25g | 30g | 35g | 40g | 15g | 105g |
| Magnesium Stearate | ?3g | 3g | 4g | 4g | 3g | 8g |
Preparing method: capecitabine and amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, Magnesium Stearate are sieved respectively; Microcrystalline Cellulose, amylum pregelatinisatum, Sodium Croscarmellose and Magnesium Stearate were dried by the fire 1～2 hour under 60～80 ℃ of conditions respectively, cross 60～80 mesh sieves; The bulk drug that takes by weighing by the prescription of table 1; Adopt the equivalent method of progressively increasing to carry out mixing amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone; Add Magnesium Stearate again; Mixing, and the control mixing time obtains mixed powder again in the 5min; After sampling detects, open tabletting machine, mixed powder is carried out 1000 of direct pressed powders, dressing, promptly get.
Experimental example 1
This Test Example detects related substance in the prepared capecitabine tablet of embodiment 4, and this test is carried out according to 2010 editions second appendix VIIIP residual solvent of Chinese Pharmacopoeia assay method, appendix XIXF medicine impurity analysis governing principle, and its result sees table 2:
The assay of table 2 related substance
| Preparation | Methyl alcohol | Acetonitrile | Normal heptane | Other related substance |
| First group | Up to specification | Up to specification | Up to specification | Up to specification |
| Second group | Up to specification | Up to specification | Up to specification | Up to specification |
| The 3rd group | Up to specification | Up to specification | Up to specification | Up to specification |
| The 4th group | Up to specification | Up to specification | Up to specification | Up to specification |
| The 5th group | Up to specification | Up to specification | Up to specification | Up to specification |
| The 6th group | Up to specification | Up to specification | Up to specification | Up to specification |
Experimental example 2
This Test Example has been investigated capecitabine crystalline stability provided by the invention
This test is carried out according to 2005 editions second appendix XIX C of Chinese Pharmacopoeia medicine stability test governing principle, and the result is following:
Table 3, accelerated test result
| |
0 month | 1 month | 2 months | 3 months | 6 months |
| 1 | 99.9％ | 99.9％ | 99.8％ | 99.6％ | 99.4％ |
| 2 | 100.0％ | 100.0％ | 99.9％ | 99.7％ | 99.5％ |
| 3 | 99.9％ | 99.9％ | 99.8％ | 99.6％ | 99.4％ |
| 4 | 100.3％ | 100.1％ | 99.8％ | 99.4％ | 98.3％ |
| 5 | 100.1％ | 100.0％ | 99.6％ | 99.1％ | 98.2％ |
Table 4, long-term test results
| |
0 month | 3 months | 6 months | 9 months | 12 months | 18 months |
| 1 | 99.9％ | 99.9％ | 99.9％ | 99.8％ | 99.7％ | 99.5％ |
| 2 | 100.0％ | 100.0％ | 99.9％ | 99.8％ | 99.7％ | 99.6％ |
| 3 | 99.9％ | 99.9％ | 99.8％ | 99.7％ | 99.6％ | 99.5％ |
| 4 | 100.3％ | 100.2％ | 99.9％ | 99.6％ | 99.1％ | 98.6％ |
| 5 | 100.1％ | 100.0％ | 99.7％ | 99.5％ | 99.1％ | 98.7％ |
Wherein sample 1 is the product of embodiment 1, and sample 2 is the product of embodiment 2, and sample 3 is the product of embodiment 3;
Sample 4 is for getting commercially available capecitabine bulk drug, the capecitabine that obtains with reference to the method for patent CN102260309A embodiment 1;
Sample 5 is for getting commercially available capecitabine bulk drug, the capecitabine that obtains with re-crystallizing in ethyl acetate.
This experimental example explanation, capecitabine crystal stability provided by the invention is good, quicken, test of long duration capecitabine purity content is little, and the common capecitabine crystal stability of prior art is poor, and accelerated test and test of long duration capecitabine content are big.
Experimental example 3
This Test Example has been investigated the stability of capecitabine pharmaceutical composition provided by the invention
This test is carried out according to 2005 editions second appendix XIX C of Chinese Pharmacopoeia medicine stability test governing principle, and the result is following:
Table 5, accelerated test result
Table 6, long-term test results
Wherein sample 6 is first group a product among the embodiment 4, and sample 7 is second group a product among the embodiment 4, and sample 8 is the 3rd group a product among the embodiment 4, and sample 9 is the 4th group a product among the embodiment 4;
Sample 11 is commercially available capecitabine sheet, originates from Shanghai ltd of Roche Group, and every contains capecitabine 150mg;
This experimental example high spot reviews content and the changing conditions of its related substances of capecitabine tablet capecitabine in accelerated tests and long-term experiment; Investigate presentation of results; With respect to the capecitabine tablet of prior art, the capecitabine content is little in the capecitabine tablet provided by the invention, and stability is better; The content of related substance is few, the variation of related substance is little, has improved patient's drug safety greatly.
Other embodiment products of the present invention have also carried out identical experiment, and obtain the experimental result of same trend, but length limits, and the present invention enumerates no longer one by one.
Claims (10)
1. capecitabine; It is characterized in that; Said capecitabine is a crystal, and the X-ray powder diffraction that said capecitabine crystal uses the Cu-K alpha-ray to measure is 8.3 °, 13.2 °, 16.5 °, 22.2 °, 23.3 °, 26.1 °, 27.2 °, 31.1 °, 31.9 °, 35.6 °, 36.7 ° at 2 θ and locates to show characteristic peak.
2. the preparation method of a capecitabine as claimed in claim 1 is characterized in that, said preparation method comprises: get the capecitabine bulk drug; Be dissolved in methyl alcohol and acetonitrile by 1～2: in the mixed solvent that 1 volume ratio is made into, regulate pH to 8-9, be heated to 60～65 ℃ and process saturated solution with triethylamine; Continue to be heated to 65-70 ℃, add the medical active carbon decoloring, stir; Filter, agitation condition drips normal heptane down and is cooled to 0-5 ℃ with the speed of 1-1.5 ℃/min, filters; Get the white micro-crystals powder, use methanol wash, drying under reduced pressure.
3. pharmaceutical composition that contains the described capecitabine of claim 1.
4. pharmaceutical composition according to claim 3 is characterized in that, said pharmaceutical composition is the capecitabine oral tablet.
5. pharmaceutical composition according to claim 4; It is characterized in that; By weight, said capecitabine oral tablet comprises 100～600 parts of capecitabines, 30～150 parts of amylum pregelatinisatums, 20～160 parts of Microcrystalline Celluloses, 25～90 parts of Xylo-Mucines, 50～200 parts of low-substituted hydroxypropyl celluloses, 15～105 parts of cross-linked polyvinylpyrrolidones, 3～8 parts of Magnesium Stearates.
6. pharmaceutical composition according to claim 5; It is characterized in that; By weight, said capecitabine oral tablet comprises 100 parts of capecitabines, 30 parts of amylum pregelatinisatums, 40 parts of Microcrystalline Celluloses, 25 parts of Xylo-Mucines, 50 parts of low-substituted hydroxypropyl celluloses, 25 parts of cross-linked polyvinylpyrrolidones, 3 parts of Magnesium Stearates.
7. pharmaceutical composition according to claim 5; It is characterized in that; By weight, said capecitabine oral tablet comprises 125 parts of capecitabines, 45 parts of amylum pregelatinisatums, 38 parts of Microcrystalline Celluloses, 29 parts of Xylo-Mucines, 60 parts of low-substituted hydroxypropyl celluloses, 30 parts of cross-linked polyvinylpyrrolidones, 3 parts of Magnesium Stearates.
8. pharmaceutical composition according to claim 5; It is characterized in that; By weight, said capecitabine oral tablet comprises 150 parts of capecitabines, 50 parts of amylum pregelatinisatums, 40 parts of Microcrystalline Celluloses, 35 parts of Xylo-Mucines, 65 parts of low-substituted hydroxypropyl celluloses, 35 parts of cross-linked polyvinylpyrrolidones, 4 parts of Magnesium Stearates.
9. pharmaceutical composition according to claim 5; It is characterized in that; By weight, said capecitabine oral tablet comprises 175 parts of capecitabines, 60 parts of amylum pregelatinisatums, 45 parts of Microcrystalline Celluloses, 40 parts of Xylo-Mucines, 75 parts of low-substituted hydroxypropyl celluloses, 40 parts of cross-linked polyvinylpyrrolidones, 4 parts of Magnesium Stearates.
10. the preparation method of each described capecitabine oral tablet of claim 4-9 is characterized in that, said preparation method may further comprise the steps:
(1) capecitabine and amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, Magnesium Stearate are sieved respectively, subsequent use;
(2) Microcrystalline Cellulose, amylum pregelatinisatum, Sodium Croscarmellose and Magnesium Stearate were dried by the fire 1～2 hour under 60～80 ℃ of conditions respectively, cross 60～80 mesh sieves, subsequent use;
(3) take by weighing above-mentioned subsequent use pharmaceutical excipient by recipe quantity; With capecitabine, amylum pregelatinisatum, Microcrystalline Cellulose, Xylo-Mucine, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone; Adopt the equivalent method of progressively increasing to carry out mixing, add the Magnesium Stearate of recipe quantity again, mixing; And the control mixing time obtains mixed powder again in the 5min;
(4) after sampling detects, open tabletting machine, mixed powder is carried out direct pressed powder, dressing, promptly get.
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| CN108464972A (en) * | 2018-07-02 | 2018-08-31 | 福州大学 | A kind of anti-pulmonary hypertension oral tablet and preparation method thereof containing Snopori |
| CN117229341A (en) * | 2023-11-07 | 2023-12-15 | 成都苑东生物制药股份有限公司 | Capecitabine crystal form I and preparation method thereof |
| CN117229341B (en) * | 2023-11-07 | 2024-02-09 | 成都苑东生物制药股份有限公司 | Capecitabine crystal form I and preparation method thereof |
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