CN103251569B - Capecitabine tablet composition and preparation method thereof - Google Patents
Capecitabine tablet composition and preparation method thereof Download PDFInfo
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- CN103251569B CN103251569B CN201310208550.8A CN201310208550A CN103251569B CN 103251569 B CN103251569 B CN 103251569B CN 201310208550 A CN201310208550 A CN 201310208550A CN 103251569 B CN103251569 B CN 103251569B
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- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 title claims abstract description 68
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 229960004117 capecitabine Drugs 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 38
- 239000007916 tablet composition Substances 0.000 title claims abstract description 15
- 239000008187 granular material Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000005516 engineering process Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 26
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 16
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 16
- 229960003943 hypromellose Drugs 0.000 claims description 16
- 239000008101 lactose Substances 0.000 claims description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 16
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 16
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 16
- 239000011248 coating agent Substances 0.000 claims description 15
- 238000000576 coating method Methods 0.000 claims description 15
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 14
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 14
- 238000004132 cross linking Methods 0.000 claims description 14
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 14
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 9
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 claims description 8
- 239000007888 film coating Substances 0.000 claims description 8
- 238000009501 film coating Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 229940085837 capecitabine 150 mg Drugs 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 238000005453 pelletization Methods 0.000 claims description 6
- 229940085839 capecitabine 500 mg Drugs 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229960001375 lactose Drugs 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000002002 slurry Substances 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 230000004584 weight gain Effects 0.000 claims description 3
- 235000019786 weight gain Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 238000007906 compression Methods 0.000 abstract description 4
- 230000006835 compression Effects 0.000 abstract description 4
- 239000003826 tablet Substances 0.000 description 27
- 239000000126 substance Substances 0.000 description 11
- 229940053867 xeloda Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 6
- 229920002785 Croscarmellose sodium Polymers 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000007919 dispersible tablet Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000009702 powder compression Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- UEJQGOKMPMUMTO-UHFFFAOYSA-N C(C#C)OC1=NC=C(C(=N1)OCC#C)F Chemical compound C(C#C)OC1=NC=C(C(=N1)OCC#C)F UEJQGOKMPMUMTO-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- -1 amoxy Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- BZRPOJFQTMPGJK-UHFFFAOYSA-N carbamic acid;2-fluoropyrimidine Chemical class NC(O)=O.FC1=NC=CC=N1 BZRPOJFQTMPGJK-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000007898 rapid-disintegration tablet Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
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Abstract
The invention provides a kind of new capecitabine tablet composition and a kind of quality controllable, guarantee the preparation method of the capecitabine sheet of product stability, adopt wet granule compression tablet technique, granule can be made to have good compressibility, and epigranular, good fluidity, wearability is comparatively strong, and the feasibility of preparation technology is better, does not need to carry out micronizing process to raw material, improve the yield of raw material, decrease production process, and in prescription, supplementary product consumption is less, effectively reduces production cost.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of capecitabine tablet composition and preparation method thereof.
Background technology
Capecitabine, chemistry is by name: the fluoro-N-of 5'-deoxidation-5-[(amoxy) carbonyl] cytidine, molecular formula is: C
15h
22o
6n
3f, molecular weight is 359.35, and chemical structural formula is:
Capecitabine is the novel 5-FU prodrug of one developed by Roche Holding Ag of Switzerland, is first the oral fluoropyrimidine carbamate series antineoplastic medicament gone on the market, is used for the treatment of the novel targeted medicine of breast carcinoma, colorectal carcinoma.It can be activated and produce the competent cell poisonous substance matter of high concentration by selectivity in tumor tissues, thus improves the tolerance of tumor patient, and active anticancer is maximized.
Chinese Patent Application No. is disclose a kind of capecitabine pediatric tablets in 200780036204.9, and Chinese Patent Application No. is disclose a kind of capecitabine rapid disintegration tablet in 200980149768.2.Disclosed in above-mentioned two patents, tablet is disintegrating tablet.Because oral cavity disintegration tablet is except requiring disintegrate rapidly, also need its mouthfeel good, thus a large amount of excellent disintegrating agents and correctives to be added when tabletting, thus cause that the tablet slice, thin piece that obtains is heavy, flap-type is large, take inconvenience, so the medicine of efficient low dosage can be developed into oral cavity disintegration tablet clinically, and for the larger medicine of this principal agent of capecitabine proportion, be then not suitable for making disintegrating tablet.
Chinese Patent Application No. be disclose in 201110267016.5 a kind of can the capecitabine Pharmaceutical composition of direct powder compression, be that the capecitabine of 100 ~ 200 μm and pharmaceutically acceptable excipient form by mean diameter.Direct powder compression eliminates the step of granulation, have that operation is few, technique be simple, the advantage of time-saving energy-saving, but it is lower to there is bulk density in capecitabine itself, there is electrostatic, the feature of the poor fluidity of powder, there is tablet weight variation shortcoming that is large, easily sliver in the tablet adopting direct powder compression to obtain.Simultaneously owing to will carry out micronizing to capecitabine raw material, to control its particle diameter within the scope of 100 ~ 200 μm, operation is comparatively complicated, adds production cost.
Chinese Patent Application No. is disclose a kind of capecitabine dispersible tablet and preparation method thereof in 201210538704.5.Although dispersible tablet have taking convenience, disintegrate rapidly, absorb fast feature, as everyone knows, the medicine usually making dispersible tablet should be insoluble drug, and the dissolubility of capecitabine is better, is not suitable for making dispersible tablet.
Because the bulk density of capecitabine raw material is less, and the specification of tablet is comparatively large, and as far as possible few adjuvant need be selected to prepare tablet, and improves the bulk density of granule as far as possible.Therefore, it is conventional, easy to operate that a kind of technique is badly in need of in this area, guarantees the new recipe technique of product quality simultaneously.
Summary of the invention
For the problems referred to above, the invention provides a kind of new capecitabine tablet composition, provide a kind of quality controllable simultaneously, and guarantee the preparation method of the capecitabine sheet of product stability.
Capecitabine tablet composition of the present invention, the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg ~ 500mg, lactose 10.24mg ~ 51.20mg, microcrystalline Cellulose 15.36mg ~ 60.50mg, cross-linked carboxymethyl cellulose receive 7.50mg ~ 25.60mg, hypromellose 2.20mg ~ 12.55mg, magnesium stearate 1.92mg ~ 8.20mg.
Wherein, the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg, lactose 15.36mg, microcrystalline Cellulose 15.36mg, cross-linked carboxymethyl cellulose receive 7.68mg, hypromellose 2.64mg, magnesium stearate 1.92mg.
Or the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg, lactose 10.24mg, microcrystalline Cellulose 20.48mg, cross-linked carboxymethyl cellulose receive 7.50mg, hypromellose 2.20mg, magnesium stearate 2.50mg.
Or the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 500mg, lactose 51.20mg, microcrystalline Cellulose 51.20mg, cross-linked carboxymethyl cellulose receive 25.60mg, hypromellose 8.80mg, magnesium stearate 6.40mg.
Or the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 500mg, lactose 40.50mg, microcrystalline Cellulose 60.50mg, cross-linked carboxymethyl cellulose receive 21.45mg, hypromellose 12.55mg, magnesium stearate 8.20mg.
Present invention also offers a kind of preparation method of capecitabine tablet composition described above, comprise the following steps:
(1) prepare burden: take the capecitabine of recipe quantity, lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, capecitabine raw material crossed 80 eye mesh screens, take the hypromellose of recipe quantity, be mixed with 2.5%(w/w) aqueous solution, for subsequent use;
(2) premix: the cross-linking sodium carboxymethyl cellulose of the capecitabine, lactose, microcrystalline Cellulose and 3/4 recipe quantity that take in step (1) is mixed;
(3) granulate: the material mixed is put in wet granulator, stir 3 ~ 5min, stirred in backward material and added 2.5%(w/w) hypromellose aqueous solution wet granular, add after slurry completes, open shears, stir and shear, use pelletizing machine wet method granulate;
(4) dry: wet granular is put into drying equipment, inlet temperature, not higher than 80 DEG C, controls moisture and is less than 2%;
(5) granulate: use pelletizing machine dry method granulate;
(6) always mix: in the granule that granulate is complete, add the cross-linking sodium carboxymethyl cellulose of 1/4 recipe quantity and the magnesium stearate of recipe quantity, mixing;
(7) tabletting: control weight differential and be sheet heavy ± 5%, control hardness at 65 ± 15N, friability≤0.5%;
(8) coating: add film coating pre-mix dose Opadry 85G64872 in the water stirred, stir about 45min, obtains 20%(w/w) coating solution, for subsequent use, get plain sheet and put in coating pan, carry out coating, control coating weight gain rate in 2% ~ 4% scope.
Due to the withstand voltage Wear-resistant, high-temperature resistant of capecitabine raw material, and without other polymorphic crystal formations, therefore the present invention adopts wet granule compression tablet technique.Capecitabine sheet prepared by the present invention has the following advantages:
(1) adopt wet granule compression tablet technique, granule can be made to have good compressibility, and epigranular, good fluidity, wearability is comparatively strong, and the feasibility of preparation technology is better;
(2) do not need in prescription of the present invention to carry out micronizing process to raw material, improve the yield of raw material, decrease production process, and in prescription, supplementary product consumption is less, thus reduce production cost.
(3) adopt the capecitabine tablet composition obtained by composition and engineering of the present invention, up-to-standard, efficacy stability, can accomplish scale production smoothly.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but not limitation of the present invention, and the equivalent replacement of all any this areas done according to the disclosure of invention, all belongs to protection scope of the present invention.
Prepare capecitabine sheet 1000, the weight of each embodiment Raw is as shown in the table: (unit: g)
Embodiment 1:
Preparation technology:
(1) prepare burden: take the capecitabine of recipe quantity, lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, capecitabine raw material crossed 80 eye mesh screens, take the hypromellose of recipe quantity, be mixed with 2.5%(w/w) aqueous solution, for subsequent use;
(2) premix: the cross-linking sodium carboxymethyl cellulose of the capecitabine, lactose, microcrystalline Cellulose and 3/4 recipe quantity that take in step (1) is mixed;
(3) granulate: the material mixed is put in wet granulator, stir 3 ~ 5min, stirred in backward material and added 2.5%(w/w) hypromellose aqueous solution wet granular, add after slurry completes, open shears, stir and shear, use pelletizing machine wet method granulate;
(4) dry: wet granular is put into drying equipment, inlet temperature, not higher than 80 DEG C, controls moisture and is less than 2%;
(5) granulate: use pelletizing machine dry method granulate;
(6) always mix: in the granule that granulate is complete, add the cross-linking sodium carboxymethyl cellulose of 1/4 recipe quantity and the magnesium stearate of recipe quantity, mixing;
(7) tabletting: control weight differential and be sheet heavy ± 5%, control hardness in 60 ~ 70N, disintegration≤7 minutes, friability≤0.5%;
(8) coating: add film coating pre-mix dose Opadry 85G64872 in the water stirred, stir about 45min, obtains 20%(w/w) coating solution, for subsequent use, get plain sheet and put in coating pan, carry out coating, control coating weight gain rate in 2% ~ 4% scope.
Embodiment 2:
Preparation technology: with the preparation technology of embodiment 1, controls the hardness of tablet in 50 ~ 70N, disintegration≤7 minutes.
Embodiment 3:
Preparation technology: with the preparation technology of embodiment 1, controls the hardness of tablet in 60 ~ 80N, disintegration≤13 minutes.
Embodiment 4:
Preparation technology: with the preparation technology of embodiment 1, controls the hardness of tablet in 70 ~ 80N, disintegration≤13 minutes.
Test example 1 influence factor tests
The capecitabine tablet getting the embodiment of the present invention 1 ~ 4 preparation respectively carries out factors influencing, and detects the related substance change of tablet.
Placement condition: high temperature 60 DEG C, high humidity (RH75% ± 5%) and illumination (4500lx ± 500lx)
Result of the test sees the following form:
Table 1 related substance results contrast
Can be found out by table 1, when capecitabine sheet prepared by the embodiment of the present invention 1 ~ 4 places 10 days under high temperature 60 DEG C of conditions, related substance compared with 0 day, slightly increased, but all met American Pharmacopeia 34 editions capecitabine tablet quality standards; And when placing 10 days under high humidity (RH75% ± 5%), illumination (4500lx ± 500lx) condition, related substance compared with 0 day, had almost no change.Illustrate that this product is stable under high temperature, high humidity and illumination condition.Test example 2 accelerated test
Reference preparation 1: capecitabine sheet, trade name: xeloda (Xeloda), specification: 150mg, manufacturer: U.S. Roche Pharma (Schweiz) Ltd.
Reference preparation 2: capecitabine sheet, trade name: xeloda (Xeloda), specification: 500mg, manufacturer: Shanghai company limited of Roche Group.
Get respectively the embodiment of the present invention 1 ~ 4 prepare capecitabine tablet and reference preparation 1, reference preparation 2 sample be positioned over temperature 40 DEG C ± 2 DEG C, RH75% ± 5% condition under investigate, respectively at sampling after January, February, March and June and carrying out the change of dissolution, related substance and content, result of the test is in table 2 and table 3.
Table 2 accelerated test results contrast (specification: 150mg)
Table 3 accelerated test results contrast (specification: 500mg)
Can be found out by table 2, table 3 result of the test, embodiment of the present invention sample is at 40 DEG C ± 2 DEG C, and place 6 months under 75% ± 5% condition, compared with 0 month, indices is all without significant change.And the sample of the embodiment of the present invention is all better than the reference preparation sample of same size in dissolution, related substance and content.
Test example 3 long term test
Reference preparation 1: capecitabine sheet, trade name: xeloda (Xeloda), specification: 150mg, manufacturer: U.S. Roche Pharma (Schweiz) Ltd.
Reference preparation 2: capecitabine sheet, trade name: xeloda (Xeloda), specification: 500mg, manufacturer: Shanghai company limited of Roche Group.
Get respectively under capecitabine tablet prepared by the embodiment of the present invention 1 ~ 4 and reference preparation 1, reference preparation 2 sample are positioned over temperature 25 DEG C ± 2 DEG C, RH60% ± 10% condition and investigate, respectively at March, June, JIUYUE, December, sample after 18 months and 24 months and carry out the change of dissolution, related substance and content.
Table 4 long-term test results compares (specification: 150mg)
Table 5 long-term test results compares (specification: 500mg)
Can be found out by table 4, table 5 result of the test, embodiment of the present invention sample is placed 24 months under long term test condition, compares with 0 month, and indices is all without significant change.And the sample of the embodiment of the present invention is all better than the reference preparation sample of same size in dissolution, related substance and content.
Known by above-mentioned result of the test, adopt the capecitabine tablet composition that prescription of the present invention and technique prepare, all better, up-to-standard in dissolution, related substance and content, stable in properties; Prescription Raw, without the need to carrying out micronizing process, improves the yield of raw material, decrease production process, and supplementary product consumption is less, thus reduce production cost; Adopt wet granule compression tablet technique, granule can be made to have good compressibility, and epigranular, good fluidity, technique is conventional, easy to operate, overcomes the shortcoming of the easy sliver of direct powder compression; When the average sheet of Chinese Pharmacopoeia 2010 editions regulation tablet weighs < 0.30g, limit test of weight variation ± 7.5%, during the average sheet weight >=0.30g of tablet, limit test of weight variation ± 5%, and in the test of regulation tablet friability, less loss weight must not cross 1%, Tablets controls weight differential and is sheet heavy ± 5%, friability≤0.5%, all be better than the limit of Chinese Pharmacopoeia 2010 editions regulation, overcome the shortcoming that tablet weight variation in prior art is large, be more suitable for industrialized great production.
Claims (5)
1. a capecitabine tablet composition, it is characterized in that, the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg ~ 500mg, lactose 10.24mg ~ 51.20mg, microcrystalline Cellulose 15.36mg ~ 60.50mg, cross-linking sodium carboxymethyl cellulose 7.50mg ~ 25.60mg, hypromellose 2.20mg ~ 12.55mg, magnesium stearate 1.92mg ~ 8.20mg and film coating pre-mix dose Opadry 85G64872; The preparation technology of capecitabine tablet composition comprises the following steps:
(1) prepare burden: take the capecitabine of recipe quantity, lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, capecitabine raw material is crossed 80 eye mesh screens, take the hypromellose of recipe quantity, be mixed with the aqueous solution of 2.5% (w/w), for subsequent use;
(2) premix: the cross-linking sodium carboxymethyl cellulose of the capecitabine, lactose, microcrystalline Cellulose and 3/4 recipe quantity that take in step (1) is mixed;
(3) granulate: the material mixed is put in wet granulator, stir 3 ~ 5min, stirred in backward material and added 2.5% (w/w) hypromellose aqueous solution wet granular, add after slurry completes, open shears, stir and shear, use pelletizing machine wet method granulate;
(4) dry: wet granular is put into drying equipment, inlet temperature, not higher than 80 DEG C, controls moisture and is less than 2%;
(5) granulate: use pelletizing machine dry method granulate;
(6) always mix: in the granule that granulate is complete, add the cross-linking sodium carboxymethyl cellulose of 1/4 recipe quantity and the magnesium stearate of recipe quantity, mixing;
(7) tabletting: control weight differential and be sheet heavy ± 5%, control hardness at 65 ± 15N, friability≤0.5%;
(8) coating: add film coating pre-mix dose Opadry 85G64872 in the water stirred, stirs 45min, obtains the coating solution of 20% (w/w), for subsequent use, getting plain sheet puts in coating pan, carries out coating, controls coating weight gain rate in 2% ~ 4% scope.
2. capecitabine tablet composition according to claim 1, is characterized in that the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg, lactose 15.36mg, microcrystalline Cellulose 15.36mg, cross-linking sodium carboxymethyl cellulose 7.68mg, hypromellose 2.64mg, magnesium stearate 1.92mg and film coating pre-mix dose Opadry 85G64872.
3. capecitabine tablet composition according to claim 1, is characterized in that the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 150mg, lactose 10.24mg, microcrystalline Cellulose 20.48mg, cross-linking sodium carboxymethyl cellulose 7.50mg, hypromellose 2.20mg, magnesium stearate 2.50mg and film coating pre-mix dose Opadry 85G64872.
4. capecitabine tablet composition according to claim 1, is characterized in that the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 500mg, lactose 51.20mg, microcrystalline Cellulose 51.20mg, cross-linking sodium carboxymethyl cellulose 25.60mg, hypromellose 8.80mg, magnesium stearate 6.40mg and film coating pre-mix dose Opadry 85G64872.
5. capecitabine tablet composition according to claim 1, is characterized in that the capecitabine sheet of per unit preparation is composed of the following components: capecitabine 500mg, lactose 40.50mg, microcrystalline Cellulose 60.50mg, cross-linking sodium carboxymethyl cellulose 21.45mg, hypromellose 12.55mg, magnesium stearate 8.20mg and film coating pre-mix dose Opadry 85G64872.
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| WO2015044961A2 (en) * | 2013-09-30 | 2015-04-02 | Intas Pharmaceuticals Limited | Pharmaceutical composition comprising capecitabine and cyclophosphamide |
| CN104739800A (en) * | 2015-02-03 | 2015-07-01 | 吉林修正药业新药开发有限公司 | Capecitabine tablet composition and preparation method thereof |
| CN104644601B (en) * | 2015-02-09 | 2017-05-10 | 山东新时代药业有限公司 | Capecitabine tablet |
| CN115666516A (en) * | 2020-06-01 | 2023-01-31 | 希尔帕医疗保健有限公司 | Fast dispersing pharmaceutical compositions comprising capecitabine |
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|---|---|---|---|---|
| CN102266303A (en) * | 2011-07-07 | 2011-12-07 | 程雪翔 | Capecitabine medicinal composition and preparation method thereof |
| CN102302466A (en) * | 2011-09-09 | 2012-01-04 | 上海希迪制药有限公司 | Capecitabine medicinal composition capable of direct powder tableting, and application thereof |
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| CN102266303A (en) * | 2011-07-07 | 2011-12-07 | 程雪翔 | Capecitabine medicinal composition and preparation method thereof |
| CN102302466A (en) * | 2011-09-09 | 2012-01-04 | 上海希迪制药有限公司 | Capecitabine medicinal composition capable of direct powder tableting, and application thereof |
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| Full prescribing information for XELODA(capecitabine) tablets, film coated for oral use;处方药说明书;《美国FDA药品数据库》;20110209;第20页第11Description节 * |
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| CN103251569A (en) | 2013-08-21 |
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Address after: 611731 Chengdu province high tech Zone, west of the source road, No. 8, No. Patentee after: CHENGDU EASTON BIOPHARMACEUTICALS CO., LTD. Address before: 611731 Chengdu province high tech Zone, west of the source road, No. 8, No. Patentee before: Chengdu Easton Pharmaceutical Co., Ltd. |