CN103127016B - Bisoprolol fumarate tablet composition and preparation method thereof - Google Patents
Bisoprolol fumarate tablet composition and preparation method thereof Download PDFInfo
- Publication number
- CN103127016B CN103127016B CN201310060430.8A CN201310060430A CN103127016B CN 103127016 B CN103127016 B CN 103127016B CN 201310060430 A CN201310060430 A CN 201310060430A CN 103127016 B CN103127016 B CN 103127016B
- Authority
- CN
- China
- Prior art keywords
- bisoprolol
- bisoprolol fumarate
- tablets
- parts
- lactose
- 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.)
- Active
Links
- RZPZLFIUFMNCLY-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol Chemical compound OC(=O)\C=C\C(O)=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 RZPZLFIUFMNCLY-WLHGVMLRSA-N 0.000 title claims abstract description 50
- 229960005400 bisoprolol fumarate Drugs 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000007916 tablet composition Substances 0.000 title claims abstract 6
- 238000000034 method Methods 0.000 claims abstract description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 37
- 229960002781 bisoprolol Drugs 0.000 claims description 30
- 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 23
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 23
- 239000008101 lactose Substances 0.000 claims description 23
- 235000019359 magnesium stearate Nutrition 0.000 claims description 23
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 23
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 23
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 23
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 23
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 23
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 claims description 21
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 16
- 239000000843 powder Substances 0.000 claims description 6
- 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 5
- 238000007907 direct compression Methods 0.000 claims description 3
- 229940086888 bisoprolol fumarate 2.5 mg Drugs 0.000 claims description 2
- 229940086852 bisoprolol fumarate 5 mg Drugs 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 abstract description 6
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 57
- 238000005516 engineering process Methods 0.000 description 15
- 239000000126 substance Substances 0.000 description 13
- 230000000052 comparative effect Effects 0.000 description 11
- -1 bisoprolol fumarates Chemical class 0.000 description 10
- 238000004090 dissolution Methods 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000007919 dispersible tablet Substances 0.000 description 3
- 238000007908 dry granulation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000009702 powder compression Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000000936 membranestabilizing effect Effects 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a bisoprolol fumarate tablet composition and a bisoprolol fumarate tablet composition preparation method with the advantages of simple process, controllable quality, and ensured product stability. With the formula and process provided by the invention, the prepared bisoprolol fumarate tablet composition has the advantages of qualified quality, and stable medicine effect. The bisoprolol fumarate tablet composition can be used for effectively treating hypertension and angina.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of bisoprolol tablets composition and method of making the same.
Background technology
Hypertension and angina pectoris are the modal cardiovascular disease in the world today, are the primary causes of disease of adult's death and disability.In recent years, along with the raising day by day of social progress and living standards of the people and the continuous quickening of work rhythm, Hypertension number increases greatly.China's hypertension and angina pectoris prevalence also obviously rise, and have become one of the most serious country of these two kinds of disease harm in the world.Hypertension can cause the damage of the organs such as the heart, brain, kidney, the serious threat mankind's health and lives.
Bisoprolol fumarate is a β with higher heart selectivity
1receptor blocking agent, within the scope of therapeutic dose, this product is without obvious membrane stabilizing action or inherent sympatheticomimetic action.Long action time, take continuously control symptom good and without tolerate phenomenon, minimum to respiratory system side effect, have no lipocatabolic impact.Bisoprolol fumarate is for essential hypertension, anginal treatment clinically.
Bisoprolol fumarate's in the market oral formulations is mainly tablet and capsule.Chinese patent 200610050157.0 discloses a kind of bisoprolol Fumarate drop pills and preparation method thereof, and drop pill bioavailability is high, disintegrate leaches soon, dissolution is high, release fast, effective fast.But the relative tablet complexity of drop pill preparation technology, cost is higher.Chinese patent 200710304297.0 discloses a kind of bisoprolol fumarate dispersible tablet and preparation method thereof, for clinically providing that a kind of disintegrate leaches soon, stripping is fast, effective dispersible tablet and preparation method fast, but in this bisoprolol fumarate dispersible tablet prescription, having adopted relatively large calcium hydrogen phosphate or calcium sulfate is filler, as everyone knows, when calcium hydrogen phosphate consumption accounts for prescription most of, may occur that at elevated pressures lower sheeting layering and top split, calcium sulfate has hygroscopic feature simultaneously, after water suction, will cause tablet hardening and the problem of not disintegrate.
Bisoprolol fumarate is to damp and hot unstable, in prior art, preparing the general method of tablet or capsule is then tabletting of wet method granule processed, owing to need to drying in baking oven in pelletization, make the tablet or the capsule related substance that make higher, have a strong impact on the quality of preparation; And dry granulation tablet forming technique is comparatively complicated, need to add appropriate dry adhesives, qualified to ensure hardness or the friability of tablet, the Dissolution of Tablet fluctuation preparing is larger, and repeatability is poor.Therefore, it is simple, 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 bisoprolol tablets compositions, provide a kind of technique simple, quality controllable simultaneously, and guarantee the preparation method of the Content of Bisoprolol Fumarate Tablets of product stability.
Bisoprolol tablets compositions of the present invention, comprises the component of following mass parts: 2.5 ~ 5 parts of bisoprolol fumarates, 20 ~ 40 parts of lactose, 60 ~ 100 parts of Parteck deltaMs, 1 ~ 10 part of microcrystalline Cellulose, 1 ~ 5 part of low-substituted hydroxypropyl cellulose, 1 ~ 4 part of polyvidone, 0.1 ~ 1 part of magnesium stearate.
Preferably, said composition is made up of the component of following mass parts: 2.5 ~ 5 parts of bisoprolol fumarates, 20 ~ 35 parts of lactose, 70 ~ 100 parts of Parteck deltaMs, 3 ~ 10 parts of microcrystalline Cellulose, 2 ~ 5 parts of low-substituted hydroxypropyl celluloses, 1 ~ 3 part of polyvidone, 0.1 ~ 0.7 part of magnesium stearate.
Preferred, said composition is made up of the component of following mass parts: 2.5 ~ 5 parts of bisoprolol fumarates, 25 ~ 35 parts of lactose, 70 ~ 90 parts of Parteck deltaMs, 3 ~ 10 parts of microcrystalline Cellulose, 2 ~ 5 parts of low-substituted hydroxypropyl celluloses, 1 ~ 3 part of polyvidone, 0.3 ~ 0.7 part of magnesium stearate.
Described bisoprolol tablets compositions is made up of the component of following mass parts: 5 parts of bisoprolol fumarates, 30 parts of lactose, 80 parts of Parteck deltaMs, 10 parts of microcrystalline Cellulose, 5 parts of low-substituted hydroxypropyl celluloses, 1 part of polyvidone, 0.5 part of magnesium stearate.
Or described bisoprolol tablets compositions is made up of the component of following mass parts: 2.5 parts of bisoprolol fumarates, 25 parts of lactose, 90 parts of Parteck deltaMs, 7 parts of microcrystalline Cellulose, 4 parts of low-substituted hydroxypropyl celluloses, 1 part of polyvidone, 0.7 part of magnesium stearate.
Or described bisoprolol tablets compositions is made up of the component of following mass parts: 4 parts of bisoprolol fumarates, 30 parts of lactose, 70 parts of Parteck deltaMs, 6 parts of microcrystalline Cellulose, 3 parts of low-substituted hydroxypropyl celluloses, 2 parts of polyvidones, 0.6 part of magnesium stearate.
Or described bisoprolol tablets compositions is made up of the component of following mass parts: 3 parts of bisoprolol fumarates, 35 parts of lactose, 75 parts of Parteck deltaMs, 3 parts of microcrystalline Cellulose, 2 parts of low-substituted hydroxypropyl celluloses, 3 parts of polyvidones, 0.3 part of magnesium stearate.
Or described bisoprolol tablets compositions is made up of the component of following mass parts: 5 parts of bisoprolol fumarates, 40 parts of lactose, 60 parts of Parteck deltaMs, 1 part of microcrystalline Cellulose, 1 part of low-substituted hydroxypropyl cellulose, 4 parts of polyvidones, 1 part of magnesium stearate.
Or described bisoprolol tablets compositions is made up of the component of following mass parts: 2.5 parts of bisoprolol fumarates, 20 parts of lactose, 100 parts of Parteck deltaMs, 5 parts of microcrystalline Cellulose, 3 parts of low-substituted hydroxypropyl celluloses, 2 parts of polyvidones, 0.1 part of magnesium stearate.
Bisoprolol tablets compositions of the present invention, the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5 ~ 5mg, lactose 20 ~ 35mg, Parteck deltaM 70 ~ 100mg, microcrystalline Cellulose 3 ~ 10mg, low-substituted hydroxypropyl cellulose 2 ~ 5mg, polyvidone 1 ~ 3mg, magnesium stearate 0.1 ~ 0.7mg.
Further, the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5 ~ 5mg, lactose 25 ~ 35mg, Parteck deltaM 70 ~ 90mg, microcrystalline Cellulose 3 ~ 10mg, low-substituted hydroxypropyl cellulose 2 ~ 5mg, polyvidone 1 ~ 3mg, magnesium stearate 0.3 ~ 0.7mg.
Further, the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 5mg, lactose 30mg, Parteck deltaM 80mg, microcrystalline Cellulose 10mg, low-substituted hydroxypropyl cellulose 5mg, polyvidone 1mg, magnesium stearate 0.5mg.
Or the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5mg, lactose 25mg, Parteck deltaM 90mg, microcrystalline Cellulose 7mg, low-substituted hydroxypropyl cellulose 4mg, polyvidone 1mg, magnesium stearate 0.7mg.
The present invention also provides a kind of preparation method of bisoprolol tablets compositions described above, comprises the following steps:
(1) take each component by described mass ratio, and bisoprolol fumarate is crossed to 100 mesh sieves;
(2) adopt equivalent to progressively increase method by bisoprolol fumarate and lactose, Parteck deltaM, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyvidone mix homogeneously;
(3) to the magnesium stearate that adds recipe quantity in the medicated powder of mix homogeneously in step (2), mix homogeneously;
(4) by the medicated powder direct compression of mix homogeneously in step (3), controlled pressure, at 0.8 ~ 3.5KN, makes the hardness of tablet in 40 ~ 70N.
The present invention adopts technique of direct powder compression, having adopted the good novel adjuvant Parteck deltaM of mobility is filler, adopts the prepared bisoprolol tablets compositions of composition and engineering of the present invention, up-to-standard, efficacy stability, can effectively treat hypertension and angina pectoris.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but limitation of the present invention not, all any this areas of doing according to the disclosure of invention be equal to replacement, all belong to protection scope of the present invention.
Prepare 1000 of Content of Bisoprolol Fumarate Tablets, the weight of each embodiment Raw is as shown in the table: (unit: g)
| Raw material | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 |
| Bisoprolol fumarate | 5 | 2.5 | 4 | 3 | 5 | 2.5 |
| Lactose | 30 | 25 | 30 | 35 | 40 | 20 |
| Parteck deltaM | 80 | 90 | 70 | 75 | 60 | 100 |
| Microcrystalline Cellulose | 10 | 7 | 6 | 3 | 1 | 5 |
| Low-substituted hydroxypropyl cellulose | 5 | 4 | 3 | 2 | 1 | 3 |
| Polyvidone | 1 | 1 | 2 | 3 | 4 | 2 |
| Magnesium stearate | 0.5 | 0.7 | 0.6 | 0.3 | 1 | 0.1 |
Embodiment 1:
Preparation technology:
(1) take each component by described recipe quantity, and bisoprolol fumarate is crossed to 100 mesh sieves;
(2) adopt equivalent to progressively increase method by bisoprolol fumarate, lactose, Parteck deltaM, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyvidone mix homogeneously;
(3) to the magnesium stearate that adds recipe quantity in the medicated powder of mix homogeneously in step (2), mix homogeneously;
(4) by the medicated powder direct compression of mix homogeneously in step (3), controlled pressure, at 1.0 ~ 3.0KN, makes the hardness of tablet in 40 ~ 60N.
Embodiment 2:
Preparation technology: with the preparation technology of embodiment 1, controlled pressure, at 1.5 ~ 3.5KN, makes the hardness of tablet in 50 ~ 70N.
Embodiment 3:
Preparation technology: with the preparation technology of embodiment 1, controlled pressure, at 1.0 ~ 3.0KN, makes the hardness of tablet in 40 ~ 60N.
Embodiment 4:
Preparation technology: with the preparation technology of embodiment 1, controlled pressure, at 0.8 ~ 3.5KN, makes the hardness of tablet in 40 ~ 70N.
Embodiment 5:
Preparation technology: with the preparation technology of embodiment 1, controlled pressure, at 1.5 ~ 3.0KN, makes the hardness of tablet in 50 ~ 60N.
Embodiment 6:
Preparation technology: with the preparation technology of embodiment 1, controlled pressure, at 0.8 ~ 3.5KN, makes the hardness of tablet in 40 ~ 70N.
Comparative example 1 this embodiment is wet granule compression tablet method
Prescription: (except 95% ethanol, other components are with the embodiment of the present invention 5)
Make 1000
Preparation technology:
(1) take bisoprolol fumarate and each adjuvant of recipe quantity, and bisoprolol fumarate is crossed to 100 mesh sieves;
(2) adopt equivalent to progressively increase method by bisoprolol fumarate, lactose, Parteck deltaM, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose mix homogeneously;
(3) get the polyvidone of recipe quantity, add 95% appropriate ethanol, be prepared into solution, this solution is added in the mixed-powder that step (2) obtains, stir, prepare soft material.Soft material is crossed to 18 mesh sieves, granulation, dry in 60 DEG C of baking ovens;
(4) by 18 mesh sieve granulate for dried granule in step (3), gained granule is mixed homogeneously with the magnesium stearate of recipe quantity, tabletting.
Comparative example 2 these embodiment are compressing dry granulation
Prescription: (with the embodiment of the present invention 5)
Make 1000
Preparation technology:
(1) take bisoprolol fumarate and each adjuvant of recipe quantity, and bisoprolol fumarate is crossed to 100 mesh sieves;
(2) by recipe quantity by bisoprolol fumarate, lactose, Parteck deltaM, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyvidone mix homogeneously;
(3) granulate with dry granulating machine, 18 mesh sieve granulate for the granule of gained, mix homogeneously the granule of gained with the magnesium stearate of recipe quantity, and tabletting, to obtain final product.
Disintegration contrast test
Get respectively each 6 of the bisoprolol tablets of the embodiment of the present invention 1 ~ 6 preparation, by the requirement of Chinese Pharmacopoeia version annex XA inspection technique disintegration in 2010, carry out the mensuration of disintegration, result of the test is in table 1.
Table 1 comparison disintegration
According to the regulation of Chinese Pharmacopoeia version annex XA inspection technique disintegration in 2010, the tablet of this product should all disintegrates in 15 minutes.As can be seen from Table 1, the bisoprolol tablets of the embodiment of the present invention 1 ~ 6 preparation all in 4 minutes disintegrate complete.And adopting the disintegration of Content of Bisoprolol Fumarate Tablets prepared by comparative example 1 ~ 2 technique compared with the embodiment of the present invention 5, disintegrate is slower.Illustrate and adopt the tablet for preparing of technique of direct powder compression of the present invention, can be in shorter time disintegrate complete.
Dissolution contrast test
By the requirement of Chinese Pharmacopoeia version annex X C dissolution method in 2010, the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation dissolution 5 minutes time in different medium is compared, the results are shown in Table 2.
The dissolution comparison of table 2 in different medium
As can be seen from Table 2, the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation in 0.1M hydrochloric acid, water, pH4.5 phosphate buffer or pH6.8 phosphate buffer 5 minutes time dissolution all higher than 75%.Under comparing, Content of Bisoprolol Fumarate Tablets prepared by the embodiment of the present invention 5 dissolution 5 minutes time in each medium is lower slightly.And the Content of Bisoprolol Fumarate Tablets of comparative example 1 ~ 2 preparation in each medium the dissolution 5 minutes time all lower than the embodiment of the present invention, simultaneously in associative list 1, comparative result can be found out disintegration, the disintegration of tablet that adopts technique of direct powder compression of the present invention to make is very fast, can obviously improve the dissolution of medicine.
Influence factor's test:
Comparative example 1 ~ 2 is carried out respectively to factors influencing with the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation, and detect the variation of related substance in tablet.
Placement condition: 40 DEG C of high temperature, high humidity RH92.5% and illumination (4500lx ± 500lx)
Result of the test sees the following form:
Related substance comparison under 40 DEG C of conditions of table 3 high temperature
Related substance comparison under table 4 high humidity RH92.5% condition
Related substance comparison under table 5 illumination (4500lx ± 500lx) condition
By table, 3-5 can find out, in the time of 40 DEG C of conditions of high temperature 10 days, the related substance amount of the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation is 0.72 ~ 0.77%, and comparative example 1 ~ 2 related substance amount is 1.12% ~ 1.68%; Under high humidity RH92.5% condition, 10 days time, the related substance of the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation is 0.80%-0.85%, and comparative example 1 ~ 2 related substance is 1.24% ~ 1.74%; Under illumination (4500lx ± 500lx) condition, 10 days time, the related substance amount of the Content of Bisoprolol Fumarate Tablets of the embodiment of the present invention 1 ~ 6 preparation is 0.28 ~ 0.33%, and comparative example 1 ~ 2 related substance amount is 0.46% ~ 0.93%.Known by high temperature, high humidity, illumination effect factorial experiments, the related substance amount of Content of Bisoprolol Fumarate Tablets prepared by the present invention is all starkly lower than Content of Bisoprolol Fumarate Tablets prepared by comparative example 1 and comparative example 2.
Known by above-mentioned result of the test, the bisoprolol tablets compositions disintegrate that adopts prescription of the present invention and technique to prepare is very fast, dissolution is better, and related substance is starkly lower than the bisoprolol tablets that adopts wet granule compression tablet technique and dry granulation tablet forming technique to prepare, the tablet quality that adopts technical scheme of the present invention to make is more controlled, have made marked progress compared with prior art tool, be more suitable for industrialized great production.
Claims (4)
1. a bisoprolol tablets compositions, is characterized in that the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5～5mg, lactose 20～35mg, Parteck deltaM 70～100mg, microcrystalline Cellulose 3～10mg, low-substituted hydroxypropyl cellulose 2～5mg, polyvidone 1～3mg, magnesium stearate 0.1～0.7mg;
The preparation method of this tablet composition comprises the following steps:
(1) take each component by described mass ratio, and bisoprolol fumarate is crossed to 100 mesh sieves;
(2) adopt equivalent to progressively increase method by bisoprolol fumarate, lactose, Parteck deltaM, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyvidone mix homogeneously;
(3) to the magnesium stearate that adds recipe quantity in the medicated powder of mix homogeneously in step (2), mix homogeneously;
(4) by the medicated powder direct compression of mix homogeneously in step (3), controlled pressure, at 0.8～3.5KN, makes the hardness of tablet in 40～70N.
2. bisoprolol tablets compositions according to claim 1, is characterized in that the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5～5mg, lactose 25～35mg, Parteck deltaM 70～90mg, microcrystalline Cellulose 3～10mg, low-substituted hydroxypropyl cellulose 2～5mg, polyvidone 1～3mg, magnesium stearate 0.3～0.7mg.
3. bisoprolol tablets compositions according to claim 1, is characterized in that the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 5mg, lactose 30mg, Parteck deltaM 80mg, microcrystalline Cellulose 10mg, low-substituted hydroxypropyl cellulose 5mg, polyvidone 1mg, magnesium stearate 0.5mg.
4. bisoprolol tablets compositions according to claim 1, is characterized in that the Content of Bisoprolol Fumarate Tablets of per unit preparation is composed of the following components: bisoprolol fumarate 2.5mg, lactose 25mg, Parteck deltaM 90mg, microcrystalline Cellulose 7mg, low-substituted hydroxypropyl cellulose 4mg, polyvidone 1mg, magnesium stearate 0.7mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310060430.8A CN103127016B (en) | 2013-02-26 | 2013-02-26 | Bisoprolol fumarate tablet composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310060430.8A CN103127016B (en) | 2013-02-26 | 2013-02-26 | Bisoprolol fumarate tablet composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103127016A CN103127016A (en) | 2013-06-05 |
| CN103127016B true CN103127016B (en) | 2014-06-18 |
Family
ID=48487893
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310060430.8A Active CN103127016B (en) | 2013-02-26 | 2013-02-26 | Bisoprolol fumarate tablet composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103127016B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105213331B (en) * | 2014-04-30 | 2020-04-07 | 江苏豪森药业集团有限公司 | Medicinal preparation containing pazopanib hydrochloride and preparation method thereof |
| CN112245401A (en) * | 2020-11-09 | 2021-01-22 | 郑州卓峰制药有限公司 | A pharmaceutical tablet for treating hypertension and coronary heart disease, and its preparation method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1650849A (en) * | 2004-12-27 | 2005-08-10 | 尚宝虎 | Bisolol non intestine medicinal preparation |
| GB2444904A (en) * | 2006-12-05 | 2008-06-25 | Michael Hilary Burke | A process for the preparation of an orally administered unit dose tablet |
-
2013
- 2013-02-26 CN CN201310060430.8A patent/CN103127016B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1650849A (en) * | 2004-12-27 | 2005-08-10 | 尚宝虎 | Bisolol non intestine medicinal preparation |
| GB2444904A (en) * | 2006-12-05 | 2008-06-25 | Michael Hilary Burke | A process for the preparation of an orally administered unit dose tablet |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103127016A (en) | 2013-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104434809B (en) | A kind of olaparib solid dispersion preparation and preparation method thereof | |
| CN106176640B (en) | Pharmaceutical composition containing tofacitinib citrate and preparation method thereof | |
| CN102091050A (en) | Stable simvastatin oral tablet and preparation method thereof | |
| CN102949372A (en) | Nicergoline pill and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| CN103127016B (en) | Bisoprolol fumarate tablet composition and preparation method thereof | |
| CN106265581B (en) | Tranexamic acid tablet and preparation method thereof | |
| CN107753455B (en) | A tablet containing imidafenacin and its preparation method | |
| CN101732312A (en) | Huperzine A oral formulation and a preparation method thereof | |
| CN105213331B (en) | Medicinal preparation containing pazopanib hydrochloride and preparation method thereof | |
| CN110575442A (en) | Fermented cordyceps sinensis powder tablet | |
| CN105640903A (en) | Stable tedizolid phosphate medicine composition | |
| CN108078933A (en) | A kind of tolvaptan dispersible tablet and preparation method thereof | |
| CN108721238A (en) | A kind of lithium carbonate sustained release tablets | |
| CN106551916A (en) | A kind of olaparib capsule and preparation method thereof | |
| CN113288905A (en) | Pharmaceutical composition containing dortavir sodium, lamivudine and norfovir disoproxil fumarate | |
| CN103356494B (en) | High-stability simvastatin tablets and preparation method thereof | |
| CN102366412A (en) | Preparation method of tolvaptan tablet | |
| CN103127019B (en) | Florfenicol dispersible tablet as well as preparation method and application thereof | |
| CN106880606A (en) | A kind of proxetine hydrochloride tablets agent and preparation method thereof | |
| CN104721163A (en) | Sustained release tablet containing lamotrigine and preparing method thereof | |
| CN104666265A (en) | Promethazine hydrochloride tablet and preparation method thereof | |
| CN103239417A (en) | Preparation method of trimetazidine dihydrochloride tablet | |
| CN101467985B (en) | Bisoprolol fumarate dispersible tablet and preparation method thereof | |
| CN105193758A (en) | Gliclazide sustained release tablets 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 | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
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. |