CN104288113A - Azilsartan pharmaceutical composition and preparation method thereof - Google Patents
Azilsartan pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN104288113A CN104288113A CN201410534318.8A CN201410534318A CN104288113A CN 104288113 A CN104288113 A CN 104288113A CN 201410534318 A CN201410534318 A CN 201410534318A CN 104288113 A CN104288113 A CN 104288113A
- Authority
- CN
- China
- Prior art keywords
- azilsartan
- pharmaceutical composition
- weight portion
- preparation
- 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.)
- Pending
Links
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 239000005485 Azilsartan Substances 0.000 title claims abstract description 67
- 229960002731 azilsartan Drugs 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 34
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract 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 abstract description 27
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 27
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000008101 lactose Substances 0.000 claims abstract description 27
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 27
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 27
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 27
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 27
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 27
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims abstract description 27
- 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 26
- 229960001375 lactose Drugs 0.000 claims description 26
- 229960001866 silicon dioxide Drugs 0.000 claims description 24
- 239000002245 particle Substances 0.000 claims description 23
- 238000001035 drying Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 238000007873 sieving Methods 0.000 claims description 3
- 239000000835 fiber Substances 0.000 claims 2
- -1 hydroxy-propyl Chemical group 0.000 claims 2
- 238000004090 dissolution Methods 0.000 abstract description 32
- 239000003814 drug Substances 0.000 abstract description 12
- 239000003795 chemical substances by application Substances 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000000843 powder Substances 0.000 abstract description 6
- 238000001514 detection method Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 9
- 238000009702 powder compression Methods 0.000 description 4
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000007908 dry granulation Methods 0.000 description 3
- 238000011020 pilot scale process Methods 0.000 description 3
- 239000007962 solid dispersion Substances 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 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 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 101150059573 AGTR1 gene Proteins 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 206010068052 Mosaicism Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000003765 sex chromosome Anatomy 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an azilsartan pharmaceutical composition and a preparation method of the pharmaceutical composition. The pharmaceutical composition consists of the raw materials in parts by weight: 20 parts of azilsartan, 60-150 parts of lactose, 30-120 parts of microcrystalline cellulose, 4-10 parts of low substituted hydroxypropyl cellulose, 0.3-2 parts of silicon dioxide and 0.5-5 parts of sodium stearyl fumarate. The pharmaceutical composition is prepared by adopting a direct powder tabletting process. The dissolution rate of over 90 percent can be achieved by adopting a small amount of disintegrating agent, and the pharmaceutical composition has the advantages of high stability and fast disintegration. The preparation method disclosed by the invention is simple in production process, the corresponding equipment plant investment is reduced, and the production cost is saved. The tablets produced by adopting the direct powder tabletting process are fast in disintegration, and dissolution of the medicine is improved. The detection proves that the dissolution rate of the tablets prepared by the method disclosed by the invention is over 90 percent in 30min.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of pharmaceutical composition containing Azilsartan and preparation method thereof.
Background technology
Azilsartan is selectivity AT1 subtype angiotensin II receptor antagonist (AR Bs) class antihypertensive of new generation.It has steady blood pressure lowering, can not cause the advantage of dry cough compared with angiotensin-convertion enzyme inhibitor (ACEI) hypotensor thing.Although what gone on the market has multiple ARBs, for many patients, feritin-aldosterone system (RAS) activity is only suppressed to be not sufficient to the risk controlling blood pressure and reduce cardiovascular disease and diabetes.Research display, Azilsartan is as dual-use function ARBs of new generation, and not only 1 receptor (AT1 receptor) of antagonizing angiotensin II, also can reduce the risk of cardiovascular disease and diabetes by number of mechanisms.On April 28th, 2010, Japanese Takeda Pharmaceutical Company Limited (Takeda) completes this medicine phase iii clinical trial.Clinical trial proves, this product has good therapeutic effect, and adverse reaction rate is lower, the good feature of compliance.
Azilsartan is water-soluble hardly, and the dissolubility in water is less than 9ug/ml, and therefore, the dissolution of its preparation is the problem of a most critical.Generally need to be carried out micronization in useful in preparing drug formulations process, and control particle diameter its absorption in vivo of guarantee and clinical efficacy within the specific limits.Containing amido link in Azilsartan structure, facile hydrolysis, therefore should avoid wet granulation in formulation process as far as possible, can consider to adopt the technique such as dry granulation or direct powder compression.
Patent CN101528262A discloses a kind of pharmaceutical composition stablized and have excellent Dissolution behaviours, it is characterized in that the grease containing low melting point, low viscous binding agent, and its main feature adopts low viscous binding agent to improve the stripping of Azilsartan.But adopt low viscous binding agent often limited to the In Vitro Dissolution improving Azilsartan.
Patent CN103705510A discloses a kind of preparation method of azilsartan solid composition.Described preparation method comprises prepares suspension solution by Azilsartan, adopts the mode sprayed into join in the diluent of pharmaceutical composition after suspension solution is carried out waterproof pulverization, and drying is prepared into granule and the powder of the husky smooth pharmaceutical composition of Ah agent; Finally granule is become the medicinal minimum dose unit of Azilsartan with powder preparation.Solve and adopt conventional comminution processes when preparing Azilsartan microgranule, the problem that related substance sharply increases, be conducive to the storage period extending Azilsartan preparation.But technique is comparatively complicated, and from the steadiness of Azilsartan, medicine related substance in crushing process does not increase substantially, and what really affect related substance is moisture, because containing amido link in its structure.
The Azilsartan pharmaceutical preparation that patent CN102895205A discloses a kind of Fast Stripping is characterized in that Azilsartan particle diameter D
90be not more than 20 μm; Patent CN103260605A discloses a kind of azilsartan solid dispersion and preparation method thereof and pharmaceutical composition, and carrier material is selected from polyvidone, poloxamer, Polyethylene Glycol, hydroxypropyl cellulose, polyethylene glycol oxide; Patent CN102793680A discloses a kind of azilsartan solid dispersion, preparation method and pharmaceutical composition thereof.Azilsartan carrier material pharmaceutically acceptable with it is adopted to make solid dispersion system.
Above-mentioned patent solves the not good problem of dissolution all well, but does not really solve preparation stabilization sex chromosome mosaicism.
Summary of the invention
In order to overcome above-mentioned problems of the prior art, the first object of the present invention is to provide a kind of new Azilsartan pharmaceutical composition, by optimizing composition and the ratio of adjuvant, solve the problem that drug-eluting is undesirable, stability is bad well, obtain prescription and the relatively simple Azilsartan tablet of technique, be more suitable for industrialized great production.
The second object of the present invention is to provide the preparation method of described new Azilsartan pharmaceutical composition, and direct powder compression, compares with dry granulation with wet granulation, eliminates the process of granulation, and the method is not only simpler, decreases corresponding equipment.
For realizing the first object of the present invention, the present invention adopts following technical scheme:
A kind of Azilsartan pharmaceutical composition, wherein, described pharmaceutical composition is made up of following formula:
Wherein, Azilsartan needs to control mean diameter and is not more than 30 microns.
Preferably, described pharmaceutical composition is made up of following formula:
Wherein, Azilsartan needs to control mean diameter and is not more than 15 microns.
For realizing the second object of the present invention, the present invention adopts following technical scheme:
A preparation method for described pharmaceutical composition, the method comprises:
1) Azilsartan is carried out micronization processes, control particle diameter in OK range, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying respectively, sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
According to described preparation method, wherein, step 1) described in mean diameter be 0 ~ 30 micron.
According to described preparation method, wherein, step 2) described in drying be dry 2 ~ 4 hours under 60 ~ 80 DEG C of conditions, described sieving was 60 ~ 80 mesh sieves.
According to described preparation method, wherein said tabletting is at 5 ~ 8kg by slice, thin piece Hardness Control.
Be below detailed description of the present invention:
One aspect of the present invention provides a kind of pharmaceutical composition containing Azilsartan, and this pharmaceutical composition has and has good stability, and disintegrate is fast, thus contributes to the advantage improving drug-eluting.
Pharmaceutical composition provided by the present invention is made up of following formula:
Wherein, Azilsartan needs to control mean diameter and is not more than 30 microns.
The present invention is after having carried out a large amount of prescription screening tests, again test of many times is carried out to the consumption of supplementary material, when finding to adopt polyvinylpolypyrrolidone or cross-linked carboxymethyl cellulose sodium to make disintegrating agent, when its consumption is more than 8% of recipe quantity time, the dissolution of obtained slice, thin piece can reach more than 75%; And when its consumption is less than 5% of recipe quantity time, the dissolution of obtained slice, thin piece is lower; When the present invention makes disintegrating agent with low-substituted hydroxypropyl cellulose, when its consumption is more than 2% of recipe quantity time, the dissolution of obtained slice, thin piece can reach more than 90%; And dissolution increases along with the increase of its consumption, but when its consumption is more than 5% of recipe quantity, after continuing to increase its consumption, dissolution increases not obvious.Therefore can determine that above-mentioned prescription is the prescription of pharmaceutical composition provided by the present invention.Be its optimization formula with following formula again:
Wherein, Azilsartan needs to control mean diameter and is not more than 15 microns.
The present invention provides a kind of preparation method not needing granulation, directly pressed powder of the pharmaceutical composition containing Azilsartan of the present invention on the other hand, the method is not only simpler, decrease the investment of corresponding equipment Factory Building, save production cost, the more important thing is that the disintegration of tablet adopting the method obtained is faster, thus contribute to the stripping improving medicine, and have good stability.
Preparation method of the present invention comprises:
1) Azilsartan is carried out micronization processes, control particle diameter in OK range, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying respectively, sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
According to described preparation method, wherein, step 1) described in mean diameter be 0 ~ 30 micron.
In preparation method of the present invention, step 2) described in drying be dry 2 ~ 4 hours under 60 ~ 80 DEG C of conditions, described sieving was 60 ~ 80 mesh sieves.
In preparation method of the present invention, described tabletting is at 5 ~ 8kg by slice, thin piece Hardness Control.
Measured result angle of repose adopting the mixed-powder of the pharmaceutical composition prepared by said method is 34.5 °, and powder flowbility is good, meets the requirement of direct compression.
The present invention adopts the preparation method of direct powder compression, and compare with dry granulation tablet forming technique, tool has the following advantages.
(1) production technology is simpler, decreases the investment of corresponding equipment Factory Building, saves production cost;
(2) Azilsartan is the medicine that dissolubility is little, and the disintegration of tablet adopting technique of direct powder compression to produce is faster, contributes to the stripping improving medicine, after testing, and the tablet adopting method of the present invention to prepare stripping more than 90% in 30 minutes.
Detailed description of the invention
Be below the specific embodiment of the present invention, described embodiment is to further describe the present invention, instead of restriction the present invention.
Embodiment 1
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 2
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 20 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 3 hours respectively in 60 DEG C of baking ovens, 60 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 3
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 30 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 70 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 4
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 25 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 5
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 3 hours respectively in 60 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 6
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 7
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 8
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Embodiment 9
1, prescription
2, preparation technology
1) Azilsartan is carried out micronization processes, control particle diameter and be not more than 15 microns, take by recipe quantity, for subsequent use;
2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying 2 hours respectively in 80 DEG C of baking ovens, 80 orders sieve for subsequent use;
3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
Test example 1
This test example is to investigate the kind of disintegrating agent and consumption to the impact of the dissolution of obtained tablet.Its result of the test is as shown in table 1.
Table 1 disintegrating agent kind and consumption are on impact (the Azilsartan mean diameter D of Dissolution of Tablet
90=15.1 μm)
As can be seen from Table 1, when the consumption of disintegrating agent low-substituted hydroxypropyl cellulose is 2% of 4mg and recipe quantity, the dissolution of Azilsartan just can reach more than 90%, and the dissolution of tablet increases with the increase of low-substituted hydroxypropyl cellulose consumption, but when the consumption of low-substituted hydroxypropyl cellulose be more than 10mg namely recipe quantity more than 5% time, continue to increase its consumption, dissolution increases not obvious or does not increase; And with cross-linked carboxymethyl cellulose sodium or polyvinylpolypyrrolidone for disintegrating agent time, when its consumption reaches 16mg, dissolution fails to reach 90%; Therefore, the present invention selects low-substituted hydroxypropyl cellulose to be disintegrating agent, and its consumption is that 4 ~ 10mg is most suitable, namely recipe quantity 2 ~ 5%.
Test example 2
This test example is to investigate raw material particle size to the impact of the dissolution of obtained tablet.Its result of the test is as shown in table 2.
Table 2 raw material particle size is on the impact of Dissolution of Tablet
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mean diameter D 90(μm) | 10.2 | 15.1 | 30.4 | 41.6 | 52.8 | 90.6 | 164.5 |
| Disintegration (min) | 1.08 | 0.93 | 0.98 | 1.12 | 1.25 | 1.22 | 1.16 |
| Dissolution (%) | 97.3 | 94.7 | 85.5 | 76.8 | 66.4 | 52.3 | 38.7 |
As can be seen from Table 2, the particle diameter of raw material affects highly significant to drug dissolution, and the dissolution of Azilsartan reduces along with the increase of raw material particle size, and when raw material particle size is less than 30 μm, the dissolution of tablet is all higher than 85%; When particle diameter is less than 15 μm, the dissolution of tablet is all higher than 90%; And when raw material particle size is greater than 30 μm, the dissolution of tablet lower than 80%, and significantly reduces along with the increase of particle diameter.Therefore the particle diameter of Azilsartan raw material need control within 30 μm, and the dissolution of its preparation of guarantee is qualified.
Test example 3
This test example is the stability test of medicine of the present invention
1, accelerated test
The method pilot-scale (10000) of the embodiment of the present invention 1 is adopted to prepare three batch samples (lot number: 130501,130502,130503) by commercially available back, temperature 40 DEG C, place 6 months under the condition of relative humidity 75%, sample respectively 1st month, 2 months, 3 months, 6 the end of month at duration of test, sample for reference outward appearance, dissolution, related substance, content etc., compared with 0 month, the results are shown in following table:
Stability test-the accelerated test of table 3 medicine
Conclusion: compared with 0 month, sample appearance, dissolution, related substance and content are all substantially constant, and sample quality is stablized.
2, long term test
The method pilot-scale (10000) of the embodiment of the present invention 1 is adopted to prepare three batch samples (lot number: 130501,130502,130503) by commercially available back, temperature 25 DEG C, place under the condition of relative humidity 60%, sampling in every 3 months once, sample for reference outward appearance, dissolution, related substance, content etc., compared with 0 month, the results are shown in following table 4:
Stability test-the long term test of table 4 medicine
Conclusion: compared with 0 month, sample appearance, dissolution, related substance and content are all substantially constant, and sample quality is stablized.
Comparative example 1
This comparative example is that medicine more of the present invention compares with commercially available stability.
Adopt a batch sample (lot number: 130501) by commercially available back prepared by the method pilot-scale (10000) of the embodiment of the present invention 1, get commercially available medicine simultaneously, temperature 25 DEG C, place under the condition of relative humidity 60%, sampling in every 3 months once, sample for reference outward appearance, dissolution, related substance, content etc., compared with 0 month, the results are shown in Table 5.
Table 5 compares with the stability of commercial preparation
Conclusion: as can be seen from the above table, having good stability of Azilsartan tablet of the present invention, and the related substance of commercially available Azilsartan tablet is changed significantly over time, its stability is obviously not as the present invention.
The Azilsartan tablet of other embodiment of the present invention has also carried out identical test, and its result is similar.
Claims (6)
1. the pharmaceutical composition containing Azilsartan, it is characterized in that, described pharmaceutical composition is made up of following formula: Azilsartan 20 weight portion, lactose 60 ~ 150 weight portion, microcrystalline Cellulose 30 ~ 120 weight portion, low substituted hydroxy-propyl fiber 4 ~ 10 weight portion, silicon dioxide 0.3 ~ 2 weight portion and sodium stearyl fumarate 0.5 ~ 5 weight portion.
2. the pharmaceutical composition containing Azilsartan according to claim 1, it is characterized in that, described pharmaceutical composition is made up of following formula: Azilsartan 20 weight portion, lactose 120 weight portion, microcrystalline Cellulose 60 weight portion, low substituted hydroxy-propyl fiber 6 weight portion, silicon dioxide 0.6 weight portion and sodium stearyl fumarate 2 weight portion.
3. the preparation method of the pharmaceutical composition described in-kind of claim 1 or 2, is characterized in that, described preparation method comprises: 1) Azilsartan is carried out micronization processes, controls particle diameter in OK range, takes by recipe quantity, for subsequent use; 2) lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate are carried out drying respectively, sieve for subsequent use; 3) above-mentioned Azilsartan for subsequent use, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, silicon dioxide and sodium stearyl fumarate is taken according to recipe quantity, mix homogeneously, tabletting.
4. preparation method according to claim 3, is characterized in that, the mean diameter described in step 1) is 0 ~ 30 micron.
5. preparation method according to claim 3, is characterized in that, step 2) in, described drying is dried 2 ~ 4 hours under 60 ~ 80 DEG C of conditions, and described sieving was 60 ~ 80 mesh sieves.
6. preparation method according to claim 3, is characterized in that, described tabletting is at 5 ~ 8kg by slice, thin piece Hardness Control.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410534318.8A CN104288113A (en) | 2014-10-11 | 2014-10-11 | Azilsartan pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410534318.8A CN104288113A (en) | 2014-10-11 | 2014-10-11 | Azilsartan pharmaceutical composition and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104288113A true CN104288113A (en) | 2015-01-21 |
Family
ID=52308231
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410534318.8A Pending CN104288113A (en) | 2014-10-11 | 2014-10-11 | Azilsartan pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104288113A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030711A (en) * | 2015-09-11 | 2015-11-11 | 江苏中邦制药有限公司 | Preparation method of Azilsartan tablets |
| CN113209036A (en) * | 2021-06-04 | 2021-08-06 | 扬子江药业集团上海海尼药业有限公司 | Azilsartan tablets and preparation method and application thereof |
| CN118141930A (en) * | 2024-03-26 | 2024-06-07 | 迪沙药业集团有限公司 | Sartan drug composition and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103933000A (en) * | 2014-05-06 | 2014-07-23 | 山东新时代药业有限公司 | Azilsartan tablet and preparation method thereof |
-
2014
- 2014-10-11 CN CN201410534318.8A patent/CN104288113A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103933000A (en) * | 2014-05-06 | 2014-07-23 | 山东新时代药业有限公司 | Azilsartan tablet and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030711A (en) * | 2015-09-11 | 2015-11-11 | 江苏中邦制药有限公司 | Preparation method of Azilsartan tablets |
| CN113209036A (en) * | 2021-06-04 | 2021-08-06 | 扬子江药业集团上海海尼药业有限公司 | Azilsartan tablets and preparation method and application thereof |
| CN118141930A (en) * | 2024-03-26 | 2024-06-07 | 迪沙药业集团有限公司 | Sartan drug composition and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10537524B2 (en) | Apixaban solid composition and preparation method thereof | |
| EP2554169B1 (en) | Pharmaceutical preparation comprising phenylalanine derivative | |
| WO2015185013A1 (en) | Pharmaceutical composition containing quinoline derivative or salt thereof, and preparation method therefor | |
| CN105213333A (en) | A kind of tadanafil pharmaceutical composition and preparation method thereof | |
| WO2017020841A1 (en) | Pharmaceutical composition containing lcz696 and preparation method thereof | |
| CN103610677B (en) | A kind of Repaglinide tablet and its preparation method | |
| JP5515198B2 (en) | Mecobalamin-containing powder | |
| CN103393617B (en) | Febustat tablet and preparation method thereof | |
| CN105878202A (en) | Tofacitinib citrate tablet and preparation method thereof | |
| CN111265488B (en) | Telmisartan tablets and preparation method thereof | |
| CN105412036A (en) | Brexpiprazole orally disintegrating tablets | |
| CN105078915A (en) | Rivaroxaban tablets and preparation method for same | |
| CN111888335A (en) | Tolvaptan pharmaceutical solid preparation and preparation method thereof | |
| CN104288113A (en) | Azilsartan pharmaceutical composition and preparation method thereof | |
| CN103877051A (en) | Preparation method of ezetimibe tablet | |
| EP2902015B1 (en) | Preparation method of agomelatine solid preparation | |
| CN109875972A (en) | A kind of olmesartan medoxomil/amlodipinepharmaceutical pharmaceutical composition | |
| CN103565763B (en) | A kind of Dronedarone hydrochloride tablet and preparation method thereof | |
| CN104434845B (en) | A kind of solid pharmaceutical preparation for including the western croak of Leo | |
| CN104688743B (en) | Cefprozil suspension and preparation method thereof | |
| JP2016525554A (en) | Pharmaceutical composition of ranolazine and dronedarone | |
| CN102988297A (en) | Roflumilast solid dispersion and medicinal composition containing same | |
| CN108514550A (en) | Solid drugs and preparation method thereof containing Abiraterone acetate | |
| WO2019080830A1 (en) | Pharmaceutical composition containing quinoline derivative | |
| CN104055741A (en) | Montelukast sodium tablet 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 | ||
| CB02 | Change of applicant information |
Address after: 331800 Jiangxi city of Fuzhou province Dongxiang county rich industrial park Applicant after: Jiangxi Shi Mei pharmaceutical Limited by Share Ltd Address before: 331800 Jiangxi city of Fuzhou province Dongxiang county rich industrial park Applicant before: Jiangxi SM Pharmaceutical Co., Ltd. |
|
| COR | Change of bibliographic data | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150121 |