CN107890462A - A kind of pazopanib tablet composition - Google Patents
A kind of pazopanib tablet composition Download PDFInfo
- Publication number
- CN107890462A CN107890462A CN201711231649.4A CN201711231649A CN107890462A CN 107890462 A CN107890462 A CN 107890462A CN 201711231649 A CN201711231649 A CN 201711231649A CN 107890462 A CN107890462 A CN 107890462A
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- CN
- China
- Prior art keywords
- pazopanib
- lactose
- aerosil
- amino acid
- magnesium stearate
- 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.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
Abstract
The present invention relates to a kind of pazopanib tablet composition, belong to technical field of medicine.The technical scheme is that：In the composition of unit dose, contain the 5mg of pazopanib 1, the 2.0mg of lauryl sodium sulfate 1.2 that D90 is 100 120 microns, lactose 40 60mg, L amino acid/11 0 22mg, the 8mg of calcium monohydrogen phosphate 4, the 9mg of aerosil 4, the 2mg of magnesium stearate 1.Task-size Controlling of the invention by being reasonably formulated adjustment and main ingredient, reasonably improve the dissolution rate of main ingredient.Provide a kind of suitable industrialized production, steady quality pazopanib tablet technology for meeting standard requirement.
Description
Technical field
The present invention relates to a kind of pazopanib tablet composition, belong to technical field of medicine.
Background technology
Pazopanib（Axitinib）, alias Axitinib, chemical name：N- methyl -2- [3- ((E) -2- pyridines -2-
Base-vinyl) -1H- indoles -6- bases sulphonyl]-benzamide.Pazopanib is antineoplastic, is clinically mainly used in previously connecing
A kind of progressive stage clear-cell carcinoma of tyrosine kinase inhibitor or cytokine therapy failure is received（RCC）Adult patient.Ah
West is developed for Buddhist nun by Pfizer companies, and on January 27th, 2012, FDA approvals listing, there is 2 specifications of 1 mg pieces and 5 mg pieces.
Pazopanib is white powder, 218.4 DEG C of fusing point, slightly easy polyethylene glycol 400, is slightly soluble in methanol or ethanol, pole
Acetonitrile is slightly soluble in, is practically insoluble in water.Solubility is 0.8mg/ml in 20 DEG C of pH1.2 hydrochloric acid solutions, pH6.8 phosphate-buffereds
Solubility is 0.2 microgram/ml in solution, is typical pH dependent forms medicine.
Chinese patent application CN104013589A discloses a kind of pazopanib disintegrated tablet, technical controlling pazopanib D90
Combined in 1-50 micrometer ranges, and with hydrophilicity condiment, the technology has the problem of uniformity of dosage units is exceeded.
CN106913547A discloses the technology of another increase pharmaceutical preparation solubility, and pazopanib is dissolved in into ice vinegar
In acid, mesoporous silicon oxide is added, in the alkaline solution of sodium hydroxide, separates out the compound of pazopanib and silica.
Then mix, pelletize with filler, disintegrant etc. again, tabletting etc..The technical matters is complicated, and equipment corrosion is serious, extends GMP
The production line in workshop, adds production cost, does not apply to industrialized production.
Experiment finds that the pazopanib piece one prepared by prior art is the problem of uniformity of dosage units is not up to standard be present, two
It is that relevant material changes the problem of very fast during depositing, causes tablet quality unstable, or even do not meet clinical requirement.
The content of the invention
【Goal of the invention】
It is an object of the invention to provide a kind of suitable industrialized production, steady quality pazopanib piece for meeting standard requirement
Preparation technique.
【Technical scheme】
The technical scheme is that：A kind of pazopanib tablet composition, in the composition of unit dose, it is containing D90
The pazopanib 1-5mg of 100-120 microns, lauryl sodium sulfate 1.2-2.0mg, lactose 40-60mg, l-amino acid 10-
22mg, calcium monohydrogen phosphate 4-8mg, aerosil 4-9mg, magnesium stearate 1-2mg.
Experiment finds that granularity is too small, and static focus is serious, is unfavorable for the control of uniformity of dosage units, and granularity is too big, to dissolution
It is unfavorable to spend.Technical solution of the present invention is using the pazopanib preparation of preparation that D90 is 100-120 microns as optimum condition.
In technical solution of the present invention, the Task-size Controlling of pazopanib, calcium monohydrogen phosphate, lauryl sodium sulfate, l-amino acid,
The addition of aerosil is to complete the necessary condition of the object of the invention.
Currently preferred technical scheme is：In the composition of unit dose, contain the Ah former times that D90 is 100-120 microns
For Buddhist nun 1-5mg, lauryl sodium sulfate 1.4-1.8mg, lactose 40-60mg, l-amino acid 14-18mg, calcium monohydrogen phosphate 5.5-
8mg, aerosil 5-7.6mg, magnesium stearate 1-2mg.
Currently preferred technical scheme is：In the composition of unit dose, contain the pazopanib that D90 is 110 microns
1-5mg, lauryl sodium sulfate 1.6mg, lactose 50mg, l-amino acid 16mg, calcium monohydrogen phosphate 6mg, aerosil 6mg,
Magnesium stearate 1.5mg.
The preparation method of pazopanib tablet composition of the present invention, comprises the following steps：
Pazopanib is crushed to the granularity of needs by the first step, lauryl sodium sulfate, lactose, l-amino acid, calcium monohydrogen phosphate,
Aerosil, magnesium stearate cross 100 mesh sieves respectively；
Second step weighs the pazopanib handled through the first step of recipe quantity, adds l-amino acid, the dodecyl sulphur of recipe quantity
Sour sodium, aerosil, mix；The lactose of half recipe quantity is added, is soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum
Dry, 100 mesh sieve whole grains；
Particle obtained by 3rd step second step, the calcium monohydrogen phosphate of recipe quantity is added, the lactose of remaining half recipe quantity, is mixed,
Soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum drying, 100 mesh sieve whole grains；
Particle obtained by the step of 4th step the 3rd, adds the magnesium stearate of recipe quantity, and tabletting is aluminum-plastic packaged.
【Beneficial effect】
Pazopanib tablet composition of the present invention, by being reasonably formulated the Task-size Controlling of adjustment and main ingredient, reasonably carry
The high dissolution rate of main ingredient.Preparation method of the present invention, two step granulation techniques are used, first, it is equal to be effectively controlled content
Evenness is in the range of pharmacopoeial requirements；Second, for the dissolution rate effect of haveing a certain upgrade；Pelletized with anhydrous wetting, effectively kept away
Exempt from the introducing of moisture in tableting processes, it is stable for dissolution rate of the tablet during storage, serve positive effect.This
Inventive technique provides a kind of suitable industrialized production, steady quality pazopanib tablet preparation skill for meeting standard requirement
Art.
【Embodiment and reference examples】
Embodiment 1, pazopanib 1g, lauryl sodium sulfate 1.2g, lactose 60g, the l-amino acid 10g that D90 is 100 microns,
Calcium monohydrogen phosphate 4g, aerosil 4g, magnesium stearate 1g, preparation method prepares 1000 as described in technical scheme.
Embodiment 2, the pazopanib 5g, lauryl sodium sulfate 2.0g, lactose 40g that D90 is 120 microns, l-amino acid
22g, calcium monohydrogen phosphate 8g, aerosil 9g, magnesium stearate 2g, preparation method prepares 1000 as described in technical scheme.
Embodiment 3, the pazopanib 1g, lauryl sodium sulfate 1.6g, lactose 50g that D90 is 110 microns, l-amino acid
16g, calcium monohydrogen phosphate 6g, aerosil 6g, magnesium stearate 1.5g, preparation method prepares 1000 as described in technical scheme.
Reference examples 1, the prescription of embodiment 3, cut lauryl sodium sulfate, l-amino acid, calcium monohydrogen phosphate, the weight is by breast
Sugar is filled up.It is specific as follows：
D90 is 110 microns of pazopanib 1g, lactose 73.6g, aerosil 6g, magnesium stearate 1.5g, by following proposal
Prepare 1000：
First step pazopanib is crushed to D90 as 110 microns, and lactose, aerosil, magnesium stearate cross 100 mesh respectively
Sieve；
Second step weigh recipe quantity through the first step handle pazopanib, lactose, aerosil, mix, with anhydrous second
Alcohol wetting granulation, 25 DEG C of vacuum drying, 100 mesh sieve whole grains；
Particle obtained by 3rd step second step, adds the magnesium stearate of recipe quantity, and tabletting is aluminum-plastic packaged.
Reference examples 2, the prescription of embodiment 3, cut calcium monohydrogen phosphate, aerosil, and the weight is filled up by lactose.Specifically
It is as follows：
D90 is 110 microns of pazopanib 1g, lauryl sodium sulfate 1.6g, lactose 62g, l-amino acid 16g, magnesium stearate
1.5g, 1000 are prepared by following preparation methods：
First step pazopanib is crushed to D90 as 110 microns, and lauryl sodium sulfate, lactose, l-amino acid, magnesium stearate divide
100 mesh sieves are not crossed；
Second step weighs the pazopanib handled through the first step, lauryl sodium sulfate, the l-amino acid of recipe quantity, mixes, adds
Enter the lactose of half recipe quantity, mix, soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum drying, 100 mesh sieve whole grains；
Particle obtained by 3rd step second step, the lactose of remaining recipe quantity is added, mixed, soaked and pelletized with absolute ethyl alcohol, 25 DEG C true
Sky is dried, 100 mesh sieve whole grains；
Particle obtained by the step of 4th step the 3rd, adds the magnesium stearate of recipe quantity, and tabletting is aluminum-plastic packaged.
The prescription of reference examples 3, embodiment 3, main ingredient granularity and preparation method difference
D90 is 150 microns of pazopanib 1g, lauryl sodium sulfate 1.6g, lactose 50g, l-amino acid 16g, calcium monohydrogen phosphate
6g, aerosil 6g, magnesium stearate 1.5g, 1000 are prepared by following preparation methods：
First step pazopanib is crushed to D90 as 150 microns, lauryl sodium sulfate, lactose, l-amino acid, calcium monohydrogen phosphate,
Aerosil, magnesium stearate cross 100 mesh sieves respectively；
Second step weigh recipe quantity through the first step handle pazopanib, lauryl sodium sulfate, lactose, l-amino acid, phosphorus
Sour hydrogen calcium, aerosil, mix, soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum drying, 100 mesh sieve whole grains；
Particle obtained by 3rd step second step, adds the magnesium stearate of recipe quantity, and tabletting is aluminum-plastic packaged.
Test example 1, respectively Example 1-3 and reference examples 1-3 products respectively take 20 to carry out Determination of Content Uniformity respectively,
High performance liquid chromatography detection level, data record and table 1.
Table 1
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Reference examples 1 | Reference examples 2 | Reference examples 3 | |
| Average content, % | 99.98 | 99.97 | 100.02 | 100.09 | 99.96 | 99.98 |
| Standard deviation | 1.38 | 1.57 | 1.24 | 3.76 | 3.01 | 2.98 |
The data of table 1 illustrate that the uniformity of dosage units of product of the embodiment of the present invention is less than 2, meet standard requirement.And the content of reference examples
The uniformity is much larger than 2, is not inconsistent standardization requirement.
Test example 2, respectively Example 1-3 and reference examples 1-3 products respectively take aluminum-plastic packaged rear product 100, put respectively
It is that 65% condition is deposited 8 months in 25 DEG C, relative humidity in climatic chamber, dissolution rate is determined respectively at 0 day, August end,
Turn blue laws, 0.1mol/l hydrochloric acid solutions do dissolution medium, high performance liquid chromatography detection level, data record and table 2.
Table 2
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Reference examples 1 | Reference examples 2 | Reference examples 3 | |
| 0 day dissolution rate, % | 88.02 | 87.67 | 89.98 | 42.38 | 62.34 | 69.08 |
| August end dissolution rate, % | 87.98 | 87.58 | 89.96 | 38.56 | 54.87 | 60.12 |
The data of table 2 illustrate that the dissolution rate of product of the embodiment of the present invention was at 0 day, hence it is evident that higher than reference examples, and dissolution rate is not received and kept and put
The influence of time, illustrate that product quality of the present invention is stable, hence it is evident that be better than reference examples.
Claims (4)
1. a kind of pazopanib tablet composition, it is characterised in that be that 100-120 is micro- containing D90 in the composition of unit dose
The pazopanib 1-5mg, lauryl sodium sulfate 1.2-2.0mg, lactose 40-60mg of rice, l-amino acid 10-22mg, phosphoric acid hydrogen
Calcium 4-8mg, aerosil 4-9mg, magnesium stearate 1-2mg.
2. according to pazopanib tablet composition described in claim 1, it is characterised in that in the composition of unit dose, contain
D90 be 100-120 microns pazopanib 1-5mg, lauryl sodium sulfate 1.4-1.8mg, lactose 40-60mg, l-amino acid
14-18mg, calcium monohydrogen phosphate 5.5-8mg, aerosil 5-7.6mg, magnesium stearate 1-2mg.
3. according to pazopanib tablet composition described in claim 1, it is characterised in that in the composition of unit dose, contain
D90 is 110 microns of pazopanib 1-5mg, lauryl sodium sulfate 1.6mg, lactose 50mg, l-amino acid 16mg, phosphoric acid hydrogen
Calcium 6mg, aerosil 6mg, magnesium stearate 1.5mg.
4. the preparation method of pazopanib tablet composition described in claim 1, it is characterised in that comprise the following steps：
Pazopanib is crushed to the granularity of needs by the first step, lauryl sodium sulfate, lactose, l-amino acid, calcium monohydrogen phosphate,
Aerosil, magnesium stearate cross 100 mesh sieves respectively；
Second step weighs the pazopanib handled through the first step of recipe quantity, adds l-amino acid, the dodecyl sulphur of recipe quantity
Sour sodium, aerosil, mix；The lactose of half recipe quantity is added, is soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum
Dry, 100 mesh sieve whole grains；
Particle obtained by 3rd step second step, the calcium monohydrogen phosphate of recipe quantity is added, the lactose of remaining half recipe quantity, is mixed,
Soaked and pelletized with absolute ethyl alcohol, 25 DEG C of vacuum drying, 100 mesh sieve whole grains；
Particle obtained by the step of 4th step the 3rd, adds the magnesium stearate of recipe quantity, and tabletting is aluminum-plastic packaged.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711231649.4A CN107890462A (en) | 2017-11-30 | 2017-11-30 | A kind of pazopanib tablet composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711231649.4A CN107890462A (en) | 2017-11-30 | 2017-11-30 | A kind of pazopanib tablet composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107890462A true CN107890462A (en) | 2018-04-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711231649.4A Withdrawn CN107890462A (en) | 2017-11-30 | 2017-11-30 | A kind of pazopanib tablet composition |
Country Status (1)
| Country | Link |
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| CN (1) | CN107890462A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381440A (en) * | 2018-11-15 | 2019-02-26 | 威海贯标信息科技有限公司 | A kind of Ai Le replaces nylon 6 combination |
| WO2022116987A1 (en) * | 2020-12-02 | 2022-06-09 | 湖南慧泽生物医药科技有限公司 | Self-microemulsion composition of axitinib |
-
2017
- 2017-11-30 CN CN201711231649.4A patent/CN107890462A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381440A (en) * | 2018-11-15 | 2019-02-26 | 威海贯标信息科技有限公司 | A kind of Ai Le replaces nylon 6 combination |
| WO2022116987A1 (en) * | 2020-12-02 | 2022-06-09 | 湖南慧泽生物医药科技有限公司 | Self-microemulsion composition of axitinib |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180410 |
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| WW01 | Invention patent application withdrawn after publication |