CN102068415B - Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof - Google Patents
Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof Download PDFInfo
- Publication number
- CN102068415B CN102068415B CN2010106085908A CN201010608590A CN102068415B CN 102068415 B CN102068415 B CN 102068415B CN 2010106085908 A CN2010106085908 A CN 2010106085908A CN 201010608590 A CN201010608590 A CN 201010608590A CN 102068415 B CN102068415 B CN 102068415B
- Authority
- CN
- China
- Prior art keywords
- sulfonamide
- micropowder
- dimethoxy
- pyridine
- replaces
- 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
Abstract
The invention belongs to the field of pharmaceutic preparation and relates to a method for preparing anti-tumor preparations, in particular to carbazole sulfamide-derived anti-tumor medicine dispersible tablets and a preparation method thereof. The invention is characterized in that lactose and beta-cyclodextrin are mixed with a carbazole sulfamide-derived medicine such as N-(2, 6-dimethoxypyridine-3-substituted)-9-methyl carbazole-3-sulfamide, for mixing, and the mixture is ground to micro powder and prepared into the dispersible tablets. Therefore, the dissolution rate of the dispersible tablets can be increased.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of method for preparing of anti-tumor agent, be specifically related to a kind of carbazole sulfonamide series antineoplastic medicament dispersible tablet and preparation method thereof.
Background technology
Antitubulin is one type of effectively antitumor drug; Along with paclitaxel extensive use clinically; With to the structure of microtubule and the deep understanding of function, be that the research and development of the antitumor drug of target spot have caused the concern of whole world drugmaker day by day with the tubulin.
At present, paclitaxel and vinca Antitubulin have been successfully applied to all kinds of tumors of clinical treatment, but it is as a kind of macromolecular natural product; Its synthetic difficulty is big; Bioavailability is low, toxic side effect, particularly; The appearance of multidrug resistant glycoprotein makes its therapeutic receive serious challenge.Therefore, synthesizing new is necessary to the effective micromolecule Antitubulin of all kinds of tumors.
Chinese patent discloses patent of invention: carbazole sulfonamide derivative and preparation method thereof (Granted publication CN 1807413B); Carbazole sulfonamide derivative is one type of new micromolecule Antitubulin, not only has anti-microtubule effect, also has notable antitumor activity; And it is little to have molecular weight; Synthetic simple, the advantage that toxic and side effects is little has a good application prospect.
Active component N-(2,6-dimethoxy-pyridine-3-the replaces)-9-methyl carbazole-3-sulfonamide of N-of the present invention (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet belongs to carbazole sulfonamide derivative, and its chemical structural formula is following:
This chemical compound has notable antitumor activity, and this crude drug can be made into dispersible tablet, dispersible tablet have taking convenience, disintegrate rapidly, absorb characteristics such as fast and bioavailability height.It has, and preparation is simple, taking convenience, improves advantages such as drug bioavailability.The volume of conventional tablet, capsule is bigger, or once often needs to need use mixing in water for oral taking with multi-disc (grain), takes inconvenience, especially to always, young and have the patient of function of deglutition obstacle that certain difficulty is arranged.The dispersible tablet disintegration rate is fast, puts into water and can be dispersed into uniform suspension, taking convenience.
But it is water-soluble that this chemical compound is difficult to, and according to general dispersible tablet preparation technology, its dispersible tablet dissolution does not reach the requirement of pharmacopeia regulation far away.Making the dispersible tablet of processing that good dissolution arranged, is our urgency problems to be solved.
Summary of the invention
The object of the invention solves the dissolution problem of N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet exactly.
We find: with N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, and lactose, beta-schardinger dextrin-is milled to micropowder after mixing, and can promote its dissolution.Than using lactose, a kind of will the getting well in the beta-schardinger dextrin-separately.
We find: with N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, beta-schardinger dextrin-is milled to micropowder after mixing, and adds lactose again in above-mentioned micropowder, continues to be milled to micropowder, and its dissolution is best.
Its reason possibly be: micronized N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide mixes with the micropowder beta-schardinger dextrin-, in wet-granulation process moistening time of aqueous solution; Beta-schardinger dextrin-has played clathration; Clathrate has good wettability, so medicine obtained solubilising, simultaneously; Lactose micropowder is a water soluble adjuvant; Adsorbing the particle of a large amount of water soluble adjuvants around the micronized drug particle, so just can prevent the mutual gathering of tiny drug particle, it stably is present in the mixture.When water soluble adjuvant dissolved, tiny drug particle just directly was exposed in the dissolution medium, so dissolving (going out) speed is accelerated greatly.Therefore, beta-schardinger dextrin-, lactose has played synergism to the dissolution of drug particle.
We find: N-when milling (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, and lactose, the charge ratio of beta-schardinger dextrin-is: 1: 1～10: 1～3, W/W is better.
Can also include filler, binding agent, disintegrating agent, lubricant, correctives in the adjuvant.
Said filler is Icing Sugar, mannitol, sorbitol; Said binding agent is polyvinylpyrrolidone, hydroxypropyl cellulose; Said disintegrating agent is crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose; Said lubricant is a magnesium stearate, micropowder silica gel.Said correctives is Icing Sugar, stevioside, aspartame.
The method for preparing of N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet is following:
(1) with N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, beta-schardinger dextrin-is milled to micropowder after mixing.
(2) lactose is added in the above-mentioned micropowder, continues to be milled to micropowder.Cross 200 mesh sieves.
(3) micropowder that (2) is prepared, and crossed the filler of 100 mesh sieves, binding agent, disintegrating agent, correctives mix homogeneously add polyvinylpyrrolidone aqueous solution system soft material, and 20 mesh sieves are granulated, 60～80 ℃ of dryings, 18 mesh sieve granulate.
(4) granule that (3) is prepared and add lubricant and always mix tabletting.
Above-mentioned method for preparing can obtain following useful effect 1:
We will be according to N-(2,6-dimethoxy-pyridine-3-the replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet (A sample) of embodiment 1 formulation;
Embodiment 1 prescription deletion beta-schardinger dextrin-, the N-of preparation (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet (B sample);
Embodiment 1 prescription deletion lactose, the N-of preparation (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet (C sample);
, but do not mill the N-of preparation (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet (D sample) according to embodiment 1 prescription;
A, B, C, D sample are carried out the dissolution comparative test simultaneously, and according to the method for Chinese Pharmacopoeia version regulation in 2005, in simulated gastric fluid (0.1mol/L hydrochloric acid solution), result of the test is seen table 1:
Table 1
| Sample | Dissolution (meansigma methods) |
| A | 94％ |
| B | 71％ |
| C | 74％ |
| D | 54％ |
Can find out from last table: use beta-schardinger dextrin-simultaneously, lactose, and mill, promoted the dissolution of sample greatly.
Above-mentioned method for preparing can obtain following useful effect 2:
We will carry out study on the stability to it according to N-(2,6-dimethoxy-pyridine-3-the replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet (A sample) of embodiment 1 formulation:
Test one: hot test
Get N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet, in the horizontalization ware, be positioned in 60 ℃ of thermostatic drying chambers 10 days, in sampling in the 5th and the 10th day, detect a stability emphasis inspection item, with comparison in 0 day, the result saw table 2:
Table 2 hot test result
The result shows, these article are 60 ℃ of hot conditions held 10 days, outward appearance, content, and the basic no change of dissolution dispersing uniformity, related substance does not have significant change yet, shows that these article are comparatively stable to 60 ℃ of high temperature.
Test two: high wet test
Get N-(2,6-dimethoxy-pyridine-3-the replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet of listing In Aluminium Foil Packing, in the horizontalization ware, be put in and fill KNO
3In the exsiccator of saturated solution (25 ℃, RH 92.5%),, detect a stability emphasis inspection item in sampling in the 5th and the 10th day 25 ℃ of condition held 10 days, with 0 day relatively, the result sees table 3
Table 3 high humidity (RH 92.5%) result of the test
The result shows, these article are in RH92.5% condition held, outward appearance, content, and dissolution, the basic no change of dispersing uniformity, related substance does not have significant change yet, shows that these article are by stable to high humidity (RH 92.5%) under the listing In Aluminium Foil Packing condition.
Test three: strong illumination test
Get N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet, in the horizontalization ware, be put under the clarity detector light canopy; Regulate illumination 4500Lx, under this condition, placed 10 days; Detect in sampling in the 5th and the 10th day, with comparison in 0 day, the result saw table 4:
Table 4 exposure experiments to light result
The result shows, these article under the strong illumination condition 10 days, with 0 day relatively, outward appearance, content, related substance, dissolution, the basic no change of dispersing uniformity show that these article are stable to high light.
Conclusion:
Test shows: (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet is stable to high temperature, strong illumination to N-, also is stable by listing In Aluminium Foil Packing condition to high humidity.
Test shows: N-of the present invention (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet is write out a prescription and technology, can guarantee the quality of these article.
The specific embodiment
Following embodiment is used for further narrating the present invention, but does not do any restriction.
The preparation of embodiment 1 N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet
Prescription: (1000)
N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide 50g
Beta-schardinger dextrin-100g
Lactose 250g
Low-substituted hydroxypropyl cellulose 15g
5% polyvinylpyrrolidone aqueous solution is an amount of
Micropowder silica gel 5g
Stevioside 0.2g
Preparation technology:
(1) with 50g N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, the 100g beta-schardinger dextrin-is milled to micropowder after mixing.
(2) lactose 250g is added in the above-mentioned micropowder, continues to be milled to micropowder.Cross 200 mesh sieves.
(3) micropowder that (2) is prepared, and crossed the low-substituted hydroxypropyl cellulose 15g mix homogeneously of 100 mesh sieves, adding 5% polyvinylpyrrolidone aqueous solution system soft material, 20 mesh sieves are granulated, 60～80 ℃ of dryings, 18 mesh sieve granulate.
(4) granule that (3) is prepared adds micropowder silica gel 5g and always mixes tabletting.Process 1000.
The preparation of embodiment 2 N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet
Prescription: (1000)
N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide 100g
Beta-schardinger dextrin-100g
Lactose 100g
Crosslinked carboxymethyl fecula sodium 15g
5% polyvinylpyrrolidone aqueous solution is an amount of
Micropowder silica gel 5g
Stevioside 0.2g
Preparation technology:
(1) with 100g N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, the 100g beta-schardinger dextrin-is milled to micropowder after mixing.
(2) lactose 100g is added in the above-mentioned micropowder, continues to be milled to micropowder.Cross 200 mesh sieves.
(3) micropowder that (2) is prepared, and crossed crosslinked carboxymethyl fecula sodium 15g, the stevioside 0.2g mix homogeneously of 100 mesh sieves, adding 5% polyvinylpyrrolidone aqueous solution system soft material, 20 mesh sieves are granulated, 60～80 ℃ of dryings, 18 mesh sieve granulate.
(4) granule that (3) is prepared adds micropowder silica gel 5g and always mixes tabletting.Process 1000.
The preparation of embodiment 3 N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide dispersible tablet
Prescription: (1000)
N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide 50g
Beta-schardinger dextrin-150g
Lactose 350g
Cross-linking sodium carboxymethyl cellulose 22g
5% polyvinylpyrrolidone aqueous solution is an amount of
Micropowder silica gel 6g
Aspartame 0.2g
Preparation technology:
(1) with 50g N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, the 150g beta-schardinger dextrin-is milled to micropowder after mixing.
(2) lactose 350g is added in the above-mentioned micropowder, continues to be milled to micropowder.Cross 200 mesh sieves.
(3) micropowder that (2) is prepared, and crossed cross-linking sodium carboxymethyl cellulose 22g, the aspartame 0.2g mix homogeneously of 100 mesh sieves, adding 5% polyvinylpyrrolidone aqueous solution system soft material, 20 mesh sieves are granulated, 60～80 ℃ of dryings, 18 mesh sieve granulate.
(4) granule that (3) is prepared adds micropowder silica gel 6g and always mixes tabletting.Process 1000.
Claims (2)
1. a carbazole sulfonamide series antineoplastic medicament dispersible tablet is made up of active constituents of medicine and adjuvant, it is characterized in that: active constituents of medicine is N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide; Contain lactose, beta-schardinger dextrin-in the adjuvant; After N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, lactose, beta-schardinger dextrin-mix, be milled to micropowder; N-when milling (2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, the charge ratio of lactose, beta-schardinger dextrin-is: 1: 1～10: 1～3, W/W; Include filler, binding agent, disintegrating agent, lubricant, correctives in the adjuvant; Said filler is Icing Sugar, mannitol, sorbitol; Said binding agent is polyvinylpyrrolidone, hydroxypropyl cellulose; Said disintegrating agent is crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose; Said lubricant is a magnesium stearate, micropowder silica gel; Said correctives is Icing Sugar, stevioside, aspartame.
2. according to the dispersible tablet described in the claim 1, it is characterized in that: its preparation method is following,
(1) with N-(2,6-dimethoxy-pyridine-3-replaces)-9-methyl carbazole-3-sulfonamide, beta-schardinger dextrin-is milled to micropowder after mixing;
(2) lactose is added in the above-mentioned micropowder, continues to be milled to micropowder, cross 200 mesh sieves;
(3) micropowder that (2) is prepared, and crossed filler, disintegrating agent, the correctives mix homogeneously of 100 mesh sieves, adding polyvinylpyrrolidone aqueous solution system soft material, 20 mesh sieves are granulated, 60～80 ℃ of dryings, 18 mesh sieve granulate;
(4) granule that (3) is prepared and add lubricant and always mix tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010106085908A CN102068415B (en) | 2010-12-28 | 2010-12-28 | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010106085908A CN102068415B (en) | 2010-12-28 | 2010-12-28 | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102068415A CN102068415A (en) | 2011-05-25 |
| CN102068415B true CN102068415B (en) | 2012-02-22 |
Family
ID=44027295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010106085908A Active CN102068415B (en) | 2010-12-28 | 2010-12-28 | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102068415B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105418487B (en) * | 2015-10-27 | 2018-11-02 | 山西普德药业有限公司 | Carbazole sulfonamide derivative eutectic and preparation method thereof |
| CN105287388B (en) * | 2015-10-27 | 2019-09-17 | 山西普德药业有限公司 | High dispersive carbazole sulfonamide derivative and preparation method thereof |
| CN106880609A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of Suo Feibuwei dispersible tablets and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1807413B (en) * | 2005-09-28 | 2010-05-05 | 中国医学科学院医药生物技术研究所 | Carbazole sulfonamide derivative and its preparation method |
-
2010
- 2010-12-28 CN CN2010106085908A patent/CN102068415B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN102068415A (en) | 2011-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101710935B1 (en) | Solid dosage forms of bendamustine | |
| ES2950995T3 (en) | A tablet comprising a methoxyurea derivative and mannitol particles | |
| WO2012043709A1 (en) | Preparation for improving solubility of poorly soluble drug | |
| CN107530348A (en) | A kind of pharmaceutical composition containing jak kinase inhibitor or its officinal salt | |
| CN102631347A (en) | Gefinitib medicinal composite and method for preparing same | |
| CN103356616A (en) | Bilastine-containing pharmaceutical composition and preparation method thereof | |
| CN102600132B (en) | Oral preparation containing amisulpride | |
| CN106309403A (en) | Pharmaceutical composition containing lenalidomide, and preparation method and medical application thereof | |
| CN104771363A (en) | Chidamide solid dispersion and preparing method and application thereof | |
| CN103284962A (en) | Moxifloxacin dispersible tablet and preparation method thereof | |
| CN101816637A (en) | Leflunomide tablet preparation and preparation method thereof | |
| CN102068415B (en) | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof | |
| CN102406622A (en) | Tolvaptan solid preparation | |
| JP2015054851A (en) | Coated oral solid preparation | |
| CN103933001A (en) | Stable silodosin oral solid pharmaceutical composition and preparation method thereof | |
| CN102068431B (en) | Carbazole sulfamide-derived anti-tumor medicine tablets and preparation method thereof | |
| CN102038663B (en) | Carbazole sulfonamide antineoplastic agent capsules and preparation method | |
| ES2674951T3 (en) | Tris (hydroxymethyl) aminomethane salts of a small molecule GLP1R agonist and pharmaceutical compositions and uses thereof | |
| ES2811031T3 (en) | Process for the preparation of a pharmaceutical composition comprising a quinoline derivative or a salt thereof | |
| KR100267525B1 (en) | Cytarabine ocfosfate hard capsule | |
| CN103284953B (en) | Bicyclol solid preparation and preparation method thereof | |
| CN104546667A (en) | Solid dispersion containing posaconazole and preparation method thereof | |
| CN110404079A (en) | A kind of not carbonate containing, the quinoline of low genotoxicity impurity content or the pharmaceutical composition of its salt | |
| CN114191404A (en) | Totiravi tablet and preparation method thereof | |
| CN102068411B (en) | Carbazole sulfonamide type anti-tumor medicament granules 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 | ||
| CP03 | Change of name, title or address |
Address after: 037010 the first medical zone of Datong Economic and Technological Development Zone, Shanxi Patentee after: Shanxi Powerdone Pharmaceutics Co., Ltd. Address before: 037010 Datong economic and Technological Development Zone, Shanxi Patentee before: Shanxi Powerdone Pharmaceutical Co., Ltd. |