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High drug load tablet containing tetrahydronaphthalene amide compound or pharmaceutically acceptable salt thereof

A technology of tetralin and medicinal salt, which is applied in the field of high drug loading drug tablets, can solve the problems of increased friability, high preparation cost, poor adaptability and the like, and achieves high drug loading, short disintegration time, and adaptability. Good results

Active Publication Date: 2014-11-19
LIAONING UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Since N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5,6,7 , 8-Tetrahydronaphthalene-2-amide has a large dosage (500-1000mg / d orally), and the low drug-loading preparation has complex ingredients and a large amount of excipients, and the resulting preparation is relatively large, which may affect its clinical application. Poor safety, not convenient for children, the elderly and seriously ill patients to use
Moreover, the preparation cost is also high, which affects the price of the product and brings a greater economic burden to patients. All preparations with high drug loading are the current development trend of preparations
[0004] The drug loading of currently marketed drugs depends on the nature of the drug, and most of them are between 30-60%. When the drug loading of general drugs reaches more than 60%, the preparation process is difficult, the tablet is prone to cracks, and the friability is enhanced. The quality does not meet the requirements of the quality standard. Due to the preparation process and the quality of the tablet, it is difficult to reach more than 70%

Method used

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  • High drug load tablet containing tetrahydronaphthalene amide compound or pharmaceutically acceptable salt thereof
  • High drug load tablet containing tetrahydronaphthalene amide compound or pharmaceutically acceptable salt thereof
  • High drug load tablet containing tetrahydronaphthalene amide compound or pharmaceutically acceptable salt thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] The preparation of embodiment 1 cyclobenztinib citrate and pharmacodynamic research result

[0024] (1) Preparation and structure confirmation of cyclobenztinib citrate

[0025] Add N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5 to the reaction flask, 6,7,8-tetrahydronaphthalene-2-amide (5.33 g, 10 mmol), 200 ml of absolute ethanol, citric acid (1.01 g, 10.5 mmol), stirred and refluxed at 70°C for 0.5 hours, After cooling to room temperature, a solid precipitated out, which was filtered out by suction and recrystallized by stirring with 180 ml of ethanol. Filter and dry to get the product N-{4-methyl-3-[(4-pyridin-3 base)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)- 5.94 g of 5,6,7,8-tetrahydronaphthalene-2-amide citrate (i.e., cyclobenztinib citrate), with a yield of 94.5%. Its structural formula is as (I).

[0026]

[0027] Molecular formula: C 32 h 35 N 7 O·C 6 h 8 o 7 .

[0028] Melting point: 191-193°C....

Embodiment 2

[0039] Example 2: Containing N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5 , Tablets of 6,7,8-tetrahydronaphthalene-2-amide or a pharmaceutically acceptable salt thereof

[0040] (1) The composition of each tablet is as follows according to the percentage by weight:

[0041]

[0042] (2) Preparation method

[0043] 1) Mix cyclobenztinib citrate with diluent microcrystalline cellulose and hypromellose evenly;

[0044] 2) Add water, make the mixture wet and knead in a high-shear mixer, sieve with a sieve mill with rotating impellers, and dry;

[0045] 3) Add disintegrant crospovidone and glidant anhydrous colloidal silicon dioxide, and mix in a diffusion mixer;

[0046] 4) Add lubricant magnesium stearate and mix in a diffusion mixer;

[0047] 5) Compress the mixture obtained in step 4) with a conventional tablet press;

[0048] 6) Coating: Coating in a coating pan.

[0049] (3) Shape: The weight of each tablet is about 210mg, an...

Embodiment 3

[0050] Example 3: Containing N-{4-methyl-3-[(4-pyridin-3 base)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5 , Tablets of 6,7,8-tetrahydronaphthalene-2-amide or a pharmaceutically acceptable salt thereof

[0051] (1) The composition of each tablet is as follows according to the percentage by weight:

[0052]

[0053] (2) Preparation method

[0054] 1) Mix cyclobenztinib citrate with microcrystalline cellulose and hypromellose evenly;

[0055] 2) Add water, make the mixture wet and knead in a high-shear mixer, sieve with a sieve mill with rotating impellers, and dry;

[0056] 3) Add disintegrant crospovidone and glidant anhydrous colloidal silicon dioxide, and mix in a diffusion mixer;

[0057] 4) Add lubricant magnesium stearate and mix in a diffusion mixer;

[0058] 5) Compress the mixture obtained in step 4) with a conventional tablet press;

[0059] 6) Coating: Coating in a coating pan.

[0060] (3) Shape: The weight of each tablet is about 130mg, and the ...

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Abstract

The present invention relates to a high drug load tablet containing N-{4-methyl-3-[(4-pyridin-3yl)pyrimidin-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5,6,7,8-tetrahydronaphthalene-2-amide or a pharmaceutically acceptable salt thereof. The high drug load tablet is prepared from 30-75% by weight of N-{4-methyl-3-[(4-pyridin-3yl)pyrimidin-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5,6,7,8-tetrahydronaphthalene-2-amide or a pharmaceutically acceptable salt thereof, 1-50% by weight of a diluent, 5-40% by weight of a disintegrating agent, 0.1-10% by weight of a glidant and 0.1-5% by weight of a lubricant. The tablet contains high main drug content and relatively low excipient content, such that the tablet with a small size can be prepared so as to provide convenience for applicators.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a compound containing (N-{4-methyl-3-[(4-pyridin-3 yl)pyrimidine-2-amino]phenyl}-5-(4-methyl High drug load drug tablets of piperazin-1-yl)-5,6,7,8-tetralin-2-amide or a pharmaceutically acceptable salt thereof. Background technique [0002] N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5,6,7, 8-Tetrahydronaphthalene-2-amide is a selective tyrosine kinase inhibitor, which belongs to tetrahydronaphthalene amides, and is used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. [0003] Since N-{4-methyl-3-[(4-pyridin-3-yl)pyrimidine-2-amino]phenyl}-5-(4-methylpiperazin-1-yl)-5,6,7 , 8-Tetrahydronaphthalene-2-amide has a large dosage (500-1000mg / d orally), and the low drug-loading preparation has complex ingredients and a large amount of excipients, and the resulting preparation is relatively large, wh...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/28A61K31/506A61P35/00A61P35/02
Inventor 陈烨王洋
Owner LIAONING UNIVERSITY