Pharmaceutical composition comprising bicyclo-substituted pyrazolon azo derivative or salt thereof and preparation method thereof
Disclosed is a pharmaceutical composition containing a bicyclo-substituted pyrazolone azo derivative or a salt thereof and a preparation method thereof. In particular, the pharmaceutical composition disclosed in the present invention contains (Z)-5-(2-hydroxyl-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalene-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or a pharmaceutically acceptable salt thereof, and at least one filler optionally selected from cellulose, microcrystalline cellulose, lactose and starch. The composition has a good stability, dissolution rate and bioavailability, and the preparation process is simple, economical and quick.
1. A pharmaceutical composition, comprising (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or a pharmaceutically acceptable salt thereof, a disintegrant comprising low-substituted hydroxypropyl cellulose (L-HPC), and a filler, wherein the filler comprises at least one composite auxiliary material selected from the group consisting of cellulose-lactose, microcrystalline cellulose-lactose, and lactose-microcrystalline cellulose-starch.
2. The pharmaceutical composition according to claim 1 , wherein the filler is present in an amount of 4-95% by weight, relative to the weight of the pharmaceutical composition.
3. The pharmaceutical composition according to claim 1 , wherein the disintegrant is present in an amount of 5-30% by weight, relative to the total weight of the pharmaceutical composition.
4. The pharmaceutical composition according to claim 1 , wherein the (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or the pharmaceutically acceptable salt thereof has a particle size D90 of 10-100 μm.
5. The pharmaceutical composition according to claim 1 , wherein the (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or the pharmaceutically acceptable salt thereof has a particle size D50 of 1-20 μm.
6. The pharmaceutical composition according to claim 1 , comprising a pharmaceutically acceptable salt of (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid selected from the group consisting of an ethanolamine salt, a choline salt, a meglumine salt and a tromethamine salt.
7. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition further comprises at least one excipient selected from the group consisting of a binder, lubricant, surfactant, and glidant.
8. A method for preparing the pharmaceutical composition according to claim 1 , comprising: a) mixing (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or a pharmaceutically acceptable salt thereof with a filler, a disintegrant and at least one excipient selected from the group consisting of a binder, lubricant, surfactant, and glidant to obtain a mixture; b) granulating the mixture obtained from step a) to obtain granules and then compressing the granules into a tablet, or directly compressing the mixture into a tablet.
9. The method according to claim 8 , wherein the method further comprises mixing the granules obtained from step b) with a lubricant to prepare the tablet or fill a capsule.
10. The pharmaceutical composition according to claim 1 , wherein the composite auxiliary material is selected from the group consisting of cellulose-lactose and microcrystalline cellulose-lactose.
11. The pharmaceutical composition according to claim 3 , wherein the disintegrant is present in an amount of 8-20% by weight, relative to the total weight of the pharmaceutical composition.
12. The pharmaceutical composition according to claim 4 , wherein the (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or the pharmaceutically acceptable salt thereof has a particle size D90 of 10-50 μm.
13. The pharmaceutical composition according to claim 5 , wherein the (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid or the pharmaceutically acceptable salt thereof has a particle size D50 of 3-20 μm.
14. The pharmaceutical composition according to claim 6 , comprising a diethanolamine salt of (Z)-5-(2-hydroxy-3-(2-(3-methyl-5-oxo-1-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-4(5H)-ylidene)hydrazino)phenyl)furan-2-carboxylic acid.