Oral disintegrating tablet
An oral disintegrating tablet containing (1) D-mannitol, (2) an active ingredient, (3) one or more disintegrating agents selected from the group consisting of crospovidone and carmellose, and (4) one or more lubricants selected from the group consisting of sodium stearyl fumarate and sucrose esters of fatty acids. The oral disintegrating tablet of the present invention has some excellent properties of (1) allowing easy production in a common facility without necessitating a specialized pharmaceutical technique, (2) having an appropriate strength that does not breakdown in the process of distribution, (3) having a fast disintegrating ability in the oral cavity, and (4) also having excellent ingestion feel such as greatly reduced bitterness or gritty feel; therefore, the tablet can be suitably used as a dosage form that is suitable for aged individuals, children, and seriously ill patients.
1. A method for producing an oral disintegrating tablet, the method comprising:
(1) mixing D-mannitol, a disintegrating agent, a starch, and optionally an active ingredient;
(2) granulating the mixture with an aqueous solution of at least one selected from the group consisting of hydroxypropyl cellulose, pregelatinized starch, polyvinyl alcohol, povidone, hydroxypropylmethylcellulose, agar, and gelatin, as a binder;
(3) drying the granulated product;
(4) mixing the dried product with a lubricant and optionally an active ingredient; and
(5) subjecting the mixture to compression molding with a compressive force of from 7 kN to 11 kN,
wherein the lubricant comprises at least one member selected from the group consisting of sodium stearyl fumarate and a sucrose ester of a fatty acid, and
wherein the disintegrating agent is crospovidone or carmellose,
wherein the tablet comprises the binder in an amount of less than 3% by weight,
wherein the tablet disintegrates in an oral cavity within 30 seconds and has an absolute hardness of 2.5 N/mm 2 or more.
2. The method of claim 1 , wherein the disintegrating agent is crospovidone.
3. The method of claim 1 , wherein the lubricant is sodium stearyl fumarate.
4. The method of claim 1 , wherein the tablet comprises the at least one disintegrating agent in an amount of from 1 to 10% by weight.
5. The method of claim 4 , wherein the tablet comprises the at least one lubricant in an amount of from 0.01 to 5% by weight.
6. The method of claim 1 , wherein the D-mannitol is particulate and an average particle size of the particulate D-mannitol is greater than 10 μm and equal to or less than 500 μm.
7. The method of claim 6 , wherein the average particle size of the particulate D-mannitol is greater than 10 μm and equal to or less than 200 μm.
8. The method of claim 7 , wherein the average particle size of the particulate D-mannitol is greater than 30 μm and equal to or less than 150 μm.
9. The method of claim 1 , wherein an average particle size of the particulate D-mannitol is greater than 30 μm and a specific surface area of the D-mannitol is greater than 0.40 m 2 /g.
10. The method of claim 1 , wherein a crystal structure of the D-mannitol is a β-type crystal.
11. The method of claim 1 , wherein the binder is at least one material selected from the group consisting of hydroxypropyl cellulose and pregelatinized starch.
12. The method of claim 11 , wherein the binder is hydroxypropyl cellulose and a 2% aqueous solution of the hydroxypropyl cellulose has a viscosity of from 2 to 10 mPa·s at 20° C.
13. The method of claim 1 , wherein the tablet comprises the binder in an amount of from 0.01 to 2% by weight.
14. The method of claim 1 , wherein the starch is at least one starch selected from the group consisting of corn starch, potato starch, rice starch, wheat starch, and partially pregelatinized starch.
15. The method of claim 1 , wherein the active ingredient is amlodipine or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the active ingredient is amlodipine besylate.
17. The method of claim 1 , wherein the active ingredient is a particle granulated or coated with a coating agent.
18. The method of claim 1 , wherein the active ingredient is amlodipine, or a pharmaceutically acceptable salt thereof, granulated or coated with coating agent.
19. The method of claim 1 , wherein the active ingredient is amlodipine besylate granulated or coated with a coating agent.
20. The method of claim 1 , wherein the oral disintegrating tablet comprises:
(1) particulate D-mannitol having an average particle size of greater than 30 μm and a specific surface area of greater than 0.40 m 2 /g,
(2) from 0.1 to 50% by weight of an active ingredient,
(3) from 1 to 10% by weight of crospovidone, carmellose, or a combination thereof,
(4) 2% by weight or less of hydroxypropyl cellulose, pregelatinized starch, or a combination thereof,
(5) from 5 to 20% by weight of a starch, and
(6) from 0.1 to 5% by weight of sodium stearyl fumarate.
21. The method of claim 20 , wherein the tablet comprises the at least one binder in an amount of less than 2% by weight.
22. A method for producing an oral disintegrating tablet, the method comprising:
(1) mixing D-mannitol, a disintegrating agent, a starch, and optionally an active ingredient;
(2) granulating the mixture with an aqueous solution of at least one selected from the group consisting of hydroxypropyl cellulose, pregelatinized starch, polyvinyl alcohol, povidone, hydroxypropylmethylcellulose, agar, and gelatin, as a binder;
(3) drying the granulated product;
(4) mixing the dried product with a lubricant and optionally an active ingredient; and
(5) subjecting the mixture to compression molding with a compressive force of from 7 kN to 11 kN,
wherein the lubricant comprises at least one member selected from the group consisting of sodium stearyl fumarate and a sucrose ester of a fatty acid,
wherein the starch is at least one starch selected from the group consisting of corn starch, potato starch, rice starch, wheat starch, and partially pregelatinized starch,
wherein the D-mannitol is particulate and an average particle size of the particulate D-mannitol is greater than 30 μm and equal to or less than 150 μm, and
wherein the disintegrating agent is crospovidone or carmellose,
wherein the tablet comprises the binder in an amount of less than 3% by weight,
wherein the tablet disintegrates in an oral cavity within 30 seconds and has an absolute hardness of 2.5 N/mm 2 or more.
23. The method of claim 22 , wherein the at least one starch is corn starch.
24. The method of claim 1 , wherein the compression molding comprises tableting with a compressive force of from 9 kN to 11 kN.
25. The method of claim 22 , wherein the compression molding comprises tableting with a compressive force of from 9 kN to 11 kN.