FLASHMELT ORAL DOSAGE FORMULATION

• US 20110217342A1
• Filed: 05/16/2011
• Published: 09/08/2011
• Est. Priority Date: 04/12/2000
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Desai, Divyakant, Kothari, Sanjeev
• Granted Patent: US 8,518,421 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is provided granules for the production of flash-melt pharmaceutical oral dosage forms. In addition to one or more medicaments, the granules are composed of an excipient combination consisting of a superdisintegrant, a dispersing agent, a distributing agent, and a binder and may also include other conventional ingredients such as sweetening and flavoring agents. The subject granules are advantageous in that they are stable and can be prepared without the aid of solvents and without the need for special environments or handling. Dosage forms, especially tablets, prepared therefrom on conventional equipment disintegrate in the mouth in under about twenty five seconds.

Claims

1. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent and a binder wherein said medicament is aripiprazole and wherein said dispersing agent is calcium silicate and wherein said superdisintegrant is selected from the group of crospovidone and croscarmellose sodium.

2. A flash-melt pharmaceutical dosage form according to claim 1 wherein said dispersing agent comprises from about 20 to about 70 percent by weight of said dispersing agent based on the total weight of said dosage form.

3. A flash-melt pharmaceutical dosage form according to claim 1 wherein said dispersing agent comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form.

4. A flash-melt pharmaceutical dosage form according to claim 1 wherein greater than 50 percent of said dispersing agent by weight is comprised of calcium silicate.

5. A flash-melt pharmaceutical dosage form according to claim 1 wherein greater than 80 percent of said dispersing agent by weight is comprised of calcium silicate.

6. A flash-melt pharmaceutical dosage form according to claim 1 wherein said calcium silicate is orth-, meta- or alpha triclinic-calcium silicate.

7. A flash-melt pharmaceutical dosage form according to claim 1 wherein said calcium silicate is comprised of a combination of alpha triclinic-calcium silicate and at least one other pharmaceutical grade of calcium silicate wherein said alpha triclinic-calcium silicate comprises from about 10 percent to about 90 percent by weight of said combination.

8. A flash-melt pharmaceutical dosage form according to claim 1 wherein said medicament comprises not more than about 30 percent by weight of said medicament based on the total weight of said dosage form.

9. A flash-melt pharmaceutical dosage form according to claim 1 wherein said medicament comprises not more than about 15 percent by weight of said medicament based on the total weight of said dosage form.

10. A flash-melt pharmaceutical dosage form according to claim 1 wherein said superdisintegrant comprises from about 8 to about 12 percent by weight of said superdisintegrant based on the total weight of said dosage form.

11. A flash-melt pharmaceutical dosage form according to claim 1 wherein said superdisintegrant comprises from about 9 to about 10 percent by weight of said superdisintegrant based on the total weight of said dosage form.

12. A flash-melt pharmaceutical dosage form according to claim 1 wherein based on the total weight of said dosage form, said crospovidone comprises from about 6 to about 8 percent by weight of said crospovidone and said croscarmellose sodium comprises from about 2 to about 4 percent by weight of said croscarmellose sodium.

13. A flash-melt pharmaceutical dosage form according to claim 1 further comprising a distributing agent.

14. A flash-melt pharmaceutical dosage form according to claim 13 wherein said distributing agent comprises from about 1 to about 10 percent by weight of said distributing agent based on the total weight of said dosage form.

15. A flash-melt pharmaceutical dosage form according to claim 14 wherein said distributing agent comprises from about 1.5 to about 3 percent by weight of said distributing agent based on the total weight of said dosage form.

16. A flash-melt pharmaceutical dosage form according to claim 15 wherein said distributing agent is amorphous silica, fumed silica, diatomaceous earth, talc, kaolin or magnesium aluminum trisilicate.

17. A flash-melt pharmaceutical dosage form according to claim 1 wherein said binder is microcrystalline cellulose, hydroxypropyl cellulose, ethyl cellulose, lactose, mannitol or calcium phosphate.

18. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent, a distributing agent and a binder wherein said medicament is aripiprazole and comprises not more than about 30 percent by weight of said medicament based on the total weight of said dosage form, said dispersing agent is calcium silicate having a surface area of 1.0 m²/gm to 210 m²/gm, bulk density of 0.075 g/cc to 0.90 g/cc, true density of 1.70 g/cc to 2.90 g/cc and volatile content of less than 1 percent to 14 percent w/w and which comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form, said superdisintegrant is crospovidone and croscarmellose sodium, said crospovidone comprises from about 6 to about 8 percent by weight of said crospovidone based on the total weight of said dosage form and said croscarmellose sodium comprises from about 2 to about 4 percent by weight of said croscarmellose sodium based on the total weight of said dosage form and wherein said distributing agent is amorphous silica, fumed silica, distomaceous earth, talc, kaolin or magnesium aluminum trisilicate and comprises from about 1 to about 10 percent by weight of said distributing agent based on the total weight of said dosage form.

19. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent, a distributing agent and a binder wherein said medicament is aripiprazole and comprises not more than about 30 percent by weight of said medicament based on the total weight of said dosage form, said dispersing agent is calcium silicate having a surface area of 1.0 m²/gm to 210 m²/gm, bulk density of 0.075 g/cc to 0.90 g/cc, true density of 1.70 g/cc to 2.90 g/cc and volatile content of less than 1 percent to 14 percent w/w and which comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form, said superdisintegrant is crospovidone and croscarmellose sodium, wherein said crospovidone comprises about 7 percent by weight of said crospovidone based on the total weight of said dosage form and wherein said croscaremellose comprises about 3 percent by weight of said crospovidone based on the total weight of said dosage form, and wherein said distributing agent is amorphous silica, fumed silica, distomaceous earth, talc, kaolin or magnesium aluminum trisilicate and comprises from about 10 to about 50 percent by weight of said distributing agent based on the total weight of said dosage form.

20. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent, a distributing agent and a binder wherein said medicament is aripiprazole and comprises not more than about 20 percent by weight of said medicament based on the total weight of said dosage form, said dispersing agent is calcium silicate having a surface area of 1.0 m²/gm to 210 m²/gm, bulk density of 0.075 g/cc to 0.90 g/cc, true density of 1.70 g/cc to 2.90 g/cc and volatile content of less than 1 percent to 14 percent w/w and which comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form, said superdisintegrant is crospovidone and croscarmellose sodium, and wherein said crospovidone comprises about 7 percent by weight of said crospovidone based on the total weight of said dosage form and wherein said croscarmellose comprises about 3 percent by weight of said crospovidone based on the total weight of said dosage form, and wherein said distributing agent is amorphous silica, fumed silica, distomaceous earth, talc, kaolin or magnesium aluminum trisilicate and comprises from about 10 to about 50 percent by weight of said distributing agent based on the total weight of said dosage form.

21. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent, a distributing agent and a binder wherein said medicament is aripiprazole and comprises not more than about 10 percent by weight of said medicament based on the total weight of said dosage form, said dispersing agent is calcium silicate having a surface area of 1.0 m²/gm to 210 m²/gm, bulk density of 0.075 g/cc to 0.90 g/cc, true density of 1.70 g/cc to 2.90 g/cc and volatile content of less than 1 percent to 14 percent w/w and which comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form, said superdisintegrant is crospovidone and croscarmellose sodium and wherein said crospovidone comprises about 7 percent by weight of said crospovidone based on the total weight of said dosage form and wherein said croscarmellose sodium comprises about 3 percent by weight of said crospovidone based on the total weight of said dosage form.

22. A flash-melt pharmaceutical dosage form comprising a medicament, a superdisintegrant, a dispersing agent, a distributing agent and a binder wherein said medicament is aripiprazole and comprises not more than about 5 percent by weight of said medicament based on the total weight of said dosage form, said dispersing agent is calcium silicate having a surface area of 1.0 m²/gm to 210 m²/gm, bulk density of 0.075 g/cc to 0.90 g/cc, true density of 1.70 g/cc to 2.90 g/cc and volatile content of less than 1 percent to 14 percent w/w and which comprises from about 35 to about 45 percent by weight of said dispersing agent based on the total weight of said dosage form, said superdisintegrant is crospovidone and croscarmellose sodium and wherein said crospovidone comprises about 7 percent by weight of said crospovidone based on the total weight of said dosage form and wherein said croscarmellose comprises about 3 percent by weight of said crospovidone based on the total weight of said dosage form.