Pharmaceutical excipient having improved compressability

• US 5,585,115 A
• Filed: 01/09/1995
• Issued: 12/17/1996
• Est. Priority Date: 01/09/1995
• Status: Expired due to Term

• Current Assignee: J Rettenmaier & Sohne GmbH Company KG
• Original Assignee: Edward Mendell Co., Inc.
• Inventors: Staniforth, John H., Hunter, Edward A., Sherwood, Bob E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US08/370,576
• Time in Patent Office: 708 Days
• Field of Search: 424/489, 424/469, 424/470, 424/480, 424/494
• US Class Current: 424/489
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2036 Silicones; Polysiloxanes
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: Y10S 977/727 formed from biological material
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/775 Nanosized powder or flake, e.g. nanosized catalyst
• CPC Class Codes: Y10S 977/801 Drug
• CPC Class Codes: Y10S 977/89 Deposition of materials, e.g. coating, cvd, or ald
• CPC Class Codes: Y10S 977/896 Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

A microcrystalline cellulose-based excipient having improved compressibility, whether utilized in direct compression, dry granulation or wet granulation formulations, is disclosed. The excipient is an agglomerate of microcrystalline cellulose particles and from about 0.1% to about 20% silicon dioxide particles, by weight of the microcrystalline cellulose, wherein the microcrystalline cellulose and silicon dioxide are in intimate association with each other. The silicon dioxide utilized in the novel excipient has a particle size from about 1 nanometer to about 100 microns. Most preferably, the silicon dioxide is a grade of colloidal silicon dioxide.

Claims

1. An excipient composition comprising a particulate agglomerate of microcrystalline cellulose coprocessed with from about 0.1% to about 20% by weight silicon dioxide, the microcrystalline cellulose and silicon dioxide being in intimate association with each other and said silicon dioxide being integrated with or partially coating said microcrystalline cellulose, said silicon dioxide portion of said agglomerate being derived from a silicon dioxide having an average primary particle size from about 1 nm to about 100 μ

m.

2. The composition of claim 1, wherein said silicon dioxide portion of said agglomerate is derived from a silicon dioxide having an average primary particle size from about 5 nm to about 40 μ

m.

3. The composition of claim 1, wherein said silicon dioxide portion of said agglomerate is derived from colloidal silicon dioxide.

4. The composition of claim 1, wherein said silicon dioxide is included in amount from about 0.1% to about 20% by weight, based on the weight of microcrystalline cellulose.

5. The composition of claim 1, wherein said silicon dioxide is from about 0.5% to about 10% by weight, based on the weight of said microcrystalline cellulose.

6. The composition of claim 1, wherein said silicon dioxide is included in an amount of from about 1.25% to about 5%, based on the weight of said microcrystalline cellulose.

7. The composition of claim 1, wherein said excipient particles have an average particle size of from about 10 μ

m to about 1,000 μ

m.

8. The composition of claim 1, wherein said excipient particles have an average particle size of from about 10 μ

m to about 500 μ

m.

9. The composition of claim 1, wherein said excipient particles have an average particle size of from about 30 μ

m to about 250 μ

m.

10. The composition of claim 1, wherein said excipient particles have a moisture content from about 0.5% to about 15%.

11. The composition of claim 1, wherein said excipient particles further comprise a member of the group consisting of non-silicon metal oxides, starches, starch derivatives, surfactants, polyalkylene oxides, celluloses, cellulose ethers, cellulose esters and mixtures thereof.

12. The composition of claim 1, wherein said silicon dioxide portion of said agglomerate is derived from a silicon dioxide having a surface area from about 10 m² /g to about 500 m² /g.

13. The composition of claim 1, wherein said silicon dioxide portion of said agglomerate is derived from a silicon dioxide having a surface area from about 175 m² /g to about 350 m² /g.

14. The composition of claim 1, wherein said excipient has a bulk density from about 0.2 g/ml to about 0.6 g/ml.

15. The composition of claim 3, wherein said excipient has a bulk density from about 0.35 g/ml to about 0.55 g/ml.

25. The composition of claim 1, which has been wet granulated.

26. The composition of claim 1, which has been incorporated into a solid form.

27. The composition of claim 1, which has been wet granulated with an active agent.

28. The composition of claim 26, wherein said composition has been wet granulated with, wherein said excipient particles further comprise a member of the group consisting of non-silicon metal oxides, starches, starch derivatives, surfactants, polyalkylene oxides, celluloses, cellulose ethers, cellulose esters and mixtures thereof.

16. An excipient composition, comprising from about 1% to about 99% of an excipient comprising a particulate agglomerate of microcrystalline cellulose coprocessed with from about 0.1% to about 20% silicon dioxide by weight of said microcrystalline cellulose, the microcrystalline cellulose and silicon dioxide being in intimate association with each other and said silicon dioxide being integrated with or partially coating said microcrystalline cellulose, and the silicon dioxide portion of said agglomerate being derived from a silicon dioxide having an average primary particle size from about 1 nm to about 100 μ

m, and from about 99% to about 1% of an active ingredient.

17. The composition of claim 16, wherein the silicon dioxide portion of said agglomerate is derived from a silicon dioxide having an average primary particle size from about 5 nm to about 40 μ

m.

18. The composition of claim 16, wherein the silicon dioxide portion of said agglomerate is derived from colloidal silicon dioxide.

19. The composition of claim 16 which has been wet granulated.

20. The composition of claim 18, which has been wet granulated.

21. The composition of claim 16, which has been incorporated into a solid form.

22. An excipient composition, comprising a particulate excipient of microcrystalline cellulose integrated with from about 0.1% to about 20% silicon dioxide by weight of said microcrystalline cellulose, said silicon dioxide coprocessed with and partially coating said microcrystalline cellulose and silicon dioxide portion of said excipient being derived from silicon dioxide having a surface area from about 10 m² /g to about 500 m² /g.

23. The composition of claim 22, wherein said silicon dioxide portion of said excipient is derived from silicon dioxide having a surface area from about 175 m² /g to about 350 m² /g.

24. The composition of claim 22, wherein said silicon dioxide portion of said excipient is derived from colloidal silicon dioxide.

29. The composition of claim 22, which has been wet granulated.

30. The composition of claim 22, which has been wet granulated with an active agent.

31. The composition of claim 22, wherein said excipient particles further comprise member of the group consisting of non-silicon metal oxides, starches, starch derivatives, surfactants, polyalkylene oxides, celluloses, cellulose ethers, cellulose esters and mixtures thereof.