Details for Patent: 6,746,693
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| Title: | Pharmaceutical excipient having improved compressibility |
| 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 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 1 nanometer to about 100 microns. Most preferably, the silicon dioxide is a grade of colloidal silicon dioxide. An extra low moisture excipient is provided which exhibits improved compressibility as compared to conventional microcrystalline cellulose, while providing a moisture content of of from about 0.5 to 2.5% LOD, preferably between about 0.5 and about 1.8%, more preferably between 0.8 and 1.5%, and most preferably between about 0.8 and about 1.2%. |
| Inventor(s): | Staniforth; John N. (Bath, GB), Sherwood; Bob E. (Amenia, NY), Hunter; Edward A. (Cadosia, NY) |
| Assignee: | J. Rettenmaier & Soehne GmbH + Co. KG (Rosenberg, DE) |
| Filing Date: | Oct 08, 2002 |
| Application Number: | 10/266,518 |
| Claims: | 1. A method for preparing a pharmaceutical excipient comprising: forming an aqueous slurry of microcrystalline cellulose in the form of a wet cake; forming an aqueous slurry of silicon dioxide having a particle size of from about 1 nm to about 100 .mu.m; separately introducing said microcrystalline slurry and said silicon dioxide slurry into a drying apparatus for combination therein to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight. 2. The method of claim 1, wherein said aqueous slurry of microcrystalline cellulose slurry contains from about 0.5% to about 25% microcrystalline cellulose by weight in the form of a wet cake. 3. The method of claim 1, wherein said aqueous slurry of microcrystalline cellulose contains from about 15% to about 20% microcrystalline cellulose in the form of a wet cake. 4. The method of claim 1, wherein said aqueous slurry of microcrystalline cellulose contains from about 17% to about 19% microcrystalline cellulose in the form of a wet cake. 5. The method of claim 1, wherein said silicon dioxide is colloidal silicon dioxide. 6. The method of claim 1, wherein said silicon dioxide has a surface area from about 10 m.sup.2 /g to about 500 m.sup.2 /g. 7. The method of claim 1, wherein said silicon dioxide has a surface area from about 50 m.sup.2 /g to about 500 m.sup.2 /g. 8. The method of claim 1, wherein said silicon dioxide has a surface area from about 175 m.sup.2 /g to about 350 m.sup.2 /g. 9. The method of claim 1, wherein said silicon dioxide is present in an amount from about 0.5% to about 10% by weight, based on the weight of said microcrystalline cellulose. 10. The method of claim 1, wherein said silicon dioxide is present in an amount from about 1.25% to about 5% by weight, based on the weight of said microcrystalline cellulose. 11. The method of claim 1, wherein said agglomerated particles have an average particle size from about 10 .mu.m to about 1,000 .mu.m. 12. The method of claim 1, wherein said agglomerated particles have an average particle size from about 10 .mu.m to about 500 .mu.m. 13. The method of claim 1, wherein said agglomerated particles have an average particle size from about 30 .mu.m to about 250 .mu.m. 14. The method of claim 1, wherein said agglomerated particles have a moisture content of from about 0.5 to about 15%. 15. The method of claim 1, wherein said agglomerated particles have a moisture content of from about 2.5 to about 6%. 16. The method of claim 1, wherein said agglomerated particles have a moisture content of from about 3.0 to about 5%. 17. The method of claim 1, wherein said drying of said aqueous slurry of microcrystalline cellulose and said aqueous slurry of silicon dioxide is accomplished by a method selected from the group consisting of spray drying, flash drying, ring drying, micron drying, tray drying, vacuum drying, radio-frequency drying and microwave drying. 18. The method of claim 1, wherein said drying of said aqueous slurry of microcrystalline cellulose and said aqueous slurry of silicon dioxide is accomplished by spray drying. 19. A method for preparing a solid dosage form, comprising: (a) forming an aqueous slurry of microcrystalline cellulose in the form of a wet cake; (b) forming an aqueous slurry of silicon dioxide having a particle size of from about 1 nm to about 100 .mu.m; (c) separately introducing said microcrystalline slurry and said silicon dioxide slurry separately into a drying apparatus for combination therein to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight. (d) mixing an active ingredient with said agglomerated particles; (e) incorporating said mixture obtained in step (d) into a plurality of solid unit doses. 20. The method of claim 19, further comprising wet granulating said mixture obtained in step (c) prior to incorporating said mixture into said solid unit doses. 21. The method of claim 19, wherein said aqueous slurry of microcrystalline cellulose slurry contains from about 0.5% to about 25% microcrystalline cellulose by weight in the form of a wet cake. 22. The method of claim 19, wherein said aqueous slurry of microcrystalline cellulose contains from about 15% to about 20% microcrystalline cellulose in the form of a wet cake. 23. The method of claim 19, wherein said aqueous slurry of microcrystalline cellulose contains from about 17% to about 19% microcrystalline cellulose in the form of a wet cake. 24. The method of claim 19, wherein said silicon dioxide is colloidal silicon dioxide. 25. The method of claim 19, wherein said silicon dioxide has a surface area from about 10 m.sup.2 /g to about 500 m.sup.2 /g. 26. The method of claim 19, wherein said silicon dioxide has a surface area from about 50 m.sup.2 /g to about 500 m.sup.2 /g. 27. The method of claim 19, wherein said silicon dioxide has a surface area from about 175 m.sup.2 /g to about 350 m.sup.2 /g. 28. The method of claim 19, wherein said silicon dioxide is present in an amount from about 0.5% to about 10% by weight, based on the weight of said microcrystalline cellulose. 29. The method of claim 19, wherein said silicon dioxide is present in an amount from about 1.25% to about 5% by weight, based on the weight of said microcrystalline cellulose. 30. The method of claim 19, wherein said agglomerated particles have an average particle size from about 10 .mu.m to about 1,000 .mu.m. 31. The method of claim 19, wherein said agglomerated particles have an average particle size from about 10 .mu.m to about 500 .mu.m. 32. The method of claim 19, wherein said agglomerated particles have an average particle size from about 30 .mu.m to about 250 .mu.m. 33. The method of claim 19, wherein said agglomerated particles have a moisture content of from about 0.5 to about 15%. 34. The method of claim 19, wherein said agglomerated particles have a moisture content of from about 2.5 to about 6%. 35. The method of claim 19, wherein said agglomerated particles have a moisture content of from about 3.0 to about 5%. 36. The method of claim 19, wherein said drying of said aqueous slurry of microcrystalline cellulose and said aqueous slurry of silicon dioxide is accomplished by a method selected from the group consisting of spray drying, flash drying, ring drying, micron drying, tray drying, vacuum drying, radio-frequency drying and microwave drying. 37. The method of claim 19, wherein said drying of said aqueous slurry of microcrystalline cellulose and said aqueous slurry of silicon dioxide is accomplished by spray drying. |
