Details for Patent: 6,471,994
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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 about 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 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: | Edward Mendell Co., Inc. (Patterson, NY) |
| Filing Date: | Aug 27, 1999 |
| Application Number: | 09/384,130 |
| Claims: | 1. A method for preparing a pharmaceutical excipient, comprising: forming an aqueous slurry containing a mixture of microcrystalline cellulose in the form of a wet cake and silicon dioxide having a surface area from about 10 m.sup.2 /g to about 500 m.sup.2 /g, wherein said slurry comprises from about 0.5% to about 25% by weight microcrystalline cellulose in the form of a wet cake; and drying said slurry to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose and 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 slurry contains from about 15% to about 20% microcrystalline cellulose in the form of a wet cake. 3. The method of claim 1, wherein said slurry contains from about 17% to about 19% microcrystalline cellulose in the form of a wet cake. 4. The method of claim 1, wherein said silicon dioxide is colloidal silicon dioxide. 5. The method of claim 1, wherein said drying further comprises drying the slurry of microcrystalline cellulose and silicon dioxide by a method selected from the group consisting of flash drying, ring drying, spray drying, and micron drying. 6. The method of claim 1, wherein said drying further comprises drying said slurry of microcrystalline cellulose and silicon dioxide by spray drying. 7. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having an average particle size from about 10 .mu.m to about 1,000 .mu.m. 8. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a particle size of from about 10 .mu.m to about 500 .mu.m. 9. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a moisture content of from about 0.5 to about 15%. 10. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a moisture content of from about 0.5 to about 2.5%. 11. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a moisture content of from about 0.5 to about 1.8%. 12. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a moisture content of from about 0.8 to about 1.5%. 13. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a moisture content of from about 0.8 to about 1.2%. 14. The method of claim 1, wherein said drying further comprises drying said slurry to obtain excipient particles having a particle size of from about 30 .mu.m to about 250 .mu.m. 15. The method of claim 1, further comprising adding an additional material to said slurry, said material being selected from the group consisting of non-silicon metal oxides starches, starch derivatives, surfactants, polyalkylene oxides, celluloses, cellulose ethers, and mixtures thereof. 16. A method for preparing a pharmaceutical excipient, comprising: forming an aqueous slurry containing a mixture of microcrystalline cellulose in the form of a wet cake and silicon dioxide having an average primary particle size from about 1 nm to about 100 .mu.m, wherein said slurry comprises from about 0.5% to about 25% by weight microcrystalline cellulose in the form of a wet cake, the solids content of said slurry being from about 0.5% to about 25%, by weight; and, drying said slurry to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose and silicon dioxide, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight. 17. The method of claim 16, wherein said slurry contains from about 15% to about 20% microcrystalline cellulose in the form of a wet cake. 18. The method of claim 16, wherein said slurry contains from about 17% to about 19% microcrystalline cellulose in the form of a wet cake. 19. The method of claim 16, wherein said silicon dioxide is colloidal silicon dioxide. 20. The method of claim 16, wherein said drying further comprises drying the slurry of microcrystalline cellulose and silicon dioxide by a method selected from the group consisting of flash drying, ring drying, spray drying, and micron drying. 21. The method of claim 1, wherein said drying further comprises drying the slurry by a method selected from the group consisting of flash drying, ring drying, spray drying, fluid bed drying, micron drying, and combinations thereof. 22. The method of claim 1, wherein said drying further comprises drying the slurry by a method selected from the group consisting of flash drying, ring drying, spray drying, fluid bed drying, micron drying, and combinations thereof. 23. The method of claim 16, wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.5 to about 2.5%. 24. The method of claim 16 wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.5 to about 1.8%. 25. The method of claim 16, wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.5%. 26. The method of claim 16, wherein said drying further comprises drying said slurry such that the resultant excipient particles have a moisture content of from about 0.8 to about 1.2%. |
