Pharmaceutical excipient having improved compressibility
AssigneeEdward Mendell Co., Inc.
InventorsBob E. Sherwood, John H. Staniforth, Edward A. Hunter
Life of this patent
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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.
Claims83
An aqueous slurry useful in the preparation of a compressible pharmaceutical excipient, comprising a mixture of microcrystalline cellulose in the form of a wet cake and from about 0.1 % to about 20% by weight silicon dioxide based on the weight of said microcrystalline cellulose, said silicon dioxide having an average primary particle size from about 1 nm to about 100 .mu.m, the solids content of said aqueous slurry being from about 0.5% to about 25% by weight, said silicon dioxide being present in an amount from about 0.5% to about 10%, by weight, based on the weight of said microcrystalline cellulose.
A method of enhancing the compressibility of microcrystalline cellulose in wet granulation products, comprising:
- (i) 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, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight, wherein said slurry comprises from about 0.5% to about 25% by weight microcrystalline cellulose;
- and
- (ii) drying said slurry to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide.
A method of preparing a solid dosage form, comprising:
- (a) forming an aqueous slurry containing a mixture of microcrystalline cellulose in the form of a wet cake and silicon dioxide having a particle size from about 1 nm to about 100 .mu.m, the amount of silicon dioxide being from about 0.1% to about 20% relative to the amount of microcrystalline cellulose, by weight;
- (b) drying said slurry to obtain an excipient comprising a plurality of agglomerated particles of microcrystalline cellulose in intimate association with said silicon dioxide;
- (c) mixing an active ingredient with said excipient in a ratio from about 1:99 to about 99:1;
- (d) incorporating said mixture obtained in step (c) into a plurality of solid unit doses.
The method of claim 22, wherein said aqueous slurry prepared in step (a) comprises from about 0.5% to about 25% by weight microcrystalline cellulose.
A solid dosage form of a compressed mixture of from about 1% to about 99% of an excipient comprising a particulate agglomerate of coprocessed microcrystalline cellulose and from about 0.1% to about 20% by weight silicon dioxide, the microcrystalline cellulose and silicon dioxide being in intimate association with each other, 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 .mu.m, and from about 99% to about 1% of a systemically active therapeutic agent.
A solid dosage form of a compressed mixture of from about 1% to about 99% of an excipient comprising a particulate agglomerate of coprocessed microcrystalline cellulose and from about 0.1% to about 20% by weight silicon dioxide, the microcrystalline cellulose and silicon dioxide being in intimate association with each other, 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 .mu.m, and from about 99% to about 1% of a locally active therapeutic agent.
Dependencies are inferred from the claim text.