United States Patent:  5,985,323

Assignee:  FMC Corporation (Philadelphia, PA)

Filed:  March 23, 1998

The present invention discloses an improved excipient composition for use as an excipient/binder for wet granulation of pharmaceuticals, a process for preparing the excipient composition, its use in granular pharmaceutical compositions, and compressed pharmaceutical tablets made from the granular pharmaceutical compositions. The excipient composition comprises a dried aqueous slurry of microcrystalline cellulose wetcake and a low viscosity alginate.

SUMMARY DESCRIPTION OF THE INVENTION

In one aspect, the present invention provides an excipient composition for use in wet granulation and tableting of pharmaceutically active ingredients. The excipient composition comprises particles of unattrited microcrystalline cellulose coprocessed with a low viscosity alginate. Coprocessing refers to forming and drying an aqueous slurry of microcrystalline cellulose wetcake and alginate. The excipient composition of this invention may thus be described as a dried aqueous slurry consisting essentially of unattrited microcrystalline cellulose and a low viscosity alginate.

Microcrystalline cellulose useful in the present invention is unattrited microcrystalline cellulose wetcake.

The alginate employed in this invention is preferably low viscosity sodium alginate, but may also be a sodium, calcium salt complex of low viscosity sodium alginate. Thus, the alginate may be selected from the group consisting of low viscosity sodium alginate and a sodium, calcium complex of low viscosity sodium alginate. It is thus important to use an alginate which has a viscosity in the range of about 40 cps to about 80 cps. A suitable product for this purpose is sold by KELCO Div., Monsanto Co. as KELGIN.RTM. LV.

If it is desired to use the sodium, calcium salt complex, this salt complex of the low viscosity sodium alginate is preferably formed in situ from low viscosity sodium alginate in the manner and amounts described in U.S. Pat. 5,366,472, which for this purpose is hereby incorporated herein by reference, and/or as shown in example 2 below.

In accordance with the present invention the weight ratio of the microcrystalline cellulose to the alginate is from about 95:5 to about 75:25, preferably from about 95:5 to about 95:15.

In accordance with the process aspect of this invention, the excipient composition described above is suitably prepared by (a) forming an aqueous slurry of unattrited microcrystalline cellulose wetcake, (b) adding the alginate to the stirred slurry, (c) forming a uniform slurry in which the microcrystalline cellulose and alginate are uniformly distributed, (d) drying the uniform slurry, and (e) recovering the particulate composition. The particulate composition resulting from this process is the granulation composition referred to above. It is essentially an agglomerate of the microcrystalline cellulose and alginate which has properties distinct from either of them alone and also distinct from a simple blend of the two.

In yet another aspect of the invention, there is provided a granular pharmaceutical composition comprising the excipient composition described above in admixture with a medicinally effective amount of a pharmaceutically active ingredient. The granular pharmaceutical composition is preferably prepared by blending the excipient composition with a pharmaceutically active ingredient, each in suitable amounts depending on the desired concentration or amount of active ingredient to be included in the final product, then wet granulating and drying the blend in accordance with procedures that are well known to those skilled in the pharmaceutical formulation art.

In carrying out the granulation, however, the water content of the granulated MCC/alginate excipient with an active pharmaceutical agent may need to be controlled for optimum functionality of the excipient/binder. Furthermore, the useful water content will usually vary with each pharmaceutical active agent being granulated. For example, in the case of acetaminophen, the water content of the dried granulation should be in the range of 2-3 weight %, preferably 2-2.75 weight %. When the final formulation is prepared, other components may, and probably will, introduce additional water, raising the final water content to or above 3 weight percent. It is well known that acetaminophen cannot tolerate a water content significantly above 3 weight % because of the hydrolysis that occurs.

It will also be understood by those skilled in the formulation art that various other conventional additives may be included in the granular pharmaceutical composition, such as other binders, diluents, disintegrants, lubricants, flavoring agents, sweetening agents, and the like. Likewise such additional additives may be blended with the resulting pharmaceutical composition as desired prior to tableting. The resulting tableting formulation is then utilized in a conventional manner to prepare compressed tablet formulations of various types, sizes and shapes.

Claim 1 of 8 Claims

1. An excipient composition comprising particles of a dried aqueous slurry consisting essentially of unattrited microcrystalline cellulose wetcake and a low viscosity alginate selected from the group consisting of low viscosity sodium alginate and a sodium, calcium salt complex of low viscosity sodium alginate in which the low viscosity alginate has a viscosity in the range of 40 to 80 cps.

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