United States Patent:  6,103,260

Assignee:  McNeil-PPC, Inc. (Skillman, NJ)

Filed:  July 17, 1997

The invention relates to antifoam oral solid dosage form preparations formed from a free flowing granular composition comprising an admixture of simethicone and either one or both of granular anhydrous tribasic calcium phosphate or dibasic calcium phosphate wherein the admixture is a uniform granular composition of not more than 1000 micron particle size which is suitable for compression into a solid dosage form for oral administration.

SUMMARY OF THE INVENTION

The invention relates to antifoam oral solid dosage form preparations formed from a free flowing granular composition comprising an admixture of simethicone and either one or both of granular anhydrous tribasic calcium phosphate or dibasic calcium phosphate wherein the admixture is a uniform granular composition of not more than 1000 micron particle size which is suitable for compression into a solid dosage form for oral administration. The granular anhydrous tribasic or dibasic calcium phosphate comprises about 30-90% w/w of the admixture combinate. The simethicone comprises about 10-70% w/w of the admixture combinate. In a preferred embodiment, the combinate further comprises 0.5 to 4% w/w of a silicone dioxide or 1.0-30.0% w/w of anhydrous calcium phosphate powder. The free flowing granular composition is admixed with conventional tablet binders and excipients and is compressed into the solid oral dosage forms. Preferably, the simethicone comprises greater than about 8% and less than about 20% w/w of the final blend for compression.

In another aspect of the invention, a process for producing a free flowing granular composition of a simethicone antifoam agent for compression into solid oral dosage forms is provided which comprises forming an admixture of granular anhydrous tribasic or dibasic calcium phosphate, the simethicone antifoam agent and optionally a silicon dioxide or anhydrous calcium phosphate powder by adding the simethicone to the granular tribasic or dibasic calcium phosphate and the optional silicon dioxide or anhydrous calcium phosphate powder, dry blending until uniform and shearing to assure a uniform powder. In a further aspect of the process, the granular composition is then combined with excipient materials or other active ingredients and compressed to provide the solid oral dosage form, preferably in the form of a compressed tablet, which may be further processed by coating with an aqueous film coating or enteric coating and/or gelatin dipped and printed.

Benefits of the anhydrous calcium phosphates/simethicone combinate of the present invention over the aforementioned prior art compositions are that it is both a more free flowing and more stable admixture than one comprising agglomerated maltodextrin/simethicone and it is not prone to separation of the simethicone from the substrate. A benefit over the composition of U.S. Pat. No. 4,906,478 is that the anhydrous calcium phosphate/simethicone combinates have significantly better defoaming activity as measured by U.S. Pharmacopia standards (USP 23, page 1411(Simethicone Tablets monograph).

Claim 1 of 12 Claims

1. An antifoam simethicone free-flowing granular composition suitable for use as an oral solid dosage form preparation formed by (i) preparing a granular composition consisting essentially of an admixture of (a) simethicone and (b) granular anhydrous tribasic or dibasic calcium phosphate or a mixture thereof; wherein the simethicone is adsorbed by the granular anhydrous tribasic or dibasic calcium phosphate or mixture thereof, and wherein the simethicone/calcium phosphate admixture is a uniform granular composition of not more than 1000 micron particle size, and (ii) admixing the uniform granular composition with one or more excipients to form the free-flowing granular composition.

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