United States Patent:  6,110,505

Assignee:  McNeil PPC Inc. (New Brunswick, NJ)

Filed:  April 1, 1997

The invention provides an essentially translucent liquid antacid composition with dihydroxyaluminum sodium carbonate (DASC) as the active ingredient. The DASC is prepared by co-drying DASC with a polyol, and the resulting co-dried DASC/polyol is mixed with water to form the liquid composition. The antacid composition preferably contains additional polyol to further improve the translucency of the liquid composition.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

It has been found that use of co-dried DASC/polyol forms a more translucent liquid antacid composition as compared to liquid compositions containing conventional DASC. The co-dried DASC/polyol is produced by, first, preparing DASC using conventional methods, such as by precipitation of aluminum isopropoxide with an aqueous solution of sodium bicarbonate. The precipitated DASC is filtered and washed under vacuum and the resulting wet cake is resuspended in water and polyol, e.g. sorbitol or maltitol. The resulting slurry is then spray-dried to produce a co-dried material which is pharmaceutically equivalent in antacid activity to commercially available DASC (see the Examples below).

The co-dried DASC/polyol normally contains approximately 50-90% DASC and 10-40% polyol/sorbitol by weight. To prepare the co-dried DASC/sorbitol, commercially available DASC and polyols may be used. It is preferred that the average particle size of the DASC used to make the co-dried material is less than about 1 micron, and more preferably less than about 0.5 microns.

To form the composition of the invention, the co-dried DASC/polyol is mixed with water or water and polyol to form an essentially translucent liquid antacid composition. Preferably, the co-dried DASC/polyol comprises approximately 0.5% to 5.0% by weight of the antacid composition. More preferably, the co-dried DASC/polyol comprises about 2.0 to about 5.0% by weight of the antacid composition. Most preferably, the co-dried DASC/polyol comprises about 3.0% to about 4.0% by weight of the antacid composition.

The term polyol refers to a non-toxic, pharmaceutically acceptable polyhydric alcohol. Suitable polyols include hydrogenated monosaccharides such as sorbitol, mannitol and xylitol, and hydrogenated disaccharides such as malitol, isomalt and lactitol. Sorbitol and mannitol are preferred polyols, with sorbitol being the most preferred.

Other possible components of the antacid suspension are conventional formulation aids such as suspending agents, antigelling additives, surface modifiers, preservatives, sweeteners, flavorants, waxes, colorants and diluents. Suitable additives include hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sugars, sugar alcohols, saccharin, salts, parabens, such as butyl and methyl parabens, and ethylenediamine tetra-acetic acid. It is anticipated that the antacid of the present invention may be combined with effective amounts of other active ingredients, such as antifoaming agents like simethicone, histamine H₂ -receptor-antagonists like cimetidine, ranitidine, nizatidine and famotidine, and proton-pump inhibitors such as omeprazole and lansoprazole.

A suspension formed from co-dried DASC and water is preferably combined with additional polyol to further enhance the translucency. The additional polyol as added may be in the form of a solid powder or an aqueous solution concentrated to 50-80% polyol by weight. For example, USP sorbitol solution, which is 70% w/w polyol, may be used. Preferably, about 10% to about 30% polyol solution (e.g. USP) is used to enhance translucency. Most preferably, about 20% additional polyol is used.

With or without the additional polyol, the resulting antacid composition is essentially translucent. By essentially translucent is meant translucent to the naked eye. In optical measurements, the composition would typically measure less than about 2000 NTU, preferably less than about 1500 NTU, and most preferably less than about 1000 NTU.

The concentration of the effective ingredient can vary depending on desired antacid strength. The invention allows for translucency of the liquid composition while maintaining a high ANC (Acid Neutralizing Capacity) value. Translucency has been maintained for ANC values as high as about 10.5 mEq/15 ml or higher.

The composition of the invention provides fast-acting antacid relief and high acid neutralizing capacity, with good mouth feel characteristics and desirable appearance. The antacid suspension retains substantial efficacy over a standard shelf life. Furthermore, the antacid formulation is slow settling and exhibits thixotropic properties.

A preferred formulation is as follows (all percentages are expressed as weight based on the total weight of the finished formulation). The antacid composition contains co-dried 75% DASC/25% sorbitol (by weight) in an amount effective for pharmaceutical purposes, typically about 0.5 to 5.0% by weight, approximately 67.0% to about 81.0% % by weight of water, and 10-30% by weight additional polyol. The composition may contain about 0.05% to about 0.5% by weight suspending agents, preferably hydroxyethyl cellulose, and about 0.02% to about 0.07% by weight antigelling agents, preferably edetate disodium.

One advantage of the invention herein is that preservatives are not needed in the final formulation due to the basic nature of DASC. However, preservatives may be added, in effective amounts of about 0.01% to about 0.05% by weight. The composition may also contain about 0.01% to about 0.05% by weight sweeteners, e.g. sodium saccharin. The composition will preferably contain approximately 0.2% to about 1.2% by weight flavorants and approximately 0.04% to about 0.4% % by weight food dyes.

A currently most preferred formulation is as follows: about 75.5% purified water, about 20.0% sorbitol solution (USP), about 0.12% hydroxyethyl cellulose; about 3.4% codried DASC/sorbitol, about 0.047% edetate disodium, about 0.30% sodium carbonate, about 0.0275% sodium saccharin, about 0.58% flavorants (e.g. 0.35% peppermint and 0.22% alpine creme) and about 0.00095% dyes (e.g. 0.00065% blue #1 dye and 0.00030% yellow #10 dye).

By way of explanation, it is understood that those skilled in the art need only understand the nature of the recipe for the starting materials to make the antacid composition of the invention herein. It is well understood in this particular art that one can describe the final product by referring back to the precursor or starting materials, since such a description is sufficient for the reproducibility of the product.

The composition of the invention my be prepared as follows. First, the additional polyol is dissolved in water. Optionally, a suspending agent, such as hydroxyethyl cellulose (HEC), may be added to the polyol/water mixture and mixed until the polyol and suspending agent are completely dissolved. The co-dried DASC/polyol (i.e. DASC/sorbitol) is added to the solution and thoroughly mixed until the liquid is free of lumps. Once the codried DASC/sorbitol has been dispersed in the polyol solution, other optional formulation aids may be added. The suspension is then milled and pasteurized.

Claim 1 of 13 Claims

1. An essentially translucent aqueous antacid composition comprising from about 0.5 to about 5.0% by weight of co-dried DASC/polyol as an antacid active ingredient and containing about 10 to about 30% by weight of an additional polyol to render the composition essentially translucent.

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