Title: Chewable tablets containing mannitol and aspartame

United States Patent:  6,296,868

Assignee:  Advanced Technology Pharmaceuticals Corporation (Dacula, GA)

Filed:  November 19, 1998

Chewable tablets and particulate food and pharmaceutical products are disclosed which are made from agglomerates comprising an alcohol sugar such as mannitol and a high intensity sweetener such as Aspartame from which agglomerate tablets may be directly compressed, and processes for making the agglomerates and tablets. The tablets or particulate product containing the agglomerate may contain active ingredients blended with the agglomerate or as part of the agglomerate structure. Tablets and particulate products according to the invention can contain active ingredients such as pharmaceuticals (e.g., antacids, analgesics, cough medicine, drugs, etc.) breath sweeteners, vitamins and dietary supplements, to name a few. The high intensity sweetener containing agglomerates can also be used to make solid food mix type products such as sugar free ice tea mixes.

SUMMARY OF The INVENTION

The above and other objects and advantages, which will be apparent to those skilled in the art, are achieved in the present invention which is directed to, in a broad aspect, an agglomerate sweetener composition comprising an alcohol sugar such as mannitol and a high intensity sweetener. The agglomerate typically has a porous, high surface area void-like structure and is preferably made using a fluidized bed process. The agglomerates preferably comprise mannitol as the alcohol sugar and Aspartame as the high intensity sweetener. A water soluble binder is used to form the agglomerate and is selected from the group consisting of an alcohol sugar which can be the same as the alcohol sugar forming the base of the composition, a water soluble carbohydrate, maltodextrin, polyvinylpyrrolidone and carboxy methyl cellulose (CMC) among others. The preferred binders are the same alcohol sugar forming the base and maltodextrin.

The quantity of water-soluble binder is an effective amount needed to form the agglomerate and is in the range of up to about 10 percent by weight of the agglomerate,(including the high intensity sweetener), and preferably from about 1 percent to about 5 percent. The alcohol sugar particles comprise about 80 percent to about 97 percent and the high intensity sweetener about 1 percent to 10 percent by weight of the agglomerate (including the high intensity sweetener). The ranges vary depending on the product in which the agglomerate is to be used. The particle size of the materials used to make the agglomerates and the particulate size of the agglomerates may likewise vary widely as described below.

A tablet made according to the present invention is directly compressed from the high surface area porous alcohol sugar based high intensity sweetener agglomerate particles preferably using a relatively low tabletting pressure to form a relatively soft, quick-liquefying interior and a relatively hard, protective outer shell which resists liquefaction even though it is formed from the same agglomerate particles which form the tablet interior. At least some of the ingredients of the agglomerate particles jn the interior of the tablet quickly dissolve or partially dissolve when the tablet is broken into pieces and contacted with small amounts of a liquid, particularly water and/or saliva, as during mastication for example, and any remaining ingredients which do not dissolve in the liquid become dispersed in the liquid and dissolved ingredients, so that the resulting liquid is smooth and essentially without perceivable grit. The relatively hard outer shell resists liquefaction until it is broken, for example, by chewing. Accordingly, the overall preferred chewable tablet structure is such that the tablet is storage stable and easily portable, thereby providing a unit dose in a most convenient form, but is also readily liquefied and melts in the saliva of the mouth during mastication without requiring water or some other liquid, so that the tablet provides all of the benefits normally associated only with liquid dosage forms.

Quick-liquifying, chewable tablets are shown in U.S. Pat. No. 4,684,534, which patent is incorporated herein by reference and which patent is assigned to the assignee of the present invention. The patent discloses carbohydrate-based agglomerates, a method for making the agglomerates and tablets made from the agglomerate.

The storage stable high intensity sweetener containing agglomerate comprises an alcohol sugar, high intensity sweetener and a water-soluble binder. The agglomerate may be used in food products without an active ingredient. Typically the agglomerate is used with an active ingredient such as in an ice tea mix or an antacid tablet. The agglomerate is preferably blended with an active ingredient in the formulation. The active ingredient and agglomerate can also be mixed together to;cause the active ingredient to be entrained by and dispersed in the agglomerate. This agglomerate can then be added to the product formulation. The active ingredient can also be formed as part of the agglomerate during the agglomeration process. The high intensity sweetener can be absorbed onto a water-soluble agglomerate but this method and agglomerate composition are not preferred.

The agglomerate as formed has a bulk density which is relatively low compared to the alcohol sugar base and high intensity sweetener which are used to make the agglomerate and is typically in the range of about 0.35 gm/cc to about 0.55 gm/cc. A substantial part of the agglomerate consists of voids, i.e., pores or ducts, which provide an extremely large surface area capable of entraining and dispersing substantial quantities of active ingredients ordinarily about 10 percent to about 50 percent by weight of the finished agglomerate (which includes the entrained active ingredient). The agglomerate has particular utility as a direct compression agglomerate from which tablets according to the invention can be made particularly chewable tablets which liquify in saliva.

A preferred process for making the alcohol sugar and high intensity sweetener agglomerate comprises the steps of forming a fluidized bed of the alcohol sugar and high intensity sweetener particles, intermittently spraying a solution of the water soluble binder in a droplet size into the fluidized bed so as to cause intimate commingling of solution, alcohol sugar and high intensity sweetener particles and adhesion together of alcohol sugar particles and high intensity sweetener particles to form agglomerated particles, drying the particles in the fluidized bed between intermittent sprayings, and continuing spraying and drying until the desired amount of binder solution has been sprayed into the bed. Thereafter, the agglomerated particles are dried to a desired moisture content or the equilibrium moisture content. The amount of liquid binder solution sprayed corresponds to a binder content in the agglomerate of from about 1 percent to about 10 percent by weight to the agglomerate. The alcohol sugar and high intensity sweetener agglomerate and active ingredient and other ingredients such as lubricants, flavors, etc. are mixed, preferably in a low shear blender, to form a blend for tabletting by direct compression or for use as a flowable food or pharmaceutical product.

The agglomerate composition can also be made using a granulating procedure whereby the alcohol sugar, high intensity sweetener and binder are mixed together to form a paste like material, screened, dried and sized.

The agglomerate can, as formed, be used to entrain the active ingredient and other materials such as a lubricant and flavors in the formulation to be made into a product. In addition, an agglomerate containing the active ingredient as part of the agglomerate structure can be formed by the process described above for the agglomerate formed without an active ingredient, except that the active ingredient is mixed with the alcohol sugar and high intensity sweetener particles and a fluidized bed is formed of this mixture. The active ingredient and/or high intensity sweetener may also be added with the binder. Agglomerates formed with an active ingredient have a porous structure similar to that of agglomerates formed without an active ingredient.

The preferred method to form the agglomerate is by a fluidized bed process wherein the alcohol sugar and high intensity sweetener are fluidized and a binder solution sprayed onto the fluidized bed.

It is preferred that the alcohol sugar particles used to make the agglomerate pass about 50 mesh (particle size less than about 300 microns). The high intensity sweetener typically passes about 300 mesh (particle size less than about 50 microns). Mesh sizes given therein refer to the U.S. Standard Sieve Series. The final particle size of the agglomerate is preferably greater than about 80 mesh (111 microns).

A process for making a tablet from the alcohol sugar-high intensity sweetener agglomerates described above, typically including about 0.4 percent to about 1 percent of a lubricant, comprises compressing the agglomerate particles which were mixed with any active ingredient, flavors, etc., in a conventional tablet-forming apparatus to a hardness sufficient to hold the tablet together and preferably substantially destroy the open pore structure of the agglomerate at the surface of the tablet while substantially maintaining the open pore, i.e., large surface area, structure of the agglomerate in the interior of the tablet. Thus, the agglomerate is compressed so that the interior of the tablet preferably retains the essential porous structure and other physical characteristics of the agglomerate which enable it to liquify quickly, while the physical characteristics of the agglomerate are changed primarily at the surface of the tablet.

For the materials described herein, it has been found that the tablets are preferably compressed to a hardness generally about 3 kp to about 8 kp or higher, preferably about 6 kp, which compression forms an interior which essentially retains the physical structure of the agglomerate. A thinner outer shell is preferred since more force is required to break a tablet with a thicker shell and less material is provided in the interior of a tablet having a thicker shell. Since the thickness of the outer shell has been found to increase with tablet hardness, a preferred range for compression of the agglomerate is a hardness of about 3 kp to about 6 kp.

Pressures applied to compress the agglomerates into tablets having a hardness of about 3 kp to 6 kp were found to be in the order of about one-third the pressures ordinarily used to make tablets.

The term "high intensity sweetener" is used herein in a broad sense and encompasses any high intensity sweetener material which can be formed into an agglomerate or entrained in an agglomerate. The preferred high intensity sweetener is Aspartame but other high intensity sweeteners such as Acesulfame, Alatame, Steviasides, saccharin, cyclamates, etc., may also be employed to make the agglomerate high intensity sweetener composition of the invention. The term "active ingredient" is used herein in a broad sense and means a pharmaceutical such as an arntacid, analgesic or drug; or a flavor, breath sweetener, vitamin, dietary supplement, or nutrient; or the like and combinations thereof. Active ingredients include but are not limited to food acids; insoluble metal and mineral hydroxides, carbonates, oxides, polycarbophils and salts thereof; adsorbates of active drugs on a magnesium trisilicate base and on a magnesium aluminum silicate base.

Claim 1 of 16 Claims

Thus, having described the invention, what is claimed is:

1. An agglomerate particulate intense sweetener composition comprising an alcohol sugar and an intense sweetener wherein the particles have voids therein and a bulk density lower than the alcohol sugar and intense sweetener components.

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