Title:  Chewable tablet

United States Patent:  6,146,661

Assignee:  Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP)

Filed:  March 24, 1998

PCT NO:  PCT/JP96/02869

102(e) Date:  March 24, 1998

PCT PUB. Date:  April 10, 1997

Foreign Application Priority Data:  Oct 03, 1995[JP] (7-291612)

Chewable tablets prepared by incorporating a sugar alcohol with a dissolution endotherm of 20 calories or more per gram of a gastrointestinally active ingredient such as a mucous membrane repairing agent or an antacid are provided. The chewable tablets enable the gastrointestinally active ingredient to be orally administered with ease, without water and free from displeasing intrabuccal sensations characteristic of a gastrointestinally active ingredient.

DISCLOSURE OF THE INVENTION

We, the inventors, have conducted in-depth studies to improve the intrabuccal sensations characteristic of chewable tablets as a gastrointestinal drug. These studies have found that this objective can be attained by incorporating not less than a specific amount of a sugar alcohol into the gastrointestinally active ingredient; such a finding led us to accomplish the present invention.

That is, this invention concerns chewable tablets containing a sugar alcohol with a dissolution endotherm of 20 calories or more per gram of a gastrointestinally active ingredient.

The gastrointestinally active ingredient used in the invention may be any pharmaceutically active ingredient for a gastrointestinal drug, such as a mucous membrane repairing agent or an antacid. The particle size of the starting material for the gastrointestinal drug should desirably be small, but any commercially available grade poses no problem. The gastrointestinally active ingredient may be a single ingredient or a mixture of two or more ingredients.

Examples of the mucous membrane repairing agent are sucralfate, sodium azulene sulfonate, aldioxa, glycyrrhizic acid and its salts, L-glutamine, copper chlorophyllin potassium, histidine hydrochloride, porcine gastric wall pepsin decomposition product, and methylmethionine sulfonium chloride.

The antacid includes not only a common antacid generally recognized as being effective in neutralizing gastric acid, but also an H₂ receptor blocking antisecretory effective in healing the gastrointestinal tract. Examples of the antacid are sucralfate, dried aluminum hydroxide gel, magnesium aluminosilicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesia alumina hydrate, aluminum hydroxide gel, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogenphosphate, and calcium hydrogenphosphate. Examples of the H₂ receptor blocking antisecretory are ranitidine, cimetidine, famotidine, nizatidine and roxatidine acetate.

The sugar alcohol used in the invention may be any sugar alcohol in common use, such as sorbitol, erythritol, xylitol or mannitol. The dissolution endotherm of any of the various sugar alcohols is 24 cal/g for sorbitol, 43 calg for erythritol, 35 cal/g for xylitol, or 29 cal/g for mannitol (measured in accordance with the customary method by accurately weighing about 0.5 g of the sugar alcohol, and dissolving it in 20 ml of distilled water at 25^oC.).

These sugar alcohols may be used alone or as a mixture of two or more. Any of them is incorporated in such an amount that the dissolution endotherm will be 20 cal or more per gram of the gastrointestinally active ingredient, whereby gastrointestinal chewable tablets with satisfactory intrabuccal sensation when orally administered can be produced. In the chewable tablets of the invention, the amount of the sugar alcohol incorporated is determined by calculation such that it gives a dissolution endotherm of 20 cal or more per gram of the gastrointestinally active ingredient as described above. The upper limit of the amount of the sugar alcohol incorporated in one chewable tablet is restricted by the size of the tablet and the contents of the ingredients other than the sugar alcohol, including the gastrointestinally active ingredient, in one tablet. Assume that 500 mg of a gastrointestinally active ingredient, 5 mg of an excipient, and 5 mg of a binder are contained, with the rest being xylitol (the sugar alcohol used in the invention), are used in the preparation of 1 g of a chewable tablet in accordance with the invention. In this case, the amount of xylitol incorporated is 490 mg. The dissolution endotherm of the sugar alcohol in the chewable tablet is calculated at 34.3 cal per gram of the gastrointestinally active ingredient.

As noted above, the lower limit of the amount of the sugar alcohol incorporated in the invention is 20 cal as a dissolution endotherm per gram of the gastrointestinally active ingredient in the chewable tablet. Whereas its upper limit is not restricted as far as it is within the range in which chewable tablets can be molded. Within this range, it is possible to select the type and the amount of incorporation of the sugar alcohol in view of the hygroscopicity, sweetness, melting point, price, and so forth. The amount of the sugar alcohol incorporated varies with the type of the gastrointestinally active ingredient used. In the case of a gastrointestinally active ingredient, such as sucralfate, which is incorporated in a high proportion, for example, the amount of the sugar alcohol incorporated expressed in terms of the dissolution endotherm is about 20 to 200 cal, preferably about 20 to 100 cal, per gram of sucralfate. On the other hand, in the case of a gastrointestinally active ingredient, such as azulene, which is incorporated in a low proportion, that amount as the dissolution endotherm is about 20 to 30,000 cal, preferably about 500 to 20,000 cal, per gram of azulene.

For the preparation of the chewable tablets of the invention, additives for use in the production of ordinary tablets may be used, unless they do harm, in addition to the gastrointestinally active ingredient and the sugar alcohol. Examples are pharmaceutically acceptable excipients, binders, lubricants, preservatives, stabilizers, colorants and flavors.

The weight of the chewable tablet of the invention is not restricted. For administration of one tablet once, for instance, the weight of one tablet is preferably about 0.5 to 2.0 g, more preferably 0.8 to 1.5 g.

The method of preparing the chewable tablet of the invention is not restricted, either. An ordinary method for producing tablets can be applied.

Claim 1 of 4 Claims

I claim:

1. A chewable tablet as a gastrointestinal drug composition in the form of a chewable tablet which contains erythritol or a mixture of erythritol and another sugar alcohol, and a gastrointestinally active ingredient, the amount of erythritol or the mixture of erythritol and said sugar alcohol expressed in terms of the dissolution endotherm per gram of the active ingredient being at least 20 cal, wherein the gastrointestinally active ingredient is at least one of

a mucous membrane repairing agent selected from the group consisting of sucralfate, sodium azulene sulfonate, aldioxa, glycyrrhizic acid and its salts, L-glutamine, copper chlorophyllin potassium, histidine hydrochloride, porcine gastric wall pepsin decomposition product, and methylmethionine sulfonium chloride,

an antacid selected from the group consisting of fried aluminum hydroxide gel, magnesium aluminosilicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesia alumina hydrate, aluminum hydroxide gel, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogenphosphate, and calcium hydrogenphosphate, or

an H₂ receptor blocking antisecretory selected from the group consisting of ranitidine, cimetidine, famotidine, nizatidine and roxatidine acetate.

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