JP2973751B2 - Method for producing flavored oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a flavored oral composition, and more particularly to a method for producing a flavored oral composition excellent in masking the taste of a drug exhibiting an unpleasant taste.

[0002]

2. Description of the Related Art Conventionally, various formulations have been found in order to mask the taste of drugs having an unpleasant taste.
For example, JP-A-49-81526 discloses that macrolide antibiotics include polyvinyl acetal diethylaminoacetate (hereinafter abbreviated as AEA), cellulose acetate dibutylaminohydroxypropyl ether, and dimethylaminoethyl methacrylate-methacrylate. A wall material polymer selected from the group consisting of a polymer (hereinafter abbreviated as Eudragit E) and ethylcellulose, and an inert material obtained by dissolving or dispersing one or more selected from the group consisting of wax, higher fatty acid and higher fatty acid insoluble salt, Dissolved in a volatile organic solvent and then spray dried to collect the resulting coated macrolide antibiotic particles.

[0003]

However, in the above method,
Since an organic solvent such as methylene chloride, chloroform, cyclohexane, carbon tetrachloride, methyl ethyl ketone, acetone, methyl alcohol, ethyl alcohol and isopropyl alcohol is used to dissolve the coating agent, a drying step for removing the solvent is required. as a result,
The coating film becomes porous, and the drying process requires a great deal of time, equipment, labor, cost, and the like. Further, in this process, there is a danger of ignition or explosion during the operation, and furthermore, the solvent remains in the product, and there is a concern that the effect on the human body may be caused.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, heat-melted a low-melting substance to a temperature higher than the melting point and dispersed a gastric-soluble polymer compound therein. Alternatively, a method for producing a flavored oral composition comprising uniform particles with a masked unpleasant taste by melting or heating granulating a dissolved coating composition and a drug exhibiting an unpleasant taste is found. The present invention has been completed.

[0005] The melt granulation or heat granulation method of the present invention comprises:
For example, a coating composition obtained by dispersing or dissolving a gastric-soluble polymer compound in a low-melting substance heated to a melting point or higher and a drug are mixed at a high temperature, and then spray-cooled and granulated, or the coating composition is fluidized. Fluid bed granulation method of spraying a drug, or a method of stirring and granulating the coating composition and the drug while heating with a stirring granulator, followed by cooling to obtain a granulated product.

The unpleasant-tasting drugs used in the present invention include macrolide antibiotics such as erythromycin, clarithromycin, kitasamycin, josamycin, acetylspiramycin, midecamycin, roxistamycin and azithromycin.

The gastric-soluble polymer compound used in the present invention includes AEA, Eudragit E, or a mixture thereof.

The low-melting substance used in the present invention is a water-insoluble or poorly water-soluble substance having a melting point of 40 to 120 ° C. which is acceptable for pharmaceuticals, such as paraffin, microcrystalline wax, ceresin, hydrogenated oil, Wood wax, cocoa butter, carnauba wax, beeswax, cetanol, stearyl alcohol, myristic acid, palmitic acid, stearic acid, titanium stearate, calcium oleate, glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, or a mixture thereof can give. Glyceryl monostearate as a more preferred low melting point substance,
Examples include stearyl alcohol, stearic acid, or mixtures thereof.

The proportion of the gastrosoluble polymer compound in the coating composition used in the present invention is 1 to 60% by weight. A particularly preferred ratio of the gastrosoluble polymer compound is 5 to 40%.

[0010] The composition thus obtained is used as it is or, if necessary, by mixing pharmaceutically acceptable additives such as excipients, disintegrants, binders, lubricants, coloring agents and the like. Solid oral preparations such as granules, powders, capsules, tablets, and dry syrups.

Examples of the excipients and disintegrants include mannitol, sorbitol, xylitol, maltitol, glucose, sucrose, lactose, crystalline cellulose, calcium hydrogen phosphate, starch, sodium carboxymethyl starch, dextrin, carboxyvinyl polymer, and polyethylene. Glycol, carboxymethylcellulose, carboxymethylcellulose calcium, sodium bicarbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide and the like. Examples of the binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, polyvinyl alcohol, pullulan and the like. Examples of the lubricant include magnesium stearate, calcium stearate, polyoxyl stearate, talc, sucrose fatty acid ester, dimethylpolysiloxane and the like. As a coloring agent,
For example, tar dyes and the like can be mentioned. Any of these pharmaceutically acceptable additives can be used in general for solid preparations, and is not particularly limited.

[0012]

According to the present invention, it has become possible to produce a flavored oral composition comprising particles having a uniform surface, which masks unpleasant taste. Furthermore, the flavored oral preparation of a macrolide antibiotic obtained in the present invention does not impair the dissolution of the drug, and therefore can be taken very easily as an oral preparation such as a syrup for children.

[0013]

EXAMPLES The present invention will be specifically described below with reference to examples and test examples.

Example 1 700 g of stearyl alcohol was melted at about 100 ° C.
100 g of Eudragit E was dispersed and dissolved therein. 200 g of clarithromycin was added to the mixture thus obtained.
After the dispersion, spray cooling and granulation was performed using a spray drying apparatus “L-12 model manufactured by Okawara Kakoki Co., Ltd.” under the conditions of an inlet temperature of 50 ° C. and a rotating disk of 10,000 rpm. As a result, about 950 g of a 20% clarithromycin pharmaceutical composition was obtained. Using this pharmaceutical composition, a taste test shown in Test Example 1 described below was performed. As a result, the composition was excellent with little bitterness.

Example 2 700 g of stearic acid was melted at about 80 ° C., and A
200 g of EA was dispersed and dissolved. After 200 g of erythromycin was dispersed in the obtained mixture, the mixture was cooled and granulated using the above-mentioned spray drying apparatus under the conditions of an inlet temperature of 40 ° C. and a rotating disk of 10,000 rpm. As a result, about 930 g of a 20% erythromycin pharmaceutical composition was obtained. As a result of a taste test of the present composition, bitterness was hardly felt.

Comparative Example 1 Lactose 60 g, starch 90 g, clarithromycin 40
Using g, granules were produced in accordance with the granules in the 12th Revised Japanese Pharmacopoeia General Rules for Preparations. 950 g of this granule was put into a coating apparatus “Doria Coater manufactured by Powrex Co., Ltd.”, and a solution prepared by dissolving 10 g of AEA, 1.5 g of stearic acid, and 5 g of polyethylene glycol 6000 in 42 g of ethanol and 42 g of methylene chloride was used. Using,
Coating was performed. As a result, about 1 kg of the coated granules of clarithromycin was obtained.

Test Example 1 500 g of the pharmaceutical composition of Example 1 was mixed with 450 g of sugar and 50 g of hydroxypropylcellulose, and the mixture was subjected to fluidized-bed granulation with purified water to produce about 1 kg of 10% clarithromycin dry syrup. . 1g of this dry syrup
Was taken by 10 healthy adults, and a bitterness evaluation test was carried out. The bitterness was evaluated by a taste test.

Test Example 2 A dissolution test was carried out on the clarithromycin pharmaceutical compositions produced in Example 1 and Comparative Example 1, and the dissolution rates shown in Table 1 were obtained. As the test method, the 12th revised Japanese Pharmacopoeia Dissolution Test Method 2 was used. As an eluate, an acetate buffer having a pH of 4.0 was used, and the paddle rotation speed was 100 rpm. As a result, almost no difference was observed in the dissolution rate.

[0019]

[Table 1]

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-63-303928 (JP, A) JP-A-61-268622 (JP, A) JP-A-49-81526 (JP, A) (58) Field (Int.Cl. ⁶ , DB name) A61K 9/50 A61K 31/71 A61K 47/30 A61K 47/44

Claims (1)

(57) [Claims] 1. A low melting substance is heated and melted to a temperature higher than its melting point.
A clothing composition in which a gastric-soluble polymer compound is dispersed or dissolved at a ratio of 1 to 60% by weight , and a macrolide antibiotic.
A method for producing a flavoring oral composition, comprising granulating a substance by a melt granulation method or a heat granulation method.