JPH03227916A - Foamable drug preparation composition - Google Patents

Abstract

PURPOSE:To obtain a foamable drug preparation composition utilizable over a wide application range such as drugs for internal use, foods and cosmetics and stably preservable over a long period by coating the surface of an organic acid crystal with a sugar. CONSTITUTION:Crystal particles (preferably having a diameter of <=850mum) of an organic acid such as tartaric acid or citric acid are fluidized with a centrifugal flow coating granulator, etc., and the surface of the particle is Wet by spraying water, simple syrup, etc., to the surface. A sugar such as lactose or refined sucrose is scattered and attached to the surface in an amount of 50-500wt.% based on the organic acid to obtain the objective composition. The composition may be properly compounded, in addition to the above essential components, with various drug-active components, flavors, colorants, surfactants, etc. It can be formed in the form of a chewable tablet, granule, particle, powder, etc., for enjoying the foaming feeling by directly throwing into the mouth. Since the sugar applied to the organic acid crystal is soluble in water, there is no problems such as delay of dissolution, generation of insoluble material and lowering of foaming property.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an effervescent pharmaceutical composition that is stable even after long-term storage.

[Prior art and problems to be solved by the invention] Generally, effervescent pharmaceutical compositions are produced by combining a carbonate and an organic acid. Also, carbonate and organic acid react to generate carbon dioxide gas, making it extremely unstable.

Conventionally, methods have been used to block moisture by devising packaging formats, but even with this method, the moisture contained in the excipients etc. reacts and generates carbon dioxide gas, which is not expected when used. There was a problem that the objective could not be achieved.

In order to solve these drawbacks, a method of blending a moisture absorbing agent such as anhydrous sodium sulfate (Japanese Patent Application Laid-open No. 44013/1983) has been proposed.
(Japanese Unexamined Patent Publication No. 1987-70), method of blending a stabilizer
610) and a method of blending weakly reactive sodium monofumarate with organic acids (Japanese Unexamined Patent Publication No. 51-26214), but these methods have insufficient moisture absorption effects and are difficult to use as internal medicines. may be unsuitable for use in
It has drawbacks such as being impractical as it is only used in some bath preparations, and is still unsatisfactory.

Therefore, there has been a desire for an effervescent pharmaceutical composition that can be used in a wide range of applications, including internal medicines, foods, cosmetics, etc., and is stable even when stored for a long period of time.

[Means to solve the problem]

Under these circumstances, the inventors of the present invention conducted extensive research and found that the above-mentioned problems can be solved by coating the surface of an organic acid crystal with sugar, thereby completing the present invention.

That is, the present invention provides an effervescent pharmaceutical composition containing an organic acid whose crystal surface is coated with saccharide, and an effervescent pharmaceutical composition containing (a) the organic acid and (b) a carbonate. It is.

The organic acid used in the present invention is not particularly limited as long as it is generally used in effervescent pharmaceutical compositions, and examples thereof include ascorbic acid, succinic acid, tartaric acid, citric acid, malic acid, fumaric acid, etc. It will be done. These organic acids can be used alone or in combination of two or more.

Examples of sugars that coat the surface of organic acid crystals include monosaccharides such as glucose, fructose, lactose, sucrose, mannitol, xylitol, starch, and cellulose; disaccharides;
Examples include sugar alcohols and polysaccharides. These saccharides can be used alone or in combination of two or more.

In the present invention, the crystal particle size of the organic acid varies depending on the dosage form of the effervescent preparation using it, but is preferably 850 μm or less, and the particle size of the coating saccharide is 2 times the crystal particle size of the organic acid.
It is preferably 0% or less. In addition, the amount of saccharide is an amount that can sufficiently cover the crystal surface of the organic acid, for example, 50 to 50% sugar to the organic acid.
00% by weight, especially 100-300% by weight is preferred.

In order to coat the surface of an organic acid crystal with sugar, for example, the organic acid crystal is first fluidized using a sugar coating pan or a centrifugal fluid coating granulator, and water, simple syrup, or polymer is dissolved in this. After spraying alcohol or the like to wet the surface of the organic acid crystals, sugars are sprayed and attached. This operation may be repeated to deposit a predetermined amount of saccharide.

The effervescent pharmaceutical composition of the present invention is thus obtained (a)
It can be obtained by mixing the effervescent pharmaceutical composition of the present invention containing an organic acid whose crystal surface is coated with saccharide and (b) carbonate. The carbonate is not particularly limited as long as it is generally used in effervescent preparations, and includes, for example, sodium hydrogen carbonate, potassium carbonate, sodium carbonate, calcium carbonate, ammonium carbonate, magnesium carbonate, and the like.

3- The effervescent pharmaceutical composition of the present invention can be made into various dosage forms that are normally used as effervescent preparations, but unlike those in which the crystal surface of an organic acid is coated with a polymer or the like, organic acid Chewable tablets, granules, fine granules,
Powders and the like are preferred.

In addition to the above-mentioned essential components, the foamable pharmaceutical composition of the present invention may also contain components used in ordinary foamable pharmaceuticals. Examples of the other components include various medicinal ingredients, flavoring agents, coloring agents, surfactants, and the like.

[Action and effect of the invention]

In the effervescent pharmaceutical composition of the present invention, since the organic acid is reliably isolated from carbonate and water, the two do not react and are stable even when stored for a long period of time. In addition, since the saccharides coating the organic acid crystals are water-soluble, there are no problems with conventional effervescent formulations, such as delayed dissolution of organic acids, formation of insoluble substances, or decreased effervescence, resulting in good effects. Demonstrated.

4 〔Example〕 Next, the present invention will be explained in more detail with reference to Examples.

Example 1 200 g of tartaric acid (particle size 127 to 297 μm) was added to a centrifugal flow type coating granulator (CF-36 manufactured by Freund Sangyo Co., Ltd.).
The lactose (
Gradually sprinkle 400 g (particle size: 10-30 μm) to coat the tartaric acid crystal surface with lactose. Thereafter, it was dried at 50° C. and passed through a No. 30 sieve to obtain 585 g of a foamable pharmaceutical composition remaining on the No. 200 sieve.

Example 2 1000 g of citric acid (particle size 127 to 297 μm) was coated in a sugar coating film coating device (FM-2 manufactured by Freund Sangyo Co., Ltd.).
Place a sugar-coated pan attached to a mold, roll it at 40 revolutions per minute, spray water at a rate of 5 ml per minute to moisten it, and gradually sprinkle 1000 g of white sugar (particle size 10 to 30 μm). Then, the surface of the citric acid crystals is coated with white sugar.

Thereafter, it was dried at 50°C, passed through a No. 30 sieve, and 1980 g of the foamable pharmaceutical composition remained on the No. 200 sieve.
I got it.

Example 3 Calcium fine granules: (Ingredients) (%) Precipitated calcium carbonate 30 xylitol
52 Lactose 4 Hydroxypropyl cellulose 2 Effervescent pharmaceutical composition of Example 1 12 Flavor
Trace amount (manufacturing method) Mix precipitated calcium carbonate, xylitol and lactose,
After kneading this with a 15% ethanol solution of hydroxypropyl cellulose and ethanol, it was granulated using an extrusion granulator (Fuji Paudal EXR-60 type 0.45 mm screen), and dried at 50°C. 30
The fine grains pass through a No. 200 sieve and remain on a No. 200 sieve. The effervescent pharmaceutical composition of Example 1 and fragrance were mixed with the fine granules, and the mixture was stick-packaged to obtain calcium fine granules.

Example 4 Sedative Chuapul tablets: (Ingredients) (%) Meclizine hydrochloride 6.2 Chlorpheniramine maleate 025 Xylitol
63.75D-Mannitol 10.5
5 Light silicic anhydride 3 Carboxymethyl cellulose 1.25 Hydroxypropyl cellulose 1 Magnesium stearate
3 Talc 3 Example 20 Composition for effervescent preparation 4 Sodium hydrogen carbonate 4 Fragrance Trace amount (manufacturing method) Meclizine hydrochloride, chlorpheniramine maleate, xylitol, D-mannitol, light silicic anhydride, and carboxymethyl cellulose were mixed, and this was mixed. After kneading with lθ% ethanol 7-nol solution of hydroxypropylcellulose and ethanol, the mixture was heated to 50°C.
Dry and then sieve. After passing through a No. 20 sieve, magnesium stearate, talc, the effervescent pharmaceutical composition of Example 2, sodium hydrogen carbonate, and fragrance were mixed, and the mixture was made into tablets using a Kikusui rotary tablet machine to a diameter of 8 mm.
, sedative chewable tablets weighing 400 square meters were obtained.

Comparative Example 1 200 g of tartaric acid (particle size 127 to 297 μm) was added to a centrifugal flow type coating granulator (CF-36 manufactured by Freund Sangyo Co., Ltd.).
0-8 type), centrifugally flowed at 120 revolutions per minute, heated to 40°C, and sprayed with a 5% ethanol solution of hydroxypropyl cellulose at a rate of 5 ml per minute, while drying the hydroxypropyl cellulose. Coat up to 5% by weight of tartaric acid. Thereafter, it is dried at 50° C. and then passed through a No. 30 sieve to obtain 205 g of the foamable pharmaceutical composition remaining on the No. 200 sieve.

Calcium fine granules were obtained in the same manner as in Example 3 using the obtained foamable pharmaceutical composition.

Comparative Example 2 8- Example 4 using the effervescent pharmaceutical composition obtained in Comparative Example 1
Chewable sedative tablets were obtained in the same manner as above.

Test Example 1 The formulations obtained in Examples 3 and 4 and Comparative Examples 1 and 2 were tested for stability and foaming delay.

For stability, heat-seal packaging with aluminum packaging material,
When it was left in an atmosphere at 50°C for one month and the presence or absence of gas generation was confirmed, both Examples 3 to 4 and Comparative Example 1 did not generate gas and showed good stability, but Comparative Example 2 slightly Gas generation was observed.

Regarding the delay in foaming, Examples 3 and 4 foamed quickly in the mouth, but Comparative Examples 1 and 2 had a delay in foaming and did not have a foamy feeling.

As described above, the effervescent pharmaceutical composition of the present invention has an effect equivalent to or better than that coated with a polymer when stored, and also does not interfere with the reaction between the organic acid and carbonate during use. This allows the user to fully enjoy the effervescent feeling during the day, making it easier to take oral medicines that require long-term administration.

that's all

Claims (1)

[Claims] 1. An effervescent pharmaceutical composition containing an organic acid whose crystal surface is coated with saccharide. 2. (a) an organic acid whose crystal surface is coated with sugar; and (b)
) Effervescent pharmaceutical compositions containing carbonates.