JP6171683B2 - Solid preparation - Google Patents

Description

  The present invention relates to a stabilized solid preparation for internal use containing ambroxol.

  Ambroxol or its salt (eg, ambroxol hydrochloride), an airway lubrication expectorant, is effective in expectoration and is widely used in the treatment of acute bronchitis, bronchial asthma, chronic bronchitis, colds, respiratory diseases, etc. ing.

  However, the content of ambroxol or a salt thereof may decrease over time when a solid preparation is produced by adding a widely used additive to a solid preparation for internal use. (See Patent Documents 1 and 2).

JP-A-2005-350448 JP 2006-117544 A

  Therefore, an object of the present invention is to provide a solid preparation for internal use which contains ambroxol or a salt thereof as an active ingredient, and a decrease in the content thereof over time is suppressed, and a method for producing the same.

  This inventor earnestly examined in order to suppress the fall of the content about the solid formulation for internal use which mix | blended the ambroxol or its salt. As a result, by mixing the mixed powder containing ambroxol or a salt thereof and stearic acid in a fluidized bed dryer at a temperature equal to or higher than the melting point of stearic acid, It has been found that a granulated product containing ambroxol or a salt thereof in which a decrease in the content is suppressed can be prepared.

  The aspect of the present invention completed based on this finding is that a mixed powder containing 4 parts by mass or more of stearic acid with respect to 1 part by mass of ambroxol or a salt thereof is equal to or higher than the melting point of stearic acid in a fluidized bed dryer. It is an ambroxol-containing solid preparation for internal use obtained by allowing it to flow at a temperature of 5 ° C and then solidifying by cooling.

  According to the present invention, it is possible to provide an ambroxol-containing solid preparation for internal use containing ambroxol or a salt thereof and suppressing a decrease in the content thereof by a simple production method.

  "Ambroxol-containing solid preparation for internal use" is a mixture of ambroxol or a salt thereof and stearic acid and, if necessary, known additives commonly used for solid preparations for internal use, It is obtained by cooling and solidifying after flowing in a fluidized bed dryer at a temperature equal to or higher than the melting point of stearic acid. The embodiment is “formulation particles” for solid preparations for internal use.

  The content (formulation) of “ambroxol or a salt thereof” is 0.1 to 12% by mass in the solid preparation for internal use, preferably 0.5 to 8.0% by mass, more preferably 1.0 to It is 4.0 mass%.

  The content (formulation) of “stearic acid” is 4 parts by mass or more with respect to 1 part by mass of ambroxol or a salt thereof from the viewpoint of stabilization of ambroxol or a salt thereof in a solid preparation for internal use. Preferably, it is 7 parts by mass or more.

  The melting point of stearic acid is 67-70 ° C. (see Shida Shoji et al., “Chemical Dictionary”, page 643, published by Morikita Publishing Co., Ltd., August 31, 1983).

  The “fluidized bed dryer” is an apparatus for supplying warmed fluidized air to the can body and drying the powder while flowing and circulating the powder.

  The fluidized bed dryer includes a fluidized bed granulator having the above function, a fluidized bed granulator, a rolling fluidized bed granulator having a rolling function, and the like.

  As the flow conditions, the supply air temperature should be equal to or higher than the melting point of stearic acid to be blended, and the supply air flow should be the fluidized air necessary for the uniform powder circulation of the mixed powder containing ambroxol or its salt and stearic acid. The flow rate should be sufficient to allow the granulation to progress and form drug particles, the cooling temperature should be set to room temperature, and the air supply rate should be the flow required for the powder to flow and circulate uniformly. The air volume is sufficient to supply chemical air.

  As a method for producing “ambroxol-containing solid preparation for internal use”, a powder for granulation by mixing ambroxol or a salt thereof, stearic acid and, if necessary, known additives commonly used for internal preparations for internal use. The granulating powder is heated at a temperature equal to or higher than the melting point of stearic acid while flowing in a fluidized bed dryer, and stearic acid is melted and granulated as a binder (so-called melt granulation). The method of classifying with a sieve and preparing as “formulation particles” can be mentioned.

  In addition, other active ingredients and known additives can be blended with the preparation particles as long as the effects of the present invention are not impaired. Known additives include those listed in “Pharmaceutical Additives Encyclopedia 2007” edited by Japan Pharmaceutical Additives Association (2007, Yakuji Nippo).

  Furthermore, “solid preparations for internal use containing ambroxol” can be prepared by mixing the preparation particles with other active ingredients and known additives to provide powders or granules. It is also possible to provide it as a tablet by filling it and providing it as a capsule, or by mixing the preparation particles with other excipients and compressing (tabletting) it.

  Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.

Example 1
Ambroxol hydrochloride 3.0g
Stearic acid 29.7g
D-mannitol 164.3 g
Light anhydrous silicic acid 1.0g
After weighing the above components, they are mixed and filled into a fluidized bed granulator / dryer (trade name: FL-LABO; manufactured by Freund Corporation), under the conditions of a supply air temperature of 100 ° C. and a supply air flow rate of 0.3 m ³ / min. After granulating by heating while flowing, the mixture was classified with a 500 μm sieve, and the classified sieve product was forcibly sieved with a 500 μm sieve and mixed with the classified sieve product, 3.0 g of talc to obtain a preparation. .

Example 2
Ambroxol hydrochloride 9.0g
Stearic acid 59.2g
D-mannitol 523.1 g
Light anhydrous silicic acid 3.0g
The above components were weighed and mixed, and 495 g of the mixed powder was charged into a fluidized bed granulation dryer (trade name: FLO-1; manufactured by Freund Corporation), the supply air temperature was 100 ° C., and the supply air flow rate was 0.3 m ³ /. The mixture is heated and granulated while flowing under the condition of minute, and then classified with a 500 μm sieve. The classified product is forcibly sieved with a 500 μm sieve, and 396 g of the classified sieve product is mixed with 4.0 g of talc. Thus, a preparation was obtained.

Example 3
Ambroxol hydrochloride 9.1g
Stearic acid 39.5g
D-mannitol 542.6g
Light anhydrous silicic acid 3.0g
The above components were weighed and mixed, and 495 g of the mixed powder was charged into a fluidized bed granulation dryer (trade name: FLO-1; manufactured by Freund Corporation), the supply air temperature was 100 ° C., and the supply air flow rate was 0.3 m ³ /. The mixture is heated and granulated while flowing under the condition of minute, and then classified with a 500 μm sieve. The classified product is forcibly sieved with a 500 μm sieve, and 396 g of the classified sieve product is mixed with 4.0 g of talc. Thus, a preparation was obtained.

Comparative Example 1
Ambroxol hydrochloride 3.0g
Macrogol 6000 29.7g
D-mannitol 164.3 g
Light anhydrous silicic acid 1.0g
After weighing the above components, they are mixed and filled into a fluidized bed granulator / dryer (trade name: FL-LABO; manufactured by Freund Corporation), under the conditions of a supply air temperature of 100 ° C. and a supply air flow rate of 0.3 m ³ / min. After granulating by heating while flowing, the mixture was classified with a 500 μm sieve, and the classified sieve product was forcibly sieved with a 500 μm sieve and mixed with the classified sieve product, 3.0 g of talc to obtain a preparation. .

Comparative Example 2
Ambroxol hydrochloride 3.0g
29.7 g of glyceryl monostearate
D-mannitol 164.3 g
Light anhydrous silicic acid 1.0g
After weighing the above components, they are mixed and filled into a fluidized bed granulator / dryer (trade name: FL-LABO; manufactured by Freund Corporation), under the conditions of a supply air temperature of 100 ° C. and a supply air flow rate of 0.3 m ³ / min. After granulating by heating while flowing, the mixture was classified with a 500 μm sieve, and the classified sieve product was forcibly sieved with a 500 μm sieve and mixed with the classified sieve product, 3.0 g of talc to obtain a preparation. .

Comparative Example 3
Ambroxol hydrochloride 3.0g
Sucrose fatty acid ester (S-370) 29.7 g
D-mannitol 164.3 g
Light anhydrous silicic acid 1.0g
After weighing the above components, they are mixed and filled into a fluidized bed granulator / dryer (trade name: FL-LABO; manufactured by Freund Corporation), under the conditions of a supply air temperature of 100 ° C. and a supply air flow rate of 0.3 m ³ / min. After granulating by heating while flowing, the mixture was classified with a 500 μm sieve, and the classified sieve product was forcibly sieved with a 500 μm sieve and mixed with the classified sieve product, 3.0 g of talc to obtain a preparation. .

Comparative Example 4
Ambroxol hydrochloride 3.0g
Sucrose fatty acid ester (J-1805) 29.7 g
D-mannitol 164.3 g
Light anhydrous silicic acid 1.0g
After weighing the above components, they are mixed and filled into a fluidized bed granulator / dryer (trade name: FL-LABO; manufactured by Freund Corporation), under the conditions of a supply air temperature of 100 ° C. and a supply air flow rate of 0.3 m ³ / min. After granulating by heating while flowing, the mixture was classified with a 500 μm sieve, and the classified sieve product was forcibly sieved with a 500 μm sieve and mixed with the classified sieve product, 3.0 g of talc to obtain a preparation. .

Test Example 1 Component Quantitative Test (1) Method Using 3.0 g of the preparation particles prepared in Examples 1 and 2 and Comparative Examples 1 to 4, the component content of ambroxol hydrochloride was measured using a spectrophotometer (UV-1800; (Manufactured by Shimadzu Corporation). The results are shown in Table 1 below.

(2) Results From Table 1, it is considered that in Comparative Examples 1 to 4, the components are decomposed over time and are not suitable as preparations for use in pharmaceutical products.
On the other hand, in Examples 1 and 2, the decomposition of the components over time is not confirmed, and it appears that it functions sufficiently as a preparation used for pharmaceuticals.

(3) Discussion From the results of Test Example 1, compared to the preparations of Comparative Examples 1 to 4, in the preparations of Examples 1 and 2, the decrease in the content of ambroxol hydrochloride with time was suppressed and stable. It is believed that a formulation can be provided.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an ambroxol-containing solid preparation for internal use that suppresses a decrease in the content of ambroxol or a salt thereof over time, and it is expected to contribute to the development of the pharmaceutical industry.

Claims (1)

A mixed powder containing 4 parts by mass or more of stearic acid with respect to 1 part by mass of ambroxol or a salt thereof is fluidized at a temperature equal to or higher than the melting point of stearic acid in a fluidized bed dryer, and then cooled and solidified. The manufacturing method of the solid formulation for internal use containing an ambroxol obtained by this.