JP2003277266A - Mixed powder for distribution and tablet or capsule using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a caffeine-containing mixed powder capable of uniformly distributing a content of an effective component at distribution and to provide a capsule and a tablet using the powder. <P>SOLUTION: The mixed powder for distribution contains an anhydrous caffeine powder in which ≥90 mass% powder has a particle size of 100-500 μm and ≤5 mass% powder has a particle size of less than 100 μm and two or more kinds of an effective component powder. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION This invention relates to a dispensing powder mix for filling capsules and for tableting. The present invention also relates to capsules and tablets using the mixed powder.

[0002]

BACKGROUND OF THE INVENTION Caffeine has an action of stimulating and exciting a respiratory center and a vasomotor center, an action of increasing contractility of myocardium, a diuretic action, an analgesic action such as migraine, a cold medicine, an analgesic,
It is used in many formulations such as slimming drugs. Usually, a plurality of active ingredients other than caffeine are prescribed in these drugs, and they are often formulated into an internal solution, powder, tablets, capsules and the like. Generally, powders, tablets and capsules are prepared by mixing raw material powders with a mixer and transferring the mixed powders to a capsule filling machine or a tableting machine for filling or tableting. However, when caffeine is mixed with other active ingredient powder, the compatibility with other active ingredients is not good, and when the drug is dispensed from the mixer, it is difficult to evenly distribute the drug, and the tableting is performed. Classification also occurred in the filling machine and the filling machine, and there was a problem that the contents in one tablet, one capsule, and one bag were likely to vary due to these.
It is thought that caffeine is unevenly distributed in the vicinity of the inner wall of the mixer or silo, and as a result, other drugs are also unevenly distributed.
This is a problem peculiar to formulations containing caffeine. In order to solve this, a method in which caffeine is mixed with another drug and all the active ingredients are wet-granulated into granules can be considered, but caffeine whiskers are generated depending on the compounding ingredients. Therefore, there has been a demand for a caffeine-containing mixed powder for distribution, which maintains uniformity during distribution without granulating caffeine and other drugs.

[0003]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a caffeine-containing mixed powder capable of uniformly distributing the content of the active ingredient at the time of distribution. Another object of the present invention is to provide capsules and tablets using the powder.

[0004]

DISCLOSURE OF THE INVENTION As a result of investigations, the present inventors have found that by using a caffeine powder having a specific particle size, a mixed drug powder formulated with a plurality of active ingredients containing caffeine can be obtained. They have found that they can be uniformly distributed, and have completed the present invention.

That is, the present invention contains <1> anhydrous caffeine powder having a particle size of 100 to 500 μm of 90% by mass or more and particle size of less than 100 μm of 5% by mass or less, and two or more kinds of active ingredient powders. A mixed powder for distribution, characterized in that <2> A lubricant is further contained, <1
The mixed powder for distribution as described in <>. <3> A capsule, wherein a part of the mixed powder of <1> or <2> is filled in a capsule. <4> A tablet, wherein a part of the mixed powder of <1> or <2> is distributed to a die of a tableting machine and tableted. I will provide a. Hereinafter, the present invention will be described in detail.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The anhydrous caffeine used in the mixed powder for distribution of the present invention has a particle size of 100 to 500 μm of 90% by mass or more and a particle size of less than 100 μm of 5% by mass or less, preferably 3% by mass or less. Is a powder. If there are many fine powders of 100 μm or less and sparse particles exceeding 500 μm, the mixed powder cannot be uniformly distributed. Preferably, the average particle size is 150 to 450 μm, preferably 250 to 400
Use μm powder. Further, the bulk density is preferably 0.4 to 0.85 g / cm ³ , and more preferably 0.5 to 0.8 g / cm ³ .

As the anhydrous caffeine powder, it is preferable to use a powder obtained by crushing a solid substance and sizing, but a powder obtained by granulating a fine powder to a desired particle size together with a binder and an excipient is used. You can also In the case of a granulated product, the caffeine content in the granulated product is 10 to 99% by mass, preferably 30 to 95% by mass.
Is preferred. The content of the caffeine powder in the mixed powder for distribution is preferably 80% by mass or less. More preferably 1 to 70% by mass, particularly preferably 5
Is about 50% by mass. Within this range, a mixed powder having good uniformity during distribution can be obtained.

As the active ingredient powder used in the mixed powder for distribution of the present invention, acetaminophen, aspirin, ethenzamide, ibuprofen, bromvalerylurea, allylisopropylacetylurea, aspirin aluminum, caffeine, sodium caffeine benzoate. , Lactylphenetidine, sazapyrine, salicylamide, sodium salicylate, aminoacetic acid, magnesium silicate,
Synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium carbonate, magnesium aluminometasilicate, tranexamic acid, dihydroxyaluminum aminoacetate (aluminum glycinate),
Aluminum hydroxide / sodium hydrogen carbonate co-precipitation product, aluminum hydroxide / sodium hydrogen carbonate co-precipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate co-precipitation product, lactylphenetidine, isothipendyl hydrochloride, diphenyl hydrochloride Pyraline, diphenhydramine hydrochloride, difeterol hydrochloride, triprolidine hydrochloride, triperenamine hydrochloride, tonzylamine hydrochloride phenetadine hydrochloride, metzirazine hydrochloride, diphenhydramine salicylate diphenyldisulfonic acid carbinoxamine, alimemazine tartrate, diphenylpyrameline tannic acid diphenhydrinate, theocylate diphenylpyrameline, hydropadisilate, napadisilate Salt, carbinoxamine maleate, dl-chlorpheniramine maleate, d-chlorf maleate Niramine, difeterol phosphate, aloclamide hydrochloride, cloperastine hydrochloride, pentoxyberine citrate, tipepidine citrate, sodium dibunate, dextromethorphan hydrobromide, dextromethorphan phenol phthaline salt, tipebidine hibenzate, cloperastine fendizoate. , Codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride,
Noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacol sulfonate, guaifenesin, sodium caffeine benzoate, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts and vitamins
C and its derivatives and salts thereof, hesperidin and its derivatives and salts thereof, and the like.

The powder is preferably a solid material crushed to a desired particle size, but a fine powder is granulated to a desired particle size together with a binder, an excipient, and optionally other drugs. It is also possible to use the powder. By mixing a plurality of the above powders and mixing them with the caffeine powder, a mixed powder that can be uniformly distributed can be obtained. The content of the active ingredient powder in the total powder is preferably 1 to 99% by mass, more preferably 5 to 95% by mass.

The content ratio of the caffeine powder and the other active ingredient powder is preferably caffeine powder: other active ingredient powder = 1: 20 to 10: 1. More preferably 1:
It is in the range of 10 to 5: 1, particularly preferably 1: 8 to 5: 1.

It is preferable to add a lubricant to the mixed powder for distribution of the present invention. Lubricants include magnesium stearate, silicone oil, dimethylpolysiloxane, gum arabic, cocoa butter, carnauba wax,
Hydrous silicon dioxide, dried aluminum hydroxide gel, glycerin, magnesium silicate, liquid paraffin, crystalline cellulose, sucrose fatty acid ester, stearyl alcohol, stearic acid, gelatin, lactose, sucrose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, fumaric acid , Beeswax, hydrogenated castor oil, talc and the like. Preferred lubricants are magnesium stearate and dimethyl polysiloxane.

The lubricant is preferably 0.0 in the mixed powder.
The amount is 001 to 10% by mass, more preferably 0.001 to 5% by mass. By blending a lubricant, even better distribution uniformity can be obtained, and the fluidity of the powder is also good.

In addition to the above, the mixed powder for distribution of the present invention includes
If necessary, an excipient, a binder, a disintegrating agent, a sweetening agent, a flavoring agent, a flavoring agent, a dye and the like can be added within a range that does not impair the effects of the present invention.

Excipients include gum arabic, ethyl cellulose, kaolin, citric acid or its salt, stearic acid or its salt, dextran, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, macrogol, calcium hydrogen phosphate, phosphorus. Examples thereof include sodium hydrogen acidate.

As a binder, gum arabic, degree of substitution 5
3.4-77.5% hydroxypropyl cellulose,
Examples include methyl cellulose, gelatin, and partially pregelatinized starch.

Examples of the disintegrant include cellulose or its derivative, starch or its derivative and the like. Examples of the sweetening agent include sugars such as sucrose, fructose, glucose, lactose and reduced maltose, sugar alcohols such as lactitol, maltitol, sorbitol, erythritol and xylitol, saccharin, saccharin sodium, aspartame, stevia and amalti. Examples of the corrigent include acidity components such as ascorbic acid, tartaric acid, malic acid and citric acid, flavor components such as inosinic acid and sodium glutamate, and enzymatically decomposed lecithin.

Examples of the fragrance include terpenoids such as menthol, limonene, linalool, cineole, pinene and citroneol, and essential oils containing them (mint oil, mint oil, orange oil, lemon oil, mandarin oil, etc.) and the like. To be

The caffeine-containing mixed powder for distribution of the present invention may be distributed as it is and individually packaged as a powder preparation, but it may be distributed to a mortar of a tableting machine to form tablets or using a capsule filling machine. It is preferably distributed in capsules to give capsules. When forming a tablet, the mixed powder for distribution may be tableted alone, or may be a multi-layer tablet with other components.

The uncoated tablets include Opadry, methacrylic acid copolymer, glycerin, liquid paraffin, silicone resin, stearic acid, gelatin, sorbitol,
Film coating of corn oil, polyvinyl alcohol, macrogol, calcium hydrogen phosphate, sodium hydrogen phosphate, etc., ethyl cellulose, crystalline cellulose, gum arabic powder, lactose, macrogol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, macrogol It is also preferable to cover them with sugar coating.

When used as capsules, capsules containing gelatin, hydroxypropylmethylcellulose or the like can be filled.

[0021]

[Examples] <Example 1 and Comparative Example 1> 35
Anhydrous caffeine 1000g, acetaminophen 1500g, allyl isopropyl acetylurea with a particle size of 0-500μm
500 g and 250 g of corn starch are put into a ribbon mixer R-5 type (manufactured by Tokuju Kosakusho Co., Ltd.) and mixed for 10 minutes.
The mixed powder of Example 1 was obtained. On the other hand, in Example 1 described above, instead of anhydrous caffeine having a particle size of 350 to 500 μm preliminarily sieved, 1000 g of anhydrous caffeine previously passed through an opening of 100 μm was used, except that in Example 1 By mixing in the same manner, a mixed powder of Comparative Example 1 having the same composition as that of Example 1 was prepared. The mixed powders of Example 1 and Comparative Example 1 were sampled at 6 points respectively from a ribbon mixer, and the contents of anhydrous caffeine, acetaminophen and allylisopropylacetylurea were measured by a liquid chromatograph method. The uniformity was compared. Hereinafter, all the results are shown in Table 2. The criterion is
The following criteria were used. (The following judgment criteria are common) <Judgment criteria> ○: Standard deviation 2% or less of 6-point measured values ×: Standard deviation 2% or more of 6-point measured values

<Example 2 and Comparative Example 2> Using a sieve in advance
1600 g of anhydrous caffeine with a particle size of 350 to 500 μm, 2600 g of acetaminophen, 2600 g of ibuprofen and 400 g of crystalline cellulose are put into a Bohle container mixer 20 type (manufactured by Kotobuki Sangyo Co., Ltd.), mixed for 10 minutes, and further 4 g of magnesium stearate is added Then, the mixture was mixed for 3 minutes to obtain a mixed powder of Example 2. On the other hand, in Example 2 above,
The same procedure as in Example 2 was repeated except that 1600 g of anhydrous caffeine that had been passed through an opening of 100 μm was used in place of anhydrous caffeine that had been preliminarily sieved to a particle size of 350 to 500 μm. A mixed powder of Comparative Example 2 having the same composition as that of Example 2 was prepared. The mixed powders of Example 2 and Comparative Example 2 described above were sampled at 6 points respectively from a Bohle container mixer, and the contents of anhydrous caffeine, acetaminophen and ibuprofen were measured by a liquid chromatographic method, and the uniformity of the contents was measured. Were compared.

<Example 3 and Comparative Example 3> Further, the mixed powder of Example 2 and Comparative Example 2 was mixed with a rotary tableting machine L.
The tablets of Example 3 and the tablets of Comparative Example 3 were obtained using IBRA (Kikusui Seisakusho). For these two types of tablets,
6 times every 10 minutes, anhydrous caffeine,
The contents of acetaminophen and ibuprofen were measured by liquid chromatography to compare the uniformity of the contents.

<Example 4 and Comparative Example 4> Aspirin 1500
g and acetaminophen 900 g with ribbon mixer R-5
Pour into a mold (made by Tokuju Kosakusho Co., Ltd.) and mix for 2 minutes, then add 24 g of dimethylpolysiloxane and mix for 5 minutes.
360 g of anhydrous caffeine, 90 g of allylisopropylacetylurea, and 30 g of corn starch, which had been made to have a particle size of 100 to 500 μm by using a sieve in advance, were added and mixed for 10 minutes to obtain a mixed powder of Example 4. On the other hand, in Example 4 above,
The same procedure as in Example 4 was repeated, except that 360 g of anhydrous caffeine that had been passed through an opening of 100 μm was used in place of anhydrous caffeine that had been made to have a particle size of 100 to 500 μm by using a sieve in advance. A mixed powder of Comparative Example 4 having the same composition as that of Example 4 was prepared. The mixed powders of Example 4 and Comparative Example 4 were each sampled at 6 points from a ribbon mixer, and the contents of aspirin, acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography. The content uniformity was compared.

<Example 5 and Comparative Example 5> Furthermore, the mixed powder of Example 4 and Comparative Example 4 was filled with a capsule filling machine GKF-40.
A type 0 capsule (manufactured by Bosch Wrapping Machine Co., Ltd.) was used to obtain a capsule of Example 5 and a capsule of Comparative Example 5. These two types of capsules were sampled 6 times every 10 minutes, and the contents of aspirin, acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography to compare the uniformity of the contents. .

<Example 6 and Comparative Example 6> 5000 g of acetaminophen was placed in a fluidized bed granulator SPIR-A-FLOW 5 type (manufactured by Freund Sangyo Co., Ltd.) and 1667 g of a 2% aqueous solution of hydroxypropyl cellulose was used as a binder to form a granular composition. The thing (granulation composition) was obtained. 4590 the obtained granular composition
g, 1800 g of anhydrous caffeine, which was previously made into a particle size of 100 to 500 μm using a sieve, allylisopropylacetylurea 450
g, 600 g of crystalline cellulose and 300 g of carboxymethyl cellulose are charged into a Bohle container mixer type 20 (manufactured by Kotobuki Sangyo Co., Ltd.), mixed for 10 minutes, further charged with 36 g of magnesium stearate, mixed for 5 minutes, and mixed powder of Example 6 Got On the other hand, in Example 6 above, except that 360 g of anhydrous caffeine that had been passed through 100 μm in advance was used instead of anhydrous caffeine that had been preliminarily sieved to a particle size of 100 to 500 μm, By mixing in the same manner, a mixed powder of Comparative Example 6 having the same composition as that of Example 6 was prepared. The mixed powders of Example 6 and Comparative Example 6 were sampled at 6 points respectively from a Bohle container mixer, and the contents of aspirin, acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography. , And content uniformity was compared.

<Example 7 and Comparative Example 7> Aspirin 6250
g of corn starch and 695 g of corn starch were put into a Bohle container mixer type 20 (manufactured by Kotobuki Sangyo Co., Ltd.) and mixed for 10 minutes, then a dry granulator roller compactor TF-208.
After granulating with a mold (manufactured by Freund Sangyo Co., Ltd.), sizing was performed to obtain a granulated product A. The following tablets were produced from these mixed powders and granules using a rotary tableting machine LIBRA (manufactured by Kikusui Seisakusho).

[0028]

[Table 1] These two types of tablets were sampled 6 times every 10 minutes, and coated with 1% by mass of plain tablets using Opadry according to a conventional method. The contents of aspirin, acetaminophen, anhydrous caffeine and allylisopropylacetylurea in these coated tablets were measured by liquid chromatography to compare the uniformity of the contents.

<Example 8 and Comparative Example 8> Ibuprofen
3250 g and lactose 650 g were placed in a fluidized bed granulator SPIR-A-FLOW5 type (manufactured by Freund Sangyo Co., Ltd.), and 1114 g of a 7% aqueous solution of polyvinyl alcohol was used as a binder to form a granular composition A.
(Granulated composition A) was obtained. Also, acetaminophen 40
30 g was placed in a fluid bed granulator SPIR-A-FLOW5 type (manufactured by Freund Sangyo Co., Ltd.) to obtain granular composition B (granulation composition B) using 3472 g of a 5% aqueous solution of hydroxypropyl cellulose as a binder. 1034 g of the obtained granular composition A,
881 g of granular composition B, 100-500 μm using a sieve beforehand
520 g of anhydrous caffeine with a particle size of 390 g, allylisopropylacetylurea 390 g, and low-substituted hydroxypropylcellulose 390 g are put into a double cone mixer W-60 type (manufactured by Tokuju Seisakusho), mixed for 20 minutes, and further magnesium stearate 13 g is added. The mixture was charged and mixed for 5 minutes to obtain a mixed powder of Example 8. On the other hand, in Example 8 described above, except that 520 g of anhydrous caffeine that had been passed through an opening of 100 μm was used instead of anhydrous caffeine that had been granulated to a particle size of 100 to 500 μm in advance using a sieve, By mixing in the same manner, a mixed powder of Comparative Example 8 having the same composition as that of Example 8 was prepared. The mixed powders of Example 8 and Comparative Example 8 were sampled at 6 points respectively from a Bohle container mixer, and the contents of ibuprofen, acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography. , And content uniformity was compared.

<Example 9 and Comparative Example 9> Furthermore, the mixed powder of Example 8 and Comparative Example 8 was mixed with a rotary tableting machine L.
Tablets of Example 9 and Comparative Example 9 were obtained using IBRA (Kikusui Seisakusho). For these two types of tablets,
Sampling was performed 6 times every 10 minutes, and 1% by mass of the uncoated tablets was coated with Opadry according to a conventional method. The contents of ibuprofen, acetaminophen, anhydrous caffeine and allylisopropylacetylurea in these coated tablets were measured by liquid chromatography to compare the uniformity of the contents.

<Example 10 and Comparative Example 10> 1000 g of anhydrous caffeine, 1500 g of acetaminophen, 500 g of etenzamid, and 400 g of crystalline cellulose, which had been preliminarily sieved to a particle size of 250 to 400 μm, were added to a ribbon mixer R-5 type (Tokuju Kogyo). (Manufactured by Tosho Co., Ltd.) and mixed for 10 minutes to obtain a mixed powder of Example 10. On the other hand, in the above-mentioned Example 10, instead of anhydrous caffeine having a particle size of 250 to 400 μm preliminarily sieved, anhydrous caffeine 1 previously passed through an opening of 100 μm 1
A mixed powder of Comparative Example 10 having the same composition as that of Example 10 was prepared by mixing in the same manner as in Example 10 except that 000 g was used. The mixed powders of Example 10 and Comparative Example 10 were sampled at 6 points respectively from a ribbon mixer, and the contents of anhydrous caffeine, acetaminophen and ethenzamid were measured by a liquid chromatograph method to confirm the uniformity of the contents. Compared.

<Example 11 and Comparative Example 11> Anhydrous caffeine 1600 g and acetaminophen 2600 g, allylisopropylacetylurea 400 g, corn starch 800 g, and low-substituted hydroxypropylcellulose, which had been preliminarily sieved to a particle size of 250 to 500 μm. 200 g of the mixture was put into a Bohle container mixer type 20 (manufactured by Kotobuki Sangyo Co., Ltd.) and mixed for 15 minutes to obtain a mixed powder of Example 11. On the other hand, in Example 11 above, instead of anhydrous caffeine having a particle size of 250 to 500 μm preliminarily sieved, 100 μm mesh size was previously opened.
Was mixed in the same manner as in Example 11 except that 1600 g of anhydrous caffeine passed through was used to prepare a mixed powder of Comparative Example 11 having the same composition as in Example 11 above. Example 1 above
The mixed powders of 1 and Comparative Example 11 were sampled at 6 points respectively from a Bohle container mixer, and the contents of anhydrous caffeine, acetaminophen and allylisopropylacetylurea were measured by a liquid chromatographic method, and the uniformity of the contents was measured. Were compared.

<Example 12 and Comparative Example 12> Furthermore, the mixed powder of Example 11 and Comparative Example 11 was used in Example 1 using a rotary tableting machine LIBRA (manufactured by Kikusui Seisakusho).
2 tablets and Comparative Example 12 tablets were obtained. These two types of tablets were sampled 6 times every 10 minutes, and the contents of anhydrous caffeine, acetaminophen and allylisopropylacetylurea were measured by liquid chromatography to compare the uniformity of the contents.

<Example 13 and Comparative Example 13> 3000 g of acetaminophen and 500 g of lactose were used in a fluidized bed granulator SPIR-A-FL.
OW5 type (manufactured by Freund Corporation) was used to obtain granular composition A (granulation composition A) using 1200 g of a 5% aqueous solution of hydroxypropyl cellulose as a binder. Further, 3500 g of ibuprofen was placed in a fluidized bed granulator SPIR-A-FLOW5 type (manufactured by Freund Sangyo Co., Ltd.) to obtain granular composition B (granulation composition B) using 2450 g of hydroxypropylcellulose 5% aqueous solution as a binder. . Obtained granular composition A
1050 g, Granular Composition B 985 g, 300 using a sieve beforehand
Anhydrous caffeine 455g, allylisopropylacetylurea 230g, corn starch 4 ~ 500μm particle size
50 g of the mixture was put into a double cone mixer W-60 type (manufactured by Tokuju Seisakusho) and mixed for 20 minutes, and further 10 g of magnesium stearate was added and mixed for 5 minutes to obtain a mixed powder of Example 13. On the other hand, in Example 13 above, instead of anhydrous caffeine having a particle size of 300 to 500 μm preliminarily sieved, anhydrous caffeine 455 previously passed through an opening of 100 μm was used.
Mixing as in Example 13 above except using g,
A mixed powder of Comparative Example 13 having the same composition as that of Example 13 was prepared. The mixed powders of Example 13 and Comparative Example 13 were sampled at 6 points respectively from a Bohle container mixer, and the contents of acetaminophen, ibuprofen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography. ,
The content uniformity was compared.

<Example 14 and Comparative Example 14> Furthermore, the mixed powders of Example 13 and Comparative Example 13 were subjected to Example 1 using a rotary tableting machine LIBRA (manufactured by Kikusui Seisakusho).
4 tablets and Comparative Example 14 tablets were obtained. These 2 types of tablets were sampled 6 times every 10 minutes, and the content of acetaminophen, ibuprofen, anhydrous caffeine and allylisopropylacetylurea in the tablets was measured by liquid chromatography to confirm the uniformity of the content. Compared.

<Example 15 and Comparative Example 15> 1800 g of acetaminophen, 450 g of anhydrous caffeine previously sized to a particle size of 350 to 500 μm using a sieve, 100 g of allylisopropylacetylurea and 100 g of crystalline cellulose were added to a ribbon mixer R-5. The mixture was put into a mold (manufactured by Tokuju Kosakusho Co., Ltd.) and mixed for 15 minutes, then 10 g of magnesium stearate was added and mixed for 5 minutes to obtain a mixed powder of Example 15. On the other hand, Example 1 above
In Example 5, mixing was carried out in the same manner as in Example 15 above, except that 450 g of anhydrous caffeine that had been passed through an opening of 100 μm was used in place of anhydrous caffeine that had been preliminarily sieved to a particle size of 350 to 500 μm. A mixed powder of Comparative Example 15 having the same composition as that of Example 15 was prepared. The mixed powders of Example 15 and Comparative Example 15 were sampled at 6 locations from a ribbon mixer, and the contents of acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by a liquid chromatograph method. The uniformity was compared.

<Example 16 and Comparative Example 16> Furthermore, the mixed powder of Example 16 and Comparative Example 16 was used in a capsule filling machine GKF-400 type (manufactured by Bosch Packing Machine Co., Ltd.) to obtain the capsule of Example 16. An agent and a capsule of Comparative Example 16 were obtained.
These two types of capsules were sampled six times every 10 minutes, and the contents of acetaminophen, anhydrous caffeine and allylisopropylacetylurea were measured by liquid chromatography to compare the uniformity of the contents.

<Example 17 and Comparative Example 17> 615 g of anhydrous caffeine and 995 g of ibuprofen, 400 g of etenzamid, 150 g of bromvalerylurea, and 95 g of crystalline cellulose, which had been preliminarily sieved to a particle size of 100 to 400 μm, were added to a ribbon mixer R-5 type ( Tokuju Seisakusho Co., Ltd.) and mixed for 10 minutes to obtain a mixed powder of Example 17. On the other hand, Example 1 above
In Example 7, mixing was performed in the same manner as in Example 17 except that 615 g of anhydrous caffeine that had been passed through an opening of 100 μm was used in place of anhydrous caffeine that had been preliminarily sieved to a particle size of 100 to 400 μm. A mixed powder of Comparative Example 17 having the same composition as that of Example 17 was prepared. The mixed powders of Example 17 and Comparative Example 17 were each sampled at 6 points from a ribbon mixer, and the contents of anhydrous caffeine, ibuprofen, etenzamid and bromvalerylurea were measured by a liquid chromatographic method, and the uniformity of the contents was measured. Were compared.

[0039]

[Table 2]

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 45/06 A61K 45/06 A61P 7/10 A61P 7/10 9/00 9/00 11/16 11 / 16 25/06 25/06 (72) Hiroomi Kojima 1-3-7 Honjo, Sumida-ku, Tokyo F-Term (reference) within Lion Corporation 4C076 AA36 AA53 BB01 CC01 CC03 CC11 CC15 EE38 FF05 FF09 4C084 AA23 MA02 MA35 MA37 MA52 NA20 ZA052 ZA072 ZA082 ZA362 ZA602 4C086 AA01 AA02 CB05 MA03 MA04 MA10 MA35 MA37 MA52 NA20 ZA05 ZA07 ZA08 ZA36 ZA60 4C206 AA01 AA02 GA31 HA26 MA03 MA04 MA12 MA55 MA57 NA07 ZA05 ZA05 ZA05

Claims (4)

[Claims] 1. An anhydrous caffeine powder having a particle size of 100 to 500 μm of 90% by mass or more and a particle size of less than 100 μm of 5% by mass or less, and two or more kinds of active ingredient powders, Mixed powder for distribution. 2. The powder mixture for distribution according to claim 1, further comprising a lubricant. 3. A capsule, wherein a part of the mixed powder according to claim 1 or 2 is filled in a capsule. 4. A tablet characterized in that a part of the mixed powder according to claim 1 or 2 is distributed to a die of a tableting machine and tableted.