JP2003128543A - Solid pharmaceutical preparation containing ascorbic acid or its salt and calcium pantothenate, and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid pharmaceutical preparation containing ascorbic acid or its salt and calcium pantothenate easily produced. SOLUTION: This solid pharmaceutical preparation contains the ascorbic acid or its salt and a calcium pantothenate wherein the pharmaceutical preparation has an equilibrium relative humidity in the preparation not more than 60%.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a solid preparation containing ascorbic acid or a salt thereof and calcium pantothenate and a method for producing the same.

[0002]

2. Description of the Related Art It is known that when calcium pantothenate is mixed with ascorbic acid or a salt thereof in a preparation, decomposition of calcium pantothenate is remarkably accelerated. Therefore, conventionally, in order to produce a solid preparation containing ascorbic acid or a salt thereof and calcium pantothenate, for example, a sugar-coated tablet, by blending calcium pantothenate in the sugar-coating layer, and preventing contact between the two, pantothenic acid It was trying to stabilize calcium. However, this method has a problem that the manufacturing is complicated. As a solution to this problem, Japanese Patent No. 28917
JP-A-44 discloses a stabilized composition containing calcium pantothenate, which has good compatibility with ascorbic acid or its salt. If this is used, a solid preparation in which calcium pantothenate is stable can be obtained. However, there is a need for a solid preparation in which calcium pantothenate is more stable and easy to manufacture.

[0003]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a solid preparation solid preparation containing ascorbic acid or a salt thereof and calcium pantothenate, in which calcium pantothenate is stable and easy to produce. It is in.

[0004]

Means for Solving the Problems As a result of intensive studies for achieving the above-mentioned object, the present inventors have surprisingly reduced the water content (equilibrium relative humidity (ERH)) in a solid preparation. According to the above, it was found that a solid preparation containing calcium as pantothenate and calcium as pantothenate, which is stable, can be easily produced. further,
It was found that a more stable solid preparation can be produced by dry-blending a composition containing calcium pantothenate, and completed the present invention. That is, the present invention provides: (1) a solid preparation containing ascorbic acid or a salt thereof and a calcium pantothenate-containing composition, wherein the equilibrium relative humidity in the preparation is 60% or less; (2) The above calcium pantothenate-containing composition is a mixture of calcium pantothenate and a lactate or carbonate of magnesium or calcium, which is neutral or basic per se in the presence of water and / or a lower alcohol,
Then, the solid preparation according to (1) above, which is a composition obtained by drying the mixture; and (3) the composition containing calcium pantothenate in a dry manner, as described in (1) above. The present invention provides a method for producing a solid preparation and the like.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Equilibrium relative humidity (E
RH) means the equilibrium relative humidity (ERH) indicated by the space inside the closed container when about 1 g of the solid preparation of the present invention is placed in the closed container at 25 ° C., and the following formula: Equilibrium relative humidity (ERH) ) = (P / PS) × 100 [In the formula, P represents the water vapor pressure on the surface of the substance, and PS represents the water vapor pressure on pure water at the same temperature as the substance. ] It can be obtained by the calculation formula represented by. The equilibrium relative humidity can be easily measured by a commercially available apparatus for measuring water activity, and for example, in the present specification, a commercially available measuring apparatus, Hygroscope (trade name, manufactured by Rotronic (Switzerland), Gunze) It is measured using Sangyo Co., Ltd.). The equilibrium relative humidity (ERH) in the formulations of the invention is 6
0% or less is preferable. By controlling the equilibrium relative humidity (ERH) in the preparation in this manner, the decomposition of calcium pantothenate is highly suppressed.

The ascorbic acid or salt thereof used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but ascorbic acid salts include, for example, sodium salt, potassium salt, calcium salt, Zinc salt,
Examples thereof include magnesium salts. Ascorbic acid is preferably used.

The calcium pantothenate-containing composition used in the present invention is preferably the composition described in Japanese Patent No. 2891744. The composition can be produced according to the method described in the publication, but specifically, calcium pantothenate and a lactate or carbonate of neutral or basic magnesium or calcium per se are mixed with water and / or. Obtained by mixing in the presence of lower alcohol and then drying the mixture. Among them, particularly preferable is a composition obtained by mixing calcium pantothenate and calcium lactate in the presence of water, and then drying the mixture. The composition is also available as a commercial product (trade name: calcium pantothenate type S, BASF Takeda Vitamin).

In the solid preparation of the present invention, vitamins other than ascorbic acid or its salt may be further blended, if necessary. Examples of vitamins that can be used in the present invention include vitamin B ₁ derivatives (fursultiamine hydrochloride, dicethiamine hydrochloride, octothiamine, shicothiamine, bis-ibutyamine, bisbentiamine, benfotiamine, etc.), vitamin B ₁ (thiamine hydrochloride, nitric acid, etc.). Thiamine, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, etc.), vitamin B ₂ (riboflavin, riboflavin phosphate sodium, riboflavin butyrate riboflavin etc.), vitamin B ₆ (pyridoxine hydrochloride, pyridoxal phosphate etc.), vitamin C (ascorbine) acid, sodium ascorbate, calcium ascorbate, etc.), vitamin B _{12 (cyanocobalamin,} hydrochloric hydroxocobalamin acetate hydroxocobalamin, mecobalamin etc.), vitamin E (succinate d-alpha Tocopherol, succinate dl-alpha-tocopherol calcium acetate d-alpha-tocopherol acetate dl-alpha-tocopherol, etc.), nicotinic acid, nicotinic acid amide,
Calcium pantothenate, calcium pantothenate type S, biotin, gamma-oryzanol, orotic acid,
Examples thereof include glucuronolactone, glucuronic acid amide, and yoquinin.

In the solid preparation of the present invention, an excipient, a binder, a disintegrating agent, a lubricant and the like can be added if necessary.

The excipients and binders that can be used in the present invention include cellulose and its derivatives, starch and its derivatives, synthetic polymer compounds and sugars. Examples of cellulose and its derivatives that can be used in the present invention include crystalline cellulose, powdered cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, hydroxyethyl cellulose and the like. Examples of starch and its derivatives that can be used in the present invention include corn starch, dextrin, pregelatinized starch, partially pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch, cyclodextrin and the like. Examples of the synthetic polymer compound that can be used in the present invention include polyvinylpyrrolidone, aminoalkylmethacrylate copolymer E, methacrylic acid copolymer L, aminoalkylmethacrylate copolymer RS, methacrylic acid copolymer S, carboxyvinyl polymer, polyvinyl alcohol. , Polyvinyl acetal diethylamine acetate, and the like. Examples of sugars that can be used in the present invention include sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol, erythritol, powdered maltose starch syrup and the like.

Examples of the disintegrant that can be used in the present invention include croscarmellose sodium, carmellose calcium, low-substituted hydroxypropyl cellulose, crospovidone and the like. Lubricants that can be used in the present invention include magnesium stearate, calcium stearate, sucrose fatty acid ester and the like.

The solid preparation of the present invention may be in any form such as granules, fine granules, plain tablets, film tablets, thin-layer sugar-coated tablets, sugar-coated tablets and chewable tablets. The production of the solid preparation in the present invention is carried out according to the dosage form, according to the granulation handbook (edited by Japan Powder Industrial Technology Association, Ohmsha), the formulation design of the oral administration preparation (Kyoto University, Graduate School of Pharmaceutical Sciences, Professor Mitsuhashi Hashida, It may be prepared by a general method described in publications such as Yakuhin Jikho Co., Ltd.), powder compression molding technology (Powder Engineering / Formulation and Particle Design Subcommittee, Nikkan Kogyo Shimbun).
For example, ascorbic acid or a salt thereof, a composition containing calcium pantothenate, optionally added vitamins, an excipient, and a binder are mixed, granulated, and then sized to obtain a sized powder. Then, an uncoated tablet can be obtained by mixing the obtained sized powder with a disintegrant and a lubricant and tableting.

The suitable equilibrium relative humidity (ERH) in the solid preparation of the present invention is mainly achieved by adjusting the drying conditions during the granulation. The drying conditions are such that the equilibrium relative humidity in the obtained solid preparation is measured by a commercially available apparatus for measuring water activity as described above, and if the obtained numerical value is higher than the intended equilibrium relative humidity (ERH), drying is performed. It can be easily determined by tightening the conditions. The drying conditions vary depending on the amount of water used during mixing of the formulation components and granulation, but the air supply temperature is usually about 50 to 10
The temperature of exhaust gas is 0 ° C (preferably 55 to 95 ° C), and is usually about 35 to 68 ° C (preferably 38 to 65 ° C). When performing film coating, thin-layer sugar coating, and sugar coating, a coating machine using an aeration type coating machine such as a dria coater (Pawreck), aqua coater (Freund industry), high coater (Freund industry), etc. is used. It is achieved by spraying the liquid as a mist of 1000 μm or less and adjusting the coating conditions such as the supply temperature, the supply air volume, and the injection speed.

In particular, the calcium pantothenate-containing composition is preferably blended in a dry form in the preparation. This can be carried out, for example, by wet-granulating ascorbic acid, a binder, an excipient and the like, and then mixing the obtained sized powder with a component containing a calcium pantothenate-containing composition. The mixture can then be tabletted. This makes it possible to obtain a solid preparation in which calcium pantothenate is more stable.

The uncoated tablets thus obtained can be subjected to film coating, thin layer sugar coating and sugar coating, if necessary. As the film coating base in the present invention, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, aminoalkylmethacrylate copolymer E, aminoalkylmethacrylate copolymer L, aminoalkylmethacrylate copolymer RS, aminoalkylmethacrylate
Copolymer S, carboxyvinyl polymer, polyvinyl alcohol, polyvinyl acetal diethylamine acetate and the like can be mentioned. Examples of sugar-coated and thin-layer sugar-coated bases in the present invention include sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol,
Erythritol, powdered reduced maltose syrup and the like can be mentioned.
In the present invention, when film coating, sugar coating, and thin layer sugar coating are performed, if necessary, an excipient, a coating agent, a binder, a plasticizer, a coloring agent and the like can be added. In the present invention, talc, precipitated calcium carbonate, titanium oxide and the like can be mentioned as excipients for carrying out film coating, sugar coating and thin layer sugar coating. In the present invention, examples of the plasticizer for film coating, sugar coating, and thin layer sugar coating include macrogol 6000, copolyvidone, and triethyl citrate.

If desired, the solid preparation of the present invention may be provided with a scent and taste in order to improve its ingestability. For example, a scent and taste can be imparted by adding a flavoring agent, a flavoring agent, or a flavoring agent. The flavoring agents or fragrances that can be used in the present invention include, for example, peppermint oil, eucalyptus oil, cinnamon oil, fennel oil, clove oil, orange oil, lemon oil, rose oil, fruit flavor, banana flavor, strawberry flavor. , Mint flavor, peppermint flavor, dl-menthol, 1-menthol and the like. As the corrigent, sugar, sugar alcohol, a high-intensity sweetener, and an acidulant can be added. Examples of sugars and sugar alcohols used in the present invention as a corrigent include sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol, erythritol, powdered maltose starch syrup and the like. The high-intensity sweetener used in the present invention as a corrigent is an artificially synthesized sweetener whose sweetness is several times or more that of sugar, preferably about 100.
Double or more, specifically, aspartame, stevia, saccharin, dipotassium glycyrrhizin, thaumatin, sucralose, acesulfame K and the like can be mentioned. Examples of the acidulant used in the present invention as a corrigent include citric acid, malic acid, tartaric acid, and ascorbic acid.

[0017]

The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example 1 2700 g of ascorbic acid, 54 g of riboflavin,
D-α-Tocopherol succinate (regular particle size product)
225 g, powdered maltose starch syrup 351 g, and crystalline cellulose 240.8 g were sprayed with a 6% hydroxypropylcellulose (HPC-L) aqueous solution 2700 g in a fluidized bed granulator (FD-5S, Powrex) to form a fluidized bed. Grain. After fluidized bed granulation, supply temperature 70 ℃
Then, it was dried to an exhaust temperature of 48 ° C. to obtain a granulated powder.
Then, the particles were sized by a particle sizer (Power Mill, Showa Kagaku Kikai) to obtain a sized powder. The obtained sized powder 3318 g, L-
Cysteine 640 g, calcium pantothenate type S 184.8 g, crystalline cellulose 345.2 g,
240 g of low-purity hydroxypropyl cellulose, 24 g of special calcium silicate (Fluorite RE), and 48 g of magnesium stearate were mixed in a mixer (tumbler mixer, Showa Kagaku Kikai), and the resulting mixed powder was rotary-typed. With a tableting machine, a mortar with a diameter of 8.8 mm and an R-face punch with a radius of curvature of 7.0 mm weighs 300 m per tablet.
g to give a thickness of 5.2 mm to obtain plain tablets. 120 g of hydroxypropylmethylcellulose (TC-5MW) was added to 3240 g of the above plain tablet and purified water was added.
Using a coating liquid dissolved in 1080 g, a coating machine (Doria coater DRC-500, Powrex) was used to supply air at a temperature of 70 ° C. and air supply at an air flow of 4 m ³ / mi.
n, liquid injection rate 10 g / min, 2% of the uncoated tablet weight was coated, and further erythritol 918.5 g, talc 48
5.3 g, titanium oxide 34.7 g, crystalline cellulose (Avicel PH-F20) 86.6 g, and gum arabic powder 207.9 g were dissolved in purified water 2827 g and used as a coating solution to suspend a coating machine (Doria Coater DRC- 500, Paulec), supply air temperature
60 ° C, supply air volume 4m ³ / min, injection speed 20g
3 for the uncoated tablet weight under coating conditions of / min
8% coating amount. Furthermore, using a coating solution prepared by dissolving 540 g of erythritol and 60 g of Macrogol 6000 in 980 g of purified water, a coating machine (Doria coater DRC-500, Powrex) was used to supply air at a temperature of 55 ° C. and air supply of 4 m ³ / mi
Under the coating conditions of n and liquid injection rate of 17 g / min, 5% of the uncoated tablet weight was coated to obtain a thin layer sugar-coated tablet. The thin-layered sugar-coated tablets were coated with a slight amount of a polishing liquid (carnauba wax, ethanol-n-hexane solution in which white wax was dissolved), and polishing was performed.
The measured equilibrium relative humidity (ERH) was 24.3%.

Example 2 Ascorbic acid 2700 g, calcium pantothenate type S 207.9 g, riboflavin 54 g, succinate d-α-tocopherol (regular particle size product)
225 g, powdered reduced maltose starch syrup 351 g, and crystalline cellulose 251.1 g were mixed with a fluidized bed granulator (FD-5S, Powrex) to prepare 6% hydroxypropyl cellulose (H
By spraying 2700 g of PC-L) aqueous solution,
Fluid bed granulate. After fluidized bed granulation, at the air supply temperature of 70 ° C,
Drying was carried out to an exhaust temperature of 48 ° C. to obtain a granulated powder. After that, the particles are sized with a particle sizer (Power Mill, Showa Kagaku Kikai),
A sized powder was obtained. The obtained sized powder (3512 g), L-cysteine (640 g), crystalline cellulose (336 g), low-substituted hydroxypropyl cellulose (240 g), special calcium silicate (Fluorite RE) (24 g), and magnesium stearate (48 g) were mixed with a mixer (tumbler mixer,
(Showa Kagaku Kikai Co., Ltd.), and the resulting mixed powder is rotator-type tableting machine with a die having a diameter of 8.8 mm and a radius of curvature of 7.0 mm.
R face punch, weight per tablet 300 mg, thickness
Tablets were made to have a size of 5.2 mm to obtain plain tablets. Using a coating solution prepared by dissolving 120 g of hydroxypropylmethylcellulose (TC-5MW) in 1080 g of purified water in 3240 g of the above plain tablets, a coating machine (Doria Coater DRC-500, Powrex), supply temperature 70 ° C, supply air Air volume 4m ³ / min, injection speed 1
Under coating conditions of 0 g / min, 2% of the uncoated tablet weight was coated, and further, erythritol 918.5 g, talc 485.3 g, titanium oxide 34.7 g, crystalline cellulose (Avicel PH-F2.
0) 86.6 g, gum arabic powder 207.9 g were dissolved and suspended in purified water 2827 g, and a coating machine (Doria coater DRC-50) was used.
0, Paulec), supply temperature 60 ℃, supply air volume
Under the coating conditions of 4 m ³ / min and a liquid injection rate of 20 g / min, 38% of the uncoated tablet weight is coated. Further, using a coating solution prepared by dissolving 540 g of erythritol and 60 g of Macrogol 6000 in 980 g of purified water, a coating machine (Doria coater DRC-500, Powrex) was used to supply air at a temperature of 5
5 ° C, supply air volume 4m ³ / min, injection speed 17g /
5% of uncoated tablet weight under min coating conditions
The amount was coated to obtain a thin-layer sugar-coated tablet. The thin-layered sugar-coated tablets were coated with a slight amount of a polishing liquid (carnauba wax, a solution of ethanol-n-hexane in which white wax was dissolved) and polished. The measured equilibrium relative humidity (ERH) was 22.5%.

Test Example 1 The thin-layer sugar-coated tablets of Example 1 and Example 2 were placed in a glass bottle and 50
The bottle was kept sealed at 1 ° C for 1 month, and the residual rate of calcium pantothenate in the thin layer dragee was measured by the following test method. The results are shown in Table 1. [Test method] Sample solution preparation method Sample powder [Calcium pantothenate (C ₁₈ H ₃₂ Ca
N ₂ O ₁₀ ) [amount corresponding to about 0.01 g] is precisely measured, and exactly 100 ml of a 0.05 mol / L ammonium dihydrogen phosphate solution is added. Shake vigorously for 20 minutes to extract, then centrifuge and decant the supernatant to 0.45 μm.
It filtered with the filter of and the filtrate was made into the sample solution. Standard Solution Preparation Calcium Pantothenate Type S [Calcium Pantothenate (C ₁₈ H _{3 2} CaN ₂ O ₁₀ ) About 0.01 g
[Amount corresponding to.] And add 0.05 mol / L ammonium dihydrogen phosphate solution to dissolve, and add exactly 1
00 ml was used as a standard solution. HPLC condition detector: UV absorptiometer (measurement wavelength: 210 nm) Column: YMC-Pack ODS AM-312 Column temperature: Constant temperature around 25 ° C. Mobile phase: 0.05 mol / L ammonium dihydrogen phosphate solution (pH 3. 5) / Methanol mixture (19/1) Flow rate: 1.5 mL / min Injection volume: 20 μL

[0021]

[Table 1]

In both Example 1 and Example 2, the tablet had a low water content (ERH 60% or less), and therefore the stability of calcium pantothenate was good. Comparing Example 1 and Example 2, the stability of calcium pantothenate was better in the tablet of Example 1 in which calcium pantothenate Type S was dry-blended. According to Example 1 and Example 2 of the present invention, a stable solid preparation containing ascorbic acid or a salt thereof and calcium pantothenate could be produced without complication of production.

Example 3 2700 g of ascorbic acid, 54 g of riboflavin,
D-α-Tocopherol succinate (regular particle size product)
225 g, powdered maltose starch syrup 351 g, and crystalline cellulose 240.8 g were sprayed with a 6% hydroxypropylcellulose (HPC-L) aqueous solution 2700 g in a fluidized bed granulator (FD-5S, Powrex) to form a fluidized bed. Grain. After fluidized bed granulation, supply temperature 70 ℃
Then, it was dried to an exhaust temperature of 43 ° C. to obtain a granulated powder.
Then, the particles were sized by a particle sizer (Power Mill, Showa Kagaku Kikai) to obtain a sized powder. The obtained sized powder 3318 g, L-
Cysteine 640 g, calcium pantothenate type S 184.8 g, crystalline cellulose 345.2 g,
240 g of low-purity hydroxypropyl cellulose, 24 g of special calcium silicate (Fluorite RE), and 48 g of magnesium stearate were mixed in a mixer (tumbler mixer, Showa Kagaku Kikai), and the resulting mixed powder was rotary-typed. With a tableting machine, a mortar with a diameter of 8.8 mm and an R-face punch with a radius of curvature of 7.0 mm weighs 300 m per tablet.
g to give a thickness of 5.2 mm to obtain plain tablets. The measured value of ERH was 32.5%.

Example 4 2700 g of ascorbic acid, 54 g of riboflavin,
D-α-Tocopherol succinate (regular particle size product)
225 g, powdered maltose starch syrup 351 g, and crystalline cellulose 240.8 g were sprayed with a 6% hydroxypropylcellulose (HPC-L) aqueous solution 2700 g in a fluidized bed granulator (FD-5S, Powrex) to form a fluidized bed. Grain. After fluidized bed granulation, supply temperature 70 ℃
Then, it was dried to an exhaust temperature of 39 ° C. to obtain a granulated powder.
Then, the particles were sized by a particle sizer (Power Mill, Showa Kagaku Kikai) to obtain a sized powder. The obtained sized powder 3318 g, L-
Cysteine 640 g, calcium pantothenate type S 184.8 g, crystalline cellulose 345.2 g,
240 g of low-purity hydroxypropyl cellulose, 24 g of special calcium silicate (Fluorite RE), and 48 g of magnesium stearate were mixed in a mixer (tumbler mixer, Showa Kagaku Kikai), and the resulting mixed powder was rotary-typed. With a tableting machine, a mortar with a diameter of 8.8 mm and an R-face punch with a radius of curvature of 7.0 mm weighs 300 m per tablet.
g to give a thickness of 5.2 mm to obtain plain tablets. The same plain tablet as in Example 3 was produced. The measured value of ERH was 44.3%.

Comparative Example 1 Ascorbic acid 2700 g, Riboflavin 54 g,
D-α-Tocopherol succinate (regular particle size product)
225 g, powdered maltose starch syrup 351 g, and crystalline cellulose 240.8 g were sprayed with a 6% hydroxypropylcellulose (HPC-L) aqueous solution 2700 g in a fluidized bed granulator (FD-5S, Powrex) to form a fluidized bed. Grain. After fluidized bed granulation, supply temperature 70 ℃
Then, it was dried to an exhaust temperature of 33 ° C. to obtain a granulated powder.
Then, the particles were sized by a particle sizer (Power Mill, Showa Kagaku Kikai) to obtain a sized powder. The obtained sized powder 3318 g, L-
Cysteine 640 g, calcium pantothenate type S 184.8 g, crystalline cellulose 345.2 g,
240 g of low-purity hydroxypropyl cellulose, 24 g of special calcium silicate (Fluorite RE), and 48 g of magnesium stearate were mixed in a mixer (tumbler mixer, Showa Kagaku Kikai), and the resulting mixed powder was rotary-typed. With a tableting machine, a mortar with a diameter of 8.8 mm and an R-face punch with a radius of curvature of 7.0 mm weighs 300 m per tablet.
g to give a thickness of 5.2 mm to obtain plain tablets.

Test Example 2 The plain tablets of Example 3, Example 4 and Comparative Example 1 were placed in a glass bottle,
The bottles were sealed and stored at 50 ° C. for 1 month, and the residual ratio of calcium pantothenate in uncoated tablets was measured in the same manner as in Test Example 1. The results are shown in Table 2.

[0027]

In both Example 3 and Example 4, the tablets had a low water content (ERH 60% or less), and therefore the stability of calcium pantothenate was good. Comparing Example 3 and Example 4 with Comparative Example 1, calcium pantothenate Type S
The stability of calcium pantothenate in the tablet of Comparative Example 1 in which the water content was not lowered even when the compound was dry-blended was poor. According to Examples 3 and 4 of the present invention, a stable solid preparation containing ascorbic acid or a salt thereof and calcium pantothenate could be produced without complication of production.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/12 A61K 47/12 F term (reference) 4C076 AA31 AA36 AA43 AA49 BB01 CC22 CC24 DD37 DD43 FF63 GG05 4C086 AA10 BA18 MA05 MA34 MA52 ZC21 ZC28 4C206 AA10 GA36 MA05 MA54 MA72 NA03 ZC21

Claims (3)

[Claims] 1. A solid preparation comprising ascorbic acid or a salt thereof and a calcium pantothenate-containing composition, wherein the equilibrium relative humidity in the preparation is 60% or less. 2. The calcium pantothenate-containing composition is obtained by mixing calcium pantothenate with a lactate or carbonate of magnesium or calcium, which is neutral or basic in itself, in the presence of water and / or a lower alcohol. The solid preparation according to claim 1, which is a composition obtained by drying the mixture, and then drying the mixture. 3. The method for producing a solid preparation according to claim 1, wherein the calcium pantothenate-containing composition is blended in a dry form.