JP5248733B2 - Volatilization-preventing solid preparation and method for producing the same - Google Patents

Description

  The present invention relates to a volatilization-preventing solid preparation, and more specifically, a chemical container that is produced by sublimation of the drug while containing the drug that is volatile or its decomposition product is volatile. The present invention relates to a volatilization-preventing solid preparation that suppresses generation of unpleasant odor from the whisker and the preparation, and a method for producing the same.

  In general, the solid preparation is hermetically stored in a medicine container such as a glass bottle. However, depending on the nature of the drug contained in the solid preparation, it is known that the value of the product is reduced when the product is stored.

  For example, a sublimable drug such as ibuprofen has a problem that when stored in a closed container such as a glass bottle, the inner wall of the glass bottle becomes cloudy (whisker) over time, reducing the commercial value. As the method for preventing whisker of ibuprofen, a method of storing a solid preparation containing ibuprofen and polyvinylpyrrolidone, magnesium oxide and sodium bicarbonate in a closed system (Patent Document 1), a solid preparation containing ibuprofen, A method of storing a desiccant in a closed system (Patent Document 2), and a method of coating 5 to 60% of the sugar coating weight of the uncoated tablet with a sugar coating liquid containing a saccharide, an excipient and a binder (Patent Document 3). ), And a method of applying undercoating with saccharides (Patent Document 4) has been reported.

  In addition, caffeine and the like have a problem that whisker crystals (whiskers) grow during storage and lower the product value. As a method for preventing whisker such as caffeine, a method of coexisting a caffeine-containing preparation, a beard crystal-forming drug-containing preparation and charcoal, silicic anhydride or (and) montmorillonite (Patent Documents 5 and 6), a sublimation drug (Patent Document 7), a method of containing β-1,4 glucan powder having a specific size and specific surface area in a pharmaceutical formulation that easily generates whiskers (Patent Document 7) Patent Document 8) and a method of adding an antacid to caffeine (Patent Document 9) have been reported. Furthermore, a method of adding activated carbon or bentonite to caffeine (hydrate) (Non-Patent Document 1), and a method of mixing white alundum or light anhydrous silicic acid (Aerosil 200) with anhydrous caffeine (Non-Patent Document 2). ) Has been reported. Furthermore, a method of blending a sublimable drug and polyvinylpyrrolidone (Patent Document 10) has been reported.

  On the other hand, cysteines and the like have a problem of generating an unpleasant odor from these. As a method for preventing the smell of chemicals that generate odors such as cysteines, a sugar coating containing 5% to 60% of the weight of the uncoated tablet using a sugar coating liquid containing a sugar, an excipient and a binder ( Patent Document 11) and a method for reducing unpleasant odor formed by dry blending of L-cysteine (Patent Document 12) have been reported.

  However, any of these methods has a problem that the effect is insufficient or the manufacturing process becomes complicated.

JP-A-8-193027 JP-A-8-333247 JP2002-179559 JP2002-241275 Japanese Patent Publication No.56-37970 Japanese Examined Sho 56-53525 JP 61-129138 A JP-A 63-267733 JP-A-2-85214 JP 2000-247870 JP2002-179559 JP2002-179559 Yamada et al., Pharmaceutical Journal, 96 (10), 1223-1228, (1976) Yuasa et al., Pharmacology, 41 (3), 161-171, (1981)

  Therefore, in a solid preparation containing a drug that itself is volatile or its decomposition product is volatile (hereinafter, these are referred to as “volatile chemicals”) more easily than conventional techniques. There has been a demand for the provision of technology capable of reducing the occurrence of whiskers and unpleasant odors caused by the above.

  In order to reduce the occurrence of whiskers and unpleasant odor due to the volatile drug, the present inventors have conducted intensive research to solve the above problems, and at least to a solid preparation containing the volatile drug, It has been found that carboxymethylcellulose or a salt thereof may be contained as a volatilization-preventing agent, and the present invention has been completed.

  That is, the present invention is a volatilization-preventing solid characterized in that it contains at least a chemical that is volatile in itself or a decomposition product thereof that is volatile, and carboxymethylcellulose or a salt thereof as a volatilization-preventing agent. A formulation is provided.

  Further, the present invention provides a method for producing a solid preparation containing a drug that is volatile in itself or a decomposition product of the volatile compound and carboxymethyl cellulose or a salt thereof as a volatilization-preventing agent. Is used in a kneading step, a granulating step, or a coating step, and a method for producing a volatilization-preventing solid preparation is provided.

  ADVANTAGE OF THE INVENTION According to this invention, generation | occurrence | production of the whisker of the solid formulation containing a volatile chemical | medical agent and generation | occurrence | production of an unpleasant odor can be reduced.

  The volatilization-preventing solid preparation of the present invention (hereinafter referred to as “the present invention formulation”) is composed of at least a volatile drug and carboxymethylcellulose or a salt thereof as a volatilization-preventing drug.

  Among these, a volatile drug is one in which the drug itself is volatile, or a part of the drug is decomposed and this decomposed product is volatilized. For example, when a solid preparation containing these drugs is stored. Furthermore, it refers to a sublimable drug that sublimes the drug or an odorous drug that generates an unpleasant odor. More specific examples of sublimation agents include ibuprofen, caffeine (anhydrides, hydrates, etc.), menthols such as L-menthol, benzoic acids such as benzoic acid, salicylic acids such as methyl salicylate, D- Examples include camphors such as camphor, isopropylantipyrine, etenzamide, carbamazepine and the like. Examples of odorous agents that generate unpleasant odors include cysteines such as L-cysteine, vitamin B such as thiamine hydrochloride, thiamine nitrate, bistamine amine, thiamine disulfide, bisbenchamine, octotiamine, and fursultiamine hydrochloride. , Vitamin C such as ascorbic acid and calcium ascorbate, vitamin E such as dl-α-tocopherol calcium succinate and dl-α-tocopherol acetate, ibuprofen and the like. One or more of these sublimable drugs or drugs that generate an unpleasant odor can be used.

  In addition, carboxymethylcellulose or a salt thereof (hereinafter referred to as “carboxymethylcelluloses”) as a volatilization-preventing agent used in the preparation of the present invention can be used as long as it can prevent or reduce volatilization of the volatilizing agent. There is no particular limitation. Specific carboxymethyl celluloses include carboxymethyl cellulose, carboxymethyl cellulose potassium, carboxymethyl cellulose calcium, and carboxymethyl cellulose sodium, and one or more of these can be used.

  Among these carboxymethyl celluloses, sodium carboxymethyl cellulose is preferable. There are various grades of sodium carboxymethylcellulose, but when used as a coating agent, a low viscosity grade is preferred. The viscosity range of such a low viscosity grade is 1 to 2,000 cps, more preferably 1 when a 1% aqueous solution of sodium carboxymethylcellulose is prepared and measured with a B-type viscometer (25 ° C., 60 rotations). One having a viscosity of ˜1,000 cps, particularly preferably 1 to 500 cps. Specific product names include CMC Daicel <Product No. 1105>, CMC Daicel <Product No. 1107>, CMC Daicel <Product No. 1110>, Japanese Pharmacopoeia CMC Daicel <Product No. 1120>, CMC Daicel <Product No. 1205>, CMC Daicel <Product No.> 1207>, CMC Daicel <Part No. 1210>, CMC Japanese Pharmacopoeia CMC Daicel <Part No. 1220> (all manufactured by Daicel Chemical Industries, Ltd.) and the like.

  The carboxymethylcelluloses may be used as they are, but a solution obtained by dissolving or (and) suspending them in a solvent (hereinafter referred to as “CMC solution”) may be used. The solvent used in this CMC solution is not particularly limited as long as it is a solvent that can dissolve or (and) suspend carboxymethylcelluloses, and examples thereof include water, alcohol, and a mixed solution thereof. The solubility and viscosity of this CMC solution can be changed by changing the temperature, pH, adding ions, and the like. Moreover, you may add the postscript excipient | filler, binder, disintegrating agent, lubricant, etc. to this CMC liquid as needed.

  The preparation of the present invention can be produced by a method for producing solid preparations such as conventional fine granules, granules, tablets, capsules, etc., except that the volatile drug and the carboxymethylcelluloses as a volatilization preventing drug are essential components. it can. In this case, it is preferable to use carboxymethylcelluloses in the kneading step, granulation step or coating step, and it is particularly preferable because the solid preparation obtained when used in the coating step has gloss.

  In the present invention, the kneading step refers to a drug and an excipient (including a binder, a disintegrant, etc.) before granulating with a stirring granulator, an extrusion granulator or the like in a production process of a conventional solid preparation. ). In this kneading step, the carboxymethyl celluloses are added as they are, or (and) as a CMC solution to drugs and excipients, or by spraying the CMC solution. In this case, the addition amount of carboxymethylcelluloses is preferably 0.1 to 50% by mass, more preferably 0.2 to 30% by mass, particularly 0.5 to 20%, based on the total amount of the drug and excipients. Mass% is preferred. Moreover, 0.4-60 mass% is preferable with respect to a volatile chemical | medical agent, Furthermore, 1-40 mass% is preferable, and 2-30 mass% is especially preferable.

  In the present invention, the granulation step refers to a step of granulating a drug and an excipient (including a binder, a disintegrant, etc.) with a fluidized bed granulator or the like in a production process of a conventional solid preparation. . In this granulation step, the carboxymethyl celluloses are added as they are, or (and) as a CMC solution to drugs and excipients, or by spraying the CMC solution. In this case, the addition amount of carboxymethylcelluloses is preferably 0.1 to 50% by mass, more preferably 0.2 to 30% by mass, particularly 0.5 to 20%, based on the total amount of the drug and excipients. Mass% is preferred. Moreover, 0.4-60 mass% is preferable with respect to a volatile chemical | medical agent, Furthermore, 1-40 mass% is preferable, and 2-30 mass% is especially preferable.

  Further, in the present invention, the coating step refers to a step of coating a produced granule or tablet with a fluidized bed granulator or a sugar coating machine in a conventional solid preparation manufacturing process. In this coating step, the carboxymethyl celluloses are sprayed onto the granules or tablets as they are or (and) as a CMC solution to coat the granules or tablets. In this case, the addition amount of carboxymethylcelluloses is preferably 0.1 to 50% by mass, more preferably 0.2 to 30% by mass, particularly 0.5 to 20%, based on the total amount of the drug and excipients. Mass% is preferred. Moreover, 0.4-60 mass% is preferable with respect to a volatile chemical | medical agent, Furthermore, 1-40 mass% is preferable, and 2-30 mass% is especially preferable.

  If necessary, the inside, outside or both sides of the carboxymethylcellulose coating can be coated with another coating agent or the like. For example, a tablet is coated with carboxymethylcellulose, and sugar coating is further applied. The effect of the preparation of the present invention can be obtained even if carboxymethyl cellulose is added to the sugar coating formulation, but it is preferable to coat only the surface of granules or tablets with carboxymethyl cellulose. The preparation of the present invention coated in this way has a gloss superior to that of a solid preparation coated with a conventional coating agent such as hydroxymethylcellulose (HPMC).

  Further, additives such as excipients, binders, disintegrants, lubricants and the like that can be generally used in the pharmaceutical field may be added to the preparation of the present invention as long as the effects of the present invention are not hindered.

  Examples of excipients include lactose, starch, corn starch, pregelatinized starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, purified white sugar, sugar alcohols, light anhydrous silicic acid, silica Examples include calcium acid, titanium oxide, and precipitated calcium carbonate. One or more of these excipients can be used.

  Examples of the binder include gelatin, gum arabic powder, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, pullulan, dextrin, carboxymethylcellulose calcium, carboxymethylcellulose sodium, (methacrylic acid copolymer, etc. A) Acrylic acid derivatives, shellac, carboxyvinyl polymer, sodium carboxymethyl starch, carboxymethyl ethyl cellulose, cellulose acetate phthalate and the like. One or more of these binders can be used.

  Examples of the disintegrant include croscarmellose sodium, crospovidone, cross-linked insoluble poivinylpyrrolidone, carmellose calcium, sodium carboxymethyl starch, potato starch, corn starch, pregelatinized starch and the like. One or more of these disintegrants can be used.

  Examples of the lubricant include talc, stearic acid, magnesium stearate, sucrose fatty acid esters, polyethylene glycol and the like. One or more of these lubricants can be used.

  The volatilization-preventing solid preparation of the present invention thus obtained can be in various forms such as fine granules, granules and tablets. These volatilization-preventing solid preparations can be stored in conventional medicine bottles such as glass bottles, PTP packaging, and aluminum heat seal packaging, and reduce the occurrence of whiskers and unpleasant odors during storage. be able to.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated still in detail, this invention is not restrict | limited at all by these.

Example 1
Production of solid preparation (1):
450 g of ibuprofen, 24 g of dihydrocodeine phosphate, 60 g of dl-methylephedrine hydrochloride, 6 g of isopropamide iodide, 48 g of noscapine, 7.5 g of chlorpheniramine maleate, 300 g of ascorbic acid, 24 g of thiamine nitrate, 75 g of anhydrous caffeine, light anhydrous cellulose 1408.5 g of an excipient composed of silicic acid, lactose, hydroxypropylcellulose and the like was added to obtain a powder mixture. Purified water was added to this and wet granulated, followed by drying to prepare granules. The granules were sized with a comil (manufactured by POWREC), mixed with 15 g of talc and 12 g of magnesium stearate, and 270 mg / tablet uncoated tablet was produced with a rotary tableting machine.

  A film coating agent (hereinafter referred to as “white HPMC liquid”) made of hydroxypropylmethylcellulose (HPMC), titanium oxide, water, ethanol (7: 3: 20: 70) is applied to this uncoated tablet with a high coater (Freund Sangyo). ) To obtain 280 mg / tablet film-coated tablets (Product 1). This coated tablet was further sprayed with a film coating agent (2.5% aqueous solution) consisting of sodium carboxymethylcellulose (CMC Daicel <Part No. 1110>: manufactured by Daicel Chemical Industries, Ltd.) and water, 282.5 mg / tablet, 285 mg. A film-coated tablet was obtained. These will be referred to as Invention Product 1 and Invention Product 2, respectively.

Comparative Example 1
Production of comparative solid preparation (1):
The film-coated tablet obtained in Example 1 (Product 1) was sprayed with a film coating agent (2.5% aqueous solution) consisting of HPMC and water to obtain 282.5 mg / tablet and 285 mg / tablet film-coated tablet. . These are referred to as comparative product 1 and comparative product 2, respectively.

Example 2
Production of solid preparation (2):
To 450 g of ibuprofen and 240 g of anhydrous caffeine were added 536 g of an excipient composed of crystalline cellulose, low-substituted hydroxypropylcellulose, lactose and the like to obtain a powder mixture. To this, 200 g of a 5% aqueous solution of sodium carboxymethylcellulose (CMC Daicel <Part No. 1120>: manufactured by Daicel Chemical Industries, Ltd.) was added as a kneaded liquid (paste) and wet granulated, and then dried to produce granules. . The granules were sized with a comil (manufactured by POWREC), 18 g of talc and 6 g of magnesium stearate were added and mixed, and a plain tablet of 210 mg / tablet was produced with a rotary tableting machine.

  A white HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo Co., Ltd.) to obtain 220 mg / tablet film-coated tablets. This is referred to as product 3 of the present invention.

Comparative Example 2
Production of comparative solid preparation (2):
To 450 g of ibuprofen and 240 g of anhydrous caffeine were added 536 g of an excipient composed of crystalline cellulose, low-substituted hydroxypropylcellulose, lactose and the like to obtain a powder mixture. To this, 200 g of a 5% aqueous solution of hydroxypropylcellulose was added as a kneaded solution, wet granulated, and dried to prepare granules. The granules were sized with a comil (manufactured by POWREC), 18 g of talc and 6 g of magnesium stearate were added and mixed, and a plain tablet of 210 mg / tablet was produced with a rotary tableting machine.

  A white HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo Co., Ltd.) to obtain 220 mg / tablet film-coated tablets. This is referred to as comparative product 3.

Example 3
Production of solid preparation (3):
450 g of ibuprofen, 24 g of dihydrocodeine phosphate, 60 g of dl-methylephedrine hydrochloride, 6 g of isopropamide iodide, 48 g of noscapine, 7.5 g of chlorpheniramine maleate, 300 g of ascorbic acid, 24 g of thiamine nitrate, 75 g of anhydrous caffeine, light cellulose 1396 g of an excipient composed of silicic anhydride, lactose and the like was added to obtain a powder mixture. To this, 500 g of a 2.5% aqueous solution of sodium carboxymethyl cellulose (CMC Daicel <Part No. 1120>: manufactured by Daicel Chemical Industries, Ltd.) was sprayed as a granulating liquid, granulated, and dried to prepare granules. The granules were sized with a comil (manufactured by POWREC), mixed with 15 g of talc and 12 g of magnesium stearate, and 270 mg / tablet uncoated tablet was produced with a rotary tableting machine.

  White HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo) to obtain 280 mg / tablet film-coated tablets. This is referred to as product 4 of the present invention.

Comparative Example 3
Production of comparative solid preparation (3):
450 g of ibuprofen, 24 g of dihydrocodeine phosphate, 60 g of dl-methylephedrine hydrochloride, 6 g of isopropamide iodide, 48 g of noscapine, 7.5 g of chlorpheniramine maleate, 300 g of ascorbic acid, 24 g of thiamine nitrate, 75 g of anhydrous caffeine, light cellulose 1396 g of an excipient composed of silicic anhydride, lactose and the like was added to obtain a powder mixture. This was sprayed with 500 g of a 2.5% aqueous solution of hydroxypropylcellulose as a granulating liquid, granulated, and dried to prepare granules. The granules were sized with a comil (manufactured by POWREC), mixed with 15 g of talc and 12 g of magnesium stearate, and 270 mg / tablet uncoated tablet was produced with a rotary tableting machine.

  White HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo) to obtain 280 mg / tablet film-coated tablets. This is referred to as a comparative product 4.

Example 4
Production of solid preparation (4):
To 450 g of ibuprofen, 190 g of an excipient composed of crystalline cellulose, light anhydrous silicic acid and the like was added to obtain a powder mixture. 400 g of a 2.5% aqueous solution of sodium carboxymethylcellulose (CMC Daicel <Part No. 1120>: manufactured by Daicel Chemical Industries, Ltd.) was sprayed on this as a granulating liquid, granulated, and dried to prepare granules A. Separately, dihydrocodeine phosphate 24 g, dl-methylephedrine hydrochloride 60 g, isopropamide iodide 6 g, noscapine 48 g, chlorpheniramine maleate 7.5 g, ascorbic acid 300 g, thiamine nitrate 24 g, anhydrous caffeine 75 g, crystalline cellulose, low substitution degree 118.5 g of an excipient composed of hydroxypropylcellulose, lactose and the like was added to obtain a powder mixture. 400 g of a 2.5% aqueous solution of hydroxypropylcellulose was sprayed onto this as a granulating liquid, granulated, and dried to prepare granules B. These granule A and granule B were each sized with a comil (manufactured by POWREC), then mixed, further mixed with 15 g of talc and 12 g of magnesium stearate, and mixed with a rotary tableting machine at 270 mg / tablet. Made.

White HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo) to obtain 280 mg / tablet film-coated tablets. This is referred to as product 5 of the present invention.

Example 5
Production of solid preparation (5):
To 240 g of L-cysteine and 300 g of ascorbic acid, 740 g of an excipient composed of crystalline cellulose, partially pregelatinized starch, light anhydrous silicic acid, hydroxypropylcellulose and the like was added to obtain a powder mixture. To this, 25 g of talc and 15 g of magnesium stearate were added and mixed, and an uncoated tablet of 220 mg / tablet was produced using a rotary tableting machine.

  White HPMC solution was sprayed onto the uncoated tablets with a high coater (Freund Sangyo) to obtain 230 mg / tablet film-coated tablets (Product 2). To this coated tablet, a film coating agent (2.5% aqueous solution) consisting of sodium carboxymethylcellulose (Japanese Pharmacopoeia CMC Daicel <Part No. 1120>: Daicel Chemical Industries, Ltd.) and water was sprayed, and 235 mg / tablet, 240 mg / tablet film-coated tablets were obtained. These will be referred to as the present invention product 6 and the present invention product 7, respectively.

Comparative Example 4
Production of comparative solid preparation (4):
To 450 g of ibuprofen, 190 g of an excipient composed of crystalline cellulose, light anhydrous silicic acid and the like was added to obtain a powder mixture. 400 g of a 2.5% aqueous solution of hydroxypropylcellulose was sprayed on this as a granulating liquid, granulated, and dried to prepare granules C. Separately, dihydrocodeine phosphate 24 g, dl-methylephedrine hydrochloride 60 g, isopropamide iodide 6 g, noscapine 48 g, chlorpheniramine maleate 7.5 g, ascorbic acid 300 g, thiamine nitrate 24 g, anhydrous caffeine 75 g, crystalline cellulose, low substitution degree 118.5 g of an excipient composed of hydroxypropylcellulose, lactose and the like was added to obtain a powder mixture. This was sprayed with 400 g of a 2.5% aqueous solution of hydroxypropylcellulose as a granulating liquid, granulated, and dried to prepare granules D. These granule C and granule D were each sized with a comil (made by Paulek), then mixed, further mixed with 15 g of talc and 12 g of magnesium stearate, and mixed with a rotary tableting machine at 270 mg / tablet. Made.

  White HPMC solution was sprayed on the uncoated tablets with a high coater (Freund Sangyo) to obtain 280 mg / tablet film-coated tablets. This is referred to as comparative product 5.

Comparative Example 5
Production of comparative solid preparation (5):
The film-coated tablet obtained in Example 5 (Product 2) was sprayed with a film coating agent (2.5% aqueous solution) consisting of HPMC and water to obtain film-coated tablets of 235 mg / tablet and 240 mg / tablet. These are referred to as comparative product 6 and comparative product 7, respectively.

Test example 1
Solid formulation storage test:
The solid preparations of the present invention products 1 to 5 and comparative products 1 to 5 were sealed in a colorless and transparent glass bottle, and the cloudiness of the inner wall of the glass bottle after storage at 50 ° C. for 10 days was observed. In addition, the evaluation criteria of cloudiness are shown below.

<Evaluation criteria for cloudiness>
(Evaluation) (Contents)
-: No cloudiness is observed.
±: Almost no cloudiness +: Cloudiness is recognized ++: Strong cloudiness is recognized +++: Extremely strong cloudiness is recognized

Test example 2
Gloss generation test of solid preparation:
Comparison of gloss of solid preparations was performed according to the following criteria before and after storage in Test Example 1 for the inventive products 1, 2, 6, 7 and comparative products 1, 2, 6, 7. There was no change in the gloss of the solid preparation before and after storage. The gloss evaluation criteria are shown below.

<Evaluation criteria for gloss>
(Evaluation) (Contents)
±: Gloss is hardly recognized +: Gloss is recognized ++: Gloss is strongly recognized

Test example 3
Odor generation test of solid preparation:
Samples of Invention Products 6 and 7 and Comparative Products 6 and 7 were placed in a colorless and transparent glass bottle, sealed, stored at 50 ° C. for 10 days, and then the odor immediately after the glass bottle was opened was evaluated. The evaluation standards for odor are shown below.

<Odor evaluation criteria>
(Evaluation) (Contents)
±: Almost no unpleasant odor ＋: Unpleasant odor ++: Strong unpleasant odor

  According to this invention, even if it is a solid formulation containing a volatile chemical | medical agent, volatilization of a chemical | medical agent can be prevented thru | or reduced.

Therefore, since the preparation of the present invention prevents whisker and unpleasant odor generated in the medicine container, the commercial value of the preparation can be increased.

that's all

Claims (3)

At least the following agents (A) and / or (B) that are themselves volatile or whose degradation products are volatile:
(A) ibuprofen, caffeine, menthol, benzoic acid, salicylic acid,
One or more sublimation agents selected from the group consisting of isopropylantipyrine, etenzamide, and carbamazepine (B) One type selected from the group consisting of cysteines, vitamins B, vitamins C, vitamins E, and ibuprofen Or more odorous drugs,
When,
Containing sodium carboxymethylcellulose as volatilization preventing agent, and volatilization-preventing type solid preparation, characterized by using a solution containing sodium carboxymethylcellulose only in the coating process during the production process.   The volatilization-preventing solid preparation according to claim 1, which reduces the occurrence of whiskers in the medicine container. The volatilization-preventing solid preparation according to claim 1, which reduces the generation of unpleasant odor.