JP2014088356A - Coating liquid in which high viscosity hypromellose is dispersed, and solid preparation and production method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a coating liquid for a timed-release pharmaceutical preparation which starts drug release in a digestive tract after the lapse of non-release time (lag time) which is from the start of taking a solid preparation to the start of discharge of a drug, and to provide a production method of a solid preparation coated with the coating liquid.SOLUTION: A coating liquid for a solid preparation is obtained by dispersing high viscosity hypromellose whose viscosity of 2 mass% aqueous solution is 50 mPa s or more at 20°C, in solution in which hydroxypropyl cellulose whose viscosity of 2 mass% aqueous solution is less than 50 mPa s at 20°C or low viscosity hypromellose whose viscosity of 2 mass% aqueous solution is less than 50 mPa s at 20°C is dissolved in solvent. A solid preparation is obtained by being coated with the coating liquid. A production method of the solid preparation comprises at least the steps of: applying the coating liquid to a core part containing a drug; and removing solvent in the coating liquid from the coated core part.

Description

  The present invention relates to a coating solution for time-released drug release, a solid preparation coated thereby, and a method for producing the same.

  In recent years, it has become clear that the pharmacokinetics and pharmacological effects of drugs are time-dependent, and various drug delivery methods (drug delivery systems) have been proposed to allow drugs to act accurately on diseased sites. And so on.

  As such a preparation, a sustained-release preparation mainly composed of a drug and a hydrogel-forming water-soluble polymer is coated with a water-soluble polymer (Patent Document 1), and hot water-insoluble cellulose ether is heated. There exists a thing (patent document 2) which prepares the coating liquid of a high viscosity type cellulose ether by making it disperse | distribute to water, without raising a viscosity, and coat | covers to a solid formulation.

Japanese Patent Laid-Open No. 02-083316 JP 63-005030 A

However, Patent Document 1 aims to form a hydrogel by coating an excessive amount of a water-soluble polymer, but has not yet delayed the start of drug release. Further, in Patent Document 2, since the coated film is porous, the start of drug release cannot be delayed.
Therefore, the present invention is a time-release formulation in which drug release is started in the digestive tract after elapse of a non-release time (hereinafter referred to as “lag time”) from the start of taking a solid formulation to the start of release of the drug. It is an object of the present invention to provide a coating liquid, a solid preparation coated thereby, and a method for producing the same.

The present inventors have developed a time-release preparation capable of starting a drug solution in the digestive tract after the lag time has elapsed, by obtaining a coating solution capable of forming a film that requires a long time for dissolution by a simple method. As a result of extensive research for the purpose of the above, as a result, the viscosity of a 2% by mass aqueous solution at 20 ° C. is less than 50 mPa · s, or the viscosity of a 2% by mass aqueous solution at 20 ° C. is less than 50 mPa · s. It is found that the above object is achieved by coating a solution in which high-viscosity hypromellose having a viscosity of 2% by mass at 20 ° C. is dispersed in a solution in which high-viscosity hypromellose is dispersed is 50 mPa · s or more. The present invention has been completed.
In the present invention, hydroxypropyl cellulose having a viscosity of 2% by weight aqueous solution at 20 ° C. of less than 50 mPa · s or low-viscosity hypromellose having a viscosity of 2% by weight aqueous solution at 20 ° C. of less than 50 mPa · s was dissolved in a solvent. Provided is a coating liquid for solid preparation, in which a high-viscosity hypromellose having a viscosity of 50 mPa · s or more at 20 ° C. in a 2 mass% aqueous solution is dispersed in a solution. Moreover, the viscosity of the core part containing a drug, and the viscosity of a 2% by mass aqueous solution at 20 ° C. that covers the core part is less than 50 mPa · s, or the viscosity of a 2% by mass aqueous solution at 20 ° C. is 50 mPa · s. Provided is a solid preparation comprising at least a cellulose ether layer comprising at least a low-viscosity hypromellose having a viscosity of less than s and a high-viscosity hypromellose having a viscosity of 50 mPa · s or more at 20 ° C. . Furthermore, the present invention provides a method for producing a solid preparation comprising at least a step of applying the coating liquid to a core containing a drug and a step of removing the solvent in the coating liquid from the applied core.

  According to the present invention, the drug can be released through the lag time, and the drug can be eluted in the digestive tract after the lag time has elapsed. Also, the lag time can be easily adjusted by changing the composition of the coating liquid and the coating amount.

Hereinafter, the present invention will be described in more detail.
The timed release preparation of the present invention employs a two-layer structure composed of a core and a cellulose ether layer covering the outer surface of the core, the core includes a drug, and the cellulose ether layer is 2 at 20 ° C. Hydroxypropyl cellulose having a viscosity of less than 50 mPa · s of a mass% aqueous solution or low-viscosity hypromellose having a viscosity of less than 50 mPa · s of a 2 mass% aqueous solution at 20 ° C., and a viscosity of 2% by mass aqueous solution at 20 ° C. High-viscosity hypromellose that is 50 mPa · s or more.

Hypromellose (including low-viscosity and high-viscosity hypromellose) is described as hydroxypropylmethylcellulose in the 14th revised Japanese pharmacopoeia, and was changed to hypromellose in the 15th revised Japanese pharmacopoeia. Specific examples include hypromellose having 16.5 to 30% by mass of methoxy group and 4 to 32% by mass of hydroxypropoxy group. Examples of hydroxypropylcellulose include those having a hydroxypropoxy group of 53.4 to 77.5% by mass.
The degree of substitution can also be measured by a method based on the method for measuring the degree of substitution of hypromellose and hydroxypropylcellulose defined in the 16th revision Japanese Pharmacopoeia.

  The viscosity of a 2% by mass aqueous solution of hydroxypropylcellulose or low-viscosity hypromellose used as a solution at 20 ° C. is less than 50 mPa · s, preferably 1.0 or more and less than 50 mPa · s, more preferably 2.0 or more and 17. From the viewpoint of increasing the concentration of the coating solution, it is preferably 5 mPa · s or less. The viscosity of a 2% by mass aqueous solution of high-viscosity hypromellose dispersed in a solution at 20 ° C. can be selected from 50 mPa · s or more, preferably 50 or more and 100,000 mPa · s or less depending on the purpose. Here, the viscosity of the 2% by weight hypromellose aqueous solution is the same as the method described in the 16th revised Japanese Pharmacopoeia. If the viscosity is less than 600 mPa · s, the first method is applied. Measure using a viscometer. On the other hand, when the viscosity is 600 mPa · s or more, the second method is applied, and a specified cylinder number and rotation are measured using a B-type rotational viscometer (Brookfield viscometer LV model) at a liquid temperature of 20 ° C. It means the viscosity measured under the condition of several minutes. In the present invention, “viscosity of hypromellose in a 2% by weight aqueous solution” means the viscosity measured under the above conditions, and low-viscosity hypromellose of less than 50 mPa · s is 50 mPa · s or more by the first method. High viscosity hypromellose means a viscosity measured by the first method when the viscosity is less than 600 mPa · s and by the second method when the viscosity is 600 mPa · s or more.

  The difference between low-viscosity hypromellose and high-viscosity hypromellose is mainly due to the difference in weight average molecular weight because the range of substitution degree is the same as described above. The preferred weight average molecular weight of the low viscosity hypromellose is less than 50,000, and the preferred weight average molecular weight of the high viscosity hypromellose is 50,000 or more. The molecular weight is a value measured by gel chromatography (size exclusion chromatography).

  The content of hydroxypropylcellulose or low-viscosity hypromellose contained in the solution is preferably 3 to 15% by mass, more preferably 6 to 12% by mass. If the content of hydroxypropylcellulose or low-viscosity hypromellose is low, sufficient tackiness may not be obtained, and solid matter adhesion in the coating solution may not be achieved. In some cases, proper coating cannot be performed.

  The content of the high-viscosity hypromellose contained in the coating liquid is preferably 3 to 20% by mass, more preferably 4 to 15% by mass. If the high-viscosity hypromellose content is low, coating may take a long time and productivity may be reduced, which may be undesirable.If the content is high, the solid content of the coating solution increases, which makes it difficult to feed and is desirable for operation. There may not be.

  The high-viscosity hypromellose can be used in the range of preferably 9 to 250 parts by mass, more preferably 50 to 200 parts by mass with respect to 100 parts by mass of hydroxypropylcellulose or low-viscosity hypromellose. If it is less than 9 parts by mass, it takes time for the coating process, which is not preferable in terms of productivity. When it exceeds 250 masses, there are many solid contents in a coating liquid, and liquid feeding may become difficult or uniform coating may become difficult.

The coating liquid may contain a plasticizer as necessary. Examples of the plasticizer include glycerin, polyethylene glycols, triethyl citrate, glycerin acetic acid fatty acid ester, triacetin, and dibutyl phthalate, and polyethylene glycols are particularly preferable. Two or more of the plasticizers may be blended.
The content of the plasticizer can be set to 1.0 to 50 parts by mass with respect to 100 parts by mass of hydroxypropyl cellulose, for example, when hydroxypropyl cellulose is used, and when low viscosity hypromellose is used. Moreover, it can be set as about 5.0-30 mass parts with respect to 100 mass parts of low-viscosity hypromellose.
In addition, a surfactant (such as sodium lauryl sulfate), a colorant, a pigment, or a sweetener that improves the dispersibility of the composition may be added in a commonly used amount.

The solvent contained in the coating solution may be any solvent that dissolves hydroxypropylcellulose or low-viscosity hypromellose but does not dissolve high-viscosity hypromellose.
The solvent is preferably ethanol, a mixed solution of water and ethanol (preferable mass ratio of water and ethanol is 0: 100 to 15:85), and the like.
Further, a water-soluble and water-insoluble dye may be dispersed in the solvent.
The reason for selecting a solvent that disperses the high-viscosity hypromellose without dissolving it is that the solution in which the high-viscosity hypromellose is dissolved becomes a high-viscosity solution, which not only makes it difficult to handle the coating liquid, but also makes the coating spray mist rough and appropriate. This is because the coating cannot be achieved.

  A solid preparation is obtained by applying a coating solution containing at least hydroxypropylcellulose or low-viscosity hypromellose and high-viscosity hypromellose to the core containing the drug and removing the solvent in the coating solution. Examples of solid preparations include tablets, granules, fine granules and capsules.

The drug contained in the core is not particularly limited as long as it can be administered orally. Such drugs include, for example, central nervous system drugs, cardiovascular drugs, respiratory drugs, digestive drugs, antibiotics, antitussives, antihistamines, antipyretic analgesics, diuretics, sympathomimetic drugs, Antimalarial agents, antistatic agents, psychotropic agents, vitamins and their derivatives, and the like.
Central nervous system drugs include diazepam, idebenone, aspirin, ibuprofen, paracetamol, naproxen, piroxicam, diclofenac, indomethacin, sulindac, lorazepam, nitrazepam, phenytoin, acetaminophen, etenzamide, ketoprofen and chlordiazepoxide.
Cardiovascular drugs include molsidomine, vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedivin, atenolol, spironolactone, metoprolol, vindolol, captopril, izorbitol nitrate, delapril hydrochloride, meclofenoxate hydrochloride, diltiazem hydrochloride, , Digitoxin, propranolol hydrochloride, alprenolol hydrochloride and the like.
Respiratory drugs include amlexanox, dextromethorphan, theophylline,
Examples include pseudoephedrine, salbutamol and guaifenesin.
As digestive drugs, 21 [[3-methyl-4- (2,2,2-trifluoroethoxy) -2-pyridyl] methylsulfinyl] penzimidazole and 5-methoxy-2-
[(4-Methoxy-3,5-dimethyl-2-pyridyl) methylsulfinyl] benzimidazole drugs having anti-ulcer activity such as benzimidazole, cimetidine, ranitidine, pirenzepine hydrochloride, pancreatin, bisacodyl and 5-aminosalicylic acid Etc.
Antibiotics include tarampicillin hydrochloride, bacampicillin hydrochloride, cefaclor and erythromycin.
Examples of the antitussive removal agent include noscapine hydrochloride, carbetapentane citrate, dextromethorphan hydrobromide, isoaminyl citrate, and dimemorphan phosphate.
Examples of the antihistamine include chlorpheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride.
Examples of the antipyretic analgesic / anti-inflammatory agent include ibuprofen, diclofenac sodium, flufenamic acid, sulpyrine, aspirin and ketoprofen.
Examples of the diuretic include caffeine.
Examples of sympathomimetic agents include dihydrocodeine phosphate and dl-methylephedrine hydrochloride.
Examples of the antimalarial agent include quinine hydrochloride.
Examples of the diastatic agent include loperamide hydrochloride.
Examples of the psychotropic agent include chlorpromazine.
Examples of vitamins and derivatives thereof include vitamin A, vitamin B1, fursultiamine, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, calcium pantothenate, and tranexamic acid.

The core containing the drug may contain various additives commonly used in this field such as excipients, binders, disintegrants, lubricants, anti-aggregation agents, and drug solubilizing agents. Good.
Examples of the excipient include sugars such as sucrose, lactose, mannitol and glucose, starch, crystalline cellulose, calcium phosphate and calcium sulfate.
As the binder, for example, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinylpyrrolidone, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, macrogol, Examples include gum arabic, gelatin, agar and starch.
Examples of the disintegrant include low-substituted hydroxypropylcellulose, carmellose or a salt thereof, croscarmellose sodium, sodium carboxymethyl starch, cros polyvinylpyrrolidone, crystalline cellulose, crystalline cellulose / carmellose sodium, and the like.
Examples of the lubricant and the aggregation inhibitor include talc, magnesium stearate, calcium stearate, colloidal silica, stearic acid, waxes, hardened oil, polyethylene glycols, and sodium benzoate.
Furthermore, examples of the drug solubilizer include organic acids such as fumaric acid, succinic acid, malic acid and adipic acid.
The content of these additives can be appropriately determined according to the type of drug.

Cellulose ether comprising at least hydroxypropyl cellulose or low-viscosity hypromellose and high-viscosity hypromellose that coats the drug-containing core by applying a coating liquid to the drug-containing core and removing the solvent in the coating liquid A layer is formed. In this case, it is preferable to form a cellulose ether layer comprising at least 9 parts by mass and 250 parts by mass of hydroxypropyl cellulose or low-viscosity hypromellose and high-viscosity hypromellose.
The amount of the cellulose ether layer formed on the surface of the drug-containing core varies depending on the type, shape, size, surface state of the solid preparation, and the properties of the drug and additives contained in the solid preparation. As the coating mass of the cellulose ether layer, if the solid preparation is a tablet, it is preferably 3 to 30% by mass, more preferably 6 to 20% by mass with respect to the mass of the drug-containing core, and if it is a granule or powder. The amount of the drug-containing core is preferably 10 to 300% by mass, more preferably 20 to 200% by mass. If the amount of cellulose ether layer is small, sufficient lag time may not be obtained, and if the amount of cellulose ether layer is excessive, the film will not dissolve in the intestine, and the drug will be excreted without releasing the drug. This is not preferable.
When the preferable amount of the cellulose ether layer is specified by the mass ratio with respect to the drug-containing core, it is as described above, but when the preferable amount of the cellulose ether layer is specified by the thickness, it is preferably 5 or more and 50 μm or less.

  The solid preparation containing at least the drug-containing core and the cellulose ether layer is a time-release preparation capable of obtaining a sufficient lag time due to the presence of the cellulose ether layer. A timed release formulation refers to a formulation that releases a drug in the gastrointestinal tract after a certain lag time. Here, as a fixed lag time, the time from the start of taking until 5% by mass of the drug contained in the core is released is preferably 3 to 300 minutes, more preferably 30 to 180 minutes.

Next, the manufacturing method of a solid formulation is demonstrated.
The method for producing a solid preparation includes at least a step of applying the coating liquid to a core containing a drug and a step of removing a solvent in the coating liquid.
Conventionally known means can be used for the coating apparatus used in the step of applying the coating liquid to the drug-containing core. In general, spray coating is used. In that case, pan coating equipment, drum type coating equipment, fluidized bed coating equipment, stirred fluidized coating equipment or centrifugal rolling coating equipment may be used. In addition, an air spray, an airless spray, a three-fluid spray, or the like can be used as a spray device attached to these devices.
Application of the coating liquid is performed, for example, by spraying the coating liquid onto the core containing the drug using the above-described coating apparatus.
After application of the coating solution, the solvent in the coating solution is removed by heating or the like. The solid preparation can be produced by removing the solvent by heating or the like in the coating apparatus or from the coating apparatus. When water is contained in the solvent, a commonly used drying method may be used.

  The solid preparation thus produced has a time until the drug starts to be released in the first liquid, the second liquid and the purified water in the dissolution test described in the 16th revision Japanese Pharmacopoeia, preferably from the start of the test. The lag time is 3 minutes or more and less than 300 minutes, more preferably 30 minutes or more and less than 180 minutes. A desired lag time can be appropriately obtained by changing the composition of the coating liquid and the coating amount.

EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to these examples.
<Example 1>
Riboflavin (Tokyo Tanabe Seiyaku Co., Ltd.) 2 parts by mass, lactose (Freund Sangyo Co., Ltd. Dilactose S) 90 parts by mass, low substituted hydroxypropyl cellulose (Shin-Etsu Chemical Co., Ltd., hydroxypropoxy group substitution degree 11% by mass) 8 parts by mass And 0.5 parts by mass of magnesium stearate are mixed with a powder, and a rotary tableting machine (Vergo, manufactured by Kikusui Seisakusho) is 8 mm in diameter, tableting pressure 1 t, tableting preload 0.3 t, rotation speed 20 rpm, one tablet Tableting was performed so that the weight per hit was 200 mg, and an uncoated tablet containing riboflavin in the drug was prepared.
Hydroxypropylcellulose (manufactured by Nippon Soda Co., Ltd., hydroxypropoxy group substitution degree 62 mass%, viscosity of 2 mass% aqueous solution at 20 ° C. is 8.0 mPa · s) was dissolved in ethanol so as to be 6 mass%. A solution was prepared.
While stirring the above solution, hypromellose substitution type 2208 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 23.0 mass%, hydroxypropoxy group substitution degree 9.5 mass%, 2 mass% aqueous solution as high-viscosity hypromellose. The viscosity of 3,990 mPa · s) was added to 6 mass% to prepare a coating solution.
Using the obtained coating solution, coating was performed under the following conditions until 100 parts by mass of uncoated tablets reached 20 parts by mass of hypromellose.
The coated tablets were evaluated by the dissolution test method (pure water) described in the 16th revision of the Japanese Pharmacopoeia, and the time at which drug dissolution started was determined as the lag time. The lag time was 90 minutes. It was.
<Coating conditions>
Equipment: Ventilated pan coater (inner diameter 30cm)
Charge amount: 1kg
Intake air temperature: 50-60 ° C
Exhaust temperature: 25-30 ° C
Intake air volume: 1m ³ / min
Pan rotation speed: 18rpm
Spray speed: 12-15g / min
Spray air pressure: 150kPa

<Example 2>
A high-viscosity hypromellose is substituted with a substitution degree type 2208 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 23.3 mass%, hydroxypropoxy group substitution degree 9.5 mass%, and the viscosity of a 2 mass% aqueous solution at 20 ° C. is 93, Coating was performed in the same manner as in Example 1 except that the pressure was changed to 200 mPa · s). When the dissolution time of the drug from the coated tablet was determined as the lag time by the dissolution test with pure water, the lag time was 170 minutes.

<Example 3>
A high-viscosity hypromellose is substituted with a substitution type 2910 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 29.4% by mass, hydroxypropoxy group substitution degree 9.0% by mass, 2% by weight aqueous solution at 20 ° C. with a viscosity of 3660 mPa · Coating was performed in the same manner as in Example 1 except that the procedure was changed to s). When the time at which drug dissolution started was determined as the lag time by the dissolution test with pure water from the coated tablet, the lag time was 90 minutes.

<Example 4>
A high-viscosity hypromellose is substituted with a substitution degree type 2906 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 27.9% by mass, hydroxypropoxy group substitution degree 6.1% by mass, and 2% by mass aqueous solution at 20 ° C. with a viscosity of 3920 mPa · Coating was performed in the same manner as in Example 1 except that the procedure was changed to s). When the dissolution time of the drug was determined as the lag time by the dissolution test with pure water from the coated tablet, the lag time was 90 minutes.

<Example 5>
High-viscosity hypromellose was substituted with a substitution degree type 2910 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 29.4 mass%, hydroxypropoxy group substitution degree 9.0 mass%, and the viscosity of an aqueous solution of 2 mass% at 20 ° C. was 51. The coating was performed in the same manner as in Example 1 except that the pressure was changed to 0 mPa · s). When the time at which drug dissolution started was determined as the lag time by the dissolution test with pure water from the coated tablet, the lag time was 30 minutes.

<Example 6>
Instead of the hydroxypropyl cellulose of Example 1, hypromellose substitution type 2910 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 29.1% by mass, hydroxypropoxy group substitution degree 9.1% by mass, 20 ° C.) The solution was prepared in the same manner as in Example 1 except that the solution was prepared by dissolving in a mixed solution of ethanol and water so as to be 6% by mass using a 2% by mass aqueous solution having a viscosity of 3.0 mPa · s). Coating was performed. When the time at which drug dissolution started was determined as the lag time by the dissolution test with pure water from the coated tablet, the lag time was 90 minutes.

<Example 7>
The low-viscosity hypromellose of Example 6 has a viscosity of 15.1 mPa · s (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 29.0 mass%, hydroxypropoxy group substitution degree 8.8 mass%, 2 at 20 ° C. at 20 ° C. Coating was carried out in the same manner as in Example 6 except that hypromellose was changed to hypromellose having a viscosity of 15.1 mPa · s). When the time at which drug dissolution started was determined as the lag time by the dissolution test with pure water from the coated tablet, the lag time was 90 minutes.

<Comparative Example 1>
Instead of hydroxypropylcellulose of Example 1, hypromellose substitution type 2910 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 29.7% by mass, hydroxypropoxy group substitution degree 9.0% by mass, 20 ° C.) The coating solution was prepared in the same manner as in Example 1 except that the solution was prepared by dissolving in a mixed solution of ethanol and water so that the viscosity of the 2% by mass aqueous solution was 50 mPa · s). However, the viscosity of the coating solution became too high to be fed.

<Comparative example 2>
A high-viscosity hypromellose was substituted with a substitution degree type 2910 (manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group substitution degree 28.0 mass%, hydroxypropoxy group substitution degree 9.0 mass%, and the viscosity of an aqueous solution of 2 mass% at 20 ° C. was 6. The coating was performed in the same manner as in Example 1 except that the pressure was changed to 0 mPa · s). When the time at which drug dissolution started was determined as the lag time by a dissolution test using pure water from the coated tablets, no lag time was observed.

Claims (5)

  In a solution obtained by dissolving hydroxypropyl cellulose having a viscosity of 2% by mass of an aqueous solution at 20 ° C. of less than 50 mPa · s or low viscosity hypromellose having a viscosity of 2% by mass of an aqueous solution at 20 ° C. of less than 50 mPa · s in a solvent, 20 A coating liquid for solid preparations obtained by dispersing high-viscosity hypromellose having a viscosity of 50 mPa · s or more in a 2 mass% aqueous solution at ° C.   The coating liquid for solid preparation according to claim 1, wherein the high-viscosity hypromellose is 9 parts by mass or more and 250 parts by mass or less when the hydroxypropyl cellulose or the low-viscosity hypromellose is 100 parts by mass. A core containing a drug;
Hydroxypropyl cellulose covering the core part and having a viscosity of 2% by weight of an aqueous solution at 20 ° C. of less than 50 mPa · s, or low-viscosity hypromellose having a viscosity of 2% by weight of an aqueous solution at 20 ° C. of less than 50 mPa · s; A solid preparation comprising at least a cellulose ether layer comprising at least a high-viscosity hypromellose having a viscosity of 50 mPa · s or more at 20 ° C. in a 2% by mass aqueous solution.   The solid preparation according to claim 3, wherein the high-viscosity hypromellose is 9 parts by mass or more and 250 parts by mass or less when the hydroxypropyl cellulose or the low-viscosity hypromellose is 100 parts by mass.   A method for producing a solid preparation comprising at least a step of applying the coating liquid according to claim 1 to a core containing a drug and a step of removing the solvent in the coating liquid from the applied core.