JP4059916B2 - Film coating method for solid dispersion - Google Patents

Description

  The present invention relates to a film coating method for a solid dispersion and a method for producing an aqueous film coating preparation containing a solid dispersion of a drug.

Among the pharmaceutical preparations, solid preparations such as tablets, pills, granules, etc., block the unpleasant taste and odor of the active ingredient, improve stability to light and moisture, prevent the generation of dust, enteric and sustained release For the purpose of controlling the expression of medicinal effects, etc., film coating of uncoated tablets and cores has been performed.
For example, in the case of film-coated tablets, the production thereof is often performed by a method such as spray coating a coating agent in which a coating base is dissolved in an organic solvent (Patent Documents 1 to 3). However, in recent years, emphasis has been placed on problems such as the flammability of organic solvents, recoverability of exhaust gas, economy, and retention in preparations, and water-based coatings that do not use organic solvents have been used from the viewpoint of safety and economy. (Non-Patent Document 1).

However, when the solid preparation to be coated is a solid dispersion of the drug, the drug exists in the dispersion as an amorphous substance, so it tends to be unstable with respect to moisture. However, since the drug is crystallized, the solubility and elution rate are remarkably lowered, and the absorption rate is lowered.
For example, a solid dispersion tablet of cilnidipine marketed as an antihypertensive agent (“Aterec®)
“Tablets”; Mochida Pharmaceutical Co., Ltd. and Ajinomoto Co., Inc. are also film coating preparations using an organic solvent. Ethyl cellulose is used as a coating substrate, and drug release is controlled to some extent, and an organic solvent has been considered necessary from the viewpoint of forming a uniform coating film.

In addition, commercially available tablets may be required to be divided into two or more in hospitals, pharmacies, etc., or patients themselves in order to adjust the dosage, and for this purpose, tablets with secant lines are provided. . In order to provide a score line to the solid dispersion formulation of cilnidipine, when an organic solvent-based film coating was performed on the uncoated tablet having a score line, a tablet in which dusting occurred on the surface of the score line part was obtained. The problem that occurred. The dusting on the surface of the secant part is detrimental to aesthetics and may cause the user to feel distrust in quality. Further, due to dusting on the surface of the dividing line portion, there is a possibility that the coating near the dividing line portion is likely to be peeled off at the time of division, and this may lead to a loss of aesthetics after division.
JP 55-129224 A JP-A-63-27423 Japanese Patent No. 3110794 Drug Development Vol. 11, 3.5.2, Classification of Coating Methods, Yodogawa Shoten (1989)

  The problem to be solved by the present invention is to provide a coating method using an aqueous film coating solution for a solid dispersion preparation, and to provide a film coating preparation of a solid dispersion having a good dissolution rate and surface state by the method. In particular, an object of the present invention is to provide a coating method and a coating preparation of an aqueous film coating solution of a cilnidipine solid dispersion preparation which may have a secant.

  As a result of intensive studies to solve the above-mentioned problems in aqueous coating, the present inventors have surprisingly found that a solid dispersion, particularly a solid dispersion containing cilnidipine, exhibits a good dissolution rate even when aqueous film coating is performed. It was found that by maintaining the temperature at the time of coating with an aqueous coating solution appropriately, it is possible to obtain a stable aqueous film coating formulation by avoiding quality degradation such as the formulation surface condition during coating. The present invention has been completed.

That is, the present invention is as follows.
(1) A film coating method for a solid dispersion, comprising using an aqueous coating liquid as the coating liquid.
(2) The film coating of the solid dispersion is performed using a water-based coating liquid as a coating liquid and under temperature control such that the exhaust temperature of the coating apparatus is higher than 30 ° C. and lower than 60 ° C. (1 ) Film coating method.
(3) The film coating method according to (2), wherein the exhaust temperature is 32 ° C. or higher and 55 ° C. or lower.
(4) The film coating of the solid dispersion is carried out using a water-based coating liquid as a coating liquid and under temperature control such that the product temperature of the solid dispersion is higher than 20 ° C. and lower than 56 ° C. ( The film coating method as described in 1).
(5) The film coating method as described in (4) whose product temperature is 25 degreeC or more and 50 degrees C or less.
(6) The film coating method according to any one of (1) to (5), wherein the solid dispersion is a tablet.
(7) The film coating method according to (6), wherein the tablet has a secant.
(8) The film coating method according to any one of (1) to (7), wherein the aqueous coating solution contains water or water and a water-soluble organic solvent as a solvent.
(9) The film coating method according to any one of (1) to (8), wherein the aqueous coating liquid contains only water as a solvent.
(10) The film coating method according to any one of (1) to (9), wherein the aqueous coating liquid contains a water-soluble polymer compound.
(11) The film coating method according to (10), wherein the water-soluble polymer compound is hydroxypropylmethylcellulose and / or polyethylene glycol.
(12) The film coating method according to any one of (1) to (11), wherein the aqueous coating solution contains a poorly water-soluble polymer compound.
(13) The film coating method according to (12), wherein the poorly water-soluble polymer compound is ethyl cellulose.
(14) The film coating method according to any one of (1) to (13), wherein the aqueous coating liquid contains a colorant.
(15) The film coating method according to (14), wherein the colorant is titanium oxide.
(16) The film coating method according to any one of (1) to (15), wherein the solid dispersion contains cilnidipine.
(17) The film coating method according to any one of (1) to (16), wherein the solid dispersion contains cilnidipine, hydroxypropylcellulose and / or hydroxypropylmethylcellulose phthalate.
(18) A solid dispersion coating preparation obtained by the film coating method according to any one of (1) to (17).
(19) A method for producing a solid dispersion-coated tablet comprising a step of coating a solid dispersion uncoated tablet with an aqueous coating solution containing a water-soluble polymer compound and water or water and a water-soluble organic solvent as a solvent.

According to the coating method of the present invention, there is provided a high-quality solid dispersion preparation, particularly a solid dispersion preparation containing cilnidipine, without causing a deterioration in quality during coating, although it is a coating using an aqueous coating solution. be able to. Moreover, since it is a water-based coating, the problem on the disaster prevention health and safety in the manufacturing process by using an organic solvent and the problem of the organic solvent remaining after a formulation can be avoided. Furthermore, the method of the present invention is extremely useful industrially because the organic solvent is unnecessary or can be reduced, and the equipment for discharging the organic solvent is not required.
In particular, in the case of a film-coated tablet having a score line, it is possible to provide a tablet having a good surface state of the score line part.

In the present invention, a solid dispersion refers to a solid preparation in which a drug is dispersed in an amorphous form in an inert carrier, and a solid dispersion preparation refers to a solid preparation in which the solid dispersion is coated with a coating agent. Say.
The inert carrier that forms the solid dispersion may be any solid carrier that is normally used in pharmaceutical preparations, such as excipients, binders, disintegrants, and lubricants. An agent may be contained.
Examples of excipients include lactose, mannitol, glucose, corn starch, crystalline cellulose, natural or synthetic aluminum silicate salts (such as magnesium metasilicate aluminate), talc, magnesium carbonate, calcium carbonate, etc. Alphalated starch, methylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, dextrin, gum arabic, tragacanth gum, gelatin, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose phthalate, polyethylene glycol, etc. Disintegrants include gum arabic, alginate (such as sodium), carboxymethylcellulose salt (sodium Calcium, etc.), starches, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose (L-HPC), gluconate (calcium etc.) and the like as talc, stearate (magnesium, Aluminium, calcium, etc.), gum arabic, carbanalo, carmellose salt (calcium, sodium, etc.), hydrous silicon dioxide, hydrous amorphous silicon dioxide, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, crystalline cellulose, sucrose fatty acid ester Etc.

The drug may be any poorly water-soluble drug, and examples thereof include cilnidipine, nifedipine, nisoldipine, nicardipine, nilvadipine, nimodipine, nitrendipine, manidipine, oxacillin, cloxacillin, cycloxaline, ibuprofen, diphenhydramine and the like.
Preferably, the poorly water-soluble drug is one that has a solubility in water of the 14th revised Japanese Pharmacopoeia / General Rules, and is hardly soluble or hardly soluble in the classification of solubility. That is, the solubility of the drug in water is classified as 1 mg / mL or less.

The solid dispersion may be in the form of fine granules, granules, or tablets. In the case of tablets, one or two secant lines may be provided to facilitate division. The shape of the tablet is not particularly limited, and examples thereof include a round shape, an oval shape (any oval shape excluding a perfect circle: an oval shape, an oval shape, an oval shape, an oval shape, etc.), a rhombus, a triangle, and the like. . The dividing line may be any of a flat groove type, a U-shaped groove type, or a V-shaped groove type. When the tablet is elliptical, it is preferably formed along the minor axis.
The solid dispersion is produced by an ordinary method. For example, the drug and, if necessary, the binder are dissolved in an organic solvent, mixed with the other components of the solid dispersion, and then the solvent is distilled off and dried. Thus, a method of obtaining a solid dispersion granulated product is exemplified. Examples of the mixing of the solid dispersion with the other components include a method of spraying the drug solution onto the other components, or a method of mixing and stirring the drug solution and the other components.
Examples of the organic solvent include lower alcohols such as methanol and ethanol, halogenated hydrocarbons such as dichloromethane and chloroform, and mixtures thereof.
The obtained granulated product is tableted by adding a lubricant by a usual method, if necessary, to obtain an arbitrary uncoated tablet.
For example, a solid dispersion of sinyldipine can be prepared according to the method described in Patent Document 3.

In the present invention, the aqueous coating liquid refers to an aqueous dispersion or solution of a coating agent, and means a coating liquid containing water or a mixed solution of water / water-soluble organic solvent as a medium.
Coating agent is hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), human roxyethylcellulose, cellulose derivatives such as methylhydroxyethylcellulose, methylcellulose, carboxymethylcellulose, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polypropylene glycol polyvinyl acetate part Mainly water-soluble polymer compounds such as synthetic polymer compounds such as saponified substances, polysaccharides such as starch, pullulan and guar gum, and water-insoluble polymer compounds such as ethyl cellulose and cellulose acetate, polyethylene glycol, propylene Glycol, polypropylene glycol, ethyl cellosolve, glycerin, glycerin fatty acid ester, sucrose fat Esters, polyoxyethylene sorbitan fatty acid esters, plasticizers such as triethyl citrate and triacetin, waxes such as silicone oil and stearic acid, fats and oils such as soybean oil and castor oil, and food and pigment, organic and inorganic such as titanium oxide You may mix | blend flavoring agents, such as a system colorant, saccharides, and a fragrance | flavor.
The coating agent may be a premixed coating base such as Opadry.

The amount of water in the coating liquid is appropriately set according to the type and blending amount of each component and the amount of water-soluble organic solvent added, but the preferred amount of water is 1 part by weight of the water-soluble polymer compound. On the other hand, it is realized by adding 5 to 1000 parts by weight, more preferably 7 to 100 parts by weight, particularly preferably 8 to 50 parts by weight of water as a medium.
Examples of the water-soluble organic solvent that may be added to the coating liquid include methanol, ethanol, propyl alcohol, isopropyl alcohol, acetone, methyl ethyl ketone, dioxane, tetrahydrofuran, and acetonitrile. Ethanol is particularly preferable. The addition amount of the water-soluble organic solvent is preferably 0 to 8.0 parts by weight, more preferably 0 to 2.4 parts by weight with respect to 1 part by weight of water, although it depends on the type and blending amount of each component. 1.3 parts by weight, or 0 to 0.4 parts by weight is more preferable. Of these, a medium in which only a water is used without adding a water-soluble organic solvent is particularly preferable. Here, it is sufficient that the medium is only water, and it is sufficient that the medium is substantially only water, and a slight amount of organic solvent (for example, 0.03 part by weight or less with respect to 1 part by weight of water) is allowed.

The coating method may be any of ordinary methods using a pan coating apparatus, a drum type coating apparatus, and a fluidized coating apparatus. These are preferably air-permeable coating devices.
In the present invention, the temperature is preferably controlled so that the exhaust temperature of the coating apparatus during the coating process is higher than 30 ° C. and lower than 60 ° C. Here, the coating step is a step of applying the coating liquid to the solid dispersion by spraying, and at this time, air supply and exhaust are performed.
The exhaust temperature is preferably 32 ° C. or higher and 55 ° C. or lower, more preferably 35 ° C. or higher and 45 ° C. or lower.
When the exhaust temperature is set to 30 ° C. or lower and 60 ° C. or higher, the coating film is easily peeled off, and a rough coating is not formed.
Alternatively, in the present invention, the temperature is preferably controlled so that the product temperature during the coating process is higher than 20 ° C. and lower than 56 ° C. Here, the product temperature during the coating process is the temperature of the solid dispersion during the coating process. The product temperature is measured with an infrared thermometer.
The product temperature is preferably 25 ° C. or more and 50 ° C. or less, more preferably 35 ° C. or more and 45 ° C. or less.
If the product temperature is 20 ° C. or lower, or 56 ° C. or higher, the coating film is easily peeled off, and a rough coating is not formed.
In the management of the exhaust temperature and the product temperature, the exhaust temperature and the product temperature can be adjusted, for example, by adjusting the supply air temperature, the supply air flow rate, or the coating liquid addition speed (spray speed, etc.). It is particularly preferable to adjust the supply air temperature.
The coating solution may be added by spraying or spraying, but spraying is preferred.
For coating, for example, when spray coating 1 kg uncoated tablet (250 mg / tablet) using a ventilation type coating device such as Hi-Coater (Freund Sangyo Co., Ltd.), the blast temperature is set based on the exhaust temperature standard, and the air volume is It is carried out at 1.5 to 3.5 m ³ and a spray rate of 5 g / min to 50 g / min.

The amount of the coating film with respect to the solid dispersion is 0.1 to 20 parts by weight, preferably 1 to 15 parts by weight, and more preferably 2 to 10 parts by weight with respect to 100 parts by weight of the solid dispersion.
The coating film for the solid dispersion may have two or more layers by using different coating liquids, but one layer or two layers are preferable.
After the coating process, the obtained film coating preparation may be further sufficiently dried by blowing or heating.

EXAMPLES Next, although an Example, a reference example, and a test example are given and this invention is demonstrated further more concretely, this invention is not limited to these.
[Reference example]
An ellipse containing 10 mg of cilnidipine per tablet (250 mg) and having a V-shaped secant groove as shown in FIG. 1 according to the production method of Japanese Patent No. 3110794 (Patent Document 3), that is, by the method shown below. A round uncoated tablet having a diameter of about 9 mm and a thickness of about 3.7 mm was prepared.
1) A solid dispersion granule containing cilnidipine, hydroxypropylcellulose (HPC), lactose, crystalline cellulose, macrogol 400, magnesium aluminate metasilicate, and croscarmellose sodium according to Example 2 of Patent Document 3 HPC / SD granules) are obtained.
2) Solid dispersion granules containing cilnidipine, hydroxypropylmethylcellulose phthalate (HP55), lactose, crystalline cellulose, macrogol 400, magnesium aluminate metasilicate, and croscarmellose sodium according to Example 4 of Patent Document 3 (HP55.SD granule) is obtained.
3) The HPC · SD granules and HP55 · SD granules obtained in 1) and 2) were mixed to 3/7 (weight / weight) according to Example 5 of Patent Document 3, and magnesium stearate And talc are added and tableted (tablet pressure of about 1.5 to 2.5 t) to obtain a plain tablet (250 mg) containing 10 mg of cilnidipine per tablet.

[Examples 1 to 12, Comparative Example 1]
A: Preparation of coating solution The coating solution was prepared by the following method.
1) Coating solutions of Examples 1 to 5 and 9 to 12
i) Color layer coating solution About 3528 g of water and 19.92 g of polyethylene glycol 600 are mixed with a stirrer. The mixture ethylcellulose 47.52G, mixed to the resulting mixture with polyethylene glycol 6000 19.92 g hydroxypropyl methyl cellulose 159.72g was added stirrer and (color layer 1 solution), separate from the water about 386g titanium oxide A liquid obtained by mixing 95.04 g with a homogenizer (color layer 2 liquid) is mixed well and filtered through a 100 mesh sieve to obtain a color layer coating liquid.
However, in Example 4, about 3528 g of water in the color layer 1 liquid is reduced to about 1764 g, which is a half amount.
ii) clear layer coating liquid water about 4194G, mixed polyethylene glycol 600 26.4 g, polyethylene glycol 6000 26.4 g hydroxypropyl methyl cellulose 214.2g with a stirrer. This liquid is filtered through a 100 mesh sieve to obtain a clear layer coating liquid.

2) Coating solutions of Examples 6-8
i) Color layer coating solution Prepared in the same manner as i) in 1) above. However, about 3528 g of the water for the color layer 1 is about 1058 g and about 2470 g of ethanol, and about 386 g of the water for the color layer 2 is about 386 g of ethanol.
ii) Clear layer coating solution Prepared in the same manner as ii) in 1) above. However, about 4194 g of water is about 1260 g of water and about 2934 g of ethanol.

3) Coating liquid of Comparative Example 1
i) Color layer coating solution Prepared in the same manner as i) in 1) above. However, about 3528 g of water of the color layer 1 liquid is about 1411.2 g of dichloromethane and about 2116.8 g of methanol, and about 386 g of water of the color layer 2 liquid is about 386 g of methanol.
ii) Clear layer coating solution Prepared in the same manner as ii) in 1) above. However, about 4194 g of water was added to dichloromethane 2519.
g and 1675 g of methanol.

B: Preparation of coated tablet A total of 1.2 kg of cilnidipine solid dispersion uncoated tablet (round tablet and scored tablet) obtained in Reference Example was put into Hicoater 48N (Freund Sangyo Co., Ltd.) Film-coated tablets were obtained through the following steps using the conditions shown in Table 1.
Process 1) Raw material input Process 2) Heating
Supply air temperature: 70 ° C., exhaust temperature: 55 ° C. or less, pan rotation speed: 5 rpm, heating time: heating until the exhaust temperature reaches 50 ° C. or more Step 3) Coating step 1
Coating liquid: Color layer coating liquid, spray speed: see Table 1, exhaust temperature: see Table 1, pan rotation speed: 10-15 rpm, spray time: up to coating 18 mg, air volume: 3 m ³ , atomized air: 100 L / min, pattern Air: 50L / min
Process 4) Coating process 2
Same as step 3). However, coating solution: clear layer coating solution, spray time: up to 2 mg of film (total 20 mg).

The composition of the coating film per uncoated tablet (250 mg) of the coated tablets obtained in Examples 1 to 12 and Comparative Example 1 is as follows.
Hydroxypropyl methylcellulose 10mg
Ethylcellulose 2.5mg
Polyethylene glycol 600 1.25mg
Polyethylene glycol 6000 1.25mg
Titanium oxide 5mg

In Table 1, the exhaust temperature is the temperature measured as exhaust temperature in the high coater 48N (Freund Sangyo Co., Ltd.) during the coating process, and the product temperature is determined by THERMO-HUNTER (manufactured by OPTEX) during the coating process. , Measured tablet temperature. When measuring the product temperature, tablets present at the site where the coating solution is directly sprayed are not considered.

[Test Example 1]
(Measurement of dissolution rate)
For the film-coated tablets (round tablets), the dissolution rate was measured using the 14th revised Japanese Pharmacopoeia dissolution test method 2 under the following conditions.
Test solution: 0.1% (W / V) polysorbate 80, pH6.8 phosphate buffer 900 mL
Paddle rotation speed: 75rpm
Test solution temperature: 37 ± 0.5 ℃
Results: In each of the tablets (round tablets) of Examples 1 to 12, the dissolution rate after 90 minutes and 120 minutes was within the range of ± 10% dissolution rate of the tablet of Comparative Example 1 at each time point. It was.
(Observation of tablet surface condition)
With respect to the film-coated tablets (round tablets and elliptical tablets with score lines), the surface state of the tablets was observed. The results are shown in Table 2.
Evaluation criteria:
Good: The coating surface is recognized as smooth by visual inspection. Bad: The coating surface is recognized as non-smooth, such as rough or peeled.

  The tablets of Examples 1 to 12 have the same dissolution rate as that of the organic solvent system (Comparative Example 1), and the tablets of Examples 1 to 10 whose exhaust temperature and product temperature are within the preferred range of the present invention are the surfaces. Regarding the state, both the round lock and the elliptical lock with a score line were good, and no dusting of the score line part was observed. On the other hand, in Example 11 and Example 12, both the round tablet of the tablet and the elliptical tablet with scored line have poor surface conditions, and in Comparative Example 1 where the solvent of the coating solution is an organic solvent, the scored part of the elliptical tablet with scored line is The degree of dusting on the surface was high.

[Example 13]
A film-coated tablet of the elliptical scored lock (having a V-shaped scored groove) shown in FIG. 1 was prepared by the following production method.
1) Preparation of color layer coating solution Hydroxypropylmethylcellulose 2910 12.6 kg, ethylcellulose 3.75 kg, Macrogol 600 1.58 kg, Macrogol 6000 in 154 kg of water
1.58 kg and 7.50 kg of titanium oxide are mixed with stirring to obtain a color layer coating solution.
2) Preparation of clear layer coating solution In 60 kg of water, 3.07 kg of hydroxypropylmethylcellulose 2910, 0.38 kg of Macrogol 6000, and 0.38 kg of Macrogol 600 are stirred and mixed to obtain a clear layer coating solution.
3) Coating The cilnidipine solid dispersion uncoated tablet obtained in the Reference Example is placed in a coating machine (Hi-Coater 170, Freund Industries), and the coating weight of the color layer coating is 18 mg / tablet at a spray rate of 50-100 ml / min per gun Spray. Thereafter, the clear layer coating solution is sprayed to a coating weight of 2 mg / tablet at a spray rate of 50 to 100 ml / min.
4) Drying Drying is performed at an exhaust temperature of 50 ° C. for 12 to 95 hours.

[Test Example 2]
About the film-coated tablet obtained in Example 13, the dissolution profile was compared with the commercially available “Aterec® Tablet 10” (round tablet, organic solvent coating) in the same manner as the measurement of the dissolution rate. Similar results were obtained as shown below. The tablet surface condition was also good.

It is an external appearance perspective view of an elliptical type scored lock.

Explanation of symbols

1 Tablet 2a, 2b V-shaped scored groove 3a, 3b Surface 4a Edge (flat part)

Claims (15)

The solid dispersion containing cilnidipine, using an aqueous coating solution containing hydroxypropylmethylcellulose, exhaust temperature of the coating apparatus comprises a film coated with a temperature managed at 35 ° C. 55 ℃ or more or less, full I Lum coating method . The solid dispersion containing cilnidipine, using an aqueous coating solution containing hydroxypropylmethylcellulose, product temperature of the solid dispersion comprises a film coated with a temperature management is below 50 ° C. or higher 25 ° C., full I Lum coating Method. The form of a solid dispersion is a tablet, film coating method according to any one of claims 1-2. The film coating method according to claim 3 , wherein the tablet has a secant. The film coating method according to any one of claims 1 to 4 , wherein the aqueous coating liquid contains water or water and a water-soluble organic solvent as a solvent. The film coating method according to any one of claims 1 to 5 , wherein the aqueous coating liquid contains only water as a solvent. The film coating method according to any one of claims 1 to 5, wherein the aqueous coating solution contains water and 0 to 2.4 parts by weight of a water-soluble organic solvent with respect to 1 part by weight of water as a solvent. The film coating method according to any one of claims 1 to 7 , wherein the aqueous coating liquid contains a poorly water-soluble polymer compound. The film coating method according to claim 8 , wherein the poorly water-soluble polymer compound is ethyl cellulose. Aqueous coating liquid contains a coloring agent, a film coating method according to any one of claims 1-9. The film coating method according to claim 10 , wherein the colorant is titanium oxide. The film coating method according to any one of claims 1 to 11, wherein the solid dispersion contains cilnidipine, hydroxypropylcellulose and / or hydroxypropylmethylcellulose phthalate. Obtainable by film coating method according to any one of claims 1 to 1 2, the coating formulation of the solid dispersion. A solid dispersion uncoated tablet containing cilnidipine is film-coated using an aqueous coating solution containing hydroxypropylmethylcellulose under a temperature control in which the exhaust temperature of the coating apparatus is 35 ° C. or more and 55 ° C. or less. The manufacturing method of the solid dispersion coating tablet containing. Cirnidipine comprising coating a solid dispersion uncoated tablet containing cilnidipine with a water-based coating liquid containing hydroxypropylmethylcellulose under a temperature control in which the product temperature of the solid dispersion is 25 ° C. or more and 50 ° C. or less. Of producing a solid dispersion-coated tablet containing

Images