JP2016196438A - Film coating composition and oral solid preparation and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a film coating composition in which adhesion between tablets during coating hardly occurs, and the film to be formed is excellent in flexibility and moistureproofness under high humidity conditions, even when the content ratio of PVA with a saponification degree of 85.0 to 89.0 mol% is increased.SOLUTION: A film coating composition for an oral solid preparation consists of PVA with an average saponification degree of 85.0 to 89.0 mol% satisfying the following requirements (a-1) and (a-2) and a (meth) acrylic polymer. Requirement (a-1): The solution is obtained by adding 130.0 ml of 1-propanol to 100.0 g of a 5.0 mass% aqueous solution of PVA and stirring them. The transparency of the solution at 20°C is 50.0% or less. Requirement (a-2): The solution is obtained by adding 230.0 ml of 1-propanol to 100.0 g of a 5.0 mass% aqueous solution of PVA and stirring them. The concentration of the supernatant obtained by leaving the stirred solution to stand at 20°C for 24 hours is 0.75 mass% or more.SELECTED DRAWING: None

Description

  The present invention relates to a film coating composition used for a pharmaceutical oral solid preparation, an oral solid preparation using the film coating composition, and a method for producing the same, and further has high productivity and excellent moisture resistance under high humidity conditions. The present invention relates to a film coating composition for producing a pharmaceutical oral solid preparation, an oral solid preparation and its production.

  Film coating and sugar coating are used to coat tablets containing drugs for the purpose of masking unpleasant taste of drugs, blocking oxygen, preventing moisture, improving the aesthetics of products, etc. It is a widely used technology.

  Film coating can be carried out easily in a short time compared to sugar coating, and since the thickness of the coating film can be reduced, the size of the tablet can be reduced, and the obtained oral solid preparation is also excellent in dosage. Useful.

  As a base used for film coating, various polymers such as hydroxypropylmethylcellulose (hereinafter abbreviated as HPMC) have been used. Recently, polyvinyl alcohol (hereinafter abbreviated as PVA) has been attracting attention. Yes. Since PVA film has excellent moisture resistance and gas barrier properties, it is possible to improve storage stability and odor by applying PVA film coating to solid formulations containing highly odorous drugs, drugs that are easily oxidized, or drugs that easily absorb moisture. The masking effect can be achieved.

Generally, PVA marketed as a pharmaceutical or pharmaceutical grade is a so-called partial saponification type PVA having a saponification degree in the range of 85.0 mol% to 89.0 mol%. This is because the common part of the saponification degree standard of PVA described in the official documents of Japan, the United States, and Europe is 85.0 mol% to 89.0 mol%. In order for pharmaceutical companies to be approved as pharmaceuticals in Japan, the United States and Europe, PVA used as a raw material is 85.0 mol% to 89.0 mol% PVA that conforms to saponification degree standards in Japan, the United States and Europe. There is a background that it is desirable, and it is considered that there is a reason that partially saponified PVA with high water solubility is preferable as PVA used in oral preparations.
However, when PVA having a saponification degree of 85.0 mol% to 89.0 mol%, which is commercially available for pharmaceutical use, is used as a coating base, the adhesiveness of the aqueous PVA solution is high. Or the solid preparation adheres to the inside of the coating machine, so that the spraying speed cannot be increased and the productivity is low. In addition, although PVA has high moisture resistance, there is a drawback that the moisture resistance is lowered due to inhibition of hydrogen bonding between PVA molecules by water molecules under high humidity conditions of 90% RH or more.

  As a method for improving the adhesiveness of PVA, Patent Document 1 discloses a coating composition containing PVA having a saponification degree of 90 mol% or more, water and the like. Further, Patent Document 2 discloses a film coating composition containing PVA and water-soluble polyoxyethylenes, and examples of the film coating composition of partially saponified type PVA and polyethylene glycol are exemplified. (Patent Document 2).

Furthermore, the present inventors have disclosed a method for coating using a film coating composition containing PVA and a water-soluble cellulose derivative (Patent Document 3).
Any of these methods can improve the adhesiveness of PVA and increase the spray speed as compared with coating with a partially saponification type PVA having a saponification degree of 85.0 mol% to 89.0 mol%. Coating time can be shortened.

  Further, as a method for expressing excellent moisture resistance under high humidity conditions, Patent Document 4 discloses a film coating composition containing PVA and a polymer, a plasticizer and / or a lubricant having pH-dependent solubility. In addition, (meth) acrylic polymers are exemplified as polymers having pH-dependent solubility.

JP 59-42325 A JP-A-8-59512 JP2013-253030A Special table 2012-526815 gazette

  However, the PVA of Patent Document 1 does not satisfy the saponification degree standard of the United States Pharmacopoeia (USP), and cannot be used as a raw material for pharmaceuticals for global expansion, and the saponification degree is 85.0 mol%. As compared with ˜89.0 mol% PVA, there is a problem that it cannot be used for a fast-dissolving oral solid preparation because of its low water solubility.

  Moreover, although the method of patent document 2 and 3 can anticipate the shortening effect of the coating time by adhesive improvement, polyoxyethylenes, a water-soluble cellulose derivative, etc. are included, and the moisture-proof property which PVA has originally has. It becomes a factor to reduce.

  Furthermore, although the method described in Patent Document 4 can be expected to improve the moisture resistance under high humidity conditions, the PVA-derived tackiness cannot be suppressed, and the spray speed during coating cannot be increased. Therefore, plasticizers and / or lubricants are used in combination, and compositions with a low PVA content of less than 40% by weight are exemplified. However, when a lot of lubricants are contained, the flexibility of the formed film is lowered, and the film is liable to be cracked when coated on a tablet or the like that easily expands. Moreover, since there are few polymer components in a coating layer, there also exists a fault that sufficient gas barrier property cannot be obtained. If an attempt is made to increase the ratio of PVA in the film coating composition in order to improve the flexibility and gas barrier properties of the film, the problem arises that the spray rate cannot be increased due to the adhesiveness of PVA and the productivity is lowered. In other words, the required performance of coating productivity, film flexibility and moisture resistance under high humidity conditions could not be satisfied.

  In view of the above situation, the present invention uses a PVA that meets the saponification degree standard of PVA described in the official documents of Japan, the United States, and Europe, that is, the saponification degree is 85.0 mol% to 89.0 mol%. However, even when the content ratio of PVA in the film coating composition is increased (for example, the content ratio of PVA is 40% by mass or more), when coating is performed, adhesion between tablets in the coating hardly occurs. And a film coating composition characterized by a high productivity and a film formed under high humidity conditions having high moisture resistance and excellent flexibility. An object of the present invention is to provide an oral solid preparation and a method for producing the same.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that 85.0 mol% to 89.0 mol% of PVA and (meth) acrylic polymer satisfying specific requirements (further, By combining (at a specific ratio), it was found that tackiness is hardly expressed during coating, and by using this film coating composition, high productivity of the film coating and excellent high-humidity conditions of the formed film In addition, the inventors have found that both the moisture resistance and the flexibility of the film can be achieved, and have further researched to complete the present invention.

That is, the present invention relates to the following film coating composition for oral solid preparations.
[1] A film coating composition for an oral solid preparation comprising polyvinyl alcohol (a) having an average saponification degree of 85.0 mol% to 89.0 mol% and a (meth) acrylic polymer (b), A film coating composition for an oral solid preparation, wherein the polyvinyl alcohol (a) is polyvinyl alcohol that satisfies the following requirements (a-1) and (a-2).
Requirement (a-1): 130.0 ml of 1-propanol is added to 100.0 g of a 5.0% by weight aqueous solution of polyvinyl alcohol, and the liquid transparency at 20 ° C. of the liquid obtained by stirring is 50.0%. It is as follows.
Requirement (a-2): A supernatant obtained by adding 230.0 ml of 1-propanol to 100.0 g of a 5.0 mass% polyvinyl alcohol aqueous solution and allowing the stirred solution to stand at 20 ° C. for 24 hours. The concentration of is 0.75% by mass or more.
[2] The (meth) acrylic polymer (b) in the film coating composition contains methyl acrylate / methyl methacrylate copolymer, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methacrylic acid copolymer L, and methacrylic acid copolymer LD. The film coating composition for oral solid preparations according to [1], which is at least one selected from methacrylic acid copolymer S, carboxyvinyl polymer, dimethylaminoethyl methacrylate copolymer and polyacrylic acid.
[3] The mass ratio of the polyvinyl alcohol (a) and the (meth) acrylic polymer (b) in the film coating composition is 90:10 to 60:40 [1] or [2] The film coating composition for oral solid preparations described in 1.
[4] The mass ratio of the polyvinyl alcohol (a) in the film coating composition is 40% by mass or more, and the mass ratio of the (meth) acrylic polymer (b) is 4% by mass or more and 40% by mass or less. The film coating composition for oral solid preparations according to any one of [1] to [3].
[5] The film coating composition for oral solid preparations according to any one of [1] to [4], further comprising a plasticizer (c).
[6] The oral solid preparation according to any one of [1] to [5], wherein the viscosity of a 4% by weight aqueous solution of polyvinyl alcohol (a) is 2.0 mPa · s to 10.0 mPa · s. Film coating composition.
[7] An oral solid preparation characterized in that a tablet containing a drug is coated with the film coating composition according to any one of [1] to [6].
[8] An aqueous solution and / or an aqueous solution containing the film coating composition according to any one of [1] to [6] is applied or sprayed onto a tablet containing a drug, and the film coating composition is applied to the tablet surface. The manufacturing method of the oral solid agent characterized by including the process made to coat | cover.

  According to the present invention, it can be used for pharmaceutical preparations in Japan, the United States and Europe, and when film coating is performed, adhesion between tablets is hardly expressed, thereby shortening the coating time and making it moisture-proof even under high humidity. It is possible to provide a film coating composition capable of forming an excellent highly flexible coating film, an oral solid preparation using the same, and a method for producing the same.

Hereinafter, the present invention will be described in detail.
The film coating composition of the present invention usually indicates constituent components other than the solvent in the coating liquid used for film coating, and the weight ratio and weight ratio of each component described below are usually water and solvent. The ratio in components other than is shown.
In addition, when preparing a coating liquid using the film coating composition of the present invention, each component composed of a solid or a solid and a liquid component are mixed in advance, and then dissolved or dispersed in water or an organic solvent, A method of mixing a solution or dispersion obtained by dissolving the constituent components in water or an organic solvent can be used. The mixing, dissolving and dispersing method is not particularly limited.

[PVA]
PVA (a) used for the film coating composition for oral solid preparations of the present invention will be described in detail.
The PVA (a) used in the present invention preferably has an average degree of saponification of 85.0 mol% to 89.0 mol% and a wider saponification degree distribution than conventional PVA.
The average saponification degree of PVA is measured according to the saponification degree measuring method of JIS K6726.

  As an index representing the distribution of saponification degree, it can be expressed by the amount of PVA component that precipitates and the amount of PVA component that does not precipitate when a certain amount of 1-propanol is added to and mixed with an aqueous solution in which PVA is completely dissolved. In the invention, it is preferable to use PVA satisfying both the following requirements (a-1) and (a-2), and the meaning of the requirements will be described.

“Requirement (a-1): 130.0 ml of 1-propanol is added to 100.0 g of a 5.0 mass% polyvinyl alcohol aqueous solution, and the liquid obtained at 20 ° C. has a transparency of 50.0 at 20 ° C. % Or less. "
The stirring is preferably performed uniformly.
Although the stirring method is not particularly limited, for example, it is preferable to stir at 500 rpm using a stirrer.
Moreover, the dripping speed | rate of 1-propanol is although it does not specifically limit, For example, 10 ml / min is preferable.

The “transparency of the liquid at 20 ° C.” means, for example, a liquid that has left the liquid at 20 ° C. for a predetermined time (for example, about 30 minutes to 1 hour) and the bubbles in the liquid have fallen out to an extent that cannot be visually confirmed. The transparency of.
The transparency is preferably 30.0% or less, more preferably 20.0% or less.

Here, the measurement of transparency is carried out by using a spectrophotometer defined in JIS K0115, using a quartz or glass absorption cell having an optical path length of 20 mm, and obtaining a transmittance of 430 nm using water as a control. .
As the meaning of the transparency required here, since a PVA component having a high saponification degree is difficult to dissolve in 1-propanol, when a certain amount of 1-propanol is added to the PVA aqueous solution, a high saponification degree component is precipitated, Therefore, the transparency of 50.0% or less under the above conditions indicates that a high saponification degree component is contained, that is, the saponification degree distribution on the high saponification degree side is wide.

“Requirement (a-2): 230.0 ml of 1-propanol was added to 100.0 g of 5.0% by weight aqueous solution of polyvinyl alcohol, and the supernatant obtained by allowing the stirred solution to stand at 20 ° C. for 24 hours. The concentration of the liquid is 0.75% by mass or more. "
The stirring is preferably performed uniformly.
Although the stirring method is not particularly limited, for example, it is preferable to stir at 500 rpm using a stirrer.
Moreover, the dripping speed | rate of 1-propanol is although it does not specifically limit, For example, 10 ml / min is preferable.

  The concentration of the supernatant is preferably 0.75% by mass or more, more preferably 0.80% by mass or more.

  Here, the supernatant is obtained by, for example, adding 230.0 ml of 1-propanol to 100.0 g of a 5.0% by weight aqueous solution of polyvinyl alcohol and allowing the stirred solution to stand at 20 ° C. for 24 hours. From the liquid layer of the obtained liquid, it can be obtained by collecting 30 to 60% by weight with respect to the total amount of the liquid.

  As a method for measuring the supernatant concentration, for example, about 80 g of the supernatant is collected on a petri dish using a dropper so that no precipitation component is contained, dried at 60 ° C. for 5 hours, and then dried at 105 ° C. for 24 hours. It can be calculated from the weight of the collected liquid and the change in weight before and after drying.

As the meaning of the supernatant concentration required here, the PVA component having a low saponification degree is difficult to be precipitated by adding 1-propanol. Therefore, when a certain amount of 1-propanol is added to the PVA aqueous solution, the low saponification degree component is a liquid. It exists in a dissolved state. That is, that the concentration of the supernatant liquid is 0.75% by mass or more indicates that the saponification degree distribution on the low saponification degree side is wide.
The PVA (a) used in the film coating composition of the present invention has an average degree of saponification in the range of 85.0 mol% to 89.0 mol%, and satisfies the requirement (a-1). That is, the saponification degree distribution on the high saponification degree side is wide and satisfies the above requirement (a-2), that is, the saponification degree distribution on the low saponification degree side is wide, that is, the high saponification degree side, It is preferable that both distributions on the low saponification degree side are wide.

The PVA (a) used in the film coating composition of the present invention has a wide saponification degree distribution in order to satisfy the requirement (a-1) and the requirement (a-2).
If the transparency measured under the condition (a-1) of the PVA used is 50.0% or less, even if a coating test is performed using such PVA, it is difficult for the tablets to adhere to each other. This is preferable because defects can be prevented and the coating time can be shortened.
Moreover, if the supernatant liquid concentration measured on the conditions of the requirements (a-2) of PVA to be used is 0.75 mass% or more, even if it performs a coating test using such PVA, adhesion of tablets will be carried out. Is preferable because it is difficult to occur, coating defects can be prevented, and the coating time can be shortened.

  As a method for producing PVA used in the present invention, a known method such as saponification of a polymer of a vinyl ester monomer is used, and an example of such a vinyl ester monomer is vinyl acetate.

  The polymerization method of vinyl acetate is not particularly limited, and examples thereof include conventionally known bulk polymerization, solution polymerization, suspension polymerization, emulsion polymerization, and the like, but solution polymerization using methanol as a solvent is industrially preferable. For the solution polymerization, known initiators such as peroxides and azos can be used. By changing the mixing ratio of vinyl acetate and methanol and the polymerization yield, the polymerization degree of the resulting polyvinyl acetate can be increased. Can be adjusted. Moreover, a commercially available polyvinyl acetate resin can also be used as a raw material for obtaining PVA used for this invention.

As a saponification method of the obtained polyvinyl acetate, a conventionally known saponification method using an alkali catalyst or an acid catalyst can be applied. Among them, a methanol solution of polyvinyl acetate or a methanol solution of polyvinyl acetate, water, acetic acid A method in which an alkali such as sodium hydroxide is added to a mixed solution such as methyl, and the acetyl group of polyvinyl acetate is alcoholically decomposed while stirring and mixing is industrially preferable.
Thereafter, the obtained lump, gel or granule is pulverized, neutralized with added alkali as necessary, solids and liquids are separated, and the solids are dried to obtain PVA. be able to.

  The PVA used in the present invention can be produced by carrying out the saponification reaction in a non-uniform system. As a specific method, the concentration of the methanol solution of polyvinyl acetate during saponification is increased (for example, 55% by mass or more), and the stirring speed when adding and mixing the alkali is decreased. (For example, 20 rpm or less) a method for saponification, a method for saponification by shortening the stirring and mixing time when adding and mixing alkali, a method for saponifying in a short time by increasing the amount of alkali, Examples of the method include saponification by giving a temperature gradient or a temperature distribution to the saponification reaction system by adjusting the temperature of the methanol solution and the alkali to be added.

  In addition, there is a method of performing a saponification reaction by adding a solvent such as water and methyl acetate that affects the saponification reaction rate so as to be in a non-uniform state, which was created by performing these operations. Even when the average saponification degree is the same as that of PVA prepared by a conventional method, PVA having a wide saponification degree distribution can be produced.

  In addition to the above method, PVA in which two or more PVA powders having different saponification degrees are blended so that the weighted average saponification degree becomes a target value can also be used in the present invention as one form of PVA.

  Since the PVA used in the present invention is mainly used for a film coating composition of a pharmaceutical oral solid preparation, the average saponification degree range is defined by three official documents of pharmaceutical additive standards, US Pharmacopeia and European Pharmacopeia. It is required to be within the specification of the degree of saponification of PVA described in the above, and it is required to dissolve quickly in the body, so that it is 85.0 mol% to 89.0 mol%. When the average degree of saponification is less than 85.0 mol%, it cannot be used as a raw material for pharmaceutical preparations sold globally, and since the proportion of hydrophobic groups increases, the hydrophilicity decreases or the aqueous solution There is a problem that handling tends to be difficult because a tendency to precipitate at a high temperature appears. On the other hand, when the average saponification degree is larger than 89.0 mol%, it cannot be used as a raw material for pharmaceutical preparations sold globally, and the solubility in water is improved due to the improvement in crystallinity accompanying the increase in hydroxyl groups of PVA. When used for film coating of oral solid preparations, there is a problem that the dissolution rate is lowered.

The degree of polymerization of PVA used in the present invention is not particularly limited, but the viscosity of a 4% by mass aqueous solution (measured in accordance with JIS K6726) is preferably 2.0 mPa · s or more and 10.0 mPa · s or less, and 3.0 mPa · s or more. 7.0 mPa · s or less is more preferable.
When the viscosity of the 4% by mass aqueous solution is 2.0 mPa · s or more, the strength of the film formed on the tablet surface after coating is preferable. When the viscosity of the 4% by mass aqueous solution is 10 mPa · s or less, the viscosity is low, so that the spray rate at the time of coating can be increased and the productivity is improved, which is preferable.

[(Meth) acrylic polymer]
Examples of the (meth) acrylic polymer (b) used in the present invention include an acrylic monomer (for example, acrylic ester, acrylic acid and its salt) and a methacrylic monomer (for example, methacrylic ester, methacrylic acid and its). Does not include polymers obtained by polymerizing or copolymerizing one or more selected from salts, etc., copolymers of one or more selected from acrylic monomers and methacrylic monomers and other monomers, acrylic units, and methacrylic units Examples thereof include a copolymer obtained by graft copolymerizing at least one selected from an acrylic monomer and a methacrylic monomer.

  These (meth) acrylic polymers are preferably pharmaceutically acceptable. Specifically, for example, aminoalkyl methacrylate copolymer E (for example, EUDRAGITR EPO, EUDRAGITR E100, EUDRAGITR E12.5, etc. manufactured by Evonik Degussa) ), Aminoalkyl methacrylate copolymer RS (for example, EUDRAGITR RS100, EUDRAGITR RSPO, etc. manufactured by Evonik Degussa), aminoalkyl methacrylate copolymer RL (for example, EUDRAGITR RL100, EUDRAGITR RLPO, manufactured by Evonik Degussa), methacrylic acid copolymer L (for example, Evonik) Degussa, EUDRAGITR L100, etc.), methacrylic acid copolymer S (for example, Evonik Degussa, EU RAGITR S100, etc.), methacrylic acid copolymer LD (eg, Evonik Degussa, EUDRAGITR L30D-55, etc.), dry methacrylic acid copolymer (eg, Evonik Degussa, EUDRAGITR L100-55, etc.), aminoalkyl methacrylate copolymer RS dispersion (eg, Evonik Degussa, EUDRAGITR RL30D, EUDRAGITR RS30D, etc.) Ethyl acrylate-methyl methacrylate copolymer dispersion (for example, Evonik Degussa, EUDRAGITR NE30D, etc.), carboxyvinyl polymer (for example, CBC Carbopol R 971PNF, Carbopol RolFolColFolColFolC) 71GNF), acrylic resin alkanolamine liquid, dimethylaminoethyl Methacrylate copolymer, sodium polyacrylate, partially neutralized polyacrylic acid, 2-methyl-5-vinylpyridine methylacrylate-but methacrylate excipients such copolymers include but are not limited to these. These can be used individually by 1 type or in combination of 2 or more types.

  Among these (meth) acrylic polymers, aminoalkyl methacrylate copolymer E and methacrylic acid copolymer L are more preferable, and aminoalkyl methacrylate copolymer E is more preferably used in tablets using the film coating composition of the present invention. A film formed upon coating is preferable in that it exhibits a high moisture-proof effect and excellent flexibility.

[Plasticizer]
The film coating composition in the present invention may contain a plasticizer (c) in addition to the PVA (a) and the (meth) acrylic polymer (b).
The plasticizer (c) is preferably one that can be administered orally, and is not particularly limited. For example, polyoxyethylenes [for example, polyethylene glycol (hereinafter also abbreviated as PEG), polyoxyethylene polyoxypropylene glycol, polyethylene Water-soluble polyoxyethylenes such as glycol ether and polyethylene glycol fatty acid ester; water-insoluble polyoxyethylenes such as polyoxyethylene hydrogenated castor oil 60], sugars (eg, glucose, mannose, galactose, sucrose, lactose, maltose) , Fructose etc.), sugar alcohols (eg mannitol, erythritol, sorbitol, xylitol, lactitol, maltitol, pentaerythritol etc.), alkanediols (eg ethylene glycol) , Trimethylene glycol, tetramethylene glycol, pentamethylene glycol, hexamethylene glycol, propylene glycol, butanediol, etc.), di to tetraalkanediols (eg, diethylene glycol, triethylene glycol, etc.), polyols having 3 or more hydroxyl groups Or multimers thereof (eg, trimethylolpropane, glycerin, diglycerin, triglycerin, etc.), polypropylene glycol, higher fatty acids or esters thereof (eg, stearic acid), sulfates (eg, sodium lauryl sulfate), citric acid Examples include esters (eg, triethyl citrate), triacetin, phthalate ester plasticizers (eg, diethyl phthalate, dibutyl phthalate), polysorbates, and the like. These plasticizers can be used alone or in combination of two or more.

Among these, water-soluble polyoxyethylenes such as PEG, polyoxyethylene polyoxypropylene glycol, polyethylene glycol ether, and polyethylene glycol fatty acid ester are particularly preferable from the viewpoint of high effect of suppressing adhesion during coating.
Examples of PEG include macro goal 200, macro goal 300, macro goal 400, macro goal 600, macro goal 1000, macro goal 1500, macro goal 1540, macro goal 4000, macro goal 6000, macro goal 20000, macro goal 35000, etc. PEG having an average molecular weight of 400 to 6000 (for example, Macrogol 400, Macrogol 600, Macrogol 1000, Macrogol 1500, Macrogol 1540, Macrogol 4000) is particularly preferable.

  Polyoxyethylene polyoxypropylene glycol is a polymer obtained by addition polymerization of ethylene oxide to polypropylene glycol obtained by polymerizing propylene oxide. The average polymerization degree of ethylene oxide is 3 to 200, and the average polymerization degree of propylene oxide. Is preferably 5 to 70, in particular, the average degree of polymerization of ethylene oxide is 40 to 160, and the average degree of polymerization of propylene oxide is 5 to 70, for example, polyoxyethylene (42) polyoxypropylene (67) glycol, Polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxy Propylene (3 ) Glycol are more preferable.

  The polyethylene glycol ether is preferably polysorbate 80 (polyoxyethylene sorbitan monooleate (20E.O.)), and the polyethylene glycol fatty acid ester is preferably polyoxyl 40 stearate (polyoxyethylene 40 monostearate).

[Inorganic compounds]
The film coating composition of the present invention may contain an inorganic compound in addition to PVA (a), (meth) acrylic polymer (b) and plasticizer (c).
Examples of the inorganic compound include talc, titanium oxide, pigment, colloidal silica, and the like. These can be used alone or in combination of two or more.
Among these inorganic compounds, talc is preferable from the viewpoint of improving the adhesiveness of PVA and improving the tablet surface smoothness after coating. Titanium oxide is also preferable from the viewpoint of improving the hue of the tablet surface after coating.

[Film coating composition]
The mass ratio of the contents of PVA (a) and (meth) acrylic polymer (b) in the film coating composition of the present invention is, for example, 95: 5 to 5:95, preferably 95: 5 to 30:70 (for example, 90:10 to 60:40), more preferably 85:15 to 65:35 (for example, 80:20 to 70:30).
If the ratio of PVA is 90% or less, the moisture resistance of the coated tablet under high humidity is preferable.
On the other hand, if the ratio of PVA is 60% or more, the flexibility of the film formed on the tablet surface is excellent, and when the tablet expands due to moisture absorption, cracks are less likely to occur, and the coating film Is preferable because the solubility in water becomes high and the use as a fast dissolving tablet becomes easy.

  The mass ratio of the total amount of PVA (a) and (meth) acrylic polymer (b) to the plasticizer (c) in the film coating composition of the present invention is preferably 99: 1 to 60:40. More preferably, it is 90:10 to 70:30. If the ratio of the plasticizer is 1% by mass or more, it is preferable because the adhesiveness during coating is improved and the flexibility of the film is improved. On the other hand, if the ratio of the plasticizer is 40% by mass or less, the ratio of PVA (a) and (meth) acrylic polymer (b) in the film coating composition is high, and the moisture resistance of the coated tablet under high humidity is high. It is preferable because of its high properties.

  Moreover, as a mass ratio of PVA (a) in the film coating composition of this invention, Preferably, it is 40 mass% or more (for example, 40 mass% or more and 96 mass% or less), More preferably, it is 60 mass%. It is above (for example, 60 mass% or more and 96 mass% or less). If the mass ratio of PVA is 40% by mass or more, the flexibility of the film formed by tablet coating is improved, and when coating on a tablet that easily expands due to moisture absorption etc., it becomes difficult for the film to crack, It is preferable because the oxygen barrier property is improved and the storage stability of the coated tablet is improved.

  Furthermore, the mass ratio of the (meth) acrylic polymer (b) in the film coating composition of the present invention is preferably 4% by mass or more and 40% by mass or less, more preferably 10% by mass or more and 20% by mass. % Or less. If the ratio of the (meth) acrylic polymer (b) is 4% by mass or more, moisture resistance under high humidity conditions is improved, which is preferable. In addition, if the proportion of the (meth) acrylic polymer (b) is 40% by mass or less, the flexibility of the film formed by tablet coating is improved, and when the tablet is easily expanded, the film is cracked. This is preferable because it is less likely to occur.

  If necessary, the coating composition of the present invention is usually used in drugs for pharmaceutical preparations, lubricants such as magnesium stearate and calcium stearate, water-soluble polymers such as HPMC and hydroxypropylcellulose, surfactants and colorants. Additives such as pigments, sweeteners, coating agents, antifoaming agents and pH adjusting agents may be added. These additives can be used alone or in combination of two or more. Moreover, content in the case of adding these becomes like this. Preferably it is 1 to 200 mass parts with respect to 100 mass parts of PVA, More preferably, it is 1 to 100 mass parts.

[Oral solid preparation]
The present invention also includes an oral solid preparation coated with the film coating composition of the present invention on a tablet containing a drug.
The oral solid preparation of the present invention usually comprises a core part containing a drug and a coating part covering the core part, and the coating part contains at least the film coating composition. Examples of the core include tablets, granules, fine granules, capsules, etc. Among them, tablets are particularly preferable.
The drug is not particularly limited as long as it is an orally administrable drug.

Drug-containing tablets may contain various additives commonly used in this field, such as excipients, binders, disintegrants, lubricants, anti-aggregation agents, and solubilizing agents for pharmaceutical compounds. Good.
Examples of the excipient include sugars such as sucrose, lactose, mannitol, glucose, starch, crystalline cellulose, calcium phosphate, calcium sulfate and the like.
As binders, PVA, polyacrylic acid, polymethacrylic acid, polyvinylpyrrolidone, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, hydroxyethylcellulose, HPMC, hydroxypropylcellulose, macrogols, gum arabic, gelatin, Examples include agar and starch.

Examples of the disintegrant include low-substituted hydroxypropyl cellulose, carmellose or a salt thereof, croscarmellose sodium, sodium carboxymethyl starch, cros polyvinylpyrrolidone, crystalline cellulose, crystalline cellulose / carmellose sodium, and the like.
Further, examples of the lubricant and the aggregation inhibitor include talc, magnesium stearate, calcium stearate, colloidal silica, stearic acid, waxes, hardened oil, polyethylene glycols, sodium benzoate and the like.
Furthermore, examples of solubilizing agents for pharmaceutical compounds include organic acids such as fumaric acid, succinic acid, malic acid, and adipic acid.
These additives can be used alone or in combination of two or more. In addition, the content of these additives can be appropriately determined according to the type of the drug.

Next, the manufacturing method of the oral solid formulation of this invention is demonstrated.
The method for coating the film coating composition of the present invention on the tablet is not particularly limited, and conventionally known coating means can be used. Spray coating is generally used, but in that case, it can be performed using a pan coating device, a drum type coating device, etc., and the spray devices attached to these devices are air spray, airless. A spray or the like can be used.

  As a method for coating the tablet of the film coating composition of the present invention, for example, using the above-described coating apparatus, the film coating composition of the present invention, water or Examples thereof include a method in which a coating liquid comprising a solvent and an additive added as necessary is applied or sprayed onto a tablet or the like and dried to coat the tablet surface. The method for preparing the coating solution is a method in which the components of the film coating composition of the present invention and additives added as necessary are mixed in advance and dissolved or dispersed in an organic solvent such as water or ethanol or a mixed solution thereof. Alternatively, a method of preparing and mixing a solution in which each component of the film coating composition of the present invention and additives to be added as necessary is dissolved or dispersed in water or an organic solvent such as ethanol or a mixture thereof, respectively. Either is fine.

  The coating amount of the film coating composition coated on the surface of the tablet 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, On the other hand, it is preferably 1 to 10% by mass, more preferably 1 to 7% by mass, and particularly preferably 2 to 6% by mass. If the coating amount is too small, a complete film cannot be obtained, and sufficient moisture-proofing effect, oxygen barrier property, and odor masking effect cannot be obtained. On the other hand, if the coating amount is too large, there is a problem that the time required for coating becomes long.

  The oral solid preparation of the present invention uses a composition containing various polymers that can be commonly used for coating pharmaceutical preparations such as HPMC as components under the film layer formed by the film coating composition of the present invention. Undercoating, or overcoating on the film layer formed by the film coating composition of the present invention using a composition containing various polymers that can be commonly used for coating pharmaceutical preparations. In addition, a multilayer film-coated oral solid preparation in which a film containing a plurality of components is formed may be used.

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.
In the following Examples and Comparative Examples, “%” and “part” represent mass standards unless otherwise specified.

<Synthesis of PVA>
(Comparative Synthesis Example 1)
A commercially available polyvinyl acetate resin (JMR-30LL, degree of polymerization 590, manufactured by Nippon Acetate / Poval) was vacuum dried at 100 ° C. to remove moisture, and then dissolved in methanol to obtain a 46 mass% methanol solution of polyvinyl acetate. It was. 500 parts by mass of this solution was heated to 40 ° C., 16 parts by mass of a 3% by weight sodium hydroxide methanol solution adjusted to 35 ° C. was added, and the mixture was stirred at 300 rpm for 1 minute using a propeller type stirring blade. Saponification reaction was performed by leaving still at 40 degreeC for 40 minute (s). The obtained gel was pulverized, immersed in a mixed solvent consisting of 570 parts by mass of methanol, 230 parts by mass of methyl acetate and 17 parts by mass of water, and subjected to a saponification reaction at 40 ° C. for an additional hour with slow stirring. Then, after neutralizing by adding 1% by mass acetic acid aqueous solution so that the pH becomes 8-9, the solid and liquid were separated, and the solid was dried at 60 ° C. for 8 hours to obtain a PVA resin. It was.

  The average saponification degree of this PVA resin measured by the method of JIS K6726 was 88.3 mol%, and the viscosity of a 4% by mass aqueous solution was 5.3 mPa · s. Moreover, the transparency of the liquid at 20 ° C. when 130 ml of 1-propanol was added to 100 g of a 5.0 mass% aqueous solution of the PVA resin was 99.4%. The supernatant concentration after adding 230 ml of -propanol and allowing to stand at 20 ° C. for 24 hours was 0.62% by mass. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 1)
Comparative Synthesis Example 1 except that a sodium hydroxide solution was added to a methanol solution of polyvinyl acetate and stirred at a speed of 60 rpm for 30 seconds, and mixing was performed so that it was more uneven than normal conditions. In the same manner as above, a PVA resin was obtained.
The average saponification degree of this PVA resin measured by the method of JIS K6726 was 88.2 mol%, and the viscosity of a 4 mass% aqueous solution was 5.2 mPa · s. Moreover, the transparency of the liquid at 20 ° C. when 130 ml of 1-propanol was added to 100 g of a 5.0% by mass aqueous solution of the PVA resin was 18.5%, and 100 g of the 5.0% by mass aqueous solution of the PVA resin was 1 -The supernatant liquid density | concentration after adding 230 ml of propanols and leaving still at 20 degreeC for 24 hours was 0.83 mass%. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 2)
Comparative Synthesis Example 1 except that when a sodium hydroxide solution was added to a methanol solution of polyvinyl acetate and agitated, the agitation speed was 20 rpm for 60 seconds, and mixing was performed so that it was more uneven than normal conditions. In the same manner as above, a PVA resin was obtained.
Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 3)
When performing the saponification reaction, a PVA resin was prepared in the same manner as in Comparative Synthesis Example 1 except that the concentration of polyvinyl acetate in methanol was 55% by mass and the sodium hydroxide solution added to 500 parts by mass of this solution was 23 parts by mass. Got. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 4)
When carrying out the saponification reaction, a band heater is wound around the upper half of a mixture of a methanol solution of polyvinyl acetate and sodium hydroxide and heated to 50 ° C., and the temperature during the saponification reaction is lowered to 50 ° C. in the upper half. A PVA resin was obtained in the same manner as in Comparative Synthesis Example 1 except that a temperature gradient was provided so that half of the temperature was room temperature (25 ° C.) and the time for standing was 50 minutes. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 5)
Divide 500 parts by mass of 46% by weight methanol solution of polyvinyl acetate into separate containers in 250 parts by mass, heat to 40 ° C., and adjust to 35 ° C. with 3% by mass of sodium hydroxide in methanol. 10 parts by weight, and 6 parts by weight to the other, both of which were simultaneously stirred at 300 rpm for 1 minute, and then allowed to stand at 40 ° C. for 40 minutes to separate the saponification reaction separately. A PVA resin was obtained in the same manner as in Comparative Synthesis Example 1 except that the PVA resin was pulverized. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

(Synthesis Example 6)
40 parts by mass of commercially available PVA resin (JL-05E, saponification degree: 80.2 mol%, 4% by weight aqueous solution viscosity: 5.1 mPa · s), and commercially available PVA resin (manufactured by Nihon Vinegar / Poval) JT-05 Saponification degree: 94.0 mol%, 4 mass%, aqueous solution viscosity: 5.6 mPa · s) 60 parts by mass is put into a polyethylene bag, the bag is shaken about 100 times, and PVA powder is uniformly mixed to saponify. A PVA resin having a wide degree distribution was prepared. Table 1 shows the average saponification degree of the PVA resin, the viscosity of the 4% by mass aqueous solution, and the transparency and the concentration of the supernatant liquid when 1-propanol was added.

<Coating conditions>
Equipment: High coater (HC-FZ-Labo, manufactured by Freund Corporation)
Tablet charge: 1000g
Supply air temperature: 70-80 ° C
Exhaust temperature: 44-52 ° C
Supply air amount: 0.6 m ³ / min
Number of spray guns: 1 Spray gun Air volume (atomized air): 30 L / min
Spray gun Air volume (pattern air): 9L / min
Spray speed: Adjusted by tube pump discharge rate Pan rotation speed: 18 rpm

<Evaluation of coating time>
In the coating test, the spray speed when spraying the coating solution is started at 2.0 g / min. If the sticking between the tablets and the tablet and the bread does not occur, the spray speed is gradually increased, The spray speed was increased until sticking between tablets or between tablet and bread occurred. After that, once the spraying speed is lowered, it is confirmed that the tablet does not stick to each other or between the tablet and the bread, and the coating test is continued at the spray speed for 10 minutes so that sticking does not occur. The spray speed was set as the maximum spray speed. On the other hand, if sticking between tablets or tablets and bread occurs at an initial spray speed of 2.0 g / min, gradually decrease the spray speed and confirm that sticking does not occur at that spray speed for 10 minutes. The spray speed was taken as the maximum spray speed. Furthermore, from the maximum spray speed, the shortest coating time for applying 3% by mass of the solid content on the tablet was calculated.

<Evaluation of water vapor transmission rate>
A coating composition solution or dispersion having a solid content concentration of 10% by mass was cast on a PET sheet and dried in a thermostatic oven at 20 ° C. × 65% RH to obtain a film having a thickness of 100 μm. The water vapor permeability of the obtained film was measured under the conditions of 25 ° C. and 90% relative humidity using a method according to JIS K7129 using an L80-5000 type water vapor permeability meter (manufactured by Systech Instruments).

<Evaluation of film coating composition film>
A coating composition solution or dispersion having a solid content concentration of 10% by mass was cast on a PET sheet and dried in a thermostatic oven at 20 ° C. × 65% RH to obtain a film having a thickness of 100 μm. The obtained film was cut into a 10 cm × 3 cm rectangular shape, and the tensile elongation was measured according to the method of JIS K7127 under the following conditions.
-Equipment used: Autograph AGS-J (Shimadzu Corporation)
・ Chuck width: 3cm
・ Tensile speed: 50 mm / min.
・ Measurement room condition: 20 ℃, 65% RH

Example 1
24 parts by mass of PVA resin of Synthesis Example 1 was added to 270 parts by mass of purified water, stirred for 1 hour while heating to 80 ° C., and then stirred while cooling to 30 ° C. to obtain an aqueous solution of PVA resin. . While stirring this aqueous solution, 6 parts by mass of aminoalkyl methacrylate copolymer (Evonik Degussa, EUDRAGITR EPO) was added little by little and dispersed while stirring for 1 hour to prepare a coating solution (PVA: aminoalkyl methacrylate). Copolymer = 8: 2 concentration of aqueous solution: 10% by mass). Using this coating solution, a coating test was performed on uncoated tablets mainly composed of lactose and corn starch, and the maximum spray speed, the shortest coating time, the water vapor permeability of the coating composition and the tensile elongation of the film were evaluated. The blending ratio of the coating composition is shown in Table 2.
The maximum spray rate of the film coating solution containing the PVA of synthesis example 1 and the aminoalkyl methacrylate copolymer was 5.00 g / min, and the coating time for applying a coating of 3% by mass was 60 minutes. Moreover, the water vapor permeability at 90% RH was 200 g / m ² · day, and the elongation of the coating composition film (film) was 180%. The results are shown in Table 3.

(Example 2)
A composition in which 24 parts by mass of the PVA resin of Synthesis Example 2 and 6 parts by mass of an aminoalkyl methacrylate copolymer (Evonik Degussa, EUDRAGITR EPO) were mixed in advance was added to 270 parts by mass of purified water, and stirred at 30 ° C. for 2 hours to coat A liquid was prepared (PVA: aminoalkyl methacrylate copolymer = 8: 2 aqueous solution concentration: 10% by mass). The blending ratio of the coating composition is shown in Table 2.
Using this coating solution, a coating test was conducted on uncoated tablets mainly composed of lactose and corn starch, and the maximum spray rate, the shortest coating time, the water vapor permeability and the tensile elongation of the coating composition film were evaluated. The results are shown in Table 3.

(Examples 3 to 6)
A coating test was conducted in the same manner as in Example 1 except that the PVA resins in Synthesis Examples 3 to 6 were used in place of the PVA resin in Synthesis Example 1, and the maximum spray speed, the shortest coating time, and the coating composition film were used. The water vapor permeability and tensile elongation were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Example 7)
A coating test was conducted in the same manner as in Example 2 except that methacrylic acid copolymer L (Evonik Degussa, EUDRAGITR L100) was used instead of the aminoalkyl methacrylate copolymer of Example 1, and the maximum spray speed and the shortest coating time were obtained. The water vapor permeability and tensile elongation of the coating composition film were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Examples 8 to 10)
A coating test was conducted in the same manner as in Example 1 except that the mass ratio of PVA and aminoalkyl methacrylate copolymer in Synthesis Example 1 was changed to the ratio shown in Table 2, and the maximum spray speed, the shortest coating time, the coating composition film Water vapor permeability and tensile elongation were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Examples 11 to 12)
The concentration of PVA and aminoalkyl methacrylate copolymer of Synthesis Example 1 (Evonik Degussa, EUDRAGITR EPO), plasticizer (stearic acid, polyethylene glycol 6000) and inorganic compound (talc, titanium oxide) in the proportions shown in Table 2 are 10 A coating test was carried out in the same manner as in Example 1 except that a coating solution of mass% was prepared, and the maximum spray rate, the shortest coating time, the water vapor permeability and the tensile elongation of the coating composition film were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Comparative Example 1)
30 parts by weight of commercially available partly saponified PVA (JP-05 saponification degree: 88.2 mol%, 4% by weight aqueous solution viscosity: 5.3 mPa · s) manufactured by Nippon Vinegar and Poval are added to 270 parts by weight of purified water, 80 The mixture was stirred for 1 hour while warming to ° C., and then stirred while cooling to 30 ° C. to prepare a coating solution (PVA aqueous solution concentration: 10% by mass). Using this coating solution, a coating test was performed on uncoated tablets mainly composed of lactose and corn starch, and the maximum spray speed, the shortest coating time, the water vapor permeability and the tensile elongation of the coating composition film were evaluated. The transparency and supernatant concentration when JP-05 1-propanol used is added are shown in Table 1, the blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Comparative Example 2)
Instead of the PVA resin of Synthesis Example 1, a commercially available partially saponified PVA (JP-05 saponification degree: 88.2 mol%, 4 mass% aqueous solution viscosity: 5.3 mPa · s, manufactured by Nippon Vinegar Poval) was used. Conducted a coating test in the same manner as in Example 1, and evaluated the maximum spray rate, the shortest coating time, the water vapor permeability and the tensile elongation of the coating composition film. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Comparative Example 3)
A coating test was conducted in the same manner as in Example 1 except that the PVA resin in Comparative Synthesis Example 1 was used in place of the PVA resin in Synthesis Example 1, and the maximum spray speed, the shortest coating time, and the water vapor of the coating composition film. Permeability and tensile elongation were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Comparative Examples 4-5)
Instead of the PVA resin of Synthesis Example 1, a commercially available partially saponified PVA (JP-05 saponification degree: 88.2 mol%, 4 mass% aqueous solution viscosity: 5.3 mPa · s, manufactured by Nippon Vinegar Poval) was used. Conducted a coating test in the same manner as in Examples 11 and 12, respectively, to evaluate the maximum spray rate, the shortest coating time, the water vapor transmission rate and the tensile elongation of the coating composition film. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

(Comparative Examples 6-7)
A commercially available partially saponified PVA (JP-05 saponification degree: 88.2 mol%, 4% by weight aqueous solution viscosity: 5.3 mPa · s) and aminoalkyl methacrylate copolymer (Evonik Degussa, EUDRAGITR EPO), A coating test was conducted in the same manner as in Example 1 except that the plasticizer (polyethylene glycol 6000) and the inorganic compound (talc, titanium oxide) were changed to the ratios shown in Table 2, and the maximum spray speed, the shortest coating time, and the coating The water vapor permeability and tensile elongation of the composition film were evaluated. The blending ratio of the coating composition is shown in Table 2, and the results are shown in Table 3.

  As is apparent from Table 3, by combining PVA with a (meth) acrylic polymer such as an aminoacryl methacrylate copolymer or a methacrylic acid copolymer, compared to the case where PVA is used alone as in Comparative Example 1, the humidity condition is high. Underlying water vapor permeability is significantly improved.

  Moreover, in the prescription combining PVA and a (meth) acrylic polymer, as in Examples 1 to 10, PVA having a wide saponification degree distribution of Synthesis Examples 1 to 6 that satisfies the requirements (a-1) and (a-2) By using the resin, compared with the case of using PVA that does not satisfy the requirements (a-1) and (a-2) as in Comparative Examples 2 to 3 (that is, narrow saponification degree distribution), Improves the coating time.

  Further, even in a system using a plasticizer and an inorganic compound as in Examples 11 to 12, the PVA resin having a wide saponification degree distribution of Synthesis Examples 1 to 6 that satisfies the requirements (a-1) and (a-2) By using, compared with the case where PVA with narrow saponification degree distribution like Comparative Examples 4-5 is used, coating time is shortened, and a plasticizer and an inorganic compound are used like Comparative Examples 6-7. Compared to the case where a composition capable of increasing and shortening the coating time was used, it was confirmed that the moisture resistance under high humidity was high and excellent flexibility could be realized.

  The film coating composition of the present invention can be used for pharmaceutical preparations in Japan, the United States, and Europe. Compared with the case where a conventional film coating composition containing PVA is used, adhesion between tablets is less likely to occur, thereby reducing the coating time. Since it can be shortened and a coating film excellent in flexibility and moisture resistance under high humidity can be formed, it is industrially very useful to produce an oral solid preparation using the film coating composition of the present invention. It is.

Claims (8)

It is a film coating composition for oral solid preparations comprising polyvinyl alcohol (a) having an average saponification degree of 85.0 mol% to 89.0 mol% and a (meth) acrylic polymer (b), and the polyvinyl alcohol ( A film coating composition for oral solid preparations, wherein a) is polyvinyl alcohol that satisfies the following requirements (a-1) and (a-2):
Requirement (a-1): 130.0 ml of 1-propanol is added to 100.0 g of a 5.0% by weight aqueous solution of polyvinyl alcohol, and the liquid transparency at 20 ° C. of the liquid obtained by stirring is 50.0%. It is as follows.
Requirement (a-2): A supernatant obtained by adding 230.0 ml of 1-propanol to 100.0 g of a 5.0 mass% polyvinyl alcohol aqueous solution and allowing the stirred solution to stand at 20 ° C. for 24 hours. The concentration of is 0.75% by mass or more.   The (meth) acrylic polymer (b) in the film coating composition contains methyl acrylate / methyl methacrylate copolymer, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid. 2. The film coating composition for oral solid preparation according to claim 1, wherein the film coating composition is one or more selected from Copolymer S, carboxyvinyl polymer, dimethylaminoethyl methacrylate copolymer and polyacrylic acid.   The oral solid according to claim 1 or 2, wherein the mass ratio of the polyvinyl alcohol (a) and the (meth) acrylic polymer (b) in the film coating composition is 90:10 to 60:40. Film coating composition for pharmaceutical preparation.   The mass ratio of the polyvinyl alcohol (a) in the film coating composition is 40% by mass or more, and the mass ratio of the (meth) acrylic polymer (b) is 4% by mass or more and 40% by mass or less. The film coating composition for oral solid preparations of any one of Claims 1-3.   The film coating composition for an oral solid preparation according to any one of claims 1 to 4, further comprising a plasticizer (c).   The film coating for an oral solid preparation according to any one of claims 1 to 5, wherein the viscosity of a 4% by mass aqueous solution of the polyvinyl alcohol (a) is 2.0 mPa · s to 10.0 mPa · s. Composition.   An oral solid preparation, wherein the tablet containing a drug is coated with the film coating composition according to any one of claims 1 to 6.   The process of apply | coating or spraying the aqueous solution and / or aqueous solution containing the film coating composition of any one of Claims 1-6 on the tablet containing a drug, and making the tablet surface coat | cover the said film coating composition. A method for producing an oral solid preparation, comprising: