JP5822758B2 - Fast-dissolving moisture-proof film coating preparation and method for producing the same - Google Patents

Description

  The present invention relates to a film coating solid preparation which is excellent in moisture-proofing effect, exhibits a discoloration suppressing effect of a hydrophilic colored component-containing preparation and retains fast solubility, and a method for producing the same.

  Film coating is widely used for improving the appearance of solid preparations, maintaining the photostability of medicinal ingredients, improving the dosage by bitterness masking, and the like (for example, see Non-Patent Document 1). However, since a fast-dissolving film coating base is generally water-soluble and has low moisture-proof properties, it has been considered difficult to produce a film-coated solid preparation that simultaneously achieves high moisture-proofing properties and fast-dissolving properties. In particular, the conventional fast-dissolving film-coated solid preparation containing a hydrophilic colored component has a problem that a color bleeding phenomenon is observed under humidified conditions (see, for example, Patent Document 1).

  On the other hand, if film coating is performed using a water-insoluble coating base generally used for enteric and sustained release properties, it is considered possible to prepare a film coating solid preparation having a certain degree of moisture resistance. However, since it is a water-insoluble coating component, it is difficult to simultaneously achieve fast solubility in the film-coated solid preparation.

  In recent years, film bases that are said to be excellent in moisture-proofing effects have been marketed. However, the use of a masking agent for masking the color of uncoated tablets, and solid preparations such as tablets in the film coating manufacturing process. In order to improve the fluidity between the powders during the process, and / or the addition of a plasticizer or the like is necessary to improve manufacturability and stability over time, these concealing agents In addition, there is a problem that the moisture resistance is extremely deteriorated by using a lubricant, a plasticizer, and the like (see, for example, Non-Patent Document 2). Therefore, there is a need for a pharmaceutical formulation that has both moisture resistance and practicality such as manufacturability and stability over time.

JP 2007-145717 A

"Formulation Machine Technology Handbook" Formulation Machine Technology Study Group September 1, 2000, pages 175-177 PHARM TECH JAPAN vol. 25 No. 2 (2009) p145-p150

  An object is to provide a film-coated solid preparation that improves the moisture resistance of the solid preparation and maintains fast solubility.

  The present inventors have intensively studied to solve the above problems. As a result, it was found that when a polyvinyl alcohol copolymer is used as a film coating component, a fast-dissolving film coating solid preparation excellent in moisture resistance can be produced. Furthermore, when a polyvinyl alcohol copolymer was used as a film coating agent, a new problem in production due to adhesion between coating solid agents emerged during drying. By adding magnesium stearate as a film coating dispersion component, The present inventors have found that the problems can be solved and completed the present invention by making it possible to ensure the thickness of the film coating in a short time without reducing the spray amount during the coating process.

That is, the present invention provides the following (1) to (11).
(1) A film coating base containing a polyvinyl alcohol copolymer and magnesium stearate.
(2) A film coating solid preparation coated with a film coating base containing a polyvinyl alcohol copolymer and magnesium stearate.
(3) A solid preparation containing (A) and (B).
(A): Inner core solid containing active ingredient and additive (B): Film coating layer covering (A) coated with a film coating base containing polyvinyl alcohol copolymer and magnesium stearate (4) The solid preparation according to any one of (1) to (3), wherein the polyvinyl alcohol copolymer is a polyvinyl alcohol copolymer having a 2% by weight solution at 20 ° C. of 10 to 300 mPa · s.
(5) The solid preparation according to any one of (1) to (3), wherein the polyvinyl alcohol copolymer is a polyvinyl alcohol copolymer having a 2% by weight solution at 20 ° C. of 10 to 250 mPa · s.
(6) The solid preparation according to any one of (3) to (5), wherein the active ingredient is a hydrophilic colored component.
(7) The solid preparation according to any one of (2) to (6), wherein the film coating layer has a thickness of 40 to 400 μm.
(8) The solid preparation according to any one of (2) to (6), wherein the film coating layer has a thickness of 60 to 300 μm.
(9) The solid preparation according to any one of (2) to (8), wherein the solid preparation is a granule or a tablet.
(10) A method for suppressing discoloration of a solid preparation containing a hydrophilic colored component, by employing the solid preparation according to any one of (2) to (9).
(11) The method for producing a solid preparation according to any one of (2) to (9), wherein the production operability is improved, wherein magnesium stearate is added to the film coating base.

  According to the present invention, it is possible to provide a fast-dissolving film-coated solid preparation excellent in moisture-proof effect. Moreover, by being excellent in the moisture-proof effect, discoloration due to moisture absorption of a solid preparation containing a hydrophilic colored component can be suppressed. Furthermore, the effect which improves the manufacture workability | operativity of a film coating is acquired by employ | adopting the film coating base of this invention.

As an example of the film-coated solid preparation of the present invention, a cross-sectional view of a film-coated tablet is shown. It is the figure which showed the moisture-proof effect in the storage period (25 degreeC * 75RH) of the solid formulation of Comparative Examples 1-6 and Examples 1-4 by the time-dependent drying loss (%) of each solid formulation.

  The present invention is described in detail below.

  The “polyvinyl alcohol copolymer” in the present invention can be produced according to the methods described in International Publication Pamphlet 2005/19286 and International Publication Pamphlet 2002/17848, and is partially saponified polyvinyl alcohol having an average degree of polymerization of 100 to 2000. And at least one polymerizable vinyl monomer at a weight ratio of 6: 4 to 9: 1. A 2% by weight solution of the copolymer at 20 ° C. Is a polyvinyl alcohol copolymer having a viscosity of 10 to 300 mPa · s.

  As the polyvinyl alcohol copolymer, a partially saponified polyvinyl alcohol having an average degree of polymerization of 150 to 1000 and at least one “polymerizable vinyl monomer” are preferably copolymerized in a weight ratio of 6: 4 to 9: 1. And a polyvinyl alcohol copolymer having a viscosity of 10 to 250 mPa · s in a 2% by weight solution of the copolymer at 20 ° C.

  Here, as the polymerizable vinyl monomer to be used, acrylic acid, methacrylic acid, Macrogol (registered trademark) and the like are preferable.

  A copolymer of polyvinyl alcohol and polyethylene glycol [Macrogol (registered trademark)] is also preferable as the polyvinyl alcohol copolymer used in the present invention.

  Examples of the polyvinyl alcohol copolymer used in the present invention include trade name: Povacoat (registered trademark) (Daido Kasei Kogyo Co., Ltd., Nisshin Kasei Co., Ltd.), trade name: Kollicoat IR (BASF Japan Co., Ltd.), etc. It is commercially available and can be easily obtained.

  Magnesium stearate in the present invention is listed in the 2007 Pharmaceutical Additives Encyclopedia and can be easily obtained. Magnesium stearate is usually used as an additive for stabilizers, lubricants, brighteners, etc., usually in powder form. For example, it is generally added to a composition before tableting, so Used for the purpose of preventing adhesion. In the present invention, magnesium stearate used for the film coating layer is used as a coating agent.

  The hydrophilic colored component in the present invention means a component having a color used in a pharmaceutical composition. In addition to a component having an original color, the component is colored or colored by humidification or decomposition by humidification. In addition, it also means a component whose content decreases, and in addition to colored medicinal components, formulation additives used for formulation can be mentioned. Here, the formulation additive means a pharmaceutical additive that can be used in a known solid formulation, for example, excipient, binder, disintegrant, disintegration aid, lubricant, fluidizing agent, glossing Agent, foaming agent, moisture-proofing agent, surfactant, stabilizer, emulsifier, antioxidant, filler, preservative, preservative, sweetener, flavoring agent, cooling agent, fragrance, fragrance, colorant, base Agents, coating agents, dragees, plasticizers, dispersants, antifoaming agents and the like.

  The medicinal ingredients that can be classified as the hydrophilic colored component of the present invention include vitamin C and its derivatives and salts thereof such as ascorbic acid, calcium ascorbate, sodium ascorbate and the like; vitamin B1 and its derivatives and salts thereof Vitamin B2 and derivatives thereof and salts thereof such as riboflavin, sodium riboflavin phosphate, riboflavin butyrate and the like; vitamin B12 and derivatives thereof and salts thereof such as cyanocobalamin, hydroxocobalamin hydrochloride, hydroxoacetate Examples include cobalamin, hydroxocobalamin, mecobalamin and the like; ibuprofen; and general herbal ingredients such as carrots. The hydrophilic colored components exemplified here are: 15th revised Japanese Pharmacopoeia, 14th revised Japanese Pharmacopoeia / External Code 2002, OTC Drug Manufacturing (Import) Approval Standard (2000 version), 2007 Pharmaceutical Additives Encyclopedia, And in the 2007 Pharmaceutical Additives Handbook.

  The film coating solid preparation of the present invention comprises (A): an inner core solid containing an active ingredient and an additive, and (B): a film coating base containing a polyvinyl alcohol copolymer and magnesium stearate. It has a coated film coating layer covering (A) and may be produced by a generally used method. That is, when preparing particles containing a hydrophilic colored component, other active ingredients are blended as necessary, and further a formulation additive is added as necessary to form a solid that becomes the core of granules, tablets, etc. Manufacturing. The inner core solid is the granulated granule, the uncoated tablet in which the granule is tableted, or the above-mentioned compound is tableted as it is to form an uncoated tablet, and then the inner core solid is coated with a film coating agent (coat) Can be manufactured. The film coating solid preparation coated (coated) with the inner core solid or film coating agent may be undercoated with other coating agents such as sugar coating.

  The pharmaceutical additives used in the solid preparation of the present invention include pharmaceutically acceptable carriers such as excipients, binders, disintegrating agents, disintegrating aids, lubricants, fluidizing agents, brightening agents, and foaming. Agent, moisture-proofing agent, surfactant, stabilizer, emulsifier, antioxidant, filler, preservative, preservative, sweetener, taste-masking agent, cooling agent, fragrance, fragrance, colorant, base, coating Agents, sugar-coating agents, plasticizers, dispersants, antifoaming agents and the like, and formulation additives that can be used in conventionally known solid formulations can be used for the above purpose.

  The ratio of the polyvinyl alcohol copolymer and magnesium stearate in the film coating solid preparation of the present invention can be used in the range of 1 to 100 parts by weight of polyvinyl alcohol copolymer with respect to 1 part by weight of magnesium stearate. Part by weight is preferable, 1 to 20 parts by weight is more preferable, and 1 to 10 parts by weight is particularly preferable.

  Below, the preferable shape in case the solid formulation of this invention is a tablet is demonstrated.

  The shape of the tablet is not particularly limited. For example, when observed from the top, it is usually a circle, an ellipse, a so-called caplet shape, a rhombus, or the like, and preferably a circle.

  As a preferable shape of the tablet, the cross-sectional view shown in FIG. 1 can be mentioned, and it is composed of an R surface (upper surface or lower surface) and an O surface (side surface or band portion).

  The “diameter” in the tablet is the length from one O plane to the other O plane in the cross-sectional view (1 in FIG. 1). In addition, when the shape of a tablet is not circular, a long diameter can be used, for example. The diameter of the tablet of the present invention is preferably 2 to 15 mm, but is not limited to this range.

  The “curvature radius” in the tablet means the radius of curvature of the R surface indicated by 2 in FIG. However, when the two-stage R tablet or the shape is not circular, the radius of curvature shows a different value at the site on the R plane.

The “film coating layer” in the tablet is the thickness of the O-side film coating.
The thickness of the film coating layer in the tablet is preferably from 40 μm to 400 μm, more preferably from 60 μm to 300 μm.

  The “inner core solid substance” in the tablet is a solid substance before the film coating is applied, and the “plain tablet” is a tablet (an inner core tablet) before the film coating is applied. By applying the film coating layer of the present invention to the inner core tablet, a fast-dissolving film-coated tablet having an excellent moisture-proof effect can be produced. In particular, even when a hydrophilic colored component is contained as an active ingredient in the inner core tablet, a stable preparation in which discoloration of the preparation is suppressed can be produced.

  As a method for evaluating the moisture-proof effect of a film, a cup method based on JIS-Z-0208 is generally known. However, it has been found that the solution used for film coating has a large amount of water-insoluble components dispersed therein, making it difficult to prepare a homogeneous casting film. Therefore, in the present invention, a preparation coated with a film on a placebo tablet (fake tablet) is allowed to stand under abuse conditions of 25 ° C. and 75% relative humidity (25 ° C./75% RH), and the mass increase reaches equilibrium. The moisture-proof effect was simply evaluated using the JIS cup method or the like in the number of days until. The number of days until the mass increase reaches equilibrium is preferably 3 days or more, which is sufficiently preferable as the moisture-proof effect of the tablet, but more preferably 5 days or more. That is, as the moisture resistance of the film-coated solid preparation, if the number of days until the mass increase reaches equilibrium is 3 days or more, and more preferably 5 days or more, it is excellent in substantial moisture resistance in normal use. It can be judged.

  The fast solubility of the film-coated solid preparation of the present invention is evaluated by a disintegration test (test water: water, n = 6) of the solid preparation. As the fast solubility, if the disintegration time of the solid preparation is within 20 minutes, the fast solubility The product was judged to be excellent.

  Hereinafter, the present invention will be described in more detail with reference to examples, comparative examples, and test examples, but the scope of the present invention is not limited thereto.

  Test Example 1: Comparative test of moisture absorption of film-coated tablets (placebo tablets) under humidified conditions

1. Manufacture of tablets (plain tablet 1) Purified maltose 6000.0 g, low-substituted hydroxypropylcellulose 2000.0 g, crystalline cellulose 2000.0 g, magnesium stearate 10.0 g were added and mixed, and the diameter and curvature of 8.5 mm Tableting was performed using an R-faced punch having a radius of 6.8 mm to produce an uncoated tablet 1 having a tablet weight of 280 mg and a thickness of 5.4 mm.

2. Manufacture of test preparations

(Comparative Example 1)
The uncoated tablet 1 was used as a test tablet (placebo tablet).

(Comparative Example 2)
Hypromellose 35.0 g, titanium oxide 10.0 g, and talc 5.0 g were dispersed and dissolved in purified water 315.0 g to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in a coating pan (High Coater Lab; manufactured by Freund Sangyo Co., Ltd.), and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets.

(Comparative Example 3)
A film coating base (trade name: Opadry II85 series) 54.0 g containing a polyvinyl alcohol part saponified product was dispersed and dissolved in 306 g of purified water to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 54 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 32 rpm.

(Comparative Example 4)
Sepifilm (trade name: SEPIFILM LP030) 54.0 g was dispersed and dissolved in 396.0 g of purified water to prepare a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets.

(Comparative Example 5)
50.0 g of aminoalkyl methacrylate copolymer E [Eudragit (registered trademark) EPO], 5.0 g of sodium lauryl sulfate, 7.5 g of stearic acid, and 17.5 g of talc were dispersed and dissolved in 420.0 g of purified water to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets.

(Comparative Example 6)
60.8 g of polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)], 20.3 g of talc, and 20.3 g of titanium oxide were dispersed and dissolved in 698.7 g of 20% ethanol aqueous solution to prepare a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 54 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 32 rpm.

Example 1
Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 151.9 g, magnesium stearate 50.6 g, and titanium oxide 50.6 g were dispersed and dissolved in 20% ethanol aqueous solution 1746.9 g to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 294 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 55 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 32 rpm.

(Example 2)
Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 151.9 g, magnesium stearate 50.6 g, and titanium oxide 50.6 g were dispersed and dissolved in 20% ethanol aqueous solution 1746.9 g to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 55 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 32 rpm.

(Example 3)
Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 151.9 g, magnesium stearate 50.6 g, and titanium oxide 50.6 g were dispersed and dissolved in 20% ethanol aqueous solution 1746.9 g to obtain a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 308 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 55 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 32 rpm.

Example 4
Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 88.8 g, magnesium stearate 53.4 g, and titanium oxide 35.6 g were dispersed and dissolved in 302.2 ethanol aqueous solution 1022.2 g to prepare a coating solution. Uncoated tablet 1 (350 g; about 1250 tablets) was filled in the coating pan, and the coating solution was sprayed to 300 mg per tablet to obtain film-coated tablets. At this time, the tablet product temperature was 55 to 57 ° C., the spray speed was 2 g / min, the spray pressure was 0.12 MPa, and the pan rotation speed was 20 rpm.

3. Test method Regarding the prepared film-coated tablets of Comparative Examples 1 to 6 and Examples 1 to 4, after screening defective tablets (cobbed tablets, adhesive tablets, etc.) by visual inspection, the good products were subjected to loss on drying (80 ° C., 1 hr). , N = 1), and disintegration test (test water: water, n = 6). Further, 50 non-defective tablets were stored for 10 days under the conditions of 25 ° C. and 75% RH (open petri dish), and the tablet mass was appropriately measured. From the obtained results, the weight loss after storage was calculated using the formula (1).

In the above formula, (LOD): loss on drying after storage (%); (LOD _ini ): loss on drying at start (%); W: mass of film-coated tablet after storage (g); W _ini : at start The weight (g) of the film-coated tablet.

  Moreover, the thickness (O surface) of the film coating was evaluated using an average of the number of tests (n = 20) by an image analysis method using a microscope.

  In addition, about the comparative example 3-6 and Example 1-4 which performed film coating with the base of a polyvinyl alcohol type | system | group, evaluation of film coating workability | operativity was evaluated by the following references | standards by three steps.

A: No film coating obstacle. A coated tablet having a uniform film appearance is obtained.
B: There is a film coating failure. In some tablets, adhesion between tablets, bump tablets, and film coating peeling are observed.
C: There is a film coating failure. In most tablets, adhesion between tablets, bumps, and film coating peeling are observed.

  Tables 1 and 3 show the coating base formulations of Comparative Examples 1 to 6 and Examples 1 to 4 and the manufacturing operability at the time of coating, respectively, and disintegration and moisture absorption of Comparative Examples 1 to 6 and Examples 1 to 4 respectively. The test results of the sex are shown in Table 2, Table 4, and FIG.

<Test results>
As shown in Table 4 and FIG. 2, by selecting polyvinyl alcohol copolymer and magnesium stearate as the film coating base, the increase in mass reaches equilibrium even under the abuse condition of 25 ° C. and 75% RH. It has been found that a fast-dissolving film-coated tablet, which takes 5 days or longer to achieve excellent moisture resistance, can be produced with good film coating operability.

Test Example 2: Comparative test with film-coated tablets (vitamin-containing tablets)

2-1. Manufacture of uncoated tablets

(A) Manufacture of uncoated tablet 2 A granules: 4440.5 g of tranexamic acid, 219.1 g of calcium pantothenate, and appropriate amounts of crystalline cellulose are charged and mixed in a fluidized bed granulator and sprayed with an aqueous hydroxypropylcellulose solution as a binder. Granules were produced to make A granules.
B granule: 2588.4 g of ascorbic acid, 2070.8 g of L-cysteine, 51.8 g of pyridoxine hydrochloride and appropriate amount of crystalline cellulose are added to and mixed in a fluidized bed granulator, and sprayed with a hydroxypropylcellulose aqueous solution as a binder for granulation The powder was made into B granules.
Uncoated tablet 2: After 2738.5 g of granulated granule mixed with A granule and B granule, 153.8 g of crystalline cellulose, 76.9 g of croscarmellose sodium, and 30.8 g of magnesium stearate were added and mixed to prepare a mixed powder Tablets were produced, and tablets with a diameter of 9.5 mm, a radius of curvature of 7.6 mm, and a mass of 390 mg were produced as uncoated tablets 2.

(B) Manufacture of uncoated tablet 3 A granule: 3959.9 g of tranexamic acid, 195.4 g of calcium pantothenate, 211.2 g of nicotinamide, and tocopherol acetate (50% spray-dried product) in a fluid bed granulator. The mixture was charged and mixed, and an aqueous hydroxypropylcellulose solution was sprayed to prepare a granulated powder, which was made A granules.
B granule: 2578.2 g of ascorbic acid, 2062.6 g of L-cysteine, 103.1 g of pyridoxine hydrochloride and a suitable amount of crystalline cellulose are added to and mixed in a fluid bed granulator, and an aqueous hydroxypropylcellulose solution is sprayed to produce a granulated powder. B granules were obtained.
Uncoated tablet 3: 150.0 g of crystalline cellulose, 75.0 g of croscarmellose sodium, and 45.0 g of magnesium stearate were mixed with 2730.0 g of granulated granule in which A granule and B granule were mixed. Then, a tablet having a diameter of 8.5 mm, a radius of curvature of 6.8 mm, and a mass of 280 mg was produced as uncoated tablet 3.

2-2. Preparation of film coating solution (1) 90.0 g of hypromellose, 30.0 g of titanium oxide, 15.0 g of talc, and Macrogol 6000 15.0 are dispersed and dissolved in 810.0 g of purified water to form a coating solution (hereinafter referred to as HPMC). did.
(2) Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 60.8 g, talc 20.3 g, and titanium oxide 20.3 g were dispersed and dissolved in 208.7% ethanol aqueous solution 698.7 g to obtain a coating solution (hereinafter referred to as “coating solution”). Copolymer 1).
(3) Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 151.9 g, magnesium stearate 50.6 g, and titanium oxide 50.6 g are dispersed and dissolved in 20% ethanol aqueous solution 1746.9 g to form a coating solution. (Hereinafter referred to as Copolymer 2).
(4) Polyvinyl alcohol copolymer [trade name: Povacoat (registered trademark)] 88.8 g, magnesium stearate 53.4 g, and titanium oxide 35.6 g are dispersed and dissolved in 302.2 ethanol aqueous solution 1022.2 g to form a coating solution. (Hereinafter referred to as Copolymer 3).

2-3. Manufacture of test preparations

(Comparative Example 2-1)
Uncoated tablet 2 was filled in a coating pan and coated with hypromellose film coating solution (HPMC) to 418 mg per tablet. At this time, the thickness (O surface) of the film coating was 63.4 μm.

(Comparative Example 2-2)
The uncoated tablet 3 (unified in Table 5) was filled in the coating pan and coated with a polyvinyl alcohol copolymer film coating solution (copolymer 1) up to 303 mg per tablet. At this time, the thickness (O surface) of the film coating was 77.4 μm.

(Example 2-1)
The uncoated tablet 3 (unified in Table 5) was filled in the coating pan and coated with a polyvinyl alcohol copolymer film coating solution (copolymer 2) up to 303 mg per tablet. At this time, the thickness (O surface) of the film coating was 81.37 μm.

(Example 2-2)
The uncoated tablet 3 (unified in Table 5) was filled in the coating pan and coated with a polyvinyl alcohol copolymer film coating solution (copolymer 3) up to 303 mg per tablet. The thickness (O surface) of the film coating at this time was 77.94 μm.

2-4. Test method 50 tablets of Comparative Examples 2-1 to 2-2 and Examples 2-1 to 2-2 were stored for 4 weeks under conditions of 25 ° C. and 75% RH (opening of petri dish), and the degree of discoloration of the film-coated tablets Evaluated.

(1) Evaluation method The discoloration of the film-coated tablet was evaluated by visual inspection and a color difference meter. Visual evaluation was performed in four stages based on the following criteria for products stored at 5 ° C.

  A: No discoloration, B: Slight discoloration, C: Discoloration, D: Significant discoloration

  Further, the evaluation by the color difference meter was evaluated by calculating the ΔE value when the start time was used as a control with a spectral color meter. (N = 10)

  The thickness of the film coating was evaluated using an average of the number of tests (n = 20) by an image analysis method using a microscope.

4). Test results The results are shown in Table 5. In Example 2-1 (Copolymer 2) and Example 2-1 (Copolymer 3) in which a polyvinyl alcohol copolymer and a film coating base containing magnesium stearate were selected, in humidified conditions Thus, discoloration of the preparation containing a hydrophilic colored component was suppressed.

  A fast-dissolving film coat preparation excellent in moisture resistance and a method for producing the same can be provided.

Claims (9)

A film coating solid preparation containing a hydrophilic colored component coated with a film coating base containing a polyvinyl alcohol copolymer and magnesium stearate. A solid preparation containing (A) and (B).
(A): inner core solid containing hydrophilic colored component and additive (B): film coated with (A) coated with a film coating base containing polyvinyl alcohol copolymer and magnesium stearate Coating layer The solid preparation according to any one of claims 1 to 2 , wherein the polyvinyl alcohol copolymer is a polyvinyl alcohol copolymer having a viscosity of 10 to 300 mPa · s at 2% by weight at 20 ° C. The solid preparation according to any one of claims 1 to 2 , wherein the polyvinyl alcohol copolymer is a polyvinyl alcohol copolymer having a viscosity of 10 to 250 mPa · s at 2% by weight at 20 ° C. The solid formulation of any one of Claims 1-4 whose thickness of a film coating layer is 40-400 micrometers. The solid formulation of any one of Claims 1-4 whose thickness of a film coating layer is 60-300 micrometers. The solid preparation according to any one of claims 1 to 6 , wherein the solid preparation is a granule or a tablet. The discoloration suppression method of the solid formulation by employ | adopting the solid formulation of any one of Claims 1-7 . The manufacturing method of the solid formulation of any one of Claims 1-7 which improved manufacturing operativity characterized by adding magnesium stearate to a film coating base material.