JP7072373B2 - Film coating compositions and solids - Google Patents

Description

The present invention relates to a film coating composition and a solid preparation coated with the film coating composition.

Sugar coating protects solid core materials such as uncoated tablets from the surrounding atmosphere such as light and humidity, masks the bitterness, odor, irritation, etc. of the core material to make it easier to ingest orally, and makes it glossy. It has been applied in the past for the purpose of increasing the commercial value from the viewpoint of aesthetics. At that time, in order to reduce the influence of the moisture contained in the sugar coating liquid on the core material, film coating was appropriately performed as a pretreatment depending on the type of the core material.

Therefore, since it takes a lot of time and labor to apply the sugar coating, the manufacturing cost is high, and recently, the physical properties of the film coating itself have been improved, so that the sugar coating is relatively used. Attempts are being sought to replace film coating, which is a simple method.
However, there is still room for improvement in terms of manufacturability, glossiness, and the like.

For example, in Patent Document 1, it is proposed to spray water on a film-coated tablet as a post-treatment, and in Patent Document 2, a meltable substance that contributes to improving glossiness is used as a film coating agent, and an uncoated tablet is used as its melting point. It has been proposed that the film is heated and then brought into contact with each other, but all of these methods are required to carry out complicated work under harsh conditions, and the film coating has on the sugar coating. The superiority that had been there will be reduced.
Further, Patent Documents 3 and 4 propose to contain a substance that contributes to improving the glossiness of the film coating composition, but the substance is polyethylene glycol or talc, which are raw materials for pharmaceutical products, and is used for foods. Cannot be used.
Patent Document 5 proposes to give gloss by using glass flakes as a base, but gloss can be obtained by a combination of an additive having a specific shape other than glass flakes and other additives. Is not suggested.
Patent Document 6 proposes to impart luster by blending a water-soluble polysaccharide and talc in a fixed ratio, but since the ratio of the water-soluble polysaccharide having a film-forming ability is small, the film coat is applied. However, it was found that this composition inevitably requires delicate handling at the time of manufacture.

Japanese Unexamined Patent Publication No. 2013-087056 WO2008 / 136380 Japanese Unexamined Patent Publication No. 2012-21101 Japanese Unexamined Patent Publication No. 2013-09730 Japanese Unexamined Patent Publication No. 2004-292816 Japanese Unexamined Patent Publication No. 2012-21101

The present invention has been made by paying attention to the above-mentioned conventional problems, and the composition is composed of only the materials treated as food raw materials and food additives, and the same simple film coating method as the conventional method is used. It is an object of the present invention to provide a novel and useful composition for film coating, which can impart sufficient gloss to a solid preparation, particularly a tablet, only by coating.

As a result of diligent studies to solve the above problems, the present inventors have obtained results.
(1) The glossiness can be enhanced by smoothing the unevenness of the surface of the coated film layer by the plastic flow during drying.
(2) Even if the composition is composed only of food raw materials and food additives, if it is a specific composition, the above plastic flow can be realized.
(3) In the usual film coating method, the tablets dry while rubbing against each other, but the rubbing naturally promotes the above-mentioned plastic flow.
(4) The present invention has been made by finding that an inorganic substance having a flat surface tends to be aligned with the flat surface facing the film surface under the above plastic flow and is useful as a brightener.

In addition, the solid preparation is easy to administer and does not cause pain, and the bitterness can be improved by film coating as described above, but compounds whose medicinal effects have recently been recognized are often poorly water-soluble. .. Therefore, it is required to improve the solubility in water without adversely affecting the medicinal effect.
The present inventors have also found that, in the above-mentioned test focusing on the improvement of glossiness, the solubility in water is unexpectedly improved when the influence on the core material is confirmed. Moreover, even if the above-mentioned inorganic substances are blended, no substantial adverse effect occurs.
Therefore, the present invention can be positively used for the purpose of improving the solubility of a poorly water-soluble component in water as well as the glossiness.

The composition for film coating of the present invention is edible, has a water-soluble polymer as a base, and contains an emulsifier having a melting point of 40 to 70 ° C. and an inorganic substance having a flat surface.
Preferably, the water-soluble polymer is hydroxypropylmethyl cellulose, hydroxypropyl cellulose, or polyvinylpyrrolidone.
Preferably, the emulsifier is blended in the range of 30 to 100 parts by mass with respect to 100 parts by mass of the base.
Preferably, the emulsifier is a fatty acid ester.
More preferably, the inorganic substance is a edible food containing calcium carbonate or magnesium carbonate as a constituent.
Most preferably, the edible material is pearl powder, eggshell powder, unbaked calcium shell, limestone or dolomine.

The solid core material to be coated can positively contain a poorly water-soluble component.
Preferably, the poorly water-soluble component is selected from Huperidin A, curcuminoid, resveratrol, shogaol, gingerol, hesperidin, nobiletin, sesamin, β-cryptoxanthin, coenzyme _Q10 , astaxanthin, zeaxanthin, lutein and kelcetin. It consists of one or a combination of two or more.

The components listed as sparingly water-soluble components refer to those having a solubility of "difficult to dissolve" to "almost insoluble" in the Japanese Pharmacopoeia. This refers to a component in which the amount of water required to dissolve 1 g of the solute is 100 mL or more, that is, the solubility in water is 10,000 ppm or less. Solubility in water is 2690 ppm for hesperidin, 1-300 ppm for hesperidin, huperzine A, curcuminoid, resveratrol, shogaol, gingerol, nobiletin, sesamin, kelcetin, β-cryptoxanthin, coenzyme _Q10 , Astaxanthin, zeaxanthin and lutein are 1 ppm or less.

According to the composition for film coating of the present invention, it is possible to impart excellent gloss to the solid preparation by simply coating the solid core material with the same film coating method as before using the existing coating apparatus. can.
In particular, in the case of tablets, the glossiness and the solubility of the contained poorly water-soluble component in water can be effectively increased.

It is a change image figure under the solidification progress of a film layer in this invention. It is a test result diagram of Example 2. It is a test result diagram of Example 2. It is a test result diagram of Example 2. It is an SEM image of freshwater pearl powder (calcium carbonate). It is an SEM image of calhope (egg shell powder). It is an SEM image of Sunmag Kyowa (magnesium oxide). It is an SEM image of fluorite (calcium silicate).

(Composition for film coating)
The base is a water-soluble polymer, which has been conventionally used for film coating, and can be used in the present invention. Hydroxypropyl cellulose (HPC) and polyvinylpyrrolidone (PVP) are more preferable.
Commercially available products including the above can be used. For example, "Metro's SE-06" (Shin-Etsu Chemical Co., Ltd.) for HPMC and "Selney SL" (Nippon Soda Co., Ltd.) for HPC can be mentioned.

An emulsifier is added to the above base. This emulsifier is solid at room temperature and has a melting point of 40 to 70 ° C, preferably 50 to 60 ° C. Within this melting point range, the plastic flow of the film layer adhering to the surface of the core material is naturally promoted during the drying process while being rubbed according to the conventional film coating method.
Applicable are fatty acid esters.
Examples of the fatty acid ester include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, and polyglycerin fatty acid ester.

Commercially available products including the above can be used.
For example, as the glycerin fatty acid ester, "Poem S-100 (normal temperature: solid powder, melting point: about 67 ° C., HLB: 4.3)" (RIKEN Vitamin Co., Ltd.), "Poem J-2081V (normal temperature: solid granules, Melting point: about 62 ° C, HLB: 6) "(RIKEN Vitamin Co., Ltd.)," Poem W-60 (normal temperature: solid flakes, melting point: about 45 ° C, HLB: 9.5) "(RIKEN Vitamin Co., Ltd.), "Poem DP-95RF (normal temperature: solid beads, melting point: about 67 ° C, HLB: 8)" (RIKEN Vitamin Co., Ltd.), "Ryoto Polyglycerate S-28D (normal temperature: solid powder, melting point: about 59 ° C,) HLB: 9) ”(Mitsubishi Chemical Foods Co., Ltd.).
As sucrose fatty acid esters, "Ryoto Sugar Ester S-370F (normal temperature: solid powder, melting point: about 58 ° C, HLB: 3)" (Mitsubishi Chemical Foods Co., Ltd.), "Ryoto Sugar Ester S-1670 (normal temperature) : Solid powder, melting point: about 60 ° C, HLB: 16) "(Mitsubishi Chemical Foods Co., Ltd.)," Ryoto Sugar Ester L-1695 (normal temperature: solid powder, melting point: about 47 ° C, HLB: 16) "(Mitsubishi Chemical Foods Co., Ltd.).

When the solid core material contains a poorly water-soluble component and it is desired to increase its solubility in water, the emulsifier is preferably HLB: 6 or more, more preferably HLB: 9 or more, and more preferably HLB: 16 or more. More preferred.

It is preferable to add the emulsifier in the range of 30 to 100 parts by mass with respect to 100 parts by mass of the base. More preferably, it is blended in the range of 50 to 70 parts by mass of the emulsifier with respect to 100 parts by mass of the base.
This is because glossiness is significantly exhibited at 30 parts by mass or more, while glossiness tends to decrease when it exceeds 100 parts by mass.

Further, it is presumed that the poorly water-soluble component contained in the solid core material is emulsified by an emulsifier to increase its solubility in water. If only the emulsifier is used, the size of the formulation becomes large, but the emulsion stabilizing effect of the water-soluble polymer is conveniently exhibited, so that the formulation can be made in the same size as the conventional one. The compounding range in which the improvement in solubility is significantly exhibited also overlaps with the above range in which the glossiness is significantly exhibited, and both effects can be enjoyed at the same time.

When the coating composition is blended into the core material, chemical interaction occurs with other blending ingredients, the blending amount of other blending ingredients is limited due to size limitation, and obstacles during formulation processing. For example, segregation of components, tablet sticking, tableting problems such as capping and lamination may be caused, and further processing processes such as granulation process may be required. May reduce the degree.
Thus, in the present invention, all the components that improve the solubility of the poorly water-soluble component in water can be contained in the film coating, and the same effect as when blended in the core material can be confirmed.

It is preferable to add an inorganic substance having an edible flat surface as a brightener to this.
It is presumed that this inorganic substance is embedded in the film layer, and the plane faces the surface side of the film layer, thereby promoting specular reflection of light that has passed through the surface of the film layer and entered the layer. ..
Therefore, as long as it has a certain plane, it is considered to be applicable even if it has an amorphous shape. The degree is a size that closes the unevenness of the surface of the core material, for example, the uncoated tablet, and examples thereof include calcium carbonate and magnesium carbonate classified as food additives.
Not limited to those produced by chemical synthetic reactions, but those that meet the ingredient specifications of food additives, such as dolomite, freshwater pearls, scallop shells (unbaked calcium), eggshells, limestone, and other natural minerals are crushed into powder. Also applicable are those in the form of particles. All of these have different sizes, but the outer surface contains a "plane", and the larger ones are scaly.

Commercially available products including the above can be used. For example, Dolomite (Kyowa Hakko Bio Co., Ltd.), Freshwater Pearl Powder (Nakahara Co., Ltd.), Scallop Pearl Powder (Kyowa Hakko Bio Co., Ltd.), Calhope (Eggshell, Cupy Co., Ltd.), Special Grade Mamakarso (Natural Minerals, Nitto Flour Chemical Industry Co., Ltd.) Co., Ltd.). As shown in FIG. 1, these have an appropriate particle size (median diameter), and all have a flat surface.
Of these, scallop pearl powder (Kyowa Hakko Bio Co., Ltd.), Calhope (egg shell, Kewpie Co., Ltd.), and special grade Mamakarso (natural mineral, Nitto Flourka Industry Co., Ltd.) have a scaly particle shape. It is easier to arrange smoothly in the coating layer.
In addition, Sunmag Kyowa (Kyowa Hakko Bio Co., Ltd.) and Florite (Tomita Pharmaceutical Co., Ltd.) do not usually have a "plane" as defined in the present invention.
These shapes can be confirmed by the SEM images shown in FIGS. 5 to 8.

It is preferable to mix in the range of 50 to 300 parts by mass of the inorganic substance with respect to 100 parts by mass of the base. More preferably, it is blended in the range of 130 to 240 parts by mass of the inorganic substance with respect to 100 parts by mass of the base.
This is because the glossiness is significantly exhibited when the amount exceeds 50 parts by mass, while the glossiness tends to decrease when the amount exceeds 300 parts by mass.

Other additives, for example, a colorant, can be contained in an appropriate amount, and can be positively colored.
Examples of the colorant include edible red No. 3, edible yellow No. 1, edible yellow No. 5, and sodium riboflavin phosphate.

In the present invention, the composition for film coating is configured as described above, and is dissolved or dispersed in a solvent to prepare a coating liquid for film coating.
The solvent is water, and it is preferable to appropriately use a solvent that easily dissolves an organic substance such as ethanol.
When the solid preparation is sized for normal ingestion, the content of the composition is in the range of 1 to 20% by mass with respect to 100% by mass of the solid core material, as in the normal film coating method. It is preferably in the range of 2 to 15% by mass, and particularly preferably 3 to 10% by mass. Although it is possible to impart glossiness even if it exceeds 20% by mass, it puts pressure on productivity and cost. In particular, when a poorly water-soluble component is added to the solid core material, it is preferably set to 3% by mass or more in order to significantly improve the solubility in water.

The solid core material to be covered is not particularly limited, but in the present invention, an uncoated tablet is mainly assumed. The uncoated tablet is formed by a conventional method by appropriately including excipients, fragrances, etc. in addition to the raw materials forming the active ingredient.

The film coating method used in the present invention is not a special one, and a fixed method can be used as it is.
However, in order to promote drying under rubbing against the coating liquid placed on the surface of the solid core material, it is preferable to use a pan-type coating device capable of spraying the coating liquid while rolling the core material, for example. If "HICOATER" (Freund Sangyo Co., Ltd.) is used, the film coating process can be carried out comfortably.

FIG. 1 is an image diagram of changes in the film layer due to the progress of the film coating process. As shown in this figure, the unevenness of the surface of the film layer F changes smoothly due to rubbing, and at the same time, the flat surface S of the inorganic substance P also aligns so as to face the surface of the film layer F.
It should be noted that the inorganic substance P is exaggeratedly drawn in the shape of an ingot having an extremely large and large flat surface S so that it can be easily visually recognized. Further, the unevenness of the surface of the unlocked lock T, which is the core material, is also exaggerated. The alignment is also exaggerated.
In the finished tablet, as shown in the reflection image diagram, the surface of the film layer F becomes smooth, so that the reflection there becomes specular reflection and the glossiness is improved. Further, since the coating liquid solidifies into an amorphous state, the film layer F has a transparent feeling, and light has been easily transmitted through the film layer in the past, but the light entering the film layer F is an aligned inorganic substance P. Specular reflection is performed on the plane S of the above surface, and the glossiness is excellent.

<< Example 1 >>
(Manufacturing of manufacturing examples)
Using crystalline cellulose (VIVAPUR102, JRS PHARM) 480 g, maltitol (Amarti MR-50, Mitsubishi Shoji Food Tech) 480 g, fine silicon dioxide (Silo Page 720, Fuji Silysia Chemical) 10 g, and calcium stearate (Taipei Chemical Industry) 30 g. To make a mixed powder for tableting, use a rotary tableting machine (Pegasus 1024AHUK-AWCZ type tableting machine, Kikusui Seisakusho) to tablet with a 9 mmφ mill to a mass of 300 mg per tablet. I got a lock.
Next, a composition containing various materials in various composition ratios was dissolved and suspended in a mixed solution of purified water and ethanol to obtain 500 g of a coating solution.
Next, 1000 g of the uncoated tablet was placed in a coating machine (HICOATER HCT-30, Freund Sangyo) so that the mass increase per uncoated tablet was 10 mg (3.33% by mass with respect to 100% by mass of the solid core material). The coating was performed to obtain a film-coated tablet having a mass of 310 mg per tablet.

(Manufacturing of comparative examples)
As a comparative example, a film-coated tablet was obtained in the same manner for a composition containing an unsuitable emulsifier and a composition containing an inorganic substance having no flat surface.
(Manufacturing of control example)
As a control example, 18 g of HPMC, 10.5 g of polyethylene glycol and 34.5 g of talc were similarly dissolved and suspended in a solvent to obtain 500 g of a coating liquid. Then, a film-coated lock was obtained in the same manner.

(evaluation)
The coating gloss was visually evaluated and the results were classified.
△: Improved gloss ○: Equivalent to the one using the film coating agent using polyethylene glycol and talc ◎: More than the one using the film coating agent using polyethylene glycol and talc together

<< Example 2 >>
[Preparation of tablets]
(Preparation of tablet 1)
Using 300 g of curcumin powder, 1500 g of cornstarch, 1170 g of crystalline cellulose, and 30 g of calcium stearate, the same treatment as in Example 1 was performed to obtain a 9 mm φ300 mg tablet.
(Preparation of tablet 2)
Using 112 g of sesamin powder, 1500 g of cornstarch, 1358 g of crystalline cellulose and 30 g of calcium stearate, the same treatment as in Tablet 1 above was performed to obtain a 9 mm φ300 mg tablet.

[Preparation of coating liquid]
(Preparation of coating liquid 1 (manufacturing example))
Metrose SE-06 36 g, Ryoto Sugar Ester L-1695 (HLB16) 21 g, and Calhope 69 g were dissolved and suspended in a mixed solution of 600 g of water and 274 g of ethanol to obtain 1000 g of a coating solution.
(Preparation of coating liquid 2 (manufacturing example))
The treatment was carried out in the same manner as in Coating Liquid 1 except that Ryoto Sugar Ester L-1695 (HLB16) was changed to Poem J-2081V (HLB6) to obtain a coating liquid.
(Preparation of coating liquid 3 (production example))
A coating liquid was obtained by treating in the same manner as in the coating liquid 1 except that the Ryoto sugar ester L-1695 (HLB16) was changed to the Ryoto polyglycerate S-28D (HLB9).
(Preparation of coating liquid 4 (comparative example))
36 g of Metrose SE-06 was dissolved and suspended in a mixed solution of 300 g of water and 114 g of ethanol to obtain 500 g of a coating solution.

[Making film-coated locks]
(Manufacturing of film-coated lock 1 (manufacturing example))
Using 1000 g of tablets 1 and coating liquid 1, 10 mg per tablet was coated with a coating machine (HICOATER HCT-30, Freund Industries) to obtain film-coated tablets.
(Manufacturing of film-coated lock 2 (manufacturing example))
A film-coated tablet was obtained by treating in the same manner as the film-coated tablet 1 except that each tablet was coated with 100 mg.
(Manufacturing of film-coated lock 3 (manufacturing example))
A film-coated tablet was obtained by treating in the same manner as the film-coated tablet 1 except that each tablet was coated with 300 mg.

(Manufacturing of film-coated lock 4 (manufacturing example))
A film-coated tablet was obtained by coating 10 mg per tablet in the same manner as the film-coated tablet 1 except that the coating liquid 2 was used instead of the coating liquid 1.
(Manufacturing of film-coated lock 5 (manufacturing example))
A film-coated tablet was obtained by coating 10 mg per tablet in the same manner as the film-coated tablet 1 except that the coating liquid 3 was used instead of the coating liquid 1.

(Preparation of film-coated lock 6 (comparative example))
A film-coated tablet was obtained by coating 10 mg per tablet in the same manner as the film-coated tablet 1 except that the coating liquid 4 was used instead of the coating liquid 1.

(Manufacturing of film-coated tablet 7 (manufacturing example))
Using 1000 g of tablets 2 and coating liquid 1, 10 mg of each tablet was coated with a coating machine (HICOATER HCT-30, Freund Industries) to obtain a film-coated tablet.
(Manufacturing of film-coated lock 8 (manufacturing example))
A film-coated tablet was obtained by coating 10 mg per tablet in the same manner as the film-coated tablet 7 except that the coating liquid 3 was used instead of the coating liquid 1.

(Preparation of film-coated tablet 9 (comparative example))
A film-coated tablet was obtained by coating 10 mg per tablet in the same manner as the film-coated tablet 7 except that the coating liquid 4 was used instead of the coating liquid 1.

[Elution test 1]
The test solution was subjected to an elution test on film-coated tablets 1 to 6 at 900 mL (37 ° C.) of water and a paddle rotation speed of 50 rpm.
About 1 mL of the test solution was collected at sampling points 0, 30, 60, and 120 minutes, and the solution filtered through a 0.2 μm PTFE filter with a pore size was measured for solubility by HPLC (high performance liquid chromatography).
[Analytical test condition 1]
High Performance Liquid Chromatograph: Shimadzu Prominence
Detector: Ultraviolet absorptiometer (measurement wavelength: 245 nm)
Column: YMC Triart C18 (5 μm, 12 nm)
150 × 4.6 mm I. D.
Column temperature: 40 ° C
Mobile phase: water / acetonitrile / acetic acid = 56/43/1
Flow velocity: 1.4 mL / min
Injection volume: 50 μL

[Elution test 2]
The test solution was subjected to an elution test on film-coated tablets 7 to 9 at 900 mL (37 ° C.) of water and a paddle rotation speed of 50 rpm.
Approximately 1 mL of the test solution was sampled at sampling points 0, 30, 60, and 120 minutes, and the solution filtered through a 0.45 μm PTFE filter with a pore size was measured for solubility by HPLC.
[Analytical test condition 2]
High Performance Liquid Chromatograph: Shimadzu Prominence
Detector: Ultraviolet absorptiometer (measurement wavelength: 285 nm)
Column: COSMOSIL Packed Volume
5C18-AR 4.6 x 150 mm (Nacalai Tesque)
Column temperature: 40 ° C
Mobile phase: Methanol / water = 80/20
Flow velocity: 1.5 mL / min
Injection volume: 10 μL

(evaluation)
The solubility of the poorly water-soluble component in water is shown in FIGS. 2 to 4.
In each case, it was confirmed that the solid preparation (production example) of the present invention had improved solubility.

Claims (9)

A water-soluble polymer is used as a base, and an emulsifier having a melting point of 40 to 70 ° C. and an inorganic substance having a flat surface are blended.
The emulsifier is a fatty acid ester,
A composition for film coating of an edible solid preparation, wherein the inorganic substance is edible containing calcium carbonate or magnesium carbonate as a constituent. In the film coating composition according to claim 1,
A composition for film coating, wherein the emulsifier is blended in the range of 30 to 100 parts by mass with respect to 100 parts by mass of the base. In the film coating composition according to claim 1 or 2.
A composition for film coating, wherein the water-soluble polymer is hydroxypropylmethyl cellulose, hydroxypropyl cellulose, or polyvinylpyrrolidone. In the film coating composition according to any one of claims 1 to 3.
A composition for film coating, wherein the fatty acid ester is a glycerin fatty acid ester, a sucrose fatty acid ester, a sorbitan fatty acid ester, a propylene glycol fatty acid ester, or a polyglycerin fatty acid ester . In the film coating composition according to any one of claims 1 to 4.
A composition for film coating, characterized in that the edible material is pearl powder, eggshell powder, unbaked calcium shell, limestone, or dolomite . A solid preparation obtained by coating a solid core material with the film coating composition according to any one of claims 1 to 5 by a film coating method . The solid preparation according to claim 6, wherein the dosage form is a tablet . In the solid formulation according to claim 6 or 7.
A solid preparation characterized by containing a poorly water-soluble component in the solid core material . In the solid preparation according to claim 8,
One of the poorly water-soluble components selected from Huperidin A, curcuminoid, resveratrol, shogaol, gingerol, hesperidin, nobiletin, sesamin, β-cryptoxanthin, coenzyme Q10, _astaxanthin , zeaxanthin, lutein, and kelcetin. A solid preparation comprising a combination of two or more .

Images