JP2020132600A - Film-coated tablet and manufacturing method thereof - Google Patents

Abstract

To provide tablets coated with a film coating composition having good ink fixability, and to provide a method for manufacturing thereof.SOLUTION: This tablet contains a plain tablet containing medicinal ingredients, a coating layer containing a macromolecule having a vinyl alcohol unit in the main or side chain, and an ink deposited on the coating layer. The macromolecule can be selected from polyvinyl alcohol, partially saponified polyvinyl acetate, polyvinyl alcohol polyethylene glycol graft copolymer, and polyvinyl alcohol acrylic acid methyl methacrylate copolymer.SELECTED DRAWING: Figure 1

Description

One of the embodiments of the present invention relates to a tablet coated with a composition for film coating and a method for producing the same. For example, one embodiment of the present invention relates to a tablet coated with a film coating composition having good ink fixability and a method for producing the same.

In recent years, in order to improve the compliance of pharmaceutical products and prevent medical malpractice, tablets in which information such as the name of the medicinal ingredient and its content are directly displayed on the surface have been widely used. Examples of the method of displaying information on the surface of the tablet include laser printing and ink printing. In the former, printing is performed by discoloring the tablet surface with a laser. On the other hand, in the latter case, printing is performed by applying ink to the tablet surface by using an inkjet method or the like. In general, ink printing is superior to laser printing in that visibility and ink color can be adjusted. Patent Document 1 discloses a method of performing ink printing on an uncoated tablet composed of granules containing an active ingredient and an excipient. Further, Patent Document 2 discloses a method of performing ink printing on a film-coated tablet using hydroxypropyl cellulose or hydroxypropyl methyl cellulose as a film coating composition.

The tablet to which the ink is applied may be an uncoated tablet as in Patent Document 1 or a film-coated tablet as in Patent Document 2, but in either tablet, the ink is sufficient on the tablet surface. If the ink is not fixed to the ink, problems such as rubbing and bleeding of the print may occur due to an external impact. For example, when tablets are stored, the tablets may come into close contact with each other, causing ink to transfer from the printed surface and stain the tablets. In addition, when taking tablets, it is conceivable that the printed surface is touched with a finger, but the printed surface may be lost due to oil content of the finger or the like. In order to solve the above problem, it is conceivable to coat the tablet surface with a film coating composition having particularly good ink fixability and then perform ink printing. However, until now, film coating having good ink fixability has been performed. The composition for use has not been established.

Japanese Unexamined Patent Publication No. 2014-114280 Japanese Unexamined Patent Publication No. 2015-218268

One of the objects of the embodiment of the present invention is to provide a tablet coated with a composition for film coating and a method for producing the same. For example, one of the embodiments according to the present invention is to provide a tablet coated with a film coating composition having good ink fixability, and a method for producing the same.

One of the embodiments according to the present invention is an ink-printed film-coated tablet. This tablet contains an uncoated tablet containing a medicinal ingredient, a coating layer containing a polymer which coats the uncoated tablet and has a vinyl alcohol unit in the main chain or side chain, and an ink adhered on the coating layer.

One of the embodiments according to the present invention is a method for producing an ink-printed film-coated tablet. The method comprises coating the uncoated tablet with a coating layer containing a polymer having a vinyl alcohol unit in the main chain or side chain, and printing on the coating layer with ink.

The polymer can be selected from polyvinyl alcohol, partially saponified polyvinyl acetate, polyvinyl alcohol / polyethylene glycol / graft copolymer, and partially saponified vinyl acetate / acrylic acid / methacrylic acid ester copolymer. The coating layer may further contain a plasticizer. The plasticizer may be polyethylene glycol. Coating with a coating layer can be performed by coating a single uncoated tablet with a coating layer.

According to an embodiment of the present invention, it is possible to provide a tablet coated with a film coating composition having good ink fixability and a method for producing the same.

Schematic perspective view and sectional view of the tablet according to one of the embodiments of the present invention.

Hereinafter, each embodiment of the present invention will be described with reference to the drawings and the like. In order to clarify the explanation, the drawings may schematically represent the width, thickness, shape, etc. of each part as compared with the actual embodiment, but this is merely an example and the interpretation of the present invention is limited. It is not something to do.

1. 1. Tablets A schematic perspective view and a cross-sectional view of the tablet 100, which is one of the embodiments of the present invention, are shown in FIGS. 1 (A) and 1 (B), respectively. As shown in these figures, the tablet 100 has an uncoated tablet 102 and a coating layer 104 that covers the entire surface of the uncoated tablet 102, and further contains an ink 106 adhering to the surface of the coating layer 104. The ink 106 is attached to the surface of the coating layer 104 by printing in a manner representing information about the tablet 100 (information such as medicinal properties, dosage, number of doses, etc.). The shape of the tablet 100 is not limited, and the tablet 100 can take various shapes such as a columnar shape, a spherical shape, and an elliptical spherical shape.

The uncoated tablet 102 contains one or more kinds of a drug that functions as a medicinal ingredient and an excipient for giving the uncoated tablet 102 a certain shape.
The tablet 100 can contain a single uncoated tablet 102 in one coating layer 104. In other words, the tablet 100 may be configured to consist of a single uncoated tablet 102 and a coating layer 104 covering it. The uncoated tablet 102 may be a multi-layer tablet having two or more layers or a nucleated tablet.

There is no limitation on the type of the drug, and the drug is appropriately selected depending on the intended use of the tablet 100.

Excipients include, for example, lactose hydrate, sucrose, maltose, fructose, glucose, maltose, trehalose, dextrin, saccharides such as purulan, sugar alcohols such as mannitol, martitol, sorbitol, xylitol, erythritol, and lactitol, starch, Starches such as pregelatinized starch and partially pregelatinized starch, celluloses such as hydroxypropyl cellulose, hypromellose, ethyl cellulose, carmellose, crystalline cellulose, light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, magnesium aluminometasilicate. , Anhydrous calcium hydrogen phosphate, calcium carbonate, calcium sulfate and other inorganic compounds. All or part of these materials function not only as excipients but also as binders and disintegrants. Therefore, it can be recognized that the uncoated tablet 102 contains a binder, a disintegrant, and the like in addition to the drug and the excipient.

The uncoated tablet 102 may contain a lubricant, a colorant, or the like in addition to the drug or excipient. Examples of the lubricant include talc, starch, magnesium stearate, calcium stearate, sodium stearyl fumarate, boric acid, paraffin, cocoa butter, polyethylene glycol, leucine, sodium benzoate and the like. Examples of the colorant include iron oxide called iron sesquioxide and yellow iron sesquioxide, and tar pigments.

The coating layer 104 can contain polyvinyl alcohol or a derivative thereof as a base material. Polyvinyl alcohol and its derivatives are polymers containing vinyl alcohol as a basic repeating unit (monomer unit) in the main chain or side chain. Specifically, not only polyvinyl alcohol, but also partially saponified polyvinyl acetate, polyvinyl alcohol, etc. Examples thereof include a polyethylene glycol graft copolymer, a partially saponified vinyl acetate, an acrylic acid, and a methacrylic acid ester copolymer. In the case of a partially saponified polymer, the saponification rate (number of vinyl alcohol units / (total number of vinyl alcohol units and vinyl acetate units)) is 30% or more and less than 100%, 40% or more and 95% or less, or 50% or more. It may be 90% or less. Since these polymers have hydroxyl groups, which are highly polar groups capable of hydrogen bonding, on the main chain or side chains and have a large number of hydroxyl groups per unit weight, the ink adhered to the surface of the coating layer 104. A strong bond can be formed with 106. Therefore, the fixability of the ink 106 is high, and when the information on the medicinal ingredient is printed on the tablet 100 using the ink 106, the ink 106 bleeds on the surface of the tablet 100, the ink 106 is repelled, or the color of the ink 106 It is possible to prevent the occurrence of unevenness. This contributes to clearly printing information on the coating layer 104. Further, even if a finger or a hand touches the tablet 100 or the tablets 100 come into contact with each other, the information printed using the ink 106 is not lost, and the information can be stably stored for a long period of time. ..

The coating layer 104 may further contain a plasticizer. Examples of the plasticizer include low molecular weight compounds such as triethyl citrate, glycerin fatty acid ester, triacetin, propylene glycol, and glycerin monostearate, and polymers such as polyethylene glycol, polypropylene glycol, and a copolymer of ethylene glycol and lactide. Be done. In particular, by adding polyethylene glycol, the coating layer 104 can be uniformly formed on the uncoated tablet 102, and as a result, the ink 106 is evenly and uniformly adhered to the surface of the coating layer 104.

The coating layer 104 may further contain a metal oxide such as iron oxide or titanium oxide as a colorant in an arbitrary configuration.

The ink 106 may be either a dye or a pigment as long as it can be used as a pharmaceutical product. For example, natural dyes such as caramel dyes, anthocyanin dyes, flavonoid dyes, Monascus purpureu dyes, and gardenia dyes can be used. Alternatively, an inorganic compound such as iron oxide or titanium dioxide may be used.

Conventionally, when information is printed on the coating layer 104 using ink, the coating layer covering the uncoated tablet has a low affinity with the ink, so that clear printing cannot be performed or the adhered ink often disappears.

However, as described above, since the coating layer 104 of the tablet 100 has a high density hydroxyl group on the main chain or the side chain, a strong bond can be formed with the ink 106. Therefore, it is possible to clearly display the information on the tablet and maintain the information stably for a long period of time. Further, by adding the plasticizer exemplified by polyethylene glycol to the coating layer 104, coating becomes easy and the coating layer 104 having high uniformity can be formed. From the above, by applying the present embodiment, it is possible to supply a film-coated tablet having good ink fixability, effectively prevent accidental ingestion of a drug, or improve administration compliance.

2. 2. Method for producing tablets The method for producing tablets 100 will be described below.

First, the drug and the excipient are mixed. At this time, a disintegrant, a binder, a colorant, a lubricant and the like may be mixed at the same time. Then, the mixture is compression-molded (locked) to obtain an uncoated tablet 102.

Next, a solution containing a base material or a dispersion liquid (hereinafter, generally referred to as a coating composition) is prepared and applied to the surface of the uncoated tablet 102 obtained by compression molding. Examples of the solvent in the coating composition include water, alcohols such as ethanol and ethylene glycol, and mixed solvents of water and alcohol. The coating composition can be applied by a spray coating method in which the coating composition is sprayed onto the uncoated tablet 102. After that, the coating layer 104 is formed by distilling off the solvent remaining in the coating layer 104 formed on the uncoated tablet 102. The drug is coated by the coating layer 104.

Subsequently, the ink 106 is adhered onto the coating layer 104. Specifically, a solution or suspension of the ink 106 is applied onto the coating layer 104 by using an inkjet method or a printing method. Then, the solvent remaining in the solution or suspension of the ink 106 is removed. The information represented by the ink 106 can be arbitrarily determined according to the type of the drug, the method of administration, and the like.

1. 1. Preparation of uncoated tablets Lactose hydrate (Dilactos S, manufactured by DMV) 158.0 kg, crystalline cellulose (PH102, manufactured by Asahi Kasei) 39.6 kg, magnesium stearate (vegetable, manufactured by Taihei Kagaku Sangyo) 2.4 kg are mixed. A mixture for tableting was used. The mixture was tableted to give an uncoated tablet weighing 266 mg.

2. 2. Example 1
Polyvinyl alcohol (PE-05JPS, manufactured by Japan Vam & Poval), polyethylene glycol (Macrogol 6000, manufactured by Nichiyu), and titanium oxide (NA61, manufactured by Toho Titanium) were dispersed in water to obtain a film coating composition. .. The total amount of polyvinyl alcohol, polyethylene glycol, and titanium oxide in the composition for film coating was 12.5% by weight, and the weight ratio of these was 87.5: 3.8: 8.8. This film coating composition was coated on the above-mentioned uncoated tablets using a coating machine (HC-LABO20, manufactured by Freund Industries, the same applies hereinafter) to obtain tablets (274 mg). The weight of the coating layer in the tablet was 2.9% by weight.

3. 3. Example 2
Instead of polyvinyl alcohol, polyvinyl alcohol / polyethylene glycol / graft copolymer (Coricoat IR, manufactured by BASF) was used to obtain tablets according to the same method as in Example 1.

4. Example 3
Instead of polyvinyl alcohol, a polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer (POVACOAT TypeF, manufactured by Daido Kasei) was used to obtain tablets according to the same method as in Example 1.

5. Comparative Example 1
Hydroxypropyl methylcellulose (abbreviated as HPMC, TC-5M, manufactured by Shin-Etsu Chemical Co., Ltd.) and titanium oxide (NA61, manufactured by Toho Titanium) were dispersed in water to obtain a film coating composition. The total amount of HPMC, polyethylene glycol, and titanium oxide in the film coating composition was 12.5% by weight, and the weight ratio of these was 87.5: 3.8: 8.8. This film coating composition was coated on the above-mentioned uncoated tablets using a coating machine to obtain tablets (274 mg). The weight of the coating layer in the tablet was 2.9% by weight.

6. Comparative Example 2
A copolymer of aminoalkyl methacrylate and alkyl methacrylate (EUDRAGIT EPO, manufactured by EVONIC) was used instead of HPMC, and a mixed solvent of water and ethanol was used instead of water (water: ethanol = 3: 7 w / w). Was used to obtain tablets according to the same method as in Comparative Example 1.

7. Comparative Example 3
A copolymer of methacrylic acid and alkyl methacrylate (EUDRAGIT L100-55, manufactured by EVONIC) was used instead of HPMC, and a mixed solvent of water and ethanol was used instead of water (water: ethanol = 3: 7 w / w). Was used to obtain tablets according to the same method as in Comparative Example 1.

8. Comparative Example 4
A copolymer of alkyl methacrylate and ammonioalkyl methacrylate (EUDRAGIT RLPO, manufactured by EVONIC) was used instead of HPMC, and a mixed solvent of water and ethanol (water: ethanol = 3: 7 w / w) was used instead of water as the solvent. ) Was used to obtain tablets according to the same method as in Comparative Example 1.

Table 1 summarizes the composition of the tablets of Examples 1 to 3 and Comparative Examples 1 to 4. As shown in Table 1, the weights of the tablets were the same in Examples and Comparative Examples, and the weight ratios of the contained coating layer and the uncoated tablets were also the same.

9. Printing The tablets obtained in Examples and Comparative Examples were printed using an inkjet printing machine (IIM-Labo, manufactured by Matsuoka Machinery Works). Two types of inks used for printing were used, UCA-04 (manufactured by Mutual) containing a pigment and U310-G7 (manufactured by Mutual) containing a dye.

10. Evaluation After rubbing the surface of the printed tablet with the pad of the thumb three times, the printed state was visually confirmed. The results are shown in Table 2. As shown in this table, in Examples 1 to 3, it was confirmed that no rubbing of the print was observed regardless of which ink was used, and the printed information was not lost. On the other hand, in Comparative Examples 1 to 4, when the ink containing the dye was used, the printed information remained to some extent, but when the ink containing the pigment was used, the printing was observed to be scratched and printed. It was found that the information was easily lost. From these results, it is possible to coat the uncoated tablet with a coating layer containing a polymer having a vinyl alcohol unit in the main chain or side chain, so that not only the uncoated tablet can be coated but also the ink can be reliably fixed. Do you get it.

As described above, by applying the embodiment of the present invention, it is possible to coat tablets with high ink fixability. Therefore, the information printed using the ink can be stably maintained for a long period of time, and it is possible to effectively prevent accidental ingestion of the drug or improve the administration compliance.

The present invention can be implemented in various aspects without departing from the gist thereof, and is not construed as being limited to the description of the embodiments. In addition, those skilled in the art who appropriately add, delete, or change the design of components based on the above-described embodiments are also included in the scope of the present invention as long as the gist of the present invention is provided. Further, each embodiment can be implemented in an appropriate combination as long as they do not contradict each other. Other actions and effects different from those brought about by these embodiments, which are clear from the description of the present specification or which can be easily predicted by those skilled in the art, are naturally according to the present invention. It is understood to be brought about.

100: Tablet, 102: Uncoated tablet, 104: Coating layer, 106: Ink

Claims (5)

Uncoated tablets containing medicinal ingredients,
A film-coated tablet that covers the uncoated tablet and contains a polymer containing a vinyl alcohol unit in the main chain or side chain, and an ink adhered on the coating layer. The film-coated tablet according to claim 1, wherein the polymer is selected from polyvinyl alcohol, partially saponified polyvinyl acetate, polyvinyl alcohol / polyethylene glycol / graft copolymer, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer. The film-coated tablet according to claim 1, wherein the coating layer further contains a plasticizer. The film-coated tablet according to claim 3, wherein the plasticizer is polyethylene glycol. The film-coated tablet according to claim 1, which comprises the single uncoated tablet and the coating layer.

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