Tablets and methods for manufacturing tablets

Abstract

The present invention provides a tablet and a method for manufacturing a tablet that allows for easy formulation of coated tablets, even when calcium carbonate is used for coating the tablet. [Solution] A tablet coated with a coating layer, wherein the coating layer comprises calcium carbonate granules and a binder for binding the calcium carbonate granules together. The invention also provides a method for manufacturing a tablet coated with a coating layer, comprising a raw material preparation step of dispersing calcium carbonate granules and a binder for binding the calcium carbonate granules together in an aqueous medium to obtain a coating raw material, and a coating layer formation step of coating a tablet with the coating raw material.

Description

Technical Field

[0001] The present invention relates to tablets and a method for manufacturing tablets.

Background Art

[0002] Titanium oxide, which is widely used as a white pigment in fields such as foods, pharmaceuticals, and cosmetics, is used in tablets as a material for imparting brightness, whiteness, and hiding power when blended in its coating layer. In recent years, there has been room for discussion regarding the health effects of titanium oxide nanoparticles, and the development of alternative materials has been demanded.

[0003] Regarding this problem, for example, Patent Document 1 discloses an invention of a coating composition for forming a white film coating on a tablet, which uses calcium carbonate as a white pigment.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, according to the studies of the present inventors, when calcium carbonate is used for coating tablets, there is room for improvement in handling during production when forming the coating.

[0006] An object of the present invention is to provide a tablet and a method for manufacturing a tablet that can easily formulate a coated tablet even when calcium carbonate is used for coating the tablet, in view of the above circumstances.

Means for Solving the Problems

[0007] The inventors of this invention have diligently conducted research to achieve the above objectives and have now completed this invention.

[0008] In other words, the present invention provides a tablet coated with a coating layer, wherein the coating layer comprises calcium carbonate granules and a binder for binding the calcium carbonate granules together.

[0009] According to the tablet of the present invention, since calcium carbonate granules are incorporated into the coating layer that coats the tablet, brightness, whiteness, and opacity can be given to the tablet without using titanium dioxide.

[0010] In the above-mentioned tablets, it is preferable that the volume-based average particle diameter of the calcium carbonate particles used in the coating layer, as measured by laser diffraction particle size measurement, is 5 μm or more and 20 μm or less, and that the distribution width of the volume-based particle diameter, as measured by laser diffraction particle size measurement, represented by the following formula (1), is 1.7 or less. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

[0011] According to this method, by using calcium carbonate granules of an appropriate particle size, the increase in viscosity when mixed with an aqueous solvent to form a coating solution can be suppressed. Furthermore, by reducing the proportion of fine particle sizes that do not contribute much to brightness, whiteness, or opacity, it is possible to form the desired coating layer more efficiently.

[0012] In the above-mentioned tablets, it is preferable that the coating layer contains a plasticizer. This suppresses the increase in viscosity even when a water-soluble polypeptide or the like is used as a binder and mixed with an aqueous solvent to form a coating solution.

[0013] On the other hand, in a second aspect thereof, the present invention provides a method for producing a tablet coated with a coating layer, comprising a coating solution preparation step of dispersing or dissolving calcium carbonate granules and a binder for binding the calcium carbonate granules in an aqueous medium to obtain a coating solution, and a coating layer formation step of forming a coating layer on a tablet with the coating solution.

[0014] According to the tablet manufacturing method of the present invention, calcium carbonate granules are incorporated into the coating liquid for coating the tablets. By forming a coating layer using this, brightness, whiteness, and opacity can be given to the tablets without using titanium dioxide.

[0015] In the method for manufacturing the tablets described above, it is preferable that the volume-based average particle diameter of the calcium carbonate particles used in the coating layer, as determined by laser diffraction particle size measurement, is 5 μm or more and 20 μm or less, and that the distribution width of the volume-based particle diameter, as determined by laser diffraction particle size measurement, represented by the following formula (1), is 1.7 or less. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

[0016] According to this method, by using calcium carbonate granules of an appropriate particle size, the increase in viscosity when mixed with an aqueous solvent to form a coating solution can be suppressed. Furthermore, by reducing the proportion of fine particle sizes that do not contribute much to brightness, whiteness, or opacity, it is possible to form the desired coating layer more efficiently.

[0017] In the above method for manufacturing tablets, it is preferable that the amount of calcium carbonate granules used in the coating layer is 8 to 20% by mass in the coating solution. This allows for the formation of the desired coating layer more efficiently by adjusting the concentration of calcium carbonate granules in the coating solution.

[0018] In the above method for manufacturing tablets, it is preferable that the amount of coating liquid applied to the tablet is 20 to 80 parts by mass per 100 parts by mass of the tablet. This allows for the formation of a desired coating layer to an appropriate degree.

[0019] In the above method for producing tablets, the aqueous solvent is preferably water or aqueous ethanol, with an ethanol content of 0 to 70 (v / v)%. This allows the properties of the coating solution containing calcium carbonate granules to be appropriately maintained, thereby enabling the formation of the desired coating layer more efficiently.

[0020] In the above method for manufacturing tablets, it is preferable to form the coating layer in a temperature environment of 55 to 75°C during the coating layer formation step. This allows the aqueous solvent to evaporate appropriately when the coating liquid is applied to the tablets using a coating machine or the like, making it possible to form the desired coating layer more efficiently.

[0021] In the above method for manufacturing tablets, it is preferable to further disperse or dissolve a plasticizer in the coating solution during the coating solution preparation step. This suppresses the increase in viscosity even when a water-soluble polyparticle or the like is used as a binder and mixed with an aqueous solvent to form a coating solution.

[0022] In the method for producing the above tablets, it is preferable that the B-type viscosity (rotation speed: 60 rpm) of the coating solution is 80 to 250 mPa·s. According to this, when applying the coating solution to the tablets by a coating machine or the like, a desired coating layer can be formed more efficiently without any problem in workability.

Effects of the Invention

[0023] According to the present invention, even when calcium carbonate is used for coating tablets, the formulation of the coated tablets can be easily carried out.

Brief Description of the Drawings

[0024] [Figure 1] It is a photograph showing the appearance of a film-coated tablet prepared using Formulation 1 as the coating solution in Test Example 1. [Figure 2] It is a photograph showing the appearance of a film-coated tablet prepared using Formulation 2 as the coating solution in Test Example 1. [Figure 3] It is a photograph showing the appearance of a film-coated tablet prepared using Formulation 3 as the coating solution in Test Example 1. [Figure 4] It is a photograph showing the appearance of a film-coated tablet prepared using Formulation 4 as the coating solution in Test Example 1.

Modes for Carrying Out the Invention

[0025] The tablets provided by the present invention are tablets coated with a coating layer, and the coating layer contains calcium carbonate particles and a binder for binding the calcium carbonate particles.

[0026] As calcium carbonate granules, so-called heavy calcium carbonate, which is produced by physically crushing and classifying natural raw materials such as limestone, may be used, or so-called light calcium carbonate, which is produced by chemical synthesis, may be used. The latter, light calcium carbonate, is known to be produced by known methods such as the gasification method, the liquid-liquid reaction method using an aqueous solution of sodium carbonate and an aqueous solution of calcium hydroxide, and the caustic reaction method. Calcium carbonate produced by chemical synthesis generally has properties such as uniform particle size and shape, low impurity content, and high whiteness, and can therefore be suitably used in the present invention. The crystalline form is not limited, but the calcite type is preferred.

[0027] While not limited to this, it is preferable to use calcium carbonate granules of an appropriate particle size. As mentioned above, an appropriate particle size suppresses the increase in viscosity when mixed with an aqueous solvent to form a coating solution. Furthermore, by reducing the proportion of fine particle sizes that do not contribute much to brightness, whiteness, or opacity, it is possible to form the desired coating layer more efficiently.

[0028] Specifically, a preferred particle size is one in which the average particle diameter is 5 μm or more and 20 μm or less, and the distribution width of the volume-based particle diameter measured by laser diffraction particle size measurement represented by the following formula (1) is 1.7 or less. More preferably, the average particle diameter is 10 μm or less, and the distribution width represented by the following formula (1) is 1.2 or less. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

[0029] Laser diffraction particle size measurement can be performed using, for example, the SALD-300V (manufactured by Shimadzu Corporation).

[0030] As described above, the calcium carbonate granules having an appropriate particle size are not limited to those described above, but for example, calcium granules obtained by the methods described in Japanese Patent No. 7089310, Japanese Patent No. 6948086, Japanese Patent No. 6896310, Japanese Patent No. 2881555, etc. can be used.

[0031] On the other hand, the binding agent can be any agent that can bind the calcium carbonate granules together and hold them in place so that they can adhere to the surface of the tablet; there are no particular restrictions. Examples include hydroxypropyl methylcellulose, hydroxypropyl cellulose, and polyvinyl alcohol.

[0032] The present invention will be described in more detail below, with an example of a method for manufacturing tablets coated with a coating layer. However, this is merely an example to illustrate the present invention, and the scope of the present invention is not limited to these forms.

[0033] In one embodiment of the present invention for manufacturing tablets, the manufacturing method first involves dispersing or dissolving calcium carbonate granules and a binder in an aqueous medium to obtain a coating solution (coating solution preparation step). Then, a coating layer is formed on the tablet using the obtained coating solution (coating layer formation step).

[0034] A general-purpose coating machine can be used to form the coating layer on the tablets.

[0035] The aqueous medium used should be capable of well dispersing or dissolving the calcium carbonate particles and binder, and should be made of a material that can be used in a general-purpose coating machine. Typically, for example, water or aqueous ethanol can be preferably used. In this case, the ethanol content is preferably 0 to 70 (v / v)%. Furthermore, in the case of aqueous ethanol, the ethanol content is preferably 0 to 50 (v / v)%, more preferably 5 to 40 (v / v)%, even more preferably 10 to 30 (v / v)%, even more preferably 15 to 25 (v / v)%, even more preferably 22 to 23 (v / v)%, and most preferably 22.6 (v / v)%. If the ethanol content is high, when mixed with the calcium oxide particles having the appropriate particle size as described above, the viscosity will increase, making it more likely for the spray gun to clog or for the coating to adhere to the pan when used in a coating machine.

[0036] The viscosity of the coating solution is not limited, but when measured using B-type viscosity (rotation speed: 60 rpm), it is preferably 80 to 250 mPa·s, more preferably 100 to 200 mPa·s, and even more preferably 100 to 150 mPa·s. Within the above range, the coating solution can be applied to the tablets with good workability using a coating machine or the like.

[0037] In any unspecified embodiment, a plasticizer may be included in the coating solution. As described above, the inclusion of a plasticizer suppresses the increase in viscosity even when a water-soluble polysaccharide or the like is used as a binder and mixed with an aqueous solvent to form the coating solution. Examples of plasticizers, though not limited to those specified, include glycerin, glycerin fatty acid esters, polyethylene glycol, methylcellulose, and sorbitol. The inclusion of the plasticizer in the coating solution may, of course, be carried out by dispersing or dissolving it in an aqueous solvent together with calcium carbonate granules and the binder during the coating solution preparation process described above.

[0038] In any embodiment not limited to this, it is preferable to incorporate 8 to 20% by mass of calcium carbonate particles into the coating solution. As described above, an appropriate concentration of calcium carbonate particles in the coating solution allows for the formation of the desired coating layer more efficiently. Specifically, for example, the desired coating can be achieved in a shorter time using a general-purpose coating machine. The content of calcium carbonate particles in the coating solution may be 8 to 16% by mass, or 8 to 12% by mass.

[0039] The coating liquid used in the present invention is not limited, but for example, when its opacity is measured as follows, it is preferable that its opacity rate is 0.2 or higher, and more preferably 0.3 or higher. This makes it possible to impart to tablets opacity equivalent to that of conventional white film coatings using titanium dioxide.

[0040] (Measurement of opacity) • Coating preparation: The coating is applied to opacity test paper using a 100 μm applicator and left in a 100°C forced-air dryer for 3 minutes to obtain a coating film. • Concealment rate measurement conditions: Measure the reflectance at 45°-0° in four or more locations on the opacity test paper (white and black), and calculate the reflectance YW for white and the reflectance YB for black. Opacity = YB (reflectivity of black) / YW (reflectivity of white) *Complies with JIS K5600-4-1 (Opacity: for light-colored paints).

[0041] In any embodiment that is not limited thereto, it is preferable to form the coating layer in a temperature environment of 55 to 75°C during the coating layer formation process described above. This allows the aqueous solvent to evaporate appropriately when the coating liquid is applied to the tablets by a coating machine or the like, as described above, so that the desired coating layer can be formed more efficiently.

[0042] In any embodiment not limited thereto, the amount of the coating liquid applied to the tablet is preferably 20 to 80 parts by mass per 100 parts by mass of the tablet, and more preferably 50 to 75 parts by mass per 100 parts by mass of the tablet. Furthermore, the value obtained by subtracting the mass of the tablet before coating from the mass of the coated tablet (the ratio of the coating layer) is preferably 3 to 20 parts by mass when the total mass of the tablet coated with the coating layer is 100 parts by mass, and more preferably 5 to 10 parts by mass when the total mass of the tablet coated with the coating layer is 100 parts by mass.

[0043] The types of tablets to which the present invention is applied are not particularly limited. Examples include multivitamin tablets, multimineral tablets, plant extract tablets, turmeric tablets, etc. Furthermore, the tablets may be uncoated or undercoated with shellac or the like. [Examples]

[0044] The present invention will be further described with the following examples. However, these examples are not intended to limit the scope of the present invention.

[0045] [Test Example 1] A coating solution was prepared using each formulation shown in Table 1, and the tablets were then coated with a film.

[0046] The materials, coating solution preparation procedure, and coating conditions were as follows:

[0047] [1. Materials] 1.1 HPMC: Hydroxypropyl methylcellulose (product name "Metrolose SE-06", Shin-Etsu Chemical Co., Ltd.) 1.2 Calcium Carbonate Granules A (Product name "Corocalso-EX", Shiraishi Kogyo Co., Ltd.) 1.3 Calcium Carbonate Granules B (Product name "Colocalso-WBS", Shiraishi Calcium Co., Ltd.) 1,4 Glycerin (product name "Glycerin for Food Additives", Kao Corporation) 1.5 95% Ethanol (Product name: "General Alcohol 95% Grade 1 Fermented Undenatured Food Additive", Amakasu Chemical Industry Co., Ltd.)

[0048] [2. Coating Solution Preparation Procedure] 2.1 Mix glycerin, water, and 95% ethanol with a stirrer. 2.2 Add HPMC and stir with a stirrer until there are no lumps. 2.3 Add calcium carbonate and mix in a blender. 2.4 Sieve through an 80-mesh (125 μm opening) mesh.

[0049] [3. Coating conditions] 3.1 Coating machine: HCT-48 (Freund Industrial Co., Ltd.) 3.2 Tablet preparation quantity: 2.5 kg 3.3 Tablets used: φ8CR, 301mg (undercoated with 1mg of shellac) 3.4 Spray speed: Varies depending on the formulation. 3.5 Intake air temperature: 65℃ The amount of coating was 10-40 mg per 301 mg tablet used.

[0050] Figures 1-4 show photographs of examples of film-coated tablets prepared using formulations 1-4 as the coating solution.

[0051] [Table 1]

[0052] (Evaluation criteria for overall evaluation) ◎Excellent 〇 Good △ Slightly bad × Bad

[0053] As a result, the following became clear: (1) When any of formulations 1 to 6 was used as the coating solution, a white coating layer was formed on the surface of the tablets. However, differences were observed in handling during manufacturing and the appearance of the finished product. (2) Compared to Formulation 4, both Formulation 1 and Formulation 2 showed a tendency for roughness on the surface of the coating layer (orange peel phenomenon), clogging of the spray gun, and adhesion to the coating machine pan. This was thought to be due to the increased viscosity of the coating solution caused by the amount of calcium carbonate granules added and the ethanol content of the aqueous solvent. (3) Compared to Formulation 4, Formulation 3 tended to produce more foam during the preparation of the coating solution, and it took longer for the foam to dissipate before it could be used. In addition, dusting occurred (drying before reaching the surface of the tablets), and there was a tendency for more to adhere to the coating machine pan. This was thought to be because the spray speed in Formulation 3 was reduced compared to the alcohol-containing formulation in order to prevent the tablets from sticking together. (4) In formulation 4, compared to formulation 3, bubbles dissipated faster during solution preparation, and the spray speed during coating could also be increased. Furthermore, there were no significant problems inside the coating machine, and it had the best handling and overall evaluation among formulations 1 to 6. (5) In prescription 5, the appearance of the coated tablets was the same as in prescription 4, but, similar to prescription 3, there was a lot of foaming during the preparation of the coating solution, and it tended to take time for the foam to dissipate before it could be used. (6) In formulation 6, the appearance of the coated tablets and the foaming during the preparation of the coating solution were equivalent to formulation 4, but the cost increased due to the larger amount of ethanol used, and the weight increase of the tablets tended to be slower due to the dusting phenomenon.

[0054] [Test Example 2] For each of the coating solutions from formulations 1 to 4 used in Test Example 1, the coating was applied to opacity test paper using a 100 μm applicator, left in a 100°C forced-air dryer for 3 minutes to obtain a coating film, and then the reflectance at 45°-0° was measured at four or more white and black points on the opacity test paper. The opacity was then measured by calculating the reflectance YW for white and the reflectance YB for black.

[0055] As a result, formulation 1 had an opacity of 0.32, formulation 2 had an opacity of 0.23, formulation 3 had an opacity of 0.12, and formulation 4 had an opacity of 0.30. In all cases, the tablets were given opacity equivalent to that obtained when using a coating solution containing 2% by mass of titanium dioxide, which is a common amount used conventionally.

[0056] [Test Example 3] The particle size distribution of calcium carbonate particles A and calcium carbonate particles B used in Test Example 1 was measured using a laser diffraction particle size analyzer (SALD-300V model, manufactured by Shimadzu Corporation).

[0057] As a result, the volume-based average particle size of calcium carbonate granule A was 9.1 μm, and the volume-based average particle size of calcium carbonate granule B was 3.1 μm.

[0058] Furthermore, the particle size distribution width represented by the following formula (1) was 1.1 for calcium carbonate particle A and 2.1 for calcium carbonate particle B. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

Claims

1. A tablet coated with a coating layer, wherein the coating layer comprises calcium carbonate granules and a binder for binding the calcium carbonate granules together.

2. The tablet according to claim 1, wherein the volume-based average particle diameter of the calcium carbonate particles used in the coating layer, as determined by laser diffraction particle size measurement, is 5 μm or more and 20 μm or less, and the distribution width of the volume-based particle diameter, as determined by laser diffraction particle size measurement represented by the following formula (1), is 1.7 or less. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

3. The tablet according to claim 1 or 2, wherein the coating layer contains a plasticizer.

4. A method for producing a tablet coated with a coating layer, comprising: a coating solution preparation step of dispersing or dissolving calcium carbonate granules and a binder for binding the calcium carbonate granules in an aqueous medium to obtain a coating solution; and a coating layer formation step of forming a coating layer on a tablet using the coating solution.

5. A method for producing a tablet according to claim 4, wherein the volume-based average particle diameter of the calcium carbonate particles used in the coating layer, as determined by laser diffraction particle size measurement, is 5 μm or more and 20 μm or less, and the distribution width of the volume-based particle diameter, as determined by laser diffraction particle size measurement represented by the following formula (1), is 1.7 or less. Particle size distribution width = ([D90 value of calcium carbonate] - [D10 value of calcium carbonate]) / Volume-based average particle size of calcium carbonate measured by laser diffraction... (1) (In the formula, the D90 value is the particle size at which the cumulative volume of calcium carbonate accounts for 90% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement, and the D10 value is the particle size at which the cumulative volume of calcium carbonate accounts for 10% of the volume-based cumulative particle size distribution obtained by laser diffraction particle size measurement.)

6. The method for producing a tablet according to claim 4 or 5, wherein the amount of calcium carbonate granules used in the coating layer is 8 to 20% by mass in the coating solution.

7. The method for producing a tablet according to claim 4 or 5, wherein the amount of the coating liquid applied to the tablet is 20 to 80 parts by mass per 100 parts by mass of the tablet.

8. The method for producing tablets according to claim 4 or 5, wherein the aqueous solvent is water or aqueous ethanol, and the ethanol content is 0 to 70 (v / v)%.

9. The method for manufacturing a tablet according to claim 4 or 5, wherein the coating layer formation step is performed in a temperature environment of 55 to 75°C.

10. The method for producing a tablet according to claim 4 or 5, wherein in the coating solution preparation step, a plasticizer is further dispersed or dissolved in the coating solution.

11. The method for producing tablets according to claim 4 or 5, wherein the B-type viscosity (rotation speed: 60 rpm) of the coating liquid is 80 to 250 mPa·s.

Images