JP5459670B2 - Color fixing agent for colored granules - Google Patents

Description

  The present invention relates to a pigment fixing method or a pigment movement control method for granules colored with pigments (hereinafter referred to as colored granules), or a granule coloring method and manufacturing method including those methods.

As a coloring method for granules, there are 1) a method of spraying a solution in which a colorant is dissolved or suspended in a solvent, 2) a method of granulating after adding a colorant in advance to granule components, etc. 1) has a complicated manufacturing process, and 2) has problems such as contamination by the colorant of the manufacturing equipment. In addition, as a coloring method that is relatively advantageous in terms of facilities and environment, a dry coloring method using a powdered pigment or the like is also known. By the way, even if these coloring methods are applied to the granules, if the coloring pigments are not sufficiently incorporated into the granules or do not adhere strongly to the surface, the pigments of the obtained colored granules are However, there is a problem that the pigment cannot be sufficiently fixed due to peeling from the granule in the course of storage, packaging, transportation and the like of the granule. In particular, in the case of a dry coloring method using a powder pigment, the tendency is noticeable, and even if it is adopted as an industrial coloring method, it is not easy to color it to a sufficiently satisfactory level.
In addition, Japanese Patent Application Laid-Open No. 9-71529 and 2. Japanese Patent Application Laid-Open No. 8-333253 describe a process of mixing silicon dioxide with colored granules. It is used as an antistatic agent to improve the performance, and in the case of 2, it is only used in the process of preparation for improving the dissolution property of the tablet. That is, these documents do not describe any fixing effect of the pigment on the granule surface by silicon dioxide.

JP 9-71529 A JP-A-8-333253

  There has been a demand for the development of a method capable of easily fixing a coloring material, particularly a granule colored on its surface with a powdery coloring material.

As a result of intensive studies in view of the above problems, the present inventors have found that if colored granules and a specific additive are mixed, the pigment of the granules can be easily fixed and peeling can be suppressed. Was completed.
(1) A fixing agent for fixing a pigment to a granule, comprising at least one additive selected from the group consisting of silicon dioxide and stearic acid or a salt thereof.
(2) The fixing agent according to (1), wherein the granule surface is colored with the pigment by mixing the granule and the powder pigment, and then mixed.
(3) Before or during mixing of a composite granule composed of two or more kinds of colored granules in which the granule surface is colored with different pigments by mixing the granule and the powder pigment, or the granule and the powder pigment The fixing agent according to (1), wherein the granule surface is mixed before or during mixing of a composite granule composed of one or more kinds of colored granules and non-colored granules colored with the pigment.
(4) The fixing agent according to any one of (1) to (3), wherein the additive is silicon dioxide.
(5) The fixing agent according to any one of (1) to (3), wherein the additive is stearic acid or a salt thereof.
(6) The fixing agent according to the above (5), wherein the additive is Mg salt, Na salt or Ca salt of stearic acid.
(7) The fixing agent according to (5), wherein the additive is an Mg salt of stearic acid.
(8) The fixing according to any one of (1) to (7) above, wherein 0.05 to 10% by weight is blended with respect to the granules colored on the surface with the pigment. Agent.
(9) The fixing agent according to any one of (1) to (7) above, wherein 10 to 1000% by weight is blended with respect to the weight of the dye.

  By using the dye fixing method of the present invention, various granules colored with the dye can be easily produced.

The mixing method of a colored granule and a non-colored granule is shown. The color change by mixing colored granules and uncolored granules and the effect of the presence or absence of carplex are shown. The relationship between the coloring change by mixing and the addition amount of a carplex is shown.

The granule used in the present invention is not particularly limited, and broadly means various granules used for pharmaceuticals, agricultural chemicals, foods and the like. The shape and production method of the granule are not particularly limited, and any shape such as a spherical shape, an indeterminate shape, a cylindrical shape, or a bead can be used, but an indeterminate shape having a large surface area is preferable. The particle size of the granule is not necessarily limited, but is usually about 1 to about 1000 times, preferably about 5 to about 100 times the particle size of the fixing agent described later, and preferably about 10 to about 100 as the average particle size. The thickness is 5000 μm, more preferably about 50 to about 1000 μm, and particularly preferably about 150 to about 500 μm.
The type and content of the contents of the granule are not particularly limited, and various active pharmaceutical ingredients (eg, antibiotics, antiviral agents, central nervous agents, peripheral nerve agents, cardiovascular disease therapeutic agents, antiulcer agents) , Analgesics, etc.), pharmaceutical additives (eg, disintegrant (eg, partially pregelatinized starch, sodium carboxymethyl starch, carboxymethylcellulose calcium, low-substituted hydroxypropylcellulose (LHPC), croscarmellose sodium)), polyvinylpoly Pyrrolidone, etc.), excipients (eg, saccharides (lactose, sucrose, mannitol, etc.), corn starch, potato starch, hydroxypropyl starch, etc.), binders (eg, methylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, polyvinyl alcohol, gelatin) , Dextrin, etc.), lubricant (eg Click, Mg stearate), waxes, etc.), or the active ingredient-additives for agricultural chemicals, may include a suitable amount of food raw materials.
The dye fixing method of the present invention can be widely applied to colored granules obtained by various production methods. Preferred colored granules are of a type whose surface is colored with a dye, particularly a powdery dye. Compared with colored granules obtained by spraying with a coloring liquid, etc., or granules obtained by adding a coloring agent during granulation, this type of granule has a higher pigment on the surface. It is particularly suitable for the method of the present invention because it is easily peeled off during storage, packaging or transportation.

Although it does not specifically limit as a pigment | dye in a granule, Preferably it is a powder pigment | dye at points, such as coloring operation and equipment, For example, iron sesquioxide (red, yellow, black), aluminum lake pigment | dye (blue, yellow, red) ), Copper chlorophyllin sodium (green), vitamin B2 (yellow), Sudan III (red) and the like.
Examples of the additive (hereinafter also referred to as a fixing agent) for fixing the dye in this method include one or more selected from the group consisting of silicon dioxide and stearic acid or a salt thereof. Examples of silicon dioxide include carplex (Shionogi), Aerosil (Nippon Aerosil), etc. Among these, water-containing types are preferred. Examples of the salt of stearic acid include Mg salt, Na salt, Ca salt and the like, and Mg salt is preferable. The amount of these additives is about 0.05 to about 10%, preferably about 0.1 to about 5%, more preferably about 0, by weight with respect to the granules colored on the surface. .2 to about 2%. Further, it is about 10 to about 1000%, preferably about 30 to about 500%, more preferably about 100 to about 300%, based on the weight of the dye.
When granules and pigments, especially powder pigments, are mixed, the surface of the granules is usually coated with the pigment to produce surface-modified particles (ordered mixture). Even if a weak physical impact is applied, the ordered mixture may collapse and the pigment adhering to the granule surface may peel off. However, even such ordered mixture can be mixed with the fixing agent by the method of the present invention to fix the pigment on the surface of the granule and to suppress the peeling of the pigment. In the mixing, a commercially available mixer (eg, V type, screw, etc.) may be used. The mixing time is several minutes to several hours. The mixing speed and the like may be appropriately set according to the amount of granules to be used, the type of mixer, and the like. For example, in the case of a V-type mixer, it is about 5 to about 100 rpm, preferably about 10 to about 40 rpm. Moreover, it does not specifically limit about the manufacturing method of the granule to be used, What is necessary is just to apply wet or dry type extrusion granulation.

In addition, the granule surface is colored with a pigment by mixing the granule and the powder pigment, and then the one or more fixing agents are mixed to fix the pigment on the granule surface. It can be colored efficiently by a dry method.
Furthermore, this method can also be applied to composite granules composed of two or more types of granules colored with different pigments, or composite granules composed of one or more types of colored granules and non-colored granules. That is, by mixing one or more fixing agents before or during the mixing of such composite granules, the migration of the pigment on the surface of the granules during the mixing can be effectively suppressed, The color tone at the time of preparation can be maintained without mixing the pigment. That is, it is possible to easily control the movement of the pigment when mixing the composite granules.
Furthermore, if the fixing method and the coloring method of the present invention are used, various granules whose surface is stably colored can be easily produced, and the present invention also provides the granules thus obtained. .

Test examples are shown below.
Test example 1
In accordance with the mixing method in FIG. 1, granules colored with powdered iron sesquioxide (from granule 1) and uncolored granules (granule 2) were mixed, and changes in the color of the granules were examined. In addition, all mixing was performed at the rotational speed of 40 rpm using the 500 mlV type | mold mixer (made by Tsutsui Rikagaku Co., Ltd.). The change in brightness was measured with a color analyzer (manufactured by Tokyo Denshoku Co., Ltd.).
(1) Preparation of granules White granules 1 containing 98% of saccharides such as xylit were prepared by extrusion granulation (average particle diameter: about 350 μm). On the other hand, white granules 2 containing a pharmaceutically active ingredient, a saccharide, a disintegrant (LHPC) and the like were prepared by dry granulation or the like (average particle size: about 350 μm).
(2) Mixing of granules 1.1 Primary mixing (coloring)
1107 g of granules and 0.9 g of iron sesquioxide are mixed for 5 minutes to obtain colored granules (red).
2.2 Secondary mixing (fixing)
Above 1. The total amount of the colored granules obtained in 1 above and 1.8 g of silicon dioxide (Carplex, Shionogi) as a fixing agent are mixed for 10 minutes.

3. Third order mixing (transfer)
2. Are mixed with granules 2 to obtain composite granules.
(3) Results FIG. 2 shows the brightness change of the mixed granule when the fixing agent is added, mixed in the middle or not added. In FIG. 2, the horizontal axis represents the time of tertiary mixing, and the vertical axis represents the brightness of the entire mixed granule.
In the case of no addition of carplex, the brightness decreased with the mixing time, and it was observed that the uncolored granules (granule 2) were gradually colored, whereas when the carplex was added and mixed, there was no change in brightness. I couldn't. On the other hand, when Carplex was added during the mixing, the brightness change from that point was suppressed. From the above results, it was found that the migration of pigments between granules can be suppressed by incorporating a fixing agent before or during the mixing of composite granules.
Moreover, the brightness change when the addition amount of a carplex is changed is shown in FIG. When Carplex was added in an amount of 0.2% or more based on the total weight of the granule, the change in lightness of the colored granule was remarkably suppressed.

Test example 2
As a result of examining the fixing degree of other powdery pigments based on the method of Test Example 1, it was confirmed that aluminum lake pigment, copper chlorophyllin sodium and the like were also fixed on the granule surface by mixing of carplex. As for the fixing agent, in addition to Carplex, Aerosil (Nippon Aerosil), magnesium stearate and the like were confirmed to have a fixing effect.

Claims (9)

A fixing agent for fixing a pigment to granules containing no pigment, comprising at least one selected from the group consisting of silicon dioxide and stearic acid or a salt thereof. The fixing agent according to claim 1, wherein the granule surface is colored with the pigment by mixing the granule and the powder pigment and then mixed . Mixing the granule and the powdered pigment before or during the mixing of the composite granule composed of two or more kinds of colored granules in which the granule surface is colored with different pigments by mixing the granule and the powdered pigment 2. The fixing agent according to claim 1, wherein the granule surface is blended before or during mixing of a composite granule comprising one or more kinds of colored granules colored with the pigment and non-colored granules. The fixing agent according to claim 1, which contains silicon dioxide. The fixing agent according to any one of claims 1 to 3, comprising stearic acid or a salt thereof. 6. The fixing agent according to claim 5, comprising a Mg salt, Na salt or Ca salt of stearic acid. The fixing agent according to claim 5, comprising a Mg salt of stearic acid. The fixing agent according to claim 1, wherein 0.05 to 10% by weight is blended with respect to the granules whose surface is colored with the pigment. The fixing agent according to any one of claims 1 to 7, wherein 10 to 1000% by weight is blended with respect to the weight of the dye.

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