JPH0959146A - Fast-dissolving coating composition and method for producing the same - Google Patents

Abstract

(57) [Summary] [PROBLEMS] To provide a fast-dissolving coating agent composition which dissolves quickly at room temperature even though it contains a solid plasticizer and has less pigment separation, and a method for producing the same. [Structure] Granular hydroxypropylmethylcellulose or methylcellulose having an average particle diameter of 200 to 1000 μm, and a plasticizer that is solid at room temperature with respect to a coating base containing 30% by weight or less of particles having a particle diameter of 75 μm or less, and Add pigment and mix. The obtained mixture is heated above the freezing point of the plasticizer to give a fast-dissolving coating agent composition.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fast-dissolving coating composition which is applied to tablets such as pharmaceuticals to form a film and a method for producing the composition.

[0002]

2. Description of the Related Art Tablets for pharmaceuticals and the like are coated with a water-soluble film so that users do not feel bitterness.
Hydroxypropylmethyl cellulose is most widely used as a polymer for a water-soluble film base, that is, a coating base. A water-soluble film is obtained by dissolving hydroxypropyl methylcellulose in water to prepare a coating solution and drying the coating solution.

When the method of coating with a film was first developed (1950's), an organic coating solution was used. The organic coating liquid can be obtained in a short time by dispersing hydroxypropylmethylcellulose or the like in a poor solvent and then adding a good solvent to dissolve it. However, since the 1970s, water-based coating solutions in which the coating base is dissolved in water have been used for cost reduction and environmental protection.

The aqueous coating solution is prepared by dispersing hydroxypropyl methylcellulose or methylcellulose in hot water and then cooling to dissolve.
As another preparation method, there is a method of adding hydroxypropylmethyl cellulose or the like to water at a normal temperature (about 25 ° C.). However, the method using hot water takes time to cool,
The method using water at normal temperature requires several hours to one day to completely dissolve the coating base.

If it takes a long time to prepare the liquid, microorganisms will grow in the aqueous solution, making it difficult to store the aqueous coating liquid. In particular, when the coating liquid is prepared on the weekend, the coating liquid may have microorganisms grown at the beginning of the week (Monday). There is a method of adding an antiseptic as one of the means for preventing the growth of microorganisms, but it is not preferable for the coating liquid applied to pharmaceuticals. Therefore, there is a demand for a method of preparing an aqueous coating solution in a short time to prevent the growth of microorganisms.

[0006]

One of the means for preparing a coating solution in a short time is to use a special dissolving device such as a homomixer. However, this method is expensive and can generate a lot of bubbles.

As another means, there is a method of using a premixed product in which a pigment and a plasticizer, and in some cases, a surfactant and the like are further added to a coating base. Premixed products include solution type and powder type. The solution type premix product is used as it is or diluted with water to form a coating liquid. However, the solution type is more expensive than in-house preparation, and it is necessary to change the color and the composition of the composition for each product, which makes inventory management complicated.

[0008] Powder type premixed products are specially fair
As disclosed in JP-A-2-29655, a coating agent composition is prepared by previously mixing a coating base and a pigment, and adding a plasticizer and a surfactant therein. The powder type is prepared in water at normal temperature because the dispersibility is improved by polyethylene glycol (PEG) added as a plasticizer. However, the powder type is non-uniform, pigment particles are easily identified, and pigments may separate in the packaging during shipping. U.S. Pat.No. 5,258,436 describes that water-soluble cellulose acetate, a plasticizer, and a cellulose acetate aqueous solution containing a pigment are freeze-dried,
Methods for improving non-uniformity are described. Although this method can produce a premixed product which is uniform and has excellent redispersion solubility, freeze-drying is very expensive. Furthermore, in order to obtain a premixed product having a good dispersion solubility, the stirring conditions must be set strictly.

As a means for easily obtaining a premix product having good dispersion and solubility, a method of adding a pigment while mixing a liquid plasticizer to a granular coating base and mixing it is considered. However, this method cannot prevent transfer of the liquid plasticizer to tablets.

The present invention has been made in order to solve the above-mentioned problems, and is a fast-dissolving coating agent composition containing a solid plasticizer, which dissolves quickly at room temperature and causes less pigment separation, and a composition thereof. It is intended to provide a manufacturing method.

[0011]

The fast-dissolving coating composition of the present invention, which has been made to achieve the above-mentioned object, comprises:
Granular hydroxypropylmethylcellulose and / or methylcellulose having an average particle diameter of 200 to 1000 μm, and a coating base having a content of particles having a particle diameter of 75 μm or less of 30% by weight or less, a plasticizer and a pigment that are solid at room temperature It is included.

The coating base is preferably hydroxypropylmethylcellulose or methylcellulose, and hydroxypropylmethylcellulose is most widely used.

The average particle size of the coating base is 200-100
0 μm is preferred. If it is less than 200 μm, the dispersion effect is small, and agglomerates are generated during dissolution, which takes time to dissolve. When it exceeds 1000 μm, the dispersibility is good, but it takes time to dissolve one particle.

Particle diameter contained in the coating base 75 μm
The content of the following particles is preferably 30% by weight or less. If it exceeds 30% by weight, the average particle size is 200 μm.
Even if it is more than the above, there is a high possibility that aggregates will be generated, and it will take time to dissolve. The particle size is adjusted by changing the pulverizing and classifying conditions at the granulation or production stage.

The viscosity of a 2% by weight aqueous solution of the coating base is preferably 2 to 60 cP, particularly 2 to 20 cP. If it is less than 2 cP, the concentration of the obtained coating liquid becomes too low, and it takes time to coat the drug or the like.
If it exceeds 60 cP, the concentration of the coating liquid becomes too high, and it becomes difficult to spray the coating liquid with a machine or the like.

The plasticizer which is solid at room temperature is preferably at least one selected from polyethylene glycols having a weight average molecular weight of 950 to 25,000. These plasticizers are
When the weight average molecular weight is 1000, the freezing point is 35 to 40 ° C, and when the weight average molecular weight is 20000, the freezing point is 56 to 64 ° C. As the solid polyethylene glycol, a powdery one having an average particle diameter of 500 μm or less is preferable. When a commercially available powdery polyethylene glycol is blended, the malleability when heated and melted decreases.

The concentration of plasticizer is preferably 5 to 30% by weight, based on the coating base. If it is less than 5% by weight, the pigment is separated in the coating agent composition. If it exceeds 30% by weight, the plasticizer is likely to precipitate due to breathing. Further, in order to further improve the dispersibility, it is free to add a surfactant to the plasticizer.

In the powdery pigment, titanium oxide and / or iron oxide, which has a high density and easily causes separation, exhibits the effect of the present invention.

The pigment concentration is 1 with respect to the coating base.
-30% by weight is preferred. If it is less than 1% by weight, the heat treatment effect is small, and if it exceeds 30% by weight, the pigment tends to be separated. Also, like a normal premix product,
The lake dye may be mixed with the pigment. Other food dyes can be added to the pigment.

The method for producing the fast-dissolving coating agent composition is a coating base comprising granular hydroxypropylmethylcellulose and / or methylcellulose having an average particle size of 200 to 1000 μm, and the concentration of particles having a particle size of 75 μm or less is 30% by weight or less. A plasticizer and a pigment that are solid at room temperature are added and mixed, and then heated to a temperature above the freezing point of the plasticizer.

When mixing, it is preferable to use a mixer. Conical mixer, V-type mixer,
A high-speed stirring mixer equipped with a jacket for heating is preferable. When heating air is used as the heat medium, a fluidized bed mixer can be used. In order to prevent the separation of the pigment and obtain a uniform composition, an apparatus having a large stirring and mixing force, for example, a high speed stirring granulator is preferable.

The obtained coating agent composition is dissolved in water to prepare a coating liquid. The coating liquid is sprayed onto the drug by a coating device and dried to form a film, which covers the drug. A pharmaceutically acceptable additive such as an anti-sticking agent may be added to the coating liquid.

Examples of the coating device include a fluidized bed coating device, a pan coating device, and an aeration type rotary drum type coating device.

[0024]

EFFECTS OF THE INVENTION The fast-dissolving coating agent composition of the present invention can be quickly dissolved in water without using a special dissolution apparatus to quickly prepare an aqueous coating solution. Also,
Since there is almost no separation or uneven distribution of pigments, it is possible to always reproduce a constant color tone. Since the water-based coating liquid is prepared immediately before being applied to the drug, the storage period is shortened and microorganisms do not grow.

[0025]

Embodiments of the present invention will be described below in detail.

Example 1 An average particle size of 373 μm, a particle size distribution of 1000 μm or more is 0.6%, 71
0 to 1000 μm is 4.4%, 500 to 710 μm is 29.8%, 355 to 500 μ
m is 25.2%, 250-355 μm is 14.8%, 180-250 μm is 6.8
%, 180 μm or less is 18.4%, and a 2 wt% aqueous solution has a viscosity of 6 cP of hydroxypropylmethylcellulose 500 g,
80 g of titanium oxide (A-110: manufactured by Sakai Chemical Industry Co., Ltd.) and 80 g of polyethylene glycol 6000 (Macrogol 6000P: weight average molecular weight 7300-9300, freezing point 56-61 ° C. made by NOF CORPORATION) were put into a high-speed stirring granulator. While the jacket was heated to 70 ° C., the mixture was stirred and mixed for 10 minutes to obtain a coating agent composition.

188 ml of purified water was put into an 8 ounce bottle, a stirring blade was set, and the 8 ounce bottle was immersed in a high temperature bath at 25 ° C.
When the water temperature reached 25 ° C., 12 g of the sample (coating agent composition) was added all at once with stirring at 500 rpm, and stirring was continued until dissolution was completed. After the undissolved particles or aggregates have disappeared, pass the solution through an 18 mesh (850 μm) sieve mesh,
The time when no residue on the sieve was observed was taken as the dissolution time.
The dissolution time was 8 minutes.

The coating composition liquid of the present invention is sieved.
The particles were roughly classified into three kinds of particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh, and the titanium oxide content in each particle size was measured. Table 1 shows the results. The shaking time for sieving is 20
Minutes and an hour.

Example 2 1.0% when the average particle size is 504 μm and the particle size distribution is 1000 μm or more, 71
0 to 1000 μm is 18.5%, 500 to 710 μm is 42.5%, 355 to 500
μm is 18.5%, 250-355 μm is 7.0%, 180-250 μm is 3.8
%, 180 μm or less is 8.7%, and the viscosity of a 2 wt% aqueous solution is 3 cP of hydroxypropylmethylcellulose.
Other conditions were the same as in Example 1, and the coating agent composition was prepared and the dissolution time was measured. The dissolution time was 4 minutes.

In the same manner as in Example 1, the coating agent composition liquid was roughly classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 3 An average particle size of 429 μm, a particle size distribution of 1000 μm or more is 0.4%, 71
0 to 1000 μm is 14.0%, 500 to 710 μm is 37.4%, 355 to 500
μm is 20.6%, 250-355 μm is 7.0%, 180-250 μm is 4.6
%, 180 μm or less is 16.0%, and a 2 wt% aqueous solution has a viscosity of 15 cP of hydroxypropylmethylcellulose. Other conditions are the same as in Example 1 except that the coating composition is prepared and the dissolution time is measured. It was The dissolution time was 19 minutes.

In the same manner as in Example 1, the present coating agent composition liquid was roughly classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 4 1.0% when the average particle size is 255 μm and the particle size distribution is 1000 μm or more, 71
4.5% for 0 to 1000 μm, 11.0% for 500 to 710 μm, 355 to 500 μ
m is 16.2%, 250-355 μm is 17.9%, 180-250 μm is 15.6
%, 180 μm or less is 16.6%, and a 2 wt% aqueous solution has a viscosity of 15 cP of hydroxypropylmethylcellulose. Other conditions are the same as in Example 1 except that the coating agent composition is prepared and the dissolution time is measured. It was The dissolution time was 18 minutes.

In the same manner as in Example 1, the coating composition liquid of the present invention was classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 5 Polyethylene glycol 20000 (Macrogol 2 was used as a plasticizer.
0000: Weight average molecular weight 15,000 to 25,000, freezing point 56 to 64 ° C
The coating agent composition was prepared and the dissolution time was measured under the same conditions as in Example 1 except that 40 g of Nippon Oil & Fats) was used. The dissolution time was 12 minutes.

In the same manner as in Example 1, the coating agent composition liquid was roughly classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 6 Polyethylene glycol 4000 (Macrogol 40 as a plasticizer)
00: weight average molecular weight 2600 to 3800, freezing point 53 to 57 ° C., manufactured by NOF CORPORATION, 125 g, and other conditions were the same as in Example 1 to prepare a coating agent composition and measure dissolution time. The dissolution time was 6 minutes.

In the same manner as in Example 1, the coating agent composition liquid was roughly classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 7 As a pigment, 40 g of titanium oxide (A-110: manufactured by Sakai Chemical Industry Co., Ltd.) was used. Other conditions were the same as in Example 1 to prepare a coating composition and measure the dissolution time. . The dissolution time was 10 minutes.

In the same manner as in Example 1, the coating composition liquid of the present invention was classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Example 8 125 g of titanium oxide (A-110: manufactured by Sakai Chemical Industry Co., Ltd.) was used as a pigment, and other conditions were the same as in Example 1 to prepare a coating agent composition and measure the dissolution time. . The dissolution time was 8 minutes.

In the same manner as in Example 1, the coating composition liquid of the present invention was classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Comparative Example 1 A coating agent composition was prepared and the dissolution time was measured under the same conditions as in Example 1 except that heating with a jacket was not performed. The dissolution time was 8 minutes.

In the same manner as in Example 1, the present coating agent composition liquid was roughly classified into three particle sizes of 24 to 30 mesh, 42 to 60 mesh, and 100 mesh pass by sieving, and the titanium oxide content in each particle size was measured. Table 1 shows the results.

Comparative Example 2 0.4% when the average particle size is 50 μm and the particle size distribution is 150 μm or more, 106
~ 150μm is 4.9%, 75 ~ 106μm is 10.4%, 63 ~ 75μm is 1
1.6%, 45-63μm 24.4%, 38-45μm 22.2%, 38μm
The following is 26.1%, and 500 g of hydroxypropylmethylcellulose (TC-5R: manufactured by Shin-Etsu Chemical Co., Ltd.) having a viscosity of 6 cP in a 2% by weight aqueous solution is used, and other conditions are the same as in Example 1 to prepare a coating composition. The preparation and the dissolution time were measured. The dissolution time was 21 minutes.

The coating composition liquid of the present invention was sieved in the same manner as in Example 1 to obtain 100 to 140 mesh, 200 to 235 mesh, and 330 mes.
The particle size was roughly classified into three types of h-pass, and the titanium oxide content in each particle size was measured. The results are shown in Table 2.

Comparative Example 3 The coating agent composition was prepared and the dissolution time was measured under the same conditions as in Comparative Example 2 except that the heat treatment with the jacket was not performed. The dissolution time was 24 minutes.

As in Example 1, the coating composition liquid of the present invention was sieved to obtain 100 to 140 mesh, 200 to 235 mesh, and 330 mes.
The particle size was roughly classified into three types of h-pass, and the titanium oxide content in each particle size was measured. The results are shown in Table 2.

[0049]

[Table 1]

[0050]

[Table 2]

As shown in Table 1, it was confirmed that the coating agent compositions of Examples 1 to 8 did not change the content of titanium oxide even when shaken for 1 hour and maintained a uniform composition.

As shown in Table 1, the coating composition of Comparative Example 1 had a particle size of 150 μm when the shaking time was 20 minutes.
The titanium oxide content in the coating agent composition of m or less is higher than that in Example 1. It was confirmed that the difference was further magnified by shaking for 1 hour. When the coating agent composition was prepared, it was not subjected to heat treatment, so that the distribution of the content of titanium oxide changed.

As shown in Table 2, it was confirmed that the coating agent composition of Comparative Example 2 did not change the distribution of titanium oxide even if it was shaken for 1 hour, and maintained a uniform composition. However, since the particle diameter of the coating base is as small as 50 μm, the dissolution time is longer than that of the coating composition of Examples 1-8.

As shown in Table 2, the coating composition of Comparative Example 3 had a particle size of 45 μm when the shaking time was 20 minutes.
The titanium oxide content in the following coating agent composition is higher than that in Example 1. It was confirmed that the difference was further magnified by shaking for 1 hour. When preparing the coating composition, it is not heat treated,
The distribution of titanium oxide content has changed. Since the particle diameter of the coating base is as small as 50 μm, Examples 1 to
The dissolution time is longer than that of the coating agent composition of No. 8.

Claims (5)

[Claims] 1. A granular hydroxypropylmethylcellulose and / or methylcellulose having an average particle diameter of 200 to 1000 μm, wherein the content of particles having a particle diameter of 75 μm or less is 30.
A fast-dissolving coating agent composition comprising 5 to 30% by weight of a plasticizer solid at room temperature and 1 to 30% by weight of a pigment with respect to a coating base of not more than 10% by weight. 2. The fast-dissolving coating agent composition according to claim 1, wherein a 2 wt% aqueous solution of the coating base has a viscosity of 2 to 60 cP. 3. The fast-dissolving coating agent composition according to claim 1, wherein the plasticizer which is solid at room temperature is at least one selected from polyethylene glycol having a weight average molecular weight of 950 to 25,000. Stuff. 4. The fast-dissolving coating agent composition according to claim 1, wherein the pigment is titanium oxide and / or iron oxide. 5. Granular hydroxypropylmethylcellulose and / or methylcellulose having an average particle diameter of 200 to 1000 μm, wherein the content of particles having a particle diameter of 75 μm or less is 30.
A method for producing a fast-dissolving coating agent composition, which comprises adding a plasticizer and a pigment that are solid at room temperature to a coating base in an amount of not more than wt% and mixing them, and then heating the mixture to a temperature above the freezing point of the plasticizer .