JP7458085B2 - Disintegrant for tablets and tablets using the same - Google Patents

Description

The present invention relates to a tablet disintegrant for improving the disintegration properties of tablets and tablets using the same.

A tablet is a drug that has been molded into an easy-to-swallow form. In general, tablets are made using excipients to reduce the amount of active ingredients that are easy to handle, binders to bind the active ingredients so that they can be molded, and tablet machines to suppress the adhesion of powders and granules. It consists of a lubricant to prevent it from sticking to the mortar hole and pestle, and a coating agent to mask bitterness and odor. In addition, while it is necessary to mix the ingredients to form a tablet in this way, it is also necessary to ensure that the active ingredients of the drug are efficiently released through peristalsis of the stomach when swallowed. A disintegrant that has the property of absorbing moisture and swelling is used.

Conventionally, as a disintegrating agent, for example, calcium salt of carboxymethyl cellulose, sodium starch glycolate, agar, starch, etc. have been used. However, if highly purified ingredients are used as tablet raw materials, there may be problems with digestibility, so materials closer to natural materials may be desired as disintegrants as well. However, agar, which is used as a disintegrating agent similar to natural materials, has problems such as cracking and swelling when coated tablets are formed, and poor appearance and moldability.

Regarding disintegrants, for example, Patent Document 1 states that (1) solid or powdered agar is added with water to absorb water and swell, and then dehydrated and dried; (2) agar sol obtained by adding water to agar and dissolving it by heating; Cool to form an agar gel, freeze-dry it, and then crush it. (3) Add water to agar, heat and dissolve the resulting agar sol, cool it to form an agar gel, micronize it, and then freeze-dry it. It describes agar for tablets prepared by a method such as grinding and pulverizing.

Patent Document 2 also describes the use of soybean-derived dietary fiber as a disintegrant.

Japanese Patent Application Publication No. 10-45628 Japanese Patent Application Publication No. 2014-156436

Various ingredients that can improve the disintegration properties of tablets have been known in the past, but in order to make them more convenient to use, it has been desired to develop further materials.

The object of the present invention is to provide a novel disintegrant that is highly effective in improving the disintegration properties of tablets.

In order to achieve the above object, the present inventors conducted various studies and found that a citrus-derived dietary fiber material has an effect of promoting the disintegration of tablets, thereby completing the present invention.

That is, in its first aspect, the present invention provides a disintegrant for tablets containing as an active ingredient a citrus-derived dietary fiber material having a water retention capacity of 15 g or more per gram.

According to the disintegrant for tablets of the present invention, since the active ingredient is a citrus-derived dietary fiber material having a specific water retention capacity, the disintegration properties of the tablet obtained can be improved by incorporating this into the tablet. .

In the tablet disintegrant, the citrus-derived dietary fiber material preferably contains dietary fiber having a porous structure derived from fruit. This allows for the use of pomace, a by-product of fruit-based juice production, as an active ingredient in the present invention.

In its second aspect, the present invention provides a method for improving tablet disintegration, which comprises adding the above-mentioned tablet disintegrant to a tablet raw material.

According to the method for improving tablet disintegration of the present invention, a citrus-derived dietary fiber material, which is an active ingredient of the above-mentioned tablet disintegrant, is added to the tablet compounding raw material, thereby improving the disintegration of the tablet obtained. be able to.

In the above method, it is preferable to add the tablet disintegrant so that the content thereof is 0.1 to 60% by mass based on the total amount of the tablet. According to this, it is possible to ensure that the citrus-derived dietary fiber material is contained in the tablet in an effective amount for improving disintegration properties.

In the above method, the tablet raw material of the tablet further includes CMC-Ca, CMC-Na, sodium starch glycolate, sodium starch phosphate, methylcellulose, starch, partially pregelatinized starch, and agar. It is preferable to add one type or two or more types. According to this, other ingredients for improving disintegration are added to the raw materials for tablets together with the citrus-derived dietary fiber material, so that the effect of improving disintegration by the citrus-derived dietary fiber material in the resulting tablets is further improved. This allows for reliable performance.

In its third aspect, the present invention provides a tablet characterized by containing the above tablet disintegrant.

According to the tablet of the present invention, since the citrus-derived dietary fiber material, which is the active ingredient of the tablet disintegrant, is contained in the tablet, the disintegration properties of the tablet can be improved.

The tablet preferably contains 0.1 to 60% by mass of the tablet disintegrant based on the total amount of the tablet. This ensures that the citrus-derived dietary fiber material is contained in the tablet in an effective amount for improving disintegration.

The above tablet preferably contains the tablet disintegrant and further contains one or more selected from the group consisting of CMC-Ca, CMC-Na, sodium starch glycolate, sodium starch phosphate, methylcellulose, starch, partially pregelatinized starch, and agar. In this way, the tablet contains other ingredients for improving disintegrability along with the citrus-derived dietary fiber material, so that the effect of improving disintegrability of the resulting tablet due to the citrus-derived dietary fiber material can be more reliably exerted.

In the above tablet, the tablet is preferably a plain tablet or a coated tablet.

In the above tablet, the disintegration time measured by the disintegration test method of the 17th edition of the Japanese Pharmacopoeia for a tablet made of the same raw materials except that the disintegrant for tablets is not added. is preferably shortened by 10% or more.

Preferably, the tablet has a disintegration time of 60 minutes or less as measured by the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.

According to the present invention, the disintegration properties of tablets can be improved using the citrus-derived dietary fiber material. Furthermore, when forming coated tablets, problems in appearance and moldability such as cracks are less likely to occur.

The citrus-derived dietary fiber material used in the present invention may be any dietary fiber material derived from citrus plants (Citrus), and there are no particular restrictions on its type. For example, dietary fiber materials derived from lemons, limes, mandarin oranges, yuzu, kumquats, oranges, grapefruit, bontans, hassaku, Japanese daisies, pomelo, etc. can be used. The method for preparing the dietary fiber material is not particularly limited, but for example, after removing the juice from the fruit of a citrus plant (fruit, etc.), fruit-derived tissues such as the exocarp, endocarp, carp, core, and vascular bundle are prepared. Preferred examples include drying the portion containing the peel to form a peel, and pulverizing the peel to prepare a dietary fiber material. Usually, dietary fiber materials prepared in this way are mainly composed of insoluble dietary fibers such as cellulose and hemicellulose derived from the cell walls of citrus plants, and microscopic observation confirmed that they have a porous structure similar to a sponge structure. can. More specifically, any dietary fiber material prepared to be orally ingestible may be used.

The citrus-derived dietary fiber material used in the present invention does not have to be a material in which dietary fiber accounts for 100%, but any material whose main component is dietary fiber can be used. The dietary fiber content may be, for example, 50 to 100% by mass, 55 to 100% by mass, 60 to 95% by mass, 65 to 95% by mass, and 70 to 100% by mass. 90 mass. Note that the dietary fiber content can be measured by a well-known analytical method, for example, by AOAC method 985.29 (Prosky method).

From another point of view, the quality of the citrus-derived dietary fiber material used in the present invention may be determined by its water retention capacity. That is, the tablet needs to disintegrate efficiently in order to release the active ingredient when it is swallowed and comes into contact with an aqueous solvent such as gastric juice. This is because the property of taking in water and swelling at this time works advantageously for the disintegration of the tablet. In this regard, the citrus-derived dietary fiber material used in the present invention preferably has a water retention amount of 15 g or more, more preferably 20 g or more, per 1 g of citrus-derived dietary fiber material. If it is less than the above range, the effect of improving the disintegration properties of tablets when incorporated into tablets will be poor. Here, the water retention amount is determined by dispersing the dietary fiber material in a dry state in water, centrifuging it after standing for 24 hours, separating the water-retaining dietary fiber material, and measuring its weight. It can be calculated by subtracting the weight when the weight was present.

As the citrus-derived dietary fiber material used in the present invention, for example, commercially available dietary fiber materials such as "Helvacell AQ Plus CF" (trade name, manufactured by Helba Food Co., Ltd.) may be used.

In the present invention, the above-mentioned citrus-derived dietary fiber material is contained in a tablet to improve the disintegration properties of the tablet.

The content of the citrus-derived dietary fiber material in the tablet may be, for example, 0.1 to 60% by mass, 0.5 to 50% by mass, or 1 to 40% by mass, based on the total amount of the tablet. The content may be 3 to 30% by weight, and may be 5 to 20% by weight. If it is less than the above range, it will be difficult to obtain the effect of improving the disintegration properties of the tablet. If it exceeds the above range, it becomes difficult to incorporate the active ingredient of the drug and other ingredients into the tablet.

Whether or not the above citrus-derived dietary fiber material was able to improve the disintegration properties of tablets is determined by comparing the disintegration properties of tablets with tablets made from the same raw materials except that the above-mentioned citrus-derived dietary fiber materials are not added. It can be evaluated by comparing. The disintegration property can be determined, for example, in accordance with the disintegration test method of the 17th edition of the Japanese Pharmacopoeia. The evaluation criteria can be set arbitrarily, but typically, as a result of testing multiple tablets, the average disintegration time is 10% or more shorter than that of tablets without the addition of citrus-derived dietary fiber material. It may be set as a standard, such as to shorten the time by 30% or more. Further, for example, the standard may be set so that the disintegration time is within 60 minutes for 90% of the number of tablets tested, or it may be set on the basis that the disintegration time is within 30 minutes.

The tablets provided by the present invention can be manufactured by a normal tablet preparation method, except that the citrus-derived dietary fiber material is added to the tablet raw material. For example, any manufacturing method used in tablet manufacturing, such as direct compression, dry granulation, wet granulation, or wet tableting, can be adopted. In addition, the timing of adding the citrus-derived dietary fiber material during the tablet manufacturing process may be any timing as a tablet raw material, but in the case of wet granulation, for example, it is preferable to add it after granulation to prevent swelling due to the moisture of the binder during granulation. Alternatively, in the case of direct compression or dry granulation, it may be mixed together with other compounded raw materials when mixing the active pharmaceutical ingredient.

The tablets provided by the present invention may contain other components other than the citrus-derived dietary fiber material, as appropriate, within a range that does not impair the effects of the citrus-derived dietary fiber material. For example, binders such as crystalline cellulose, maltose, reduced maltose starch syrup, HPC (hydroxypropyl cellulose), lubricants such as calcium stearate, sucrose fatty acid ester, glycerin fatty acid ester, powdered oil, silicon dioxide, tricalcium phosphate, etc. and stabilizers such as guar gum and xanthan gum. Alternatively, colorants, flavors, sweeteners, acidulants, etc. may be mentioned.

On the other hand, in any non-limiting embodiment of the present invention, the tablet provided by the present invention may contain other disintegrants in addition to the above-mentioned citrus-derived dietary fiber material. Other disintegrants include, for example, CMC-Ca (carboxymethylcellulose calcium), CMC-Na (carboxymethylcellulose sodium), sodium starch glycolate, sodium starch phosphate, methylcellulose, starch, partially pregelatinized starch, agar, etc. Can be mentioned. In this case, one type of other disintegrants may be used, or two or more types may be used in combination.

When a disintegrant other than the above-mentioned citrus-derived dietary fiber material is contained in a tablet, its content may be, for example, 0.1 to 20% by mass, or 0.5 to 15% by mass, based on the total amount of the tablet. It may be from 1 to 10% by weight, from 1.5 to 8% by weight, and from 2 to 5% by weight. In addition, the mass ratio to the citrus-derived dietary fiber material may be 0.01:100 (the ratio of the citrus-derived dietary fiber material is the latter, the same applies hereinafter), 1:80, or 1:10. The ratio may be 1:5 or 1:1. If the content of the disintegrant other than the citrus-derived dietary fiber material in the tablet is less than the above range, it becomes difficult to obtain the effect of further improving the disintegration properties of the tablet. If it exceeds the above range, it becomes difficult to incorporate the active ingredient of the drug, the above-mentioned citrus-derived dietary fiber material, and other ingredients into the tablet.

In another embodiment of the present invention, the tablet containing the citrus-derived dietary fiber material may be in the form of an uncoated tablet that has not been coated, or may be in the form of a coated tablet that has been subjected to a coating treatment. There may be. That is, when the tablet is in the form of an uncoated tablet, the disintegration properties are improved by containing the citrus-derived dietary fiber material throughout the tablet. On the other hand, coating can improve disintegration, mask bitterness and odor, and improve stability against light and moisture. The coating process can be carried out in accordance with a general manufacturing method for coated tablets, such as film coating with shellac, zein, HPMC (hydroxypropyl methylcellulose), HPC, yeast wrap, etc., or coating with shellac, zein, etc. Any method can be employed, such as soluble coating, sugar coating with sugar, starch syrup, sugar alcohol, etc. In addition, since the citrus-derived dietary fiber material has a relatively slow swelling rate, it also has the effect of preventing cracking and disintegration of the tablet during the spraying and drying process of the coating liquid. On the other hand, agar as a disintegrating agent tends to cause cracking and disintegration during the preparation of coated tablets, so it is better not to use it in combination.

The present invention will be specifically described below with reference to Examples, but these Examples do not limit the scope of the present invention.

<Test Example 1>
The effects of incorporating citrus-derived dietary fiber materials into tablets were investigated. Specifically, tablets were prepared according to a conventional method using each formulation shown in the table below, and the disintegration time was measured according to the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.

As the citrus-derived dietary fiber material, "Helbacel AQ Plus CF-D/100" was used. In addition, this dietary fiber material was dispersed in water in a dry state, and after being allowed to stand for 24 hours, centrifugation was performed to separate the dietary fiber material that retained water, and the weight was measured. The water retention amount calculated by subtracting this amount was approximately 20 g per 1 g of dietary fiber material.

Table 2 shows the tablet materials used in Comparative Example 1-1 or Example 1-1 above.

Table 4 summarizes the tablet materials used in Comparative Example 1-2 or Example 1-2.

Table 6 summarizes the tablet materials used in Comparative Example 1-3 or Example 1-3.

As a result, as shown in the lower rows of Tables 1, 3, and 5, it is clear that when the citrus-derived dietary fiber material is added to the tablets of each combination, the disintegration time of the tablets is shortened compared to when the tablets do not contain the citrus-derived dietary fiber material. became. In addition, the hardness of the tablets having the formulations shown in Table 1 was also measured using a Kiya type hardness meter. As a result, no effect on hardness was observed even when 10% by mass of citrus-derived dietary fiber material was contained in the tablet.

<Test Example 2>
We investigated how the disintegration time of tablets changes depending on the amount of citrus-derived dietary fiber material added. Specifically, the effects of the formulations shown in Table 7 with varying contents of 0.1, 0.5, 1, 5, 20, 30, and 60% by mass were examined in the same manner as in Test Example 1. I looked it up.

Table 8 summarizes the tablet materials used in Comparative Example 2 or Examples 2-1 to 2-7.

As a result, it was found that the disintegration time was shortened when the content of the citrus-derived dietary fiber material in the tablet was in the range of 0.1 to 60% by mass.

<Test Example 3>
Other commercially available citrus-derived dietary fiber materials were also investigated for the effects of including citrus-derived dietary fiber materials in tablets. Specifically, three kinds of citrus-derived dietary fiber materials, "Citori 100M20", "Citori 100M40", and "Citori 100FG" (trade names, all manufactured by Fiberstar) were used in the formulation shown in Table 9. The effect was investigated in the same manner as Test Example 1. In addition, these dietary fiber materials were dispersed in water in a dry state, and after being allowed to stand for 24 hours, centrifugation was performed to separate the dietary fiber materials that retained water, and the weight was measured. The water retention amount calculated by subtracting the weight was less than 15g per gram of dietary fiber material in all cases.

Table 10 summarizes the tablet materials used in Comparative Example 3, Example 3, and Reference Examples 3-1 to 3-3.

As a result, only "Helvacel AQ Plus" used in Test Examples 1 and 2 as a citrus-derived dietary fiber material was found to be effective in shortening the disintegration time of tablets. This is thought to be because the three types other than "Helvacell AQ Plus" lack the ability to absorb water and swell, while "Helvacell AQ Plus" has sufficient water retention capacity necessary for tablet disintegration. It was done.

<Test Example 4>
We investigated how the disintegration time of the tablet changes when other disintegrants are added to the tablet in addition to the citrus-derived dietary fiber material. Specifically, in the formulation shown in Table 11, the effects of using CMC-Na, Na starch glycolate, starch, or agar as other disintegrants were investigated in the same manner as in Test Example 1.

Table 12 summarizes the tablet materials used in Examples 4-1 to 4-5.

As a result, it was revealed that when the citrus-derived dietary fiber material was used in combination with another disintegrant, the tablet size was further shortened than that of a tablet containing only the citrus-derived dietary fiber material.

<Test Example 5>
The effect of adding a citrus-derived dietary fiber material as a disintegrant on the preparation of coated tablets was examined. Specifically, coated tablets were prepared according to the usual method using shellac as a coating agent and the composition shown in Table 13. The disintegration time was also examined in the same manner as in Test Example 1.

Table 14 summarizes the tablet materials used in Comparative Examples 5-1 to 5-2 and Example 5.

As a result, in Comparative Example 5-1, in which CMC-Na and agar were used as disintegrants, the disintegrants swelled during the preparation of coated tablets, making the surface of the tablet powdery and causing problems in appearance. there were. In addition, in Comparative Example 5-2 in which agar was used as a disintegrant, the disintegrant swelled during the preparation of coated tablets, peeled off, and chips and cracks were observed on the surface of the tablet, causing problems in appearance. Ta. On the other hand, in Example 5, in which a citrus-derived dietary fiber material was used as a disintegrant, coating was possible without any problems. It also had excellent disintegration properties.

Claims (5)

A coated tablet containing a citrus-derived dietary fiber material as a tablet disintegrant and coated with the tablet,
The coated tablet is characterized in that the citrus-derived dietary fiber material contains dietary fiber having a porous structure derived from fruit and has a water retention capacity of 15 g or more per gram. The coated tablet according to claim 1 , containing the tablet disintegrant in an amount of 0.1 to 60% by mass based on the total amount of the tablet. The coated tablet according to claim 1 or 2, which contains the tablet disintegrant and further contains one or more members selected from the group consisting of CMC-Ca, CMC-Na, sodium starch glycolate, sodium starch phosphate, methylcellulose, starch, partially pregelatinized starch, and agar. The coated tablet according to any one of claims 1 to 3, wherein the disintegration time of the tablet, as measured by the disintegration test method of the Japanese Pharmacopoeia, Seventeenth Edition, is shortened by 10% or more compared to a tablet made of the same blend of raw materials except that the tablet disintegrant is not added. The coated tablet according to any one of claims 1 to 4 , wherein the tablet has a disintegration time of 60 minutes or less as measured by the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.