JP2005336090A - Disintegrant for tablets - Google Patents

Abstract

｛式中、Ａ^ｎ−はＣｌ⁻，ＣＯ_３ ^２−等のＳＯ_４ ^２−以外のｎ価（ｎは１以上の整数）のアニオンを示し、ｘ，ｙ，ｚおよびｍはそれぞれ次の範囲を示す、２＜ｘ≦１０，０．５＜ｙ＜１．５，０≦ｚ＜０．５，０≦ｍ＜２０｝で表されるＳＯ_４型ハイドロタルサイト類を使用する。
【選択図】なし
Disclosed is a disintegrant capable of satisfying contradictory demands at the same time, exhibiting a high level of molding strength in tablets such as pharmaceuticals, and exhibiting excellent disintegration properties when taking tablets.
The following formula (1)
[Chemical 1]

^{{Wherein, A n-is Cl} -, _CO ³ _SO ^{4 2-} Other n-valent ^2- like (n is an integer of 1 or more) denotes an anion of, x, y, z and m ranges follows respectively SO ₄ type hydrotalcites represented by 2 <x ≦ 10, 0.5 <y <1.5, 0 ≦ z <0.5, 0 ≦ m <20} are used.
[Selection figure] None

Description

  The present invention relates to a disintegrant for tablets and granules.

  Conventionally, carboxymethylcellulose calcium, starch, guar gum, CMC-Na, gum arabic, PVA, mannitol, sorbitol, erythritol and the like have been used as disintegrants used for tablets and granulated products (granules).

  Tablets and granules disintegrate in the digestive juices of the stomach and intestines after ingestion, release medicinal ingredients and absorb them in the stomach and intestines. Strength), disintegration in digestive juice, preferably disintegration in the mouth is necessary.

  The above two required characteristics are in a back-to-back relationship, and the higher the mechanical strength of the tablet, the worse the disintegration property. Conversely, the better the disintegration property, the worse the mechanical strength of the tablet. Therefore, the conventional disintegrants have good disintegration properties but have difficulty in the mechanical strength of tablets.

｛式中、Ａ^ｎ−はＣｌ⁻，ＣＯ_３ ^２−等のＳＯ_４以外のｎ価（ｎは１以上の整数）のアニオンを示し、ｘ，ｙ，ｚおよびｍはそれぞれ次の範囲を示す。２＜ｘ≦１０，０．５＜ｙ＜１．５，０≦ｚ＜０．５，０≦ｍ＜２０｝で表されるＳＯ_４を層間アニオンの主成分として含有するハイドロタルサイト類を有効成分とする錠剤用崩壊剤を提供する。 The present invention provides the following formula (1)

{In the formula, A ^n- represents an anion of n valence (n is an integer of 1 or more) other than SO ₄ such as Cl ⁻ , CO ₃ ²⁻ , and x, y, z, and m each represent the following ranges. . Hydrotalcites containing SO ₄ represented by 2 <x ≦ 10, 0.5 <y <1.5, 0 ≦ z <0.5, 0 ≦ m <20} as a main component of an interlayer anion Disintegrating agents for tablets as active ingredients are provided.

  According to the present invention, when it comes into contact with water while exhibiting high tablet strength (shape stability), water is rapidly taken in between the layers, the layer interval is expanded and expanded, and can be collapsed in a very short time. it can. The disintegrant of the present invention simultaneously functions as an excellent excipient.

  According to the present invention, two contradictory requirements, which are excellent excipient performance and excellent disintegrant performance, can be replaced by one substance. Since it is extremely disintegrating, it can provide tablets that can be taken orally without water.

Hereinafter, the present invention will be described in detail. The disintegrant of the present invention is a haloid rothalite represented by [Chemical Formula 1] containing SO ₄ as a main component of an interlayer anion. SO ₄ has a tetrahedron surrounded by four oxygen atoms in S _{4, and} is strongly bonded to either the upper layer or the lower layer formed by the hydroxide of Mg and Al in the interlayer. Since the bonding with one layer is weak and the inter-layer spacing is large compared to CO ₃ type etc., water is reversibly infiltrated between layers as much as it is the only one among hydrotalcites, The present inventor has discovered that it is easy to swell. One layer of interlayer water is present between the layers occupied by SO ₄ by drying at about 40 to 50 ° C. or higher. However, as soon as it comes into contact with water, water is taken in between the layers and two or more layers of water are formed. This increase in interlayer spacing (about 2 to 3 angstroms or more) due to the increase in interlayer water is considered to be a cause of disintegration in a very short time, exceeding that of conventional disintegrants.

The SO ₄ type hydrotalcites that are the disintegrants of the present invention are preferably such that the primary particles are small and the secondary particles are small, and such a product exhibits better formability (tablet hardness). In [Chemical Formula 1], the higher the proportion of SO ₄ ions in the total interlayer anions, the more preferable as it is apparent from the above description. In other words, those amounts of A ^n- is an anion other than SO ₄ is less is more preferable.

The production of SO ₄ type hydrotalcites is conventionally known. For example, a mixed aqueous solution of magnesium sulfate and aluminum sulfate and an aqueous solution of sodium hydroxide can be co-precipitated while maintaining the pH at about 9 or higher. Alternatively, a mixed aqueous solution of magnesium chloride and aluminum chloride and an aqueous solution of sodium hydroxide are used to coprecipitate Cl-type hydrotalcites while maintaining the pH at about 9 or higher, and then washed with sodium sulfate or magnesium sulfate. Thus, it can also be produced by a method in which Cl ⁻ is ion exchanged with SO ₄ ²⁻ . Examples of the SO ₄ -type hydrotalcites suitable as the disintegrant of the present invention produced by the above method include the following formulas (2) and (3).

  The form of the disintegrant of the present invention is a powder or a spray-dried (spray-dried) granulated product, and the latter having excellent fluidity is more preferable. For molding tablets using the disintegrant of the present invention, the following known disintegrants, excipients, lubricants and the like can be used in combination. Disintegrants include starch-based, cellulose-based, vinyl-based, sugar-alcohol-based disintegrants such as corn starch, potato starch, dextrin, hydroxypropyl starch, partially pregelatinized starch, and carboxymethyl starch sodium; Cellulose type such as roast calcium, carmellose, sodium carboxymethyl cellulose, carboxymethyl cellulose calcium; vinyl type such as polyvinyl alcohol (PVA), cross-linked polyvinyl pyrrolidene; sugar alcohols such as mannitol, sorbitol, erythritol, xylitol, maltitol, lactitol Can be used. As the excipient, for example, lactose, microcrystalline cellulose, calcium hydrogen phosphate, mannitol, hydroxypropylmethylcellulose, carboxymethylcellulose calcium and the like can be used. As the lubricant, for example, magnesium stearate, calcium stearate, talc and the like can be used. The blending amounts of the disintegrant, excipient, and lubricant with respect to the disintegrant of the present invention are 1 to 20% by weight, 1 to 50% by weight, and 1 to 10% by weight, respectively. EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited only to these.

A mixed aqueous solution of magnesium sulfate and aluminum sulfate (Mg = 2 mol / liter, Al = 1 mol / liter) and an aqueous solution of 4 mol / liter sodium hydroxide were placed in a reaction tank with an overflow of 2 liters and a Mg / Al solution. The mixed solution is 100 ml / min, the alkali is about 150 ml, the alkali is supplied in an amount of about 9.6 to 9.8 in the reaction tank, and the coprecipitation reaction is carried out at about 40 ° C. It was. Then, it filtered, washed with water, dried at about 120 ° C. and pulverized. As a result of measuring the X-ray diffraction of the obtained powder, the (003) plane spacing corresponding to the unit layer thickness showed a diffraction pattern of only 8.3 mm hydrotalcites. The chemical composition obtained by dissolving this powder in hydrochloric acid and conducting chemical analysis and thermal analysis to measure the amount of water of crystallization was as follows.
Mg _4.1 Al ₂ (OH) ₁₂ (SO ₄ ) _1.1 · 2H ₂ O

[Making tablets]
This powder, 54% by weight of SO ₄ type hydrotalcite, 40% by weight of ascorbic acid (reagent grade 1), 5% by weight of PVA (reagent), and 1% by weight of magnesium stearate (reagent) are mixed uniformly, and then tableted. Using a machine, a tablet having a thickness of 4 mm, a diameter of 12 mm, and a weight of about 800 mg was prepared at a molding pressure of 600 kg. About the obtained tablets, 5 pieces were measured with a carrier type hardness tester, and the time (seconds) required to completely disperse the hardness (kg) from the average value in water in 3 tablets each according to the Japanese Pharmacy Law. ) To measure disintegration. The results are shown in Table 1.

In Example 1, it carried out like Example 1 except using the solution of the density | concentration of Mg = 3 mol / liter and Al = 1 mol / liter as mixed aqueous solution of magnesium sulfate and aluminum sulfate. X-ray diffraction of the obtained powder showed a diffraction pattern of only hydrotalcites having a (003) plane spacing of 8.6 mm. The chemical composition obtained by conducting chemical analysis and thermal analysis of this product was as follows.
Mg ₆ Al ₂ (OH) _15.8 (SO ₄ ) _0.9 (CO ₃ ) _0.2 · 4H ₂ O
Using this SO ₄ type hydrotalcite powder, tablets were prepared in the same manner as in Example 1, and the hardness and disintegration were measured. The results are shown in Table 1.

[Comparative Example 1]
Example 1 is the same as Example 1 except that microcrystalline cellulose (Avicel PH101, manufactured by Asahi Kasei Kogyo Co., Ltd.), which is a representative excipient, is used instead of the SO ₄ type hydrotalcites of the present invention. In the same manner, the hardness and disintegration of the tablets were measured. The results are shown in Table 1.

[Comparative Example 2]
In the preparation of the tablet of Example 1, in place of SO ₄ type hydrotalcite, 51% by weight of microcrystalline cellulose and 3% by weight of disintegrant sodium carboxymethyl cellulose (trade name DST-SF) were added. A tablet was prepared in the same manner as in Example 1, and the hardness and disintegration time were measured. The results are shown in Table 1.

From the results of Table 1, it can be seen that the disintegrant of the present invention exhibits excellent molding strength and extremely excellent disintegration properties.

Claims (3)

Following formula (1)

^{{Wherein, A n-is Cl} -, _CO ³ _SO ^{4 2-} Other n-valent ^2- like (n is an integer of 1 or more) denotes an anion of, x, y, z and m ranges follows respectively Indicates. Hydrotalcites containing SO ₄ represented by 2 <x ≦ 10, 0.5 <y <1.5, 0 ≦ z <0.5, 0 ≦ m <20} as a main component of an interlayer anion Disintegrant for tablets as an active ingredient. The disintegrant for tablets according to claim 1, wherein x and y are in the following ranges, wherein x = 3 to 7, 0.8 <y <1.5. The starch-based, cellulose-based, vinyl-based, sugar alcohol-based, etc. disintegrant based on the weight of the disintegrant represented by [Chemical Formula 1] is used in combination. Disintegrant.