JPS6183132A - Composition for tablet having suppressed hygroscopic reactivity - Google Patents

Abstract

PURPOSE:To provide the titled composition for tablet, having improved moldability and long-term storability, by adding a polymeric compound having hygroscopicity, bindability and water-solubility to a composition for tablet containing a component to be kept from hygroscopic reaction or moisture. CONSTITUTION:A composition for tablet containing a component to be kept from hygroscopic reaction or moisture is mixed with 0.5-50wt% polymeric compound of formula I (R1 and R2 are H or -COOX2; at lease one of R1 and R2 is not -COOX2; R3 is H or methyl; X1 and X2 are alkali metal or ammonium) and/or formula II (A1 is H or 1-4C alkyl; A2 is -COOY, etc.; Y is 1-8C alkyl, etc.) having hygroscopicity, bindability and water-solubility. The molecular weight of polymeric compound is 300-500,000. Since the composition has excel lent moldability because of its hygroscopicity and bindability, and since it has excellent solubility in water, the wetting, dispersion and dissolution take place rapidly in the case of a table to be sued in the state dissolved in water.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a tablet composition in which undesirable physical and chemical changes due to moisture absorption are suppressed. Specifically, a tablet composition containing a "substance incompatible with incorporation or a moisture repellent" that is likely to cause undesirable physical or chemical changes due to hygroscopic reactivity.

By blending a polymer compound with caking and water solubility,
The object of the present invention is to provide a tablet composition with suppressed hygroscopic reactivity, which has improved moldability and long-term storage stability.

Compounds that tend to undergo undesirable physical or chemical changes due to moisture are often incorporated into tablet compositions. Examples include effervescent tablets containing acids such as organic carboxylic acids and sodium carbonate, which are known to be contraindicated, and calcium hypochlorite tablets, which are used as a single ingredient after being dissolved in water. Such tablets have oral and parenteral uses such as medical oral drugs, soft drink preparations, detergents, bath preparations, agricultural chemicals, rust preventives, and bleaching agents.

In order to be finished into tablets, tablet compositions having these uses are required to have mechanical strength, be able to be neatly molded, and have excellent storage stability.

For example, lubricants such as stearate, sodium benzoate, and boric acid, excipients, and binders are generally used as auxiliary agents to improve moldability.

It is well known that when forming tablets using these auxiliary agents, water acts as an important forming ingredient, and generally the water content is 0.1 to 20% by weight, depending on the powder. It is said to be used.

However, 5, for example, when mixing acid and alkali carbonate powders to make tablets, such as effervescent tablets, if even a small amount of water is present, the decomposition reaction of the alkali carbonate will proceed, and the resulting water will further inhibit the reaction. However, there is a risk that the product will be decomposed within a few days or even a few hours, and its effectiveness will not be achieved.Especially when targeting substances that are incompatible with the product due to hygroscopic reactions, moisture in the powder or moisture absorbed during storage may It is also true that they are extremely hated.

Thus, when molding powder into tablets where it is necessary to prevent undesirable reactions due to moisture, there is a mutual conflict between the two: a moderate amount of moisture is required from the molding surface, and an extremely low moisture content is required from the perspective of storage stability. In order to overcome these difficulties, we have to be subject to two constraints that have not existed until now.
Attempts have been made to use inorganic salts such as anhydrous sodium sulfate and sodium chloride, but satisfactory results have not been obtained. There are also attempts to use polymeric compounds such as CMC and starch, but these compounds are prone to mold growth and have weak wetting power, so it takes a long time for tablets to dissolve when dropped into water. , there is a drawback that powder may float up.

An object of the present invention is to provide a tablet composition that improves the drawbacks of the prior art. That is, the present invention is specified as follows.

11) A tablet composition with suppressed hygroscopic reactivity, which contains a polymer compound having hygroscopic properties, caking properties, and water solubility.

(2) The composition for tablets according to (1) above, wherein the polymer compound is composed of a polymer or copolymer of monomers represented by the following general formula [I] and/or (II). thing.

(t)　R1'R3 C=C R, C00X.

(In the formula, +RI and R2 are each independently hydrogen or -
coox, but not -COOX2 at the same time. R2 represents hydrogen or a methyl group.

Moreover, X, , and X each represent an alkali metal or an ammonium group. ] ([) HA+ C=C HA.

(In the formula, A is hydrogen or an alkyl group having 1 to 4 carbon atoms,
A2 is an acid ester group -COOY (Y is an alkyl group having 1 to 8 carbon atoms, a hydroxyalkyl group having 2 to 5 carbon atoms, or an alkanolamine group), an acid amide group, a phenyl group, a phenylsulfonic acid group, a nitrile group Or it represents an alkyl group having 1 to 4 carbon atoms. ) (3) The average molecular weight of the polymer compound is 300 to 500.0
The composition for tablets according to (2) above, characterized in that it is in the range of 00.

(4) The tablet composition described in (1), (2) or (3) above, which contains a substance that is incompatible with combination due to its hygroscopic reactivity.

(5) The tablet composition described in (1), (2), (3) or (4) above, characterized in that the polymer compound is contained in a range of 0.5 to 50% by weight.

The contents of the present invention will be explained in more detail.

In the present invention, the polymer compound used as a binder has three properties: hygroscopicity, caking property, and water solubility.

To explain each characteristic effect, first of all, hygroscopicity is caused by moisture released from the raw material powder due to external pressure or temperature rise during molding, moisture in the storage environment, or decomposition reactions that occur temporarily when exposed to high temperatures. It has the ability to absorb moisture that is generated. Regarding caking, when molding and tableting, the binder absorbs moisture to an appropriate degree and becomes sticky.
It combines with the surrounding powder and gives the tablet strength. Finally, regarding water solubility, when a tablet is thrown into water, the binder does not float to the surface of the water or remain dispersed in water for a long time, and wet dispersion and dissolution occur quickly.

The molecular weight of the polymer compound is 300 to 500,000
It is preferably in the range of 500 to 50,000.

If the molecular weight is too small, the hygroscopicity and caking properties will be poor, and if the molecular weight is too large, the water solubility will be reduced.

The amount of polymer compound used for the raw material powder is 0.5 to 50
% by weight, preferably 1 to 30% by weight. If it is too small, the storage stability will be poor, and if it is too large, the essential effects of the tablet will be diminished.

There are the following two methods of using a polymer compound as a binder in the present invention. One method is to uniformly mix the polymer with the constituent components of the powder. In this case, the particle size of the polymer compound is suitably in the range of 32 to 200 mesh. Target raw material powders include acids such as phosphoric acid, succinic acid, citric acid, tartaric acid, malic acid, malonic acid, and fumaric acid, and carbonate alkalis such as sodium carbonate, sodium bicarbonate, and sesquicarbonate. These include sodium and potassium carbonate. Another method is to coat at least one of the constituent components of the powder with a polymer compound.

Examples of powders include malic acid for substances that easily absorb moisture, hydrosulfide and calcium hypochlorite for substances that easily absorb moisture and decompose, such as salt, and benzoic acid, adipic acid, and fumaric acid for hydrophobic substances. , rubic acid, succinic acid, etc.

As for the coating method, it is important to uniformly coat the powder surface, and specifically coating methods such as spraying, dipping, and sprinkling are used.

The powder targeted by the present invention is not limited to the above-mentioned acids, salts, alkali carbonates, etc., but may include all powders that cause undesirable reactions due to moisture absorption and reduce the effectiveness as a compounding composition.

The polymer compound particularly advantageously used in the present invention has the general formula (2) R, C00X.

(However, in the formula, R7 and R2 are independently hydrogen or C0
0X2, and R1 and R1 are coox at the same time
.

and R1 is hydrogen, a methyl group, or a hydroxyl group, and X and X independently represent hydrogen, an alkali metal, or an ammonium group. A copolymer of the two or a vinyl compound of the general formula
, cooy (wherein Y represents an alkyl group having 1 to 8 carbon atoms, a hydroxyalkyl group having 2 to 5 carbon atoms, or an alkanolamine salt) represents an acid amide group, a phenyl group, or a nitrile group. ) is a copolymer with a vinyl compound represented by

Specific examples of vinyl compounds represented by the general formula ■ are:
Acrylic acid, methacrylic acid, maleic acid, fumaric acid, α
- Hydroquine acrylic acid or their alkali metal or ammonium salts, etc. In addition, examples of the vinyl compound represented by the general formula (2) include alkyl acrylates such as methyl acrylate, ethyl acrylate, butyl acrylate, and 2-ethylhexyl acrylate; alkyl methacrylates such as methyl methacrylate, ethyl methacrylate, and butyl methacrylate; and 2-hydroxyethyl Examples include acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, monoethanolamine salt or jetanolamine salt of acrylic acid, acrylamide, styrene, styrene sulfonic acid, acrylonitrile, and imbutylene.

Specific examples of particularly preferred polymer compounds include the following. General ceremony! Homopolymers and copolymers of vinyl compounds represented by include polyacrylic acid, polymethacrylic acid, polymaleic acid, poly(α- and droxyacrylic acid), (meth)acrylic acid, -maleic acid copolymer, (meth)acrylic acid, Acid-7malate copolymers and their alkali metal and ammonium salts, especially the sodium and ammonium salts. In addition, as a copolymer of a vinyl compound represented by general formula I and a vinyl compound represented by general formula ■, (meth)acrylic acid-
2-hydroxyethyl acrylate copo+, 1-v-1
Examples include (meth)acrylic acid-2-hydroxyethyl methacrymonoethanolamine salt copolymers, maleic acid-styrene sulfonic acid copolymers, and alkali metal or ammonium salts, especially sodium or ammonium salts. In the copolymer, the vinyl compound represented by the general formula (2) accounts for 50 mol% or less, preferably 30 mol% or less.

The amount of water required for forming tablets in the present invention can be effectively adjusted mainly by adjusting the amount of water in the binder, but if there is water released due to external pressure or temperature rise during tabletting, this should be taken into consideration. It goes without saying that you can include it.

By using the method according to the present invention described above, a tablet composition with excellent moldability and storage stability and suppressed hygroscopic reaction can be obtained. Further, according to the present invention, even when the tablet is for oral use, it can be applied by incorporating a food additive as a polymer compound, so the scope of use of the present invention can be further expanded.

In order to make the present invention easier to understand, specific examples of effervescent tablets will be mainly described below, but the present invention is not limited to the following specific examples.

The following test method was used to evaluate the effectiveness of the polymer compound according to the main invention as a binder for effervescent tablets.

Thoroughly mixed sample powder was placed in a tube with an inner diameter of 30 m and an outer diameter of 35 m5.
41 pieces were filled in a vinyl chloride mold having a depth of s mm, and a pressure of 30 tons was applied to the entire surface of the mold for 1 minute.

When the tablet was removed from the mold of the finished molded product, the moldability of the sample was judged as ○ if it came off cleanly, Δ if it was slightly deformed, and × if it was considerably deformed.

In addition, by placing the molded product obtained in the same manner in a laminated film packaging bag, sealing it, and storing it in a constant temperature bath at 40°C, and observing the number of days until the package swells to a certain level,
The storage stability of the samples was determined.

Regarding the measured value of water content of sample components,
Table 1 shows the test results of the compositions found in Examples 1 to 1G and Comparative Examples 1 to 4 shown below using the drying loss rate at 0° C. for 11 hours.

Example 1 Moisture 0.1% by weight 1 Adipic acid 45Ji' with particle size ranging from 20 to 200 meshes of 93mm, reagent grade sodium bicarbonate 50.9mm thoroughly dried under reduced pressure and passed through 32 meshes, and moisture content 7.2mm. Weight% and average molecular weight 4
A powder obtained by uniformly mixing sodium polyacrylate 51 with 000 and 60 mesh passes was used as a sample.

Example 2 The same procedure as in Example 1 was carried out except that 48 g of adipic acid and sodium polyacrylate 2y having an average molecular weight of 4000 and containing 0.9% by weight of water were used.

Example 3 The same procedure as in Example 1 was carried out except that the water content of adipic acid was 33% by weight and the water content of sodium polyacrylate was 3.0% by weight.

Comparative Example 1 In Example 1, instead of sodium polyacrylate,
The same procedure as in Example 1 was conducted except that commercially available special grade anhydrous sodium sulfate with a mesh pass of 60 was used.

Comparative Example 2 In Example 1, 50% of adipic acid was used without using sodium polyacrylate. The same procedure as in Example 1 was performed except that F was used.

Example 4 Ribbon type kneader with inner volume 31 with jacket, 60 mesh bath range of 75%, bulk density 0, 711/Q
Pour 1 liter of C7 malic acid into the kneader while keeping the powder temperature at 85 to 95°C by passing saturated steam into the jacket.
From the upper part, using a II nozzle, add 4% of the aqueous solution containing 30% of sodium polyacrylate with an average molecular weight of i'8000 to 30% by volume.
s cc/Hr range is 92 inches, bulk density 0.74 i
/cc of 7 malic acid coating composition crystals 1. I got xzJ.

A sample was prepared by uniformly mixing 50 g of the fumaric acid coating composition obtained by crushing and classifying the crystals with 32 mesh passes and reagent special grade carbonic acid anhydride (IJum 50.9) with 32 mesh passes.

Comparative Example 3 The same procedure as in Example 4 was carried out except that fumaric acid with a water content of 0.6% by weight and a mesh pass of 32 was used instead of the coated fumaric acid.

Example 5 Succinic acid 40.9% with a moisture content of 0.15% by weight, a particle size in the range of 20 to 200 mesh, and 40.9% of succinic acid, thoroughly dried under reduced pressure,
and reagent grade sodium bicarbonate soy with 32 mesh passes and water 3.4% by weight, average molecular weight 500.
Sodium polyacrylate with 0 mesh bath 10.
A powder obtained by uniformly mixing 9 was used as a sample.

Examples 6 to 9 In Example 5, sodium polymethacrylate (average molecular weight [13,000) with a water content of 3.6% by weight and acrylic acid with a water content of 2.2% by weight] were used instead of sodium polyacrylate in Example 5.
Maleic acid (mole ratio 70:30) copolymer sodium salt (average molecular weight 3,000), acrylic acid/2-hydroxyethyl acrylate (mole ratio 84) with water content 2.4% by weight.
:14) Copolymer) IJum salt (average molecular weight 15,
The same procedure as in Example 5 was carried out except that ammonium polymaleate (average molecular weight 700) with a water content of 4.3% by weight (average molecular weight 700) was used.

Comparative Example 4 The same procedure as in Example 5 was carried out except that sodium polyacrylate was not used and soy was used instead of succinic acid.

Example 10 As in Example 4, a jacketed ribbon with an internal volume of 31 was used in a kneader with 60 passes and a bulk density of 0.7.
5 i/cc of succinic acid was charged and the average molecular weight was reduced to 6.5 i/cc while maintaining the powder temperature at 90-100°C. 30% by weight aqueous solution of OOO sodium polyacrylate
Sprayed at a rate of 6 cc/Hr for 9 hours and heated and dried for an additional 40 minutes to obtain a moisture content of 0.4% by weight, a particle size range of 10 to 100 mesh of 97%, a bulk density of 0.80, il/
1.09 IKg of crystals of a cc phosphoric acid coating composition were obtained.

The crystals were crushed and classified to have a particle size of 96 cm in the range of 20 to 200 mesh. This succinic acid coating composition 50F,
Reagent special grade sodium bicarbonate 50! ! The sample was a powder obtained by uniformly mixing the following.

Example 11 To 90 g of calcium hypochlorite with a particle size of 20 mesh pass thoroughly dried under reduced pressure, 10.0 g of sodium polyacrylate with a moisture content of 2% by weight and with an average molecular weight of 400,000 and a particle size of 48 mesh pass was added. lit was mixed uniformly. The obtained powder was molded in the same manner as the effervescent tablet test method described above.

The tablet was removed cleanly from the mold.

Further, the molded product obtained in the same manner was placed in a polyethylene bag with a thickness of 3 mm, sealed, and stored in a constant temperature bath at 40°C. When the tablet was opened after one month, there was no change in the appearance of the surface of the tablet.

Furthermore, the rate of decrease in the amount of available chlorine was 3%.

Comparative Example 5 The same procedure as in Example 11 was carried out except that sodium polyacrylate was not used. When the tablet was removed from the mold, the υ shape collapsed.

Furthermore, when the tablet was opened after one month, the surface of the tablet was uneven. Furthermore, the rate of decrease in the amount of available chlorine was 17 inches.

Written amendment (spontaneous) Manabu Shiga, Commissioner of the Japan Patent Office, April 1985, 1, Indication of the case, 1983 Patent Application No. 203975, 2, Name of the invention Composition for tablets with suppressed hygroscopic reactivity 3. Relationship with the case of the person making the amendment Patent applicant Takafuta A5-TS, Higashi-ku, Osaka-shi, Osaka Prefecture (462)' E1 Hon Shokubai Kagaku Kogyo Co., Ltd. Representative board member Ishikawa Mitsube 4, Agent 〒-100 Nippon Shokubai Chemical Co., Ltd. Tokyo Branch 03-5, 1-2-2 Uchisaiwai-cho, Chiyoda-ku, Tokyo
02-1651 5. Column 6 of the detailed description of the invention in the specification of the application to be amended. Contents of the amendment (1) In the 7th line of page 20 of the specification, it is stated that ``The reduction rate is 3%.
Met. ” was corrected to ``The rate of decline was 0.3%.'' (2) In the same page 20, line 15, the ``f'' x 7%'' was changed to ``1. .7%.''

1985, month, and 3rd

Claims (5)

[Claims] (1) A tablet composition with suppressed hygroscopic reactivity, which contains a polymer compound having hygroscopic properties, caking properties, and water solubility. (2) Claim (1) characterized in that the polymer compound is composed of a polymer or copolymer of monomers represented by the following general formula [I] and/or [II]. Composition for tablets. [I]▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 and R_2 each independently represent hydrogen or -COOX_2, but at the same time -COOX_2
It is not. R_3 represents hydrogen or a methyl group. Moreover, X_1 and X_2 each represent an alkali metal or an ammonium group. ) [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, A_1 is hydrogen or an alkyl group with 1 to 4 carbon atoms, A_2 is an acid ester group -COOY (however, Y is an alkyl group with 1 to 8 carbon atoms) hydroxyalkyl group or alkanolamine group having 2 to 5 carbon atoms), acid amide group, phenyl group, phenylsulfonic acid group, nitrile group, or alkyl group having 1 to 4 carbon atoms). (3) Average molecular weight of the polymer compound is 300 to 500.0
Claims characterized in that it is in the range of 00 (2
) Tablet composition. (4) Claims (1) characterized in that the product contains a substance that is contraindicated in combination due to its hygroscopic reactivity or a moisture repellent substance.
), (2) or (3). (5) Claims (1) and (2) characterized in that the polymer compound is contained in a range of 0.5 to 50% by weight.
, (3) or (4).