JPS60152424A - Solid preparation - Google Patents

Abstract

PURPOSE:To provide a solid drug preparation having sufficient hardness without using a binder, by compounding a principal solid component with a specific disintegrant. CONSTITUTION:The objective solid drug preparation is prepared by mixing (A) a principal solid drug component with (B) a disintegrant comprising an intramolecular mixed salt of cellulose glycolic acid calcium salt and sodium salt wherein the substitution degree of carboxymethyl group is 0.3-0.8 based on unit glucose anhydride unit, the hydrogen atom of the carboxyl group in the carboxymethyl group is substituted essentially with calcium atom and sodium atom, and the equivalent ratio of calcium atom to sodium atom is 98:2-14:86. The mixed salt is finer than 200 mesh, and its amount in the solid preparation is 2-10wt%. It is prepared in the from of tablet, pill, granule, etc. The principal solid drug component is powdery or crystalline solid pharmaceuticals, fungicides, disinfectants, detergents, perfumery, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a solid formulation using a novel disintegrant.

Disintegrants are used along with excipients, binders, etc. in the preparation of tablets, pills, and other pharmaceutical preparations containing pharmaceuticals. A disintegrant is a drug that imparts disintegration properties to a preparation in water or gastric fluid, and includes starch, polymerized gelatin,
Alginic acid, ion exchange resin, cellulose glyco-μ acid (free acid), cellulose glyco-μ acid (free acid), low degree of substitution
Kise/L/Reese, low-substituted hydroxy 7μ cellulose, etc. are used. Among them, cellulose glyco-μ-acidic acid is tasteless, odorless, white in color, disintegrating,
It has characteristics such as high swelling ratio and compression moldability, and is most widely used. However, although cellulose glyco-μ acid strength μ-sium has good disintegration properties in water, its disintegration rate in gastric fluid is not necessarily high, and when used in large amounts, solid preparations such as tablets may lack hardness. It has been pointed out. For solid preparations, especially tablet molding, for rounding, moldability, and shape retention after molding.
Binding agents are often used. This binder is generally a water-soluble polymeric substance, which dissolves in both liquids and aqueous media to increase their viscosity. Increasing the viscosity of the medium makes it difficult to penetrate into the tablet and reduces the rate of disintegration.

The inventors of the present invention discovered that an inner salt of cellulose mucous acid-shicum in which part of it was replaced with sodium was excellent as a disintegrating agent, and thus completed the present invention. It has also been found that the disintegrant according to the present invention acts as a binder, as will be described later, and therefore the solid preparation aimed at by the present invention can be obtained without necessarily adding a binder.

Thus, according to the present invention, the solid main component and the disintegrating agent have a force μboxymethymu group substitution degree of 0.3 to 0.8 and a force μboxymethymu group substitution degree of 0.3 to 0.8, A cellulose glyco-μ acid in which the hydrogen atom of the group is substantially replaced by a sium atom and a sodium atom, and the equivalent ratio of sium atoms to sodium atoms is within the range of 98=2 to 1.4:86. A solid preparation is provided, characterized in that it contains an intramolecular mixed salt of sodium cicum.

Dosage forms of the solid preparation of this invention include tablets, pills, granules, and the like. The solid main component of this invention is a solid substance such as a powder or crystal, and is a substance (medicine) that is taken internally in a living body and exhibits physiological activity, as well as a substance that is used outside a living body to sterilize, disinfect, disinfect, etc.
Substances that have cleaning, fragrance, etc. effects (bactericidal agents, disinfectants, etc.)
cleaning agents, fragrances, etc.). These solid main components are not particularly limited, and may be used in the above-mentioned dosage form, as long as the dosage form requires disintegration in gastric fluid or water. However, the preferred solid base ingredient is a pharmaceutical,
It may be any of analgesics, anti-inflammatory drugs, antidepressants, antihypertensive drugs, anti-ulcer drugs, anti-ulcer drugs, antibiotics, herbal medicines, etc.

Cellulose glyco-calcium phosphate used in this invention
In the sodium intramolecular mixed salt, the degree of substitution of the force μ poxymethy μ group per anhydroglucose unit in the 7 μlose skeleton is suitably 0.3 or more and 0.8 or less. In addition, the hydrogen atom of the force μ boxy group in the force μ boxymethymu group actually has a force μ
196 in the water substituted by sia and sodium
The pH of the dispersion medium is suitably in the range of 5 to 7. If the carboxymethymu group substitution degree is less than 0.3, the swelling property will be low and it will not show sufficient disintegration, and if it is more than 0.8, it will easily coagulate during neutralization of alkali during the production process. The disintegrability of material 7 is rather reduced.

In addition, the ratio of the strength μsium and sodium of this intramolecular mixed salt is also important.The equivalence ratio of Shikaμsium and sodium is 9B:
2-14: 86 is appropriate. If the sodium content is less than this, the binding property will not be sufficient, and if the sodium content is too large, the disintegration property will deteriorate due to the influence of viscosity.

The intramolecular salt used in this invention is produced by neutralizing cellulose glyco-μ acid with μsium hydroxide or psium hydroxide and sodium carbonate or sodium hydroxide. The procedure is to first neutralize with the calculated amount of ash acid or μsium hydroxide, and then add sodium carbonate or sodium gold hydroxide to react, but it is better to use a mixture of the two alkalis. May be neutralized. However, when neutralizing with mixed alkali, it is preferable to divide the mixture and conduct the reaction in two or more stages.

The solid preparation of the present invention can be manufactured using the necessary ingredients according to conventionally known formulation techniques for tablets, pills, granules, and the like. Taking tablets as an example, the necessary ingredients include solid main ingredients, excipients, binders, disintegrants, etc.
Other substances include lubricants, coloring agents, and flavoring agents. Among these, the intramolecular mixed salt of cellulose glyco-μ acid y sium and sodium of the present invention is used at least as a disintegrating agent, and since it has adhesive properties, it is usually not necessary to add a separate binder. In addition, a mixture of salt with a particle size of 200 mesh is generally used, and for solid preparations 2 to 10
It is used with a weight of 96.

The method for producing the solid preparation of the present invention will be described as follows, taking pharmaceutical tablets as an example.

Pharmaceutical products are mixed evenly with excipients, disintegrants, and other additives (excluding binders), then made into granules, and then lubricants are added and compressed.

To produce the granules, the mixture is usually compressed and then ground into granules, or a suitable wetting agent is added and the granules are dried. Alternatively, the above mixture may be directly compression molded.

Next, the present invention will be explained by giving examples.

Examples 1 to 5 and Comparative Example 1 Purified cellulose glyco-μ acid containing 75% water (degree of substitution 0.39,196 pH of suspension = 4.0) 300
0 part was put into a mixer, 1 part of powdered acidic acid was added, and the mixture was stirred at 30 to 40°C for 2 hours. Furthermore, 2.2 parts of powdered sodium carbonate was added, and stirring was continued for 2 hours. The pH of the aqueous suspension containing the reaction product 196 was 6.8.

It was taken out and dried and crushed. The content of this substance μsium:
The equivalent ratio of sodium (calculated value) is 9f:3. (Example 1) According to the above method, cellulose glyco-acid was neutralized by changing the amounts of μsium subacid and sodium carbonate. The equivalent ratio of sodium to μsium contained in the reaction product calculated from the amount of alkali used is 89:11.6, respectively.
8:32.36:64.15:85 (Example 2
．． 3.4.5).

These reaction products were used as disintegrants, and trial compression (mock tablets) and tablet physical properties were measured under the following conditions.

Tablet Composition Lactose 93.5 Disintegrant 5.0 Ri~ri 10 Magnesium Stearate 0.5 100.0 Weight 96 Tableting Conditions Tablet composition 0.75f was made into tablets with a thickness of 4 using a 15 mm diameter punch Molded into.

Fill a 25m x 2m tube with pharmacopoeia 1st liquid (artificial gastric juice), drop the tablet from the water surface into the liquid, and measure the time required for complete dispersion (liquid temperature 3 CLn = It is shown as an average value of 12+.

hardness The hardness was measured using a Monsanto hardness tester.

As a comparative example, in place of the above-mentioned disintegrant, commercially available cellulose glyco-μacidicum was mixed with ECG505 manufactured by Chirin Kagaku Co., Ltd. and a degree of etherification of 0.55. A similar test was conducted using a 196 suspension with a pH of 5.2). The results are shown in Table 1.

Table 1 Disintegrant Disintegration rate Hardness Example 1 97: 3 0.39 6.8 59 1'
? , 3// 2 89:11 It 7.2 57 1
7.0 II 3 68:32 II 6.8 58 1
7.4u 4 36:64 tt 6.9 59 17
．． 1u 5 15:85 tt 6.9 71 16.
7 Comparative Example 1 100: OO,555,21061'/
,'/The simulated tablets of the examples had better disintegration properties than the comparative examples, but there was no difference in hardness.

Examples 6 to 7 and Comparative Example 2 Using the same disintegrant as used in Examples 1 and 3 and Comparative Example 1, tablets containing aspirin or Sana-min as a medicinal ingredient were prepared, and the physical properties of the tablets were measured.

Tablet composition 1) Aspirin tablet Aspirin (Mitsui Toatsu powder) 55.0 Microcrystalline cellulose (Asahi Kasei puxog 25.0 Lactose (powder)
12.0 Rigidity 2.5 Lubricant (Freund Sangyo, Lagree Wax) 0.5 Disintegrant 5.0 100.0 Weight 96 2) Sanaμmin tablet alumina/magnesium hydroxide (Kyowa Chemical Industry, Sanaμ min(8-vfNA)) 50
．． 0 Lactose (powder) 44.5 Magnesium stearate 0.5 Disintegrant 5.0 100.0 Weight 96 Tableting conditions Tablet machine: Kikusui Seisakusho, Clean Press; Recto 24 Molding conditions 2 Tablet diameter 8 Bait, Tablet The same tests as in Examples 1 to 5 were conducted using a tablet having a thickness of 4111 M and a weight of 200 da, and a tableting pressure of 1.5. The results are shown in Table 2.

Table 2 Example 6a Aspirin 6B: 32 12 6.21
/ 6b Sana μmin 6B:32 17 9.6//
7a 7. X Pirin 15:85 13 6.0η 7
b Sana-min 15:85 11 9.6 Comparative example 2a
71 Pirin 100: O237, 21/2b Sana-Min 100: 0 24 B, Example 4 had improved disintegration properties compared to the comparative example, and the hardness was at the same level.

Examples 8 to 9 and Comparative Example 3 Using the same disintegrant as used in Examples 1 and 3 and Comparative Example 1, tablets containing riboflavin as a medicinal ingredient were prepared, and the physical properties of the tablets were measured.

Riboflavin (manufactured by Orable Yakuhin Kogyo Co., Ltd., Japanese Pharmacopoeia) 1.39 Lactose (powder) 70.83 Aqueous calcium phosphate 11.11 Microcrystal seμp-se 11.11 Disintegrant 5.56 100.00 II kg6 Tableting method Mixed tableting was used, ie, after thoroughly mixing all of the above raw materials, kneading was carried out while adding an appropriate amount of water, and granulation was performed to a size of about 10 meshes. However, in the case of the comparative example, the addition of water did not result in successful granulation, so instead of water, a starch paste solution with a solid content of 8% was added, kneaded, and granulated. The granulated particles were dried at 60°C and
Magnesium stearate powder 0.55 per part by weight
and tablets were added.

Tablet press: manufactured by Hata Seisakusho, rotary type HT-p-18 Molding conditions: Tablet diameter: 8 m Weight: 180 N85 da.

Thickness j) -3.9 to 4.1 m Tests similar to Examples 1 to 5 were conducted. The results are shown in Table 3.

Table 3 tt8b // 4.0 1B1 22 6.1n8Ct
t 4.1 1B2 14 4.3II 9a, 15:
85 7.9 181 36 831/9b II 4
．． 0 182 23 69η 9c tt 4.1 1
81 12 4.4 Comparative Example 3a 1.00:0 3.9
180 48 B, 6//3b// 4.0 1+7
8 30 5Btt 3c l/4yu 17tsu 22
4.0 The comparative example could not be granulated without adding starch as a binder, but the example could be granulated without adding a binder, and the particles had good filling properties into the key press, which was rare. .

Generally, tablets with a binder added have high hardness, but in the case of the example, almost the same hardness was shown even without the addition of a binder. It was found that the disintegrant's disintegrating agent was superior, and the disintegrant used in the example also had the performance as a binder.

Claims (1)

[Scope of Claims] l. A solid main component and a disintegrating agent having the ability to permeate anhydroglucose units and having a poxymethymu group substitution degree of 0.3 to 0.8.
The hydrogen atom of the poxy group in the p-boxymethymu group is substantially replaced by the psium atom and the sodium atom, and the equivalence ratio of the psium and sodium atoms is 98=2.
~14: A solid preparation characterized by containing a cellulose glyco-μ acid power μsium/sodium intramolecular mixed salt within the range of 86. 2. The solid preparation according to claim 1, wherein the solid preparation is a tablet.