JPH0465813B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a powder composition that has excellent powder fluidity, has good quantitative feedability to a tablet molding machine, and is capable of producing tablets with little weight fluctuation.
Specifically, the present invention relates to a powder composition containing cellulose calcium glycolate having a bulk specific gravity within a specific range as a disintegrant. After solid drugs such as tablets are ingested, they disintegrate in the digestive juices of the stomach and intestines, releasing their medicinal ingredients, which are then absorbed into the human body through the walls of the stomach and intestines. While being held stable,
In order to ensure sufficient disintegration in digestive fluids, a disintegrant is often used. Calcium glycolate is most commonly used as a pharmaceutical disintegrant because it has advantages such as being tasteless, odorless, white, and having good disintegration properties, swelling ratio, compression moldability, etc. Listed in the Japanese Pharmacopoeia as methylcellulose calcium and ECG
-505 product name (manufactured by Nichirin Chemical Industry Co., Ltd.)
It is commercially available at. Its standard properties are a 1% by weight dispersion in water with a pH of 5-5.5, a particle size of 200 meshes, and a degree of substitution of carboxymethyl groups per anhydroglucose unit of 0.55-0.6. Fibrin calcium glycolate in tablet form:
It is used in an amount of 2 to 15% based on the total weight to give it disintegrability, but it has relatively poor fluidity among powder compositions, and has a diameter of 3 to 20 mm and a depth of 7 to 10 mm.
Bridges tend to form in the mm tableting machine, which tends to reduce the quantitative supply of raw material powder and granules. This low quantitative feedability causes fluctuations in tablet weight, amount of medicinal ingredients, and tablet hardness, and is unfavorable in terms of workability and quality control. The inventors of the present invention found that the quantitative feedability of this powder composition largely depends on the bulk specific gravity of the cellulose calcium glycolate used, and found that the cellulose calcium glycolate having a large bulk specific gravity was used. The present invention was achieved by recognizing that when used, the powder composition for tablet molding has good quantitative supply properties, and tablets without fluctuations in weight or hardness can be obtained. The method for producing cellulose calcium glycolate, which has a large bulk density and is used in the present invention, is basically based on the
According to the method disclosed in Publication No. 43-7960, the free acid form of cellulose glycolic acid is obtained by reacting calcium carbonate in a wet state. By setting the degree of substitution to be high and the degree of neutralization to a high pH range, it is possible to obtain cellulose calcium glycolate having a large bulk specific gravity. In addition, increasing the stirring air during the neutralization reaction and replacing about 1/3 of the calcium carbonate used for neutralization with calcium hydroxide are also favorable conditions for obtaining cellulose calcium glycolate with a large bulk specific gravity. . The bulk specific gravity of the cellulose calcium glycolate used in the present invention is 550 to 900 g/. If the bulk specific gravity is 550 g/or less, it is the same as when using a conventional commercially available product. On the other hand, it is better to have a larger bulk specific gravity, but it is difficult to manufacture a bulk specific gravity of 900g/or more.
Moreover, uniform mixing properties with other components in the powder composition may deteriorate. The bulk specific gravity referred to here is a value measured using the following method for a powder sample. Bulk specific gravity measurement method Prepare a 200ml graduated cylinder and add 200ml of powder sample.
Gradually add to the ml mark and layer. Lift the graduated cylinder so that the distance between the bottom and the floor is 5 cm, release your hand, and let the cylinder fall. After repeating this operation 10 times and reading the volume (ml), weigh the powder sample. Bulk specific gravity (g/) = [Weight (g)/Volume (ml)] x 1000 The present invention will be specifically explained below with reference to Examples. Example 1 and Comparative Example 1 Powder composition using cellulose calcium glycolate with different bulk specific gravity as a disintegrant, ascorbic acid as a medicinal ingredient, and microcrystalline cellulose (Avicel PH101, manufactured by Asahi Kasei) as an excipient. Tablets were molded from the material by direct compression method. The powder composition and tableting conditions are as follows. Powder composition Ascorbic acid 50.0 Avicel (200mesh impermeable) 42.0 Disintegrant 5.0 Talc 2.5 Magnesium stearate 0.5 100.0% by weight Tableting conditions Tableting machine: Rotary powder molding machine No. 8F-3B Kikusui Seisakusho Molding conditions: Tablet diameter: 7.6 mm Thickness: approx. 4.0 mm Powder is supplied to the molding machine using an open feed, and the tablets are compressed by changing the powder filling depth and tableting pressure level, and the average weight and weight deviation of the tablets (n = 30 ),
The average hardness, hardness deviation (n=5), degree of abrasion, and collapsibility were measured. However, the methods for measuring hardness, abrasion and disintegration are as follows. Hardness: Monsanto hardness meter Abrasion level: Kayagaki type abrasion tester 25 rotations, 20 minutes processing 100 tablets were processed and powdered, and the weight is expressed as a percentage. Disintegration: Disintegration tester according to the Japanese Pharmacopoeia (Toyama Sangyo Co., Ltd.) Measurement temperature: 37 ± 2°C Test liquid: Water and Pharmacopoeia No. 1 liquid (artificial gastric fluid) n = 10: Average value of the time required for disintegration show.
(Seconds) Table 1 shows the properties of cellulose calcium glycolate used as a disintegrant. ( ^* However, the degree of neutralization is expressed as the pH of the medium when the sample is dispersed in 100 times the volume of distilled water.)

[Table] Table 2 shows the results of measuring the physical properties of the tablets.

[Table] The tablets of Example 1 using a disintegrant with high bulk specific gravity (No. 2) are the tablets of Comparative Example 1 (No. 1 is ECG-505).
The weight fluctuation is clearly smaller than that of standard equivalent products). Furthermore, the hardness tended to be slightly higher, but this is thought to be because Example 1 had better filling properties (powder fluidity) than Comparative Example 1. Examples 2 to 3 Comparative Example 2 A similar tableting test was conducted using aspirin as the medicinal ingredient in place of ascorbic acid in Example 1 and Comparative Example 1. Powder composition Aspirin (100mesh does not pass) 55.0 Avicel (200mesh does not pass) 37.1 Disintegrant 5.0 Talc 2.4 Lovely Wax 0.5 100.0% by weight Table 2 shows the properties of cellulose calcium glycolate used as a disintegrant.

[Table] Table 4 shows the results of measuring the physical properties of the tablets. However, the number of weight measurements was 50 and the number of hardness measurements was 20.

[Table] Examples 2 and 3 using disintegrants with high bulk specific gravity
It is thought that the tablets had smaller weight fluctuations than the tablets of Comparative Example 2 and had better filling properties (powder fluidity).

Claims (1)

[Claims] 1. A powder or granular composition consisting of a medicinal ingredient, an excipient, a disintegrant, and additives added as necessary, characterized in that the disintegrant is calcium cellulose glycolate with a bulk specific gravity of 550 g/- to 900 g/- A powder composition for tablets.