JPH0222225A - Solid preparation containing inhibitor of secretion of acid in stomach - Google Patents

Abstract

PURPOSE:To obtain the title preparation of tablet, capsule, granule, etc., having excellent stability by blending an inhibitor of secretion of acid in the stomach such as benzimidazole-based compound with magnesium oxide and mannitol. CONSTITUTION:1 pt.wt. inhibitor of secretion of acid in the stomach (especially sodium salt of 2-[{4-(3-methoxypropoxy)-3-methylpyridine-2-y1}methylsulfinyl]-1H- benzimidazole) is blended with 0.2-5 pts.wt. magnesium oxide and 1.5-5 pts.wt. mannitol to give the title preparation. The preparation has improved stability by addition of magnesium oxide and mannitol, is rapidly disintegrated under a humidifying condition and in an acidic-neutral aqueous solution, is not extremely discolored and readily pharmaceutically manufactured.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a stabilized solid preparation containing a gastric acid secretion inhibitor.

[Prior Art and Problems to be Solved by the Invention] Recently developed benzimidazole compounds having an H''-ATPage inhibitory effect are therapeutic agents for peptic ulcers that strongly suppress gastric acid secretion.

Because its action is strong and persistent, it is attracting attention as a next-generation peptic ulcer treatment that can replace histamine H2 receptor antagonists such as cimetidine. In particular, 2-Nu-(
3-Methoxypropoxy)-3-methylpyridine-2-
It has been confirmed in animal experiments that the gastric acid secretion suppressing effect of sodium salt (methylsulfinyl)-18-benzimidazole is strong and has a moderate duration of action, and is expected to be clinically useful.

However, the stability of the benzimidazole-based metal compound is poor, and it rapidly decomposes and becomes significantly colored, especially under humid conditions and in an acidic to neutral aqueous solution. Therefore, when formulating these compounds into oral dosage forms, it is necessary to adequately stabilize them.

[Means to solve the problem]

As a result of intensive studies aimed at stabilizing gastric acid secretion inhibitors, the present inventors discovered that the above problems could be solved by incorporating magnesium oxide and mannitol into gastric acid secretion inhibitors, and were able to complete the present invention. It was.

That is, the present invention provides a solid preparation containing a gastric acid secretion inhibitor, which is characterized in that it contains magnesium oxide and mannitol.

In the present invention, the gastric acid secretion inhibitor is a gastric acid secretion inhibitor that rapidly decomposes under humidified conditions and in an acidic to neutral aqueous solution and is noticeably colored, and is, for example, a benzimidazole compound. Examples include {4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methylsulfinyl]-1H-benzimidazole sodium chloride.

In the present invention, commercially available magnesium oxide and mannitol may each be used, and the amounts of magnesium oxide and mannitol in the solid preparation of the present invention are as follows: 1 part by weight of the gastric acid secretion inhibitor. Desirable ranges include 0.2 to 5 parts by weight of magnesium oxide and 1.5 to 5 parts by weight of mannitol, but the range is not limited to these, and excipients such as crystalline cellulose may be added as necessary. It's okay.

The solid preparation of the present invention can take the form of any formulation that is normally orally administered to humans, such as tablets, granules, fine granules, and capsules.

The solid preparation of the present invention can be manufactured by a method similar to the manufacturing method of conventional preparations.For example, in the case of tablets, it is granulated by a method such as fluidized bed granulation or transfer granulation, and then compressed into tablets. And it is sufficient.

〔Example〕

EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 2-[{4-(3-methoxypropoxy)-3-methylbilidin-2-yl)methylsulfinyl]-1H-benzimidazole sodium salt (hereinafter referred to as compound A)
A mixture of 10 g of magnesium oxide, 2 g of magnesium oxide, and 50 g of mannitol was granulated by adding 20 g of ethanol.

After drying the product at 40°C for 4 hours and sizing it with a 20-mesh sieve, magnesium stearate 0
．． 5 g was added, mixed, and tableted using a single-shot tablet machine to obtain tablets.

Example 2 Tablets were obtained in the same manner as in Example 1 except that 5 g of magnesium oxide was used instead of 2 g of magnesium oxide.

Example 3 Tablets were obtained in the same manner as in Example 1 except that 10 g of magnesium oxide was used instead of 2 g of magnesium oxide.

Control Example 1 A mixture of 10 g of Compound A and 10 g of magnesium oxide was granulated by adding 10 g of ethanol.

After drying it at 40℃ for 4 hours and sizing it with a 20-mesh sieve, magnesium stearate 1
g was added, mixed, and tableted using a single-shot tablet machine to obtain tablets.

Example 4 10 g of compound A was mixed with 15 g of mannitol and 10 g of magnesium oxide, and 2 g of hydroxypropyl cellulose was added.
was dissolved in 10 g of ethanol and granulated to give 40
It was dried at ℃ for 4 hours. Thereafter, the mixture was sieved through a 20-mesh sieve, 1.2 g of magnesium stearate was added and mixed, and the mixture was tableted using a single-shot tablet machine to obtain tablets.

Example 5 In Example 4, instead of 10 g of magnesium oxide, 2 g of hydroxypropyl cellulose, 10 g of ethanol, 30 g of magnesium oxide, 6 g of hydroxypropyl cellulose
Tablets were obtained in the same manner as in Example 4 except that 15 g of g1 ethanol was used.

Example 6 In Example 4, 15 g of mannitol and 10 g of magnesium oxide were added.
g1 Hydroxypropylcellulose 2g1 Ethanol 1
Tablets were obtained in the same manner as in Example 4, except that 30 g of mannitol, 50 g of magnesium oxide, hydroxypropyl cellulose Log, and 50 g of ethanol were used instead of 0 g.

〔Effect of the invention〕

The effects of the present invention will be explained by the following test examples.

Test Example 1 The tablets obtained in Examples 1, 2.3 and Control Example 1 were placed in a glass bottle, sealed in a cold place (below 5°C) and at 55°C, and 25"CR875% and 40° CR175
% conditions, each was left open for 10 days.

Table 1 shows the results of changes in appearance.

As is clear from the results shown in Table 1, the appearance change was significantly improved by blending mannitol with magnesium oxide.

Table 1 ~... No change ±... Some changes observed compared to the cold place +...
・Pregnancy where a change is observed...Fence where a considerable change is observed...A significant change is observed Test Example 2 The tablets obtained in Examples 4 and 5.6 were placed in a glass bottle and placed in a cool place (below 5°C). Under conditions of 55°C, seal tightly and heat at 40°C.
The cells were left open for 10 days under the condition of 75% CRH.

Table 2 shows the results of changes in appearance.

As is clear from the results shown in Table 2, the change in appearance was significantly improved by blending magnesium oxide and mannitol in an appropriate ratio.

Table 2

Claims (1)

[Scope of Claims] 1. A solid preparation containing a gastric acid secretion inhibitor, characterized in that it contains magnesium oxide and mannitol as a gastric acid secretion inhibitor. 2. The solid preparation according to claim 1, wherein the gastric acid secretion inhibitor is a benzimidazole compound. 3. The benzimidazole compound is 2-[{4-(3-
3. The solid preparation according to claim 2, which is sodium salt of methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1H-benzimidazole. 4. The blending amount of magnesium oxide and mannitol is 0.00% of magnesium oxide and mannitol per 1 part by weight of the gastric acid secretion inhibitor.
The solid preparation according to any one of claims 1 to 3, which contains 2 to 5 parts by weight and 1.5 to 5 parts by weight of mannitol. 5. The solid preparation according to any one of claims 1 to 4, which is a tablet, capsule, or granule.