WO2002089823A1

WO2002089823A1 - Method of preserving foaming suppository

Info

Publication number: WO2002089823A1
Application number: PCT/JP2002/003424
Authority: WO
Inventors: Hideyuki Morihisa; Tetsuya Nakamoto; Chika Takeuchi; Fumio Fukata
Original assignee: Kyoto Pharmaceutical Industries, Ltd.
Priority date: 2001-04-27
Filing date: 2002-04-05
Publication date: 2002-11-14
Also published as: JPWO2002089823A1; JP4346311B2

Abstract

A method of preserving a foaming suppository characterized by standing the foaming suppository in a dry atmosphere; and a package for a foaming suppository characterized by having a form whereby the foaming suppository can be preserved in a dry atmosphere, in particular, a sealed package for a foaming suppository having the foaming suppository and a desiccant enclosed therein. Thus, foaming suppositories can be preserved in a stable state at room temperature, in particular, exceeding 15?C.

Description

Specification

How to store effervescent suppositories

Technical field

The present invention relates to a method for storing effervescent suppositories, and more particularly to a package for storing effervescent suppositories, and more particularly, to a method for preserving effervescent suppositories in which effervescent suppositories can be stably present even at room temperature. The present invention relates to a package for storing foamable suppositories.

Background art

Effervescent suppositories include, for example, effervescent suppositories containing sodium bicarbonate and anhydrous sodium dihydrogen phosphate as basic and acidic drugs, respectively, which are commonly used as laxatives for rectal administration Have been.

Effervescent suppositories generally melt in rectal secretion after rectal administration and release carbon dioxide through the normal neutralization reaction (Equation 1) between a basic drug and an acidic drug as described above. .

_{_{_{NaHCO 3 + NaH 2 P0 4 →}}} C0 2 † + H s O + Na 2 HP0 4 ( Equation 1) The released carbon dioxide gas, induced peristalsis of the large intestine, also joined reflection and irritation, raw physical It is known to provide a convenient service.

Effervescent suppositories are susceptible to ambient humidity during storage because they use a normal neutralization reaction. This is because the neutralization reaction as shown in (Equation 1) proceeds in the presence of moisture.

At present, effervescent suppositories are commercially available in a package form in which a suppository is filled in a container made of vinyl chloride as a primary container and then placed directly in a paper box.

Usually, the container made of vinyl chloride used for packaging effervescent suppositories can be used at room temperature (especially above 15 ° C to 30 ° C) because the container itself has moisture permeability. When stored under a relative humidity at which the agent absorbs moisture, the moisture absorbed causes the neutralization reaction between the basic drug and the acidic drug to proceed. As a result, the content of both drugs is reduced, and the amount of carbon dioxide released upon administration is reduced, thereby reducing the therapeutic effect.

In order to minimize the water content of the effervescent suppository during production, The power used to remove water in the process The water cannot be completely removed. Therefore, when foamable suppositories were packed in an aluminum container or the like that does not allow water to permeate in place of a chloride chloride container, when stored at room temperature or the like, the reaction proceeded due to the moisture contained in the suppository itself, and Since the gas does not permeate the aluminum, the container expands and breaks, causing loss of commercial value.

To prevent this, foaming suppositories had to be stored in a cool place (below 15 ° C) in conventional packaging.

The present invention overcomes the drawbacks of the conventionally used methods for storing effervescent suppositories, and can stably store effervescent suppositories even at a temperature exceeding the surrounding urn of 15 ° C. The purpose of this study is to develop a storage method and a package for it.

Disclosure of the invention

The inventors of the present invention have made intensive studies in view of the above problems, and have found that effervescent suppositories are placed in a dry atmosphere, and that effervescent suppositories and desiccants (particularly, silica gel) are stored in a sealed system. Further, they have found that the foamable suppository can be stably stored even at an ambient temperature of more than 15 ° C, and have further studied to complete the present invention. That is, the present invention is as follows.

[1] A method for preserving an effervescent suppository, comprising placing the effervescent suppository in a dry atmosphere. [2] A method for storing an effervescent suppository, comprising storing an effervescent suppository and a desiccant in a sealed system.

[3] The method of the above-mentioned [1] or [2], wherein the effervescent suppository contains an acidic drug and a basic drug.

[4] The storage method according to [3], wherein the acidic drug is anhydrous sodium dihydrogen phosphate, and the basic drug is sodium hydrogen carbonate.

[5] The storage method according to [2], wherein the desiccant is at least one desiccant selected from the group consisting of silica gel, calcium oxide, and calcium chloride. [6] The storage method according to [2], wherein the desiccant is silica gel.

[7] An effervescent suppository package containing an effervescent suppository, wherein the effervescent suppository is in a dry atmosphere. An effervescent suppository package, which is in a form that can be stored under the air.

[8] An effervescent suppository package in which an effervescent suppository and a desiccant are sealed.

[9] The package of the above-mentioned [7] or [8], wherein the effervescent suppository contains an acidic drug and a basic drug.

[10] The package of the above-mentioned [9], wherein the acidic drug is anhydrous sodium dihydrogen phosphate, and the basic drug is sodium hydrogen carbonate.

[11] The package according to [8], wherein the desiccant is at least one desiccant selected from the group consisting of silica gel, calcium oxide, and calcium chloride. [12] The package of the above-mentioned [8], wherein the desiccant is silica gel.

In the present invention, examples of the effervescent suppository include preparations that generate gas upon administration by a neutralization reaction between a basic drug and an acidic drug. Specific examples include rectal preparations which are laxatives that generate carbon dioxide by the reaction between a carbonate and an acidic drug. The formulation may also contain additives for various purposes.

In the present invention, examples of the “putting the effervescent suppository under a dry atmosphere” include, for example, a method of storing the effervescent suppository and the desiccant in a sealed system.

The desiccant is not particularly limited as long as it can be used with pharmaceuticals. Examples thereof include silica gel, calcium oxide, calcium chloride, and silica alumina gel (montmorillonite, alofen, zeolite, molecular sieve, etc.). Silica gel, calcium oxide, and calcium chloride are more preferable, and among them, silica gel is particularly preferable. These desiccants may be used alone or in combination. The amount of the desiccant used is usually 0.004 to 0.077 parts by weight, preferably 0.019 to 0 parts by weight, per part by weight of the foaming suppository. 0.38 parts by weight.

As used herein, the term “sealed” means a state in which gaseous moisture does not enter during daily handling or in a normal storage state (the 13th revised Japanese Pharmacopoeia). As a container for storing the effervescent suppository desiccant in a sealed system, use a sealed external The container is not particularly limited as long as it can prevent the intrusion of moisture from the container. For example, a container such as a multilayer film bag can be used. Laminated film bags made of plastic and aluminum, such as laminated film (wet) bags and stretched polypropylene aluminum laminated film (OPP) bags.

In the present invention, the container for filling the suppository is not particularly limited as long as it is a container made of a material permeable to moisture, but preferred examples thereof include a container made of Shiridani Bull, a container made of polyethylene terephthalate, a container made of polypropylene, and the like. A container made of chloride chloride is particularly preferred.

According to the present invention, effervescent suppositories can be stored at a temperature above 15 ° C, for example at room temperature, more particularly above 15 ° C to 30 ° C.

The upper limit of the temperature range in which an effervescent suppository can be stored according to the present invention varies depending on the stability at high temperatures of the base and additives contained in the suppository. For example, when using an oil-based base, a base having a melting point of 36 ° C or less is usually selected so that it melts at body temperature, so it is preferable to store the base at a temperature at least not exceeding its melting point. .

In the present invention, effervescent suppositories include sodium hydrogencarbonate and anhydrous sodium dihydrogen phosphate, and an oily base (for example, witebzol, pharmazol, cocoa butter, laurin butter, Nikkay butter, hardened oil, etc.). ) In the form of a suppository, and may contain a thickener, a dispersant, and the like in addition to the base.

The preparation is carried out by means known per se.

Examples are described below for the purpose of describing the present invention in further detail, but the present invention is not limited to these examples.

Example

[Preparation Example] Production of effervescent suppository

27,24 g of base witebzol (Mippa Trading) was melted, and 100 g of sodium hydrogen carbonate, 1,360 g of anhydrous sodium dihydrogen phosphate and light soybean soy reticin were added. After mixing in appropriate amounts, 2.6 g each was filled into a container made of butyl chloride to obtain suppositories. Was.

[Example 1] Storage package using silica gel as a desiccant

10 suppositories in a container made of vinyl chloride manufactured in the preparation example. Silica gel desiccant for packaging, type A (Fuji Silysia Chemical) 0.2 lg, 0.2 g, 0.5 lb. 1. O g was placed in a cellonium (ZPFP-30150930, Fujimori Plastic Chemical) bag, the inside air was expelled by pressing the bag, and then sealed by heat sealing using an electric sealer.

[Example 2] Storage package using calcium chloride as a desiccant

10 suppositories and 0.1 g, 0.2 g, 0.5 g, and 1. O g of calcium chloride in a container made of butyl chloride prepared in the preparation example and put in cellonium (ZPFP-30150930, Fujimori Brachemical) bags After putting inside the bag and pushing out the bag to expel the air inside, it was sealed by heat sealing using an electric sealer.

[Example 3] Storage package using calcium oxide as a desiccant

10 suppositories in a container made of butyl chloride prepared in the preparation example. Calcium oxide 0.2 g, 0.2 g, 0.5 g and 1. Og were added to cellonium (ZPFP-30150 930, Fujimori Bra Chemical) It was put in a bag, the inside air was expelled by pressing the bag, and then sealed by heat sealing using an electric sealer.

[Comparative Example 1] Package without desiccant

Put 10 suppositories in a container made of vinylinole chloride manufactured in the preparation example into a cellonium (ZPFP—30150930, Fujimori Plastic Chemical) bag, expel the internal air by holding the bag, and heat seal using an electric sealer. And sealed. [Comparative Example 2] Package in which container is placed directly in a paper box

Ten suppositories in a container made of chloride chloride prepared in Preparation Example were placed directly in a paper box. (Experimental example)

The packages manufactured in Examples and Comparative Examples were allowed to stand in an environment of 35% relative humidity and 35% relative humidity (accelerated test conditions for long-term storage tests) at a temperature of 35%. The appearance of the bag was observed over time. Determination of sodium bicarbonate

2.6 g of a suppository was weighed into a weighing bottle having a constant weight, and 0.175 g of dried anhydrous sodium dihydrogen phosphate was added thereto. To this, 1 mL of water was added, and the mixture was heated at 50 ° C for 20 minutes to completely generate carbon dioxide gas, and then dried at 130 ° C for 3 hours. After cooling in a desiccator, the weight was weighed, and the content of sodium hydrogen carbonate was determined from the amount of generated carbon dioxide gas.

Table 1 shows the measurement results of the sodium hydrogencarbonate content, and Table 2 shows the observation results of the appearance of the cellonium bag. In addition, each symbol of appearance in Table 2 indicates that the state shown in the following criteria was exhibited.

I: No change

J: Swelling of the cellonium bag is slightly observed.

+: Some expansion of the cellonium bag is observed.

+ +: Swelling of the cellonium bag is considerable.

Swelling of the cellonium bag is noticeable.

Example desiccant weight NaHCO ₃ content (%)

/,

(Desiccant) (g)

Start 1 month 2 months 4 months

0.1 101.0 100.9 100.8 Example 1 0.2 99.3 101.1 100.9

(Silica) 0.5 100.9 100.3 100.4

1.0 100.5 101.5 101.1

0.1 100.1 101.4 100.5 Example 2 0.2 100.8 100.6 100.6

(Calcium chloride) 0.5 101.0 100.6 100.8

101.1

1.0 100.7 100.2 100.8

0.1 100.4 100.1 100.1 Example 3 0.2 101.2 101.3 100.0

(Calcium oxide) 0.5 100.8 100.5 99.5

1.0 100.9 100.9 100.3 Comparative Example 1 97.5 93.8 86.0 Comparative Example 2 96.4 90.7 80.1

Table 2

Example desiccant amount

(Desiccant) (g) 1 month 2 months 4 months

0.1

Example 1 0.2

(Silica) 0.5

1.0

0.1 person + Example 2 0.2 Sat +

(Calcium chloride) 0.5 soil

1.0 Sat

0.1 Sat + Example 3 0.2 Shi

(Calcium oxide) 0.5 soil

1.0 Sat Comparative Example 1 + + + + + + From the results in Table 1 above, the sodium bicarbonate content is significantly reduced by the conventional storage method, whereas the sodium bicarbonate content is hardly reduced by the storage method of the present invention. Further, this shows that there is almost no decrease in the content of anhydrous sodium dihydrogen phosphate whose content is reduced by the reaction with sodium hydrogen carbonate. Also, from the results in Table 2, according to the storage method of the present invention, almost no change in the appearance of the package was observed even after long-term storage under an environment of 35 ° C and a relative humidity of 75%. When used as a desiccant, no change in appearance was observed.

Industrial applications

Effervescent suppositories can be stored stably at room temperature, especially at temperatures above 15 ° C. This application is based on a patent application No. 2001-132783 filed in Japan, the contents of which are incorporated in full herein.

Claims

The scope of the claims

1. A method for storing an effervescent suppository, which comprises placing the effervescent suppository in a dry atmosphere.

2. A method for storing an effervescent suppository, comprising storing the effervescent suppository and a desiccant in a sealed system.

3. The storage method according to claim 1, wherein the effervescent suppository contains an acidic drug and a basic drug.

4. The storage method according to claim 3, wherein the acidic drug is anhydrous sodium dihydrogen phosphate, and the basic drug is sodium hydrogen carbonate.

5. The storage method according to claim 2, wherein the desiccant is at least one desiccant selected from the group consisting of silica gel, calcium oxide, and calcium chloride.

6. The storage method according to claim 2, wherein the desiccant is silica gel.

7. An effervescent suppository package comprising an effervescent suppository, wherein the effervescent suppository is in a form that can be stored in a dry atmosphere.

8. An effervescent suppository package in which an effervescent suppository and a desiccant are sealed.

9. The package according to claim 7, wherein the effervescent suppository contains an acidic drug and a basic drug.

10. The package of claim 9, wherein said acidic drug is anhydrous sodium dihydrogen phosphate and said basic drug is sodium bicarbonate.

11. The package according to claim 8, wherein the desiccant is at least one desiccant selected from the group consisting of silica gel, calcium oxide, and calcium salt.

12. The package of claim 8, wherein said desiccant is silica gel.