JPH0383922A - Ibuprofen-containing composition for oral administration - Google Patents

Abstract

PURPOSE:To obtain a readily administrable composition for oral administration, containing ibuprofen and a gastric-soluble high molecular compound and capable of masking unpleasant taste or mucosal irritancy. CONSTITUTION:The objective substance obtained by containing 1-90wt.% ibuprofen or a salt thereof and a gastric-soluble high molecular compound in an amount of 1-20 pts.wt. based on 100 pts.wt. ibuprofen and, as necessary, a disintegration agent (e.g. hydroxypropyl cellulose with a low substitution degree), adding a pharmaceutically acceptable excipient or carrier, etc., thereto, kneading and granulating the resultant mixture according to a conventional method and, as necessary, drying the pharmaceutical as a fine granule or granule. The ibuprofen with antipyretic and analgesic action has unpleasant taste and mucosal irritancy, which are masked by blending the gastric-soluble high molecular compound therewith without using a coating method. Polyvinyl acetal diethylaminoacetate is cited as the gastric-soluble high molecular compound.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to an orally administered composition containing ibuprofen, which is widely used as an antipyretic analgesic. In particular,
The present invention relates to an orally administered composition that masks the unpleasant taste and mucosal irritation of ibuprofen and is easy to take.

(b) Conventional techniques and problems to be solved Ibuprofen and its salts such as sodium salt are
It is known to have an unpleasant taste and mucous membrane irritation. In an attempt to improve these drawbacks, it has been proposed that aluminum hydroxide be added (Japanese Patent Laid-Open No. 63-10
No. 1321). However, this method is applicable to the production of suspensions and tablets, and has not been applied to fine granules or single granules.

In addition, techniques for masking drugs that generally have an unpleasant taste include a method of kneading them into polymer compounds or lipids (Japanese Patent Application Laid-Open No. 64-31721), and a method of encapsulating drugs in microcapsules (U.S. Pat. No. 3,922,379). It has been known. Furthermore, a method is known in which droplets of a drug solution or suspension are coated with particles of a gastrically soluble polymer compound (Japanese Patent Application Laid-open No. 277616/1983). These latter methods have various problems compared to the method of blending aluminum hydroxide, such as requiring special equipment, complicated operations, and poor yield.

Therefore, it has been desired to provide fine granules or granules by masking ibuprofen or its salt by a simple method.

(C) Means for Solving the Problems According to the present invention, ibuprofen or a pharmaceutically acceptable salt thereof as an active ingredient and a gastric soluble amount sufficient to mask the unpleasant taste and irritation of the active ingredient. A composition for oral administration containing ibuprofen, which contains a polymer compound and optionally includes a disintegrant, a pharmaceutically acceptable excipient, or a carrier, and a method for producing the same are provided.

Pharmaceutically acceptable salts of ibuprofen of this invention include, but are not limited to, sodium salts that exhibit an unpleasant taste.

The gastric soluble polymer compound used in this invention refers to a polymer compound that has the property of being dissolved in gastric fluid.

Various types of such polymer compounds are known in the art, mainly as coating agents, and any of them can be used. For example, polyvinyl acetal diethylaminoacetate (Japanese Patent Publication No. 4G-3786), a copolymer of alkyl methacrylate and dialkylaminoalkyl methacrylate (US Pat. No. 3,070,509)
No.), copolymers of alkylvinylpyridine and other monomers (Japanese Patent Publication No. 40-2055, Japanese Patent Publication No. 37-1293)
6, Japanese Patent Publication No. 37-12936), cellulose acetate N, and N-di-n-butyl hydroxy ether (Japanese Patent Publication No. 4G-26358, 1983). Among these, polyvinyl acetal diethylaminoacetate (
available from Sankyo Co., Ltd. as “AEA r Sankyo”),
Alternatively, ethyl acrylate/butyl methacrylate/dimethylaminoethyl methacrylate copolymer (Eudragit E) is preferred.

The composition of this invention preferably contains a disintegrant.

Since the disintegrant influences the release properties and granulation properties of the active ingredient, it is desirable to select and use a disintegrant that provides good effects. From this point of view, low-substituted hydroxypropylcellulose (for example, grade LH-11, 20, 21, 2
2, 23, 31, etc.) have been found to be preferable. Particularly preferred is cellulose in which the degree of substitution with hydroxypropyl groups is about 10.0 to 13.0% (particularly those with a grade of LH-31, etc.).

On the other hand, carriers can be added, such as pharmaceutically acceptable excipients. Preferably, such excipients or carriers are solid and non-acidic.

For example, it is most preferable to use lactose (the amount used is usually 30 to 150 u for 150 iy of ibuprofen,
(preferably 37 to 43 years old). However, it is not particularly limited.

The composition of the present invention may contain a flavoring agent, a flavoring agent, a coloring agent, etc. in addition to the above-mentioned essential components and optional components. As another optional ingredient, the addition of sorbitol will provide a refreshing sensation upon oral administration.

The content of the active ingredient ibuprofen or its pharmaceutically acceptable salt in the composition of the present invention is 1 to 90% by weight,
Preferably it is 5 to 70% by weight.

The gastric soluble polymer compound is used in an amount sufficient to mask the unpleasant taste and mucous membrane irritation of the above-mentioned active ingredient. According to experiments conducted by the inventors of this invention, it is generally 1 to 20 parts by weight, preferably 3 to 10 parts by weight, per 100 parts by weight of the active ingredient.
It has been found that adding parts by weight is effective. The disintegrant can be used generally in an amount of 2 to 50 parts by weight, preferably 20 to 40 parts by weight, per 100 parts by weight of the active ingredient.

Further, the excipient or carrier can be used in an amount sufficient to adjust the above-mentioned content of the active ingredient in the presence of a gastric soluble polymer compound, an optional disintegrant, and the like.

The composition of the present invention can be easily obtained by simply kneading the active ingredient, the gastrosoluble polymer compound, and any other optional ingredients in a conventional manner, granulating it, and drying it if necessary. Therefore, there is no need to perform complicated treatments such as film coating or microcapsules as in conventional methods.

In the above method, the active ingredient is preferably used as a powder with an average particle size of 50 μm or less. Other optional ingredients may be used as powders of similar small average particle size as the active ingredient. In order to uniformly mix the gastric soluble polymer compound, it is preferable to use a solution using a lower alcohol (for example, ethanol), acetone, or a mixture of these and water as a solvent. When used as a solution, drying is required after granulation. Granulation can be carried out by a method known per se in order to form particles of the desired size as fine granules and granules. The fine granules and wi granules thus obtained can be used as they are as oral preparations. However, they could also be made into tablets, capsules, etc. The ibuprofen-containing oral preparation thus obtained can be used in the same manner as conventional ibuprofen oral preparations.

(d) Effects According to the present invention, the unique taste and mucosal irritation of ibuprofen are masked by the mere combination of a gastric soluble polymer compound without using a coating method, and in addition to being easy to take, it also has excellent properties as a preparation. The present invention provides granules or granules, the production of which can be carried out efficiently on an industrial basis.

(e) Examples The present invention will be specifically explained below with reference to Examples and Test Examples.

Example-1 6.000 g of ibuprofen with an average particle size of 50 μ or less, 1.750 g of lactose, and low-substituted hydroxypropyl cellulose (hereinafter abbreviated as L-RPC), grade LH-31
, 2,0009 were uniformly mixed with a mixer. Next, 250 g of polyvinyl acetal diethylamino acetate (hereinafter referred to as AEA) was poured into a kneading rock and mixed with ethanol t and goa9.
A uniformly dissolved solution was added to the mixture, and after about 3 portions were combined, the mixture was passed through a #20 mesh and granulated.

The granules were air-dried for 1 hour and then dried at 40° C. for 4 hours. The dried material was classified using 932g1i, fine particles,
A standard conforming product 9.7249 was obtained.

Example-2 Ibuprofen 60.0% by weight Lactose 17.5% by weight L-RPC 20.0% by weight AEA 2.5% by weight The above compositions other than AEA were mixed uniformly, and the composition was 7.5% by weight relative to AEA. A twice the amount of ethanol was added to uniformly dissolve the AEA ethanol solution, which was then kneaded and then granulated using a basket-type extrusion granulator with a diameter of 0.8xz. Furthermore, the extruded granules were air-dried for 1 hour and then dried at 40° C. for 4 hours. The dried product was classified using a #42 sieve to obtain granules.

Example-3 Sorbitol 7.5009, which was separately granulated into fine granules, was added to the fine granules 2.5009 obtained in Example-1 and mixed to prepare a fine granule containing ibuprofen 15019 in ■9. .

Example 4 Sorbitol 7.5009, which was separately granulated, was mixed with the granules 2.5009 obtained in Example 2 to prepare granules containing ibuprofen 150JI9 per gram.

Comparative Example Using hydroxypropylcellulose instead of AEA used in Example-1, the same procedure was repeated to obtain fine granules. In addition, separately granulated sorbitol 7.5009 was added to 2.500 g of fine particles and mixed, and ibuprofen 18ON? Fine granules containing were obtained.

Test Example = 1 The fine granules obtained in Example 3 of the present invention, the granules obtained in Example 4, and the fine granules obtained in the control example were each administered as ibuprofen to 10 healthy male adults in an amount of 1501 g. A considerable amount of the drug was administered, and evaluation tests for peculiar taste and mucous membrane irritation were conducted. The evaluation time was 2 points: immediately after taking the drug and 10 minutes after taking the drug. The evaluation is based on the degree of peculiar taste and mucous membrane irritation.■ There is a peculiar taste and mucous membrane irritation that cannot be tolerated. ■There is a tolerable peculiar taste and mucous membrane irritation. ■No peculiar taste or mucous membrane irritation. I went with the above three points.

The results are shown in Table 1.

From the results shown in Table 1, the oral preparation of the present invention has
It is clear that ibuprofen has almost no unpleasant taste or mucous membrane irritation, and is extremely easy to take.

Test Example-2 Eve (
Nisnis Pharmaceuticals) as ibuprofen, 150 yen each.
ut [equivalent amount was administered to 12 subjects, and the blood concentrations of both types of agents were measured. Table 2 shows parameters related to bioavailability, and Figure 1 shows changes in blood concentration.

Table 2

[Brief explanation of drawings]

FIG. 1 is a diagram showing the time course of the average blood concentration of ibuprofen in the composition according to the present invention (Example-3) and the control formulation. The 1st Akane Cape → 14-minute Xiangxiangkou (hr) of 1 liter and 1 ton

Claims (1)

[Claims] 1. Contains ibuprofen or a pharmaceutically acceptable salt thereof as an active ingredient and a gastric soluble polymer compound in an amount sufficient to mask the unpleasant taste and irritation of the active ingredient, An ibuprofen-containing composition for oral administration, optionally containing a disintegrant, a pharmaceutically acceptable excipient, or a carrier. 2. The composition according to claim 1, wherein the gastrosoluble polymer compound is polyvinyl acetal diethylaminoacetate, methyl methacrylate/butyl methacrylate, or dimethylaminoethyl methacrylate copolymer. 3. The composition according to claim 1, wherein the disintegrant is low-substituted hydroxypropylcellulose. 4. The ratio of active ingredient, disintegrant, and gastric soluble polymer compound is 1
2. A composition according to claim 1, wherein the composition is from 0:2 to 50:1 to 20 parts by weight. 5. The composition according to claim 1, wherein the active ingredient or its salt is a powder with an average particle size of 50 μm or less. 6. The composition according to claim 1, which is in the form of fine granules or granules. 7. Ibuprofen, which consists of adding a solution of a gastrically soluble polymer compound to a mixture of ibuprofen or its salt, a disintegrant, and a pharmaceutically acceptable excipient, preferably a carrier, followed by kneading, granulation, and drying. Manufacture of a composition for oral administration containing