JPH04312523A - Granule having coated layer - Google Patents

Abstract

PURPOSE:To obtain granules preventing bitterness, having a reduced dry feeling in the oral cavity. CONSTITUTION:A core substance is coated with a medicine and the surface of the medicine is further coated with a polymer substance to give granules. A polymer substance soluble in the stomach such as aminoalkyl methacrylate, an enteric polymer substance such as cellulose acetate phthalate or a polymer substance to be dissolved without being influenced by pH, such as methyl cellulose may be used as the polymer substance. Starch having 30-150mum average particle size may be used as the core substance.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention involves coating a core material with a drug,
The invention further relates to granules coated with a polymeric substance.

0002

BACKGROUND OF THE INVENTION When preparing granules of drugs that are easily decomposed by gastric juices or drugs that have a bitter taste, techniques are known in which the granules are coated with various substances. Furthermore, as a method for preventing bitterness, a method using microencapsulation is also known.

0003

[Problems to be Solved by the Invention] However, in the method of coating granules, it is difficult to completely cover the surface of the granules because the granules are amorphous and have many sharp points. Humans have a very sensitive sense of taste, and bitterness in particular is felt in very small amounts, so in order to produce granules that prevent bitterness, it is necessary to make the coating layer thick. Furthermore, when granules are coated with an insoluble coating, they have a rough feel when put in the mouth, and if they remain in the oral cavity even after swallowing, they can get stuck between the teeth and cause discomfort, which greatly affects the feeling of taking them. I have this problem. On the other hand, the method using microencapsulation has drawbacks such as a complicated manufacturing method and difficulty in removing residual solvent. As a result of intensive studies, the present inventors have found that the above-mentioned drawbacks can be solved by employing the method described below, and have completed the present invention.

0004

[Means for Solving the Problems] That is, the present invention provides a granular material in which a core substance is coated with a drug, and a polymer substance is further coated thereon. More specifically, coating the core substance with a drug,
Furthermore, by coating the granules with a polymeric substance dissolved in a solvent by an appropriate means, bitterness is prevented and the roughness in the oral cavity is also reduced. The purpose of the present invention is to prevent this bitter taste and reduce the rough feeling in the oral cavity.

The polymeric substance used in the present invention is not particularly limited, and may be gastrosoluble, enteric, or a polymeric substance that can form a film and dissolve without being affected by pH. Examples of gastrosoluble substances include aminoalkyl methacrylate copolymers, polyvinyl acetal diethylaminoacetate, etc., and enteric substances include:
Methacrylic acid ethyl acrylate copolymer, methacrylic acid methyl methacrylate copolymer, cellulose acetate phthalate, hydroxypropyl methyl cellulose
Examples include sphthalate, carboxymethylethylcellulose, hydroxypropylmethylcellulose acetate succinate, etc., and they can also form a film and
Examples of polymeric substances that dissolve without being affected by this include hydroxypropylmethylcellulose, hydroxypropylcellulose, and methylcellulose.

[0006] The drug according to the present invention is a drug having bitter taste or astringent properties, and also includes a drug that is easily decomposed by gastric acid. Drugs with bitterness or astringency include azelastine hydrochloride, biphemeran hydrochloride, S-(+)
-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido-[4,3:4,5]thieno[3,
2-f][1,2,4]triazolo[4,3-a][1
, 4] diazepine, quinidine sulfate, etc. Drugs that are easily decomposed by gastric acid include various enzyme drugs, gastric acid secretion inhibitors having a pyridine derivative structure, and the like.

[0007] The core material in the present invention means a core material having an average particle diameter of 30 to 150 μm, preferably 4 μm.
The particles are 0 to 100 μm, more preferably 40 to 80 μm. The origin of the core substance is not particularly limited, and may include starch,
Examples include lactose and mannitol, and starch having a relatively smooth surface is particularly preferred. .

[0008] For producing the granules according to the present invention, commonly used equipment such as a fluidized bed granulator can be used. For example, starch particles with an average particle size of 50 μm are fluidized in a fluidized bed granulator, and S-(
+)-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido-[4,3:4,5]thieno[
3,2-f][1,2,4]triazolo[4,3-a]
[1,4] Diazepine is sprayed and adsorbed to obtain coated granules. While stirring the obtained granules in a fluidized bed granulator, a solution of an aminoalkyl methacrylate copolymer dissolved in ethanol was sprayed onto the granules.
Granules coated with gastric soluble substances are obtained. When the obtained granules are put in the mouth, there is no bitter taste and no grainy feeling is felt.
The ratio of the coating layer applied to the granules according to the present invention to the granules before coating depends on the shape of the granules, but cannot be determined unconditionally, but is generally 1% or more, preferably 10% or more,
More preferably, it is 15% or more. The upper limit of the coating amount is not particularly limited, and if it is more than the amount that can prevent bitterness, the work efficiency will be improved.
From the point of view of cost, etc., it is preferable to have as few as possible. The smoother and more spherical the shape of the granules, the more effectively bitterness can be prevented by a small amount of the coating layer. In the case of drugs that are decomposed by stomach acid, it is necessary to cover them until decomposition is prevented. The granular material according to the present invention can be made into granules by adding excipients and the like, and can also be made into tablets by commonly used means.

[0009]

[Operation] The coated granules according to the present invention have no bitter taste or astringent properties, and do not have a rough feeling in the oral cavity, making them very easy to take.

0010

EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to these Examples. Example 1 Potato starch 1800 was added to a fluidization mixer (manufactured by Kawata Co., Ltd.)
S-(+)-(2
-chlorophenyl)-3-cyclopropanecarbonyl-
8,11-dimethyl-2,3,4,5-tetrahydro-
8H-pyrido-[4,3:4,5]thieno[3,2-f
][1,2,4]triazolo[4,3-a][1,4]
A solution containing 20 g of diazepine was added and adsorbed, and the mixture was dried at 60° C. for 8 hours using a shelf dryer (Sanwa Kaki Kogyo). After sieving through a 100-mesh sieve, a small amount of magnesium stearate is added to the above adsorbed material, mixed with a fluidization mixer, and charged into a fluidized bed device (manufactured by Freund). Granules coated by spraying with an ethanol solution of acrylate copolymer were obtained. The amount of coating was 20% based on the granules.

Example 2 300 g of coated particles obtained in Example 1, 480 g of lactose
After mixing 240 g of white sugar, 240 g of mannitol, and 150 g of cornstarch in a fluidized bed device, the mixture was granulated while spraying with a 2% aqueous hydroxypropyl cellulose solution, dried, and sized using a 32-mesh sieve. Then, granules were obtained.

Control example 1 Lactose 770g, mannitol 380g, sucrose 380g,
380g cornstarch, hydroxypropyl cellulose
S-60g was mixed using a fluidized bed granulator.
(+)-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido-[4,3:4,5]thieno[3,2 -f][1,2,4]triazolo[4,3-a
] [1,4] 20g of diazepine in water-ethanol solution 1
After spraying a solution dissolved in 0.000 g of the pellets and granulating them, the pellets were dried and sized with a 32-mesh sieve. Next, a 2% ethanol solution of aminoalkyl methacrylate copolymer was sprayed using a fluidized bed apparatus to obtain coated granules. The amount of coating was 20% based on the granules.

[0013]

[Effects of the Invention] The effects of the present invention will be explained by the following test examples. Test Example 1 Put 1 g of the granules obtained in Example 2 and the control example in your mouth, and
After 0 seconds, the contents of the oral cavity were discharged and the mouth was rinsed, and a sensory test regarding the bitterness at this time was conducted. The test was conducted with five subjects. The results are shown in Table 1.

Table 1 −−−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−
Subject 1 Subject 2 Subject 3 Subject 4 Subject 5
−−−−−−−−−−−− Example 2
± − ±
- - Control example 1
＋ ＋ ＋
＋ ＋−−−−−−−−−−−
−−−−−−−−−−−−−−−−−−−−−−−;
Not feeling bitterness ±; Slightly feeling +; Feeling bitterness As is clear from Table 1, the granular material according to the present invention has a sufficient effect of preventing bitterness.

Test Example 2 1 g of the granules obtained in Example 2 and the control example were put in the mouth, and a sensory test was conducted on the roughness. Test subject 5
The tests were conducted manually and the results are shown in Table 2. Table 2 −−−−−−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−
Subject 1 Subject 2 Subject 3 Subject 4 Subject 5 -------------
−−−−−−−−−−−−−−−−−−−−−−−−
Example 2 ±
− ± −
- Control example 1
＋ ＋ ＋
＋ ＋
−−−−−−−−−−−−−−−−−−−−−
−−−−−−−−−−−−− −; Does not feel rough ±; Slightly feels rough +; Feels rough From the results shown in Table 2, the granules according to the present invention have a rough texture. It is clear that there is little emotion.

Claims (13)

[Claims] Claim 1: Granules in which a core substance is coated with a drug and a polymer substance is further coated thereon. 2. The granular material according to claim 1, wherein the polymeric substance is a gastric soluble polymeric substance. 3. The granular material according to claim 1, wherein the polymeric substance is an enteric polymeric substance. 4. The granular material according to claim 1, wherein the polymeric substance is a polymeric substance that dissolves without being affected by the pH of the solution. 5. The granular material according to claim 1 or 2, wherein the gastrically soluble polymeric substance is an aminoalkyl methacrylate copolymer or polyvinyl acetal diethylamino acetate. 6. The enteric polymeric substance is methacrylic acid ethyl acrylate copolymer, methacrylic acid methyl methacrylate copolymer, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, carboxymethyl The granular material according to claim 1 or 3, which is one or more enteric polymeric substances selected from ethyl cellulose and hydroxypropyl methyl cellulose acetate succinate. Claim 7: The polymeric substance that dissolves without being affected by the pH of the solution is one or more polymeric substances selected from hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose. A granular material according to claim 1 or 4. 8. The granular material according to claim 1, wherein the drug has a bitter taste. 9. The drug is S-(+)-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido-[
4,3:4,5]thieno[3,2-f][1,2,4]
The granule according to any one of claims 1 to 7, which is triazolo[4,3-a][1,4]diazepine. 10. The granular material according to claim 1, wherein the core material has an average particle diameter of 30 to 150 μm. 11. The granular material according to claim 1, wherein the core substance is starch or lactose. 12. A granule characterized by using a granule in which a core substance is coated with a drug and a polymer substance is further coated thereon. 13. A tablet characterized in that it uses granules in which a core substance is coated with a drug and a polymer substance is further coated thereon.