JP2002012541A - Film coating composition and odorproof solid preparation using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technique enabling the odorproofness of an odorous medicament-containing solid preparation by a simple method in good operability. SOLUTION: The subject film coating composition comprises pullulan and a surfactant. The other objective odorproof solid preparation is obtained by coating an odorous medicament-containing solid preparation with the above composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a film coating composition, and more particularly to a film coating composition for deodorizing a solid preparation containing an odorous drug and a deodorant solid preparation coated with the same. About.

[0002]

2. Description of the Related Art In general, a solid preparation is sometimes coated with various films for the purpose of controlling dissolution after oral administration, masking bitterness, stabilizing the preparation, and the like.

Examples of the coating base used for the film coating include cellulose derivatives such as hydroxypropylmethylcellulose, hydroxypropylcellulose and ethylcellulose, and acrylic derivatives such as aminoalkyl methalkyl copolymers and methacrylic acid copolymers. Can be

[0004] By the way, it is known that some drugs have an odor that makes the recipient feel uncomfortable. Examples of such drugs include compounds having an SH group, amino acids, bucillamine, and methyl. Methionine sulfonium chloride, ranitidine hydrochloride, famotidine, nizatidine and the like can be mentioned. And, the solid preparation containing these leads to a decrease in compliance of patients taking the solid preparation due to the odor, which also affects the commercial value.

As a technique relating to deodorization of a solid preparation containing a drug having an odor, a method of applying a sugar coating with low gas permeability to the solid preparation has been known. However, this sugar coating requires complicated work steps. In addition, there is a problem that the production cost is high because the production requires a long time, and the obtained solid preparation has a large appearance and is difficult to take. In addition, it was substantially impossible to apply a sugar coating to a preparation in a dosage form such as a granule.

[0006] As another means, there is known a method in which an adsorbent such as activated carbon is put into a packaging material to indirectly perform a deodorizing means.

In such a situation, it is first conceived to deodorize the solid preparation by the film coating which has already been performed on the solid preparation. However, even when a solid preparation is coated using a coating base used for ordinary film coating, the odor generated from the drug cannot be prevented because of the high gas permeability of these film coating bases. Was.

Therefore, it is conceivable to use a film coating base having low gas permeability to deodorize a solid preparation. As a film coating base having a low gas permeability, for example, pullulan, polyvinyl acetal diethylaminoacetate, cellulose acetate phthalate, shellac, hardened oil, gelatin, and the like are known, and pullulan has particularly low oxygen permeability and is easily oxidized. It is used for stabilizing drugs (JP-A-7-70506).

However, since pullulan has strong lubricity, if it is used for coating a solid preparation, it may cause problems such as clogging of spray nozzles, adhesion between tablets, peeling-off, and occurrence of irregularities on the coating surface. In some cases, there was a problem of defective manufacturing.

[0010]

Accordingly, there has been a demand for a technique capable of deodorizing a solid preparation containing a drug having an odor by a simple method with good workability.

[0011]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems. As a result, the addition of a surfactant to pullulan has a sufficient effect on deodorization of a solid preparation. Moreover, it has been found that a film coating composition free from troubles such as clogging of spray nozzles and adhesion of tablets in the coating step can be obtained.

Further, it has been found that a film coating composition having improved adhesion between a solid preparation and a film can be obtained by adding a suspending agent to this film coating composition as required. It was completed.

That is, the present invention provides a film coating composition containing pullulan and a surfactant. The present invention also provides a film coating composition obtained by further adding a suspending agent to the above-mentioned film coating composition. Further, the present invention relates to a solid preparation having an odor-preventing property obtained by coating a solid preparation containing a drug having an odor with the above-mentioned film coating composition.

[0014]

DETAILED DESCRIPTION OF THE INVENTION Pullulan used in the film coating composition of the present invention has a maltotriose content of α-alpha.
It is a water-soluble polysaccharide having 1,6 bonds. The molecular weight of the pullulan and the method for producing the pullulan are not particularly limited, but for example, those produced by a fermentation method are preferable. The average molecular weight of pullulan is preferably 2,000,000 or less, particularly preferably 500,000 or less.

The surfactant used in the film coating composition of the present invention includes an anionic surfactant, a cationic surfactant and a nonionic surfactant. These surfactants may be used alone or in combination of two or more. Among them, examples of the anionic surfactant include an alkyl sulfate, a fatty acid salt, and a sulfonate, and preferably sodium lauryl sulfate. Examples of the nonionic surfactant include polyoxyethylene polyoxypropylene glycol, polyethylene glycol, polyoxyethylene sorbitan ester, polyoxyethylene alcohol ether, polyoxyethylene acyl ester, sorbitan acyl ester, and polyoxysorbitan acyl ester. And glycerin acyl esters. Preferably, the surfactant has a low odor of polyoxyethylene polyoxypropylene glycol having an average molecular weight of 5,900 to 12,50.
Pluronic F68 (manufactured by Asahi Denka Kogyo KK). Furthermore, examples of the cationic surfactant include a trialkylbenzylammonium salt, a tetraalkylammonium salt, and an alkylimidazolium salt. It is desirable that these surfactants are solid or semi-solid at room temperature.

The film coating composition of the present invention comprises:
It is prepared by mixing and homogenizing the above-mentioned pullulan and a surfactant, but the amount of pullulan used is 4
0 to 90% by mass (hereinafter, simply abbreviated as "%"), preferably 50 to 80%, and the amount of the surfactant is preferably 30% or less of the film coating composition, more preferably 5 to 80%. 15%.

The film coating composition of the present invention may further contain a suspending agent to further improve the adhesiveness. The suspending agents used are talc,
Examples thereof include stearic acid, waxes, sucrose fatty acid esters, metal stearate, titanium oxide, hydrated silicon dioxide, light anhydrous silicic acid, calcium carbonate, calcium lactate, and calcium sulfate. Talc is preferably used. These suspending agents may be used alone or in combination of two or more, and the amount thereof may be appropriately changed depending on the type and dosage form of the coating machine, the degree of odor, and the like.
5 to 59% of the total composition is preferred, and more preferably 15 to 59%.
50%.

The film coating composition of the present invention may contain other water-soluble film coating base components as long as the effects of the present invention are not impaired. Other water-soluble film coating base components that can be used include, for example, sodium alginate,
Examples include polyacrylic acid, polyacrylamide, polyethylenamine, starch, gelatin, polyvinyl alcohol, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinylpyrrolidone, and povidone.

The thus obtained film coating composition of the present invention can be coated with a solid preparation containing a drug having an odor to obtain a deodorant solid preparation having virtually no odor. Drugs having an odor contained in this solid preparation,
Although not limited by its structure, degree, etc., in particular, L-cysteine, DL-methionine, bucillamine, methylmethionine sulfonium chloride, ethylcysteine hydrochloride, bacampicillin hydrochloride, cefuroxime axetil, sultamicillin tosylate, diclofenamide, ranitidine hydrochloride , Famotidine, sulfur-containing compounds such as nizatidine, pindolol, sodium valproate, todralazine hydrochloride, tolperisone hydrochloride, trimetadione, salazosulfapyridine, herbal medicines, drugs with specific odors such as crude drugs, flurbiprofen, etc. Drugs having an irritating odor such as

[0020]

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

The following Examples 1-4 and Comparative Example 1
The composition ratios of the film coating compositions used in Nos. 1 to 4 are as shown in Table 1 below.

[0022]

[Table 1]

EXAMPLE 1 2,000 g of L-cysteine, 2,500 g of ascorbic acid
0 g, calcium pantothenate 200 g, low-substituted hydroxypropylcellulose 500 g, hydroxypropylcellulose 200 g and crystalline cellulose 4,
500 g was placed in a stirring granulator, and the Japanese Pharmacopoeia was added, followed by granulation to obtain a composition. This was dried, sieved with 24 mesh, mixed with 100 g of magnesium stearate, and compressed to obtain a plain tablet weighing 200 mg.

The obtained uncoated tablet (4,000 g) was coated with a tablet coating machine (manufactured by Powrex: Doria Coater DRC-50).
0), 204 g of pullulan (average molecular weight: about 200,000; manufactured by Hayashibara Co., Ltd.) and sodium lauryl sulfate 2
After dissolving 8 g in water, 100 g of talc was added, and a coating solution obtained by suspending in purified water was used.
mg of the coated tablet to give a coated tablet weighing 215 mg.

EXAMPLE 2 5,000 g of bucillamine, 800 g of low-substituted hydroxypropylcellulose, hydroxypropylcellulose
100 g was placed in a stirring granulator, and ethanol was added to carry out preliminary granulation. After drying the obtained composition and sieving through 24 mesh, it was transferred to a fluid bed granulator,
After adding and mixing 1,450 g and 500 g of D-mannitol, the mixture was granulated with a binding solution obtained by dissolving 100 g of hydroxypropylcellulose in Ethanol. After granulation, the mixture was dried, sieved with 24 mesh, mixed with 50 g of magnesium stearate, and compressed to give a weight of 16%.
0 mg of the base material was obtained.

4,000 g of the obtained uncoated tablets were placed in a tablet coating machine, and 254 g of pullulan and 36 g of sodium lauryl sulfate were dissolved in water, and 125 g of talc was added thereto. 15 mg of coating was applied to obtain a coated tablet weighing 175 mg.

Example 3 Ranitidine hydrochloride 3,360 g, crystalline cellulose 960
g, 320 g of croscarmellose sodium, 80 g of low-substituted hydroxypropylcellulose and 80 g of magnesium stearate were mixed and compressed to obtain a plain tablet of 75 mg (diameter: 7 mm). This uncoated tablet 4,
800g is put into the tablet coating machine, pullulan 64
After dissolving 9 g and 90 g of sodium lauryl sulfate in water, 319 g of talc was added thereto, and a coating solution obtained by suspending was used to coat 15 mg per tablet to obtain a coated tablet weighing 90 mg.

Example 4 Methylmethionine sulfonium chloride 1,250
g, 2,665 g of D-mannitol and 450 g of crystalline cellulose were placed in a fluidized bed granulator, and granulation was carried out by spraying a solution prepared by dissolving 90 g of hydroxypropylcellulose in 1,800 g of Ethanol in Japan. The obtained composition was dried, sieved with 24 mesh, mixed with 90 g of magnesium stearate, and compressed to obtain 9 tablets.
0 mg of uncoated tablets were obtained.

4,050 g of the uncoated tablet was placed in a tablet coating machine, and aminoalkyl methacrylate copolymer was added.
Using a coating solution prepared by dissolving 792 g of E, 99 g of glycerin fatty acid ester and 99 g of talc in ethanol of Japanese Pharmacopoeia, 20 mg was coated per tablet to obtain a waterproof coated tablet weighing 110 mg.

The obtained waterproof coated tablet 4,400 g
Was again charged into a coating machine, and 405 g of pullulan and 57 g of sodium lauryl sulfate were dissolved in water. Then, 199 g of talc was added thereto, and a coating solution obtained by suspending was used.
5 mg of coated tablets were obtained.

Comparative Example 1 4,000 g of uncoated tablet obtained in Example 1 (200 mg per tablet)
Into the above-mentioned coating machine, and 220 g of pullulan
And Macrogol 6000 (manufactured by Sanyo Chemical Co., Ltd.)
After dissolving 66 g in water, 44 g of talc was added, and using a coating solution obtained by suspension, 15 mg was coated per tablet to obtain a coated tablet weighing 215 mg.

Comparative Example 2 4,000 g of the uncoated tablet obtained in Example 2 (160 mg per tablet)
Into the above-mentioned coating machine,
After dissolving 83 g of Macrogol 6000 g in water, 55 g of talc was added thereto, and using a coating solution obtained by suspending, 15 mg was coated per tablet to weigh 17 g.
5 mg of coated tablets were obtained.

Comparative Example 3 4800 g of the uncoated tablet (75 mg per tablet) obtained in Example 3 was charged into the above-mentioned coating machine, and 705 g of pullulan was added.
After dissolving 211 g of Macrogol 6000 in water, talc
141 g was added, and the suspension was used for coating.
mg of coated tablets were obtained.

Comparative Example 4 Waterproof coated tablet obtained in Example 4, 4,400 g
(1 tablet, 110 mg) was charged into the coating machine, and 440 g of pullulan and 60000132 g of macrogol were added.
Was dissolved in water, and 88 g of talc was added thereto. Using a coating solution obtained by suspension, 15 mg was coated per tablet to obtain a coated tablet weighing 125 mg.

Example 5 The same procedure as in Example 4 was carried out up to the waterproof coating to obtain a waterproof coated tablet. This waterproof coated tablet 4,40
0 g (110 mg per tablet) was charged again into a coating machine, and a coating solution having a ratio of sodium lauryl sulfate and talc changed as shown in Table 2 below was used to coat 15 mg per tablet and weigh 125 mg. I got a tablet.

[0036]

[Table 2]

Test Example 1 The preparations obtained in Examples 1 to 5 and Comparative Examples 1 to 4 were sealed in aluminum bags and stored at 60 ° C. for 14 days. The aluminum bag was opened, and sensory evaluation of odor was performed by five panelists (A to E) according to the following evaluation criteria.

(Government evaluation criteria) <Score> <Contents> 0: No odor is felt. 1: A weak smell that tells what the smell is. 2: Odor easily perceived. 3: Strong smell. 4: Intense smell.

Table 3 shows the results of the sensory evaluation of the smell performed on Examples 1 to 3 and Comparative Examples 1 to 3. Also,
In Examples 4 and 5 and Comparative Example 4, in addition to the sensory evaluation,
The coating properties, the appearance of the coated tablets, and the defect rate (visual) were also evaluated. Table 4 shows the results.

[0040]

[Table 3]

[0041]

[Table 4]

As shown in Tables 3 and 4, the solid preparation obtained in the present invention is superior to the solid preparation obtained in Comparative Example in terms of coating properties and appearance, and clearly shows a solid preparation containing a odorous drug. The smell could be prevented.

[0043]

Industrial Applicability The film coating composition of the present invention forms a strong deodorant film and is excellent in workability in a coating process. Therefore, by coating a solid preparation containing a drug having an odor with the film coating composition of the present invention, there is substantially no odor,
It becomes possible to provide a deodorant solid preparation having excellent commercial properties. that's all

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/36 A61K 47/36 F-term (Reference) 4C076 AA44 AA58 AA60 BB01 CC21 CC40 DD24F DD25F DD27F DD29F DD41F DD43F DD68F EE27F EE30H EE30T EE51F FF05 FF07 FF09 FF21 FF29 FF52 GG16

Claims (5)

[Claims] 1. A film coating composition comprising pullulan and a surfactant. 2. The surfactant according to claim 1, wherein the surfactant is at least one surfactant selected from an anionic surfactant, a cationic surfactant and a nonionic surfactant. Film coating composition. 3. The film coating composition according to claim 1, further comprising a suspending agent. 4. A suspension agent comprising talc, stearic acid, waxes, sucrose fatty acid ester, metal stearate,
The film coating composition according to claim 3, which is one or more compounds selected from titanium oxide, hydrous silicon dioxide, light anhydrous silicic acid, calcium carbonate, calcium lactate, calcium sulfate, and silicone resin. 5. A deodorant solid preparation obtained by coating a solid preparation containing an odorous drug with the film coating composition according to any one of claims 1 to 4.