KR101318032B1 - Film coated preparation - Google Patents

Abstract

A film coating formulation containing a drug having an odor in a prescription and containing carboxymethyl cellulose sodium in a film layer.

Description

Film Coating Formulations {FILM COATED PREPARATION}

The present invention relates to film coating formulations.

It is known that some medicines have odors that may cause discomfort to the user, and preparations containing them cause a decrease in the compliance of the user, which also affects the value of the product.

In the prior art, for example, the odor could be masked as a dragee. However, the dragee has a drawback in that the tablet is enlarged and cannot be easily taken. Moreover, although it is known that the film-coated tablet coated with the film layer which mix | blended hydroxypropyl methyl cellulose masks unpleasant odor of a chemical | medical agent (Japanese Unexamined-Japanese-Patent No. 2003-300883), the effect of odor suppression was inadequate.

Patent Document 1: Japanese Unexamined Patent Publication No. 2003-300883

DISCLOSURE OF INVENTION

Problems to be solved by the invention

An object of the present invention is to provide a film coating formulation capable of reducing the odor of the drug.

Means for solving the problem

MEANS TO SOLVE THE PROBLEM As a result of earnestly examining in order to achieve the said objective, it was surprisingly found that when it coats with the film layer which mix | blended sodium carboxymethylcellulose, the odor of a prescription can be reduced and completed this invention.

That is, the present invention,

(1) a film coating formulation containing a drug having an odor in a prescription, and containing carboxymethyl cellulose sodium in a film layer,

(2) a film coating formulation containing olmesaltan metoxomil in the formulation and sodium carboxymethylcellulose in the film layer,

(3) a film coating formulation containing olmesaltan metoxomil and a medicament simultaneously in the formulation, and containing carboxymethyl cellulose sodium in the film layer;

(4) 2-amino-5-isobutyl-4- {2- [5- (N, N'-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamide] furanyl} during prescription; A film coating formulation containing thiazole and containing sodium carboxymethylcellulose in the film layer,

(5) The film coating formulation as described in any one of said (1)-(4) which is a coating composition which further contains a coating base or an excipient in a film layer,

(6) The coating base or excipient is hydroxymethylpropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethylcellulose, dextrin, maltodextrin, lactose, D-mannitol, polyvinyl alcohol The film coating formulation as described in said (5) which is 1 type, or 2 or more types of a compound chosen from a polymer, a methacrylic acid copolymer, an aminoalkyl methacrylate copolymer, and the ethyl methacrylate methyl methacrylate copolymer,

(7) the film coating formulation according to the above (5), wherein the coating base or excipient is maltodextrin or dextrin;

(8) The film coating formulation as described in any one of said (1)-(7) which further contains a plasticizer in a film layer,

(9) Plasticizers include macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, diethyl phthalate and triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, The film coating formulation as described in (8) which is 1 type, or 2 or more types of a compound chosen from acetyl triethyl citrate, triethyl citrate, tributyl citrate, and acetyl tributyl citrate,

(10) The film coating formulation according to (8), wherein the plasticizer is dextrose,

(11) The film coating formulation as described in (8) whose plasticizer is triacetin,

(12) The film coating formulation according to any one of (1) to (11), wherein the formulation is a tablet.

(13) The film coating formulation as described in any one of said (1)-(12) whose film layer is 1% (w / w) or more with respect to a prescription weight,

(14) The film coating formulation as described in any one of said (1)-(12) whose film layer is 3% (w / w) or more with respect to a prescription weight,

(15) The film coating formulation as described in any one of said (1)-(12) whose film layer is 6% (w / w) or more with respect to a prescription weight,

(16) The film coating formulation as described in any one of said (1)-(12) whose film thickness of a film layer is 1 micrometer or more,

(17) The film coating formulation as described in any one of said (1)-(12) whose film thickness of a film layer is 5 micrometers or more,

(18) The film coating formulation as described in any one of said (1)-(12) whose film thickness of a film layer is 10 micrometers or more,

(19) It provides a film coating formulation etc. in any one of said (1)-(12) whose film thickness of a film layer is 20 micrometers or more.

Effects of the Invention

Industrial Applicability According to the present invention, it is possible to provide a film coating formulation that is substantially free of odor and that is excellent in marketability.

Carrying out the invention  Best form for

In the film coating formulation in this invention, carboxymethylcellulose sodium (CMC-Na) is contained in a film layer. Thereby, the odor which a chemical | medical agent has can be reduced effectively, and the film coating formulation which is stable also with time passes is obtained. There is no restriction | limiting in particular as content of sodium carboxymethylcellulose in a film layer as long as it is an amount which can effectively reduce the odor which a chemical | medical agent has, Usually, a minimum is 20% (w / w) or more, Preferably it is 30% (w) / w) or more, More preferably, it is 40% (w / w) or more, An upper limit is 90% (w / w) or less, Preferably it is 80% (w / w) or less, More preferably, it is 70 It is below% (w / w).

In the film layer, other coating bases or excipients may be blended as necessary. The type of coating base or excipient is not particularly limited and can be appropriately selected by those skilled in the art. As such coating bases or excipients, for example, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), methyl cellulose, ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), dextrin , Maltodextrin, lactose, D-mannitol, polyvinyl alcohol polymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, ethyl acrylate methyl methyl acrylate copolymer, and the like.

In addition, if desired, the coating composition may contain one or more additives such as plasticizers, excipients, glidants, concealing agents, coloring agents, and preservatives in amounts commonly used.

The kind of plasticizer which can be used for this invention is not specifically limited, A person skilled in the art can select suitably. Such plasticizers include, for example, macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, diethyl phthalate and triethyl citrate, lauric acid, sucrose, dextrose, sorbitol And triacetin, acetyltriethyl citrate, triethyl citrate, tributyl citrate, acetyl tributyl citrate and the like.

As an excipient which can be used for this invention, lactose, mannitol, crystalline cellulose, dextrose, maltodextrin, etc. are mentioned, for example.

Examples of the lubricant that can be used in the present invention include talc, magnesium stearate, calcium stearate, stearic acid and the like.

As a concealment agent which can be used for this invention, a titanium oxide etc. are mentioned, for example.

As a coloring agent which can be used for this invention, a titanium oxide, iron oxide, iron trioxide, yellow iron trioxide, yellow No. 5 aluminum lake talc etc. are mentioned, for example.

As a preservative which can be used for this invention, a paraben etc. are mentioned, for example.

In the present invention, the active ingredient contained in the film coating formulation is not limited by its structure, degree, etc. as long as it has a malodorous drug, but preferably olmesaltanmedoxomil or 2-amino-5-isobutyl-4 -{2- [5- (N, N'-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamide] furanyl} thiazole, and particularly preferably olmesaltanmethoxomyl. In addition, olmesaltanmedoxomil is a disease originating from hypertension or hypertension (more specifically, hypertension, heart disease [angina, myocardial infarction, arrhythmia, heart failure or cardiac hypertrophy], kidney disease [diabetic renal failure, glomerulonephritis or kidney sclerosis]) Or effective for the prevention or treatment of cerebrovascular disease [cerebroinfarction or cerebral hemorrhage], and can be easily produced according to the method described in Japanese Patent No. 2022519 (US Pat. No. 5,616,599) or the like. In addition, 2-amino-5-isobutyl-4- {2- [5- (N, N'-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamide] furanyl} thiazole It is effective for the prevention or treatment of diabetes mellitus, hyperglycemia, impaired glucose tolerance, obesity, diabetes complications (preferably prevention or treatment of diabetes mellitus), and can be easily prepared according to the method described in pamphlet No. 01/47935. .

Moreover, the film coating formulation in this invention may contain another active ingredient as needed. Examples of the active ingredient include diuretics such as trichloromethiazide, hydrochlorothiazide, and benzylhydrochlorothiazide; Azelnidipine, Amlodipine, Benidipine, Benidipine, Nitrendipine, Manidipine, Nikadipine, Nifedipine, Cilnidipine, Eponini Calcium antagonists such as Efonidipine, Barnidipine, Felodipine; Insulin resistance improving agents such as Pioglitazone, Rosiglitazone, Riboglitazone, Riboglitazone, MCC-555, NN-2344, BMS-298585, AZ-242, LY-519818, and TAK-559; HMG-CoA reductase enzymes such as Pravastatin, Simvastatin, Atorvastatin, Rovavastatin, Cerivastatin, Pitavastatin, Fluvastatin ; Although AMP inhibitors, such as SMP-797 and Pactimibe, etc. are mentioned, It is not limited to these. The quantity of these active ingredients is not specifically limited, Usually, the quantity used for a formulation may be used.

As a film coating formulation in this invention, a tablet, a capsule, a powder, a fine granule, a granule, a troche agent, etc. are mentioned, for example, Preferably it is a tablet.

As a manufacturing method of the film coating formulation in this invention, if manufactured using the general method described in publications, such as Powder Technology and Pharmaceutical Processes (D. Chulia et al., Elsevier Science Pub Co (December 1, 1993)) No special restrictions.

The film coating formulation adjusted by this method can be obtained by spraying the film coating liquid containing carboxymethylcellulose sodium as a coating formulation to the object to be coated, such as a tablet and a raw drug. The object to be coated may be sub-coated as necessary. The film coat liquid is obtained by suspending and dissolving carboxymethylcellulose sodium and the above-mentioned additives blended as necessary in water. Spraying of a film coating liquid may be performed by a well-known method, such as using a commercially available film coating machine. What is necessary is just to employ | adopt the conditions in manufacture of a normal film coating formulation as these manufacturing conditions.

The amount of the film coating is not particularly limited as long as it is an amount that can effectively reduce the odor of the drug. The lower limit is usually 1% (w / w) or more, preferably 3% (w / w) based on the prescription weight. ), More preferably 6% (w / w) or more, with an upper limit of 50% (w / w) or less, preferably 20% (w / w) or less, more preferably 10% It is carried out so that it may be (w / w) or less.

The film thickness of the film layer is not particularly limited as long as it is a thickness capable of effectively reducing the odor of the drug, but usually the lower limit is 1 µm or more, preferably 5 µm or more, more preferably 10 µm or more, particularly preferably It is 20 micrometers or more, and an upper limit is 1000 micrometers or less, Preferably it is 500 micrometers or less, More preferably, it is 200 micrometers or less, Especially preferably, it is 100 micrometers or less.

The film thickness of a film layer can be measured with a super depth color 3D shape measurement microscope VK-9500 (Keyence Co., Ltd.).

What is necessary is just to administer the film coating formulation of this invention obtained in this way like a normal formulation.

Hereinafter, although an Example etc. demonstrate this invention further in detail, this invention is not limited to this.

(Example 1)

300 g of olmesaltan medoxo-mil, 1850 g of lactose, 60 g of hydroxypropylmethylcellulose, and 175 g of croscarmellose sodium were mixed with a high-speed stirring granulator (VG-10, Faurek), and then granulated by adding 500 g of purified water, followed by a fluidized bed dryer (powder). Rec). The granulated material was sized with a sizing machine (comyl, powder), and mixed with 15 g of magnesium stearate by a mixer (type V mixer, Tokuju Corporation). The obtained mixture was refined and prescribed | regulated so that it might become weight 160 mg per tablet by the rotary tableting machine (Kikusui Co., Ltd.), the R surface cutting tool of the diameter of 7 mm and the curvature radius of 8 mm.

Using a coating solution obtained by dissolving 100 g of carboxymethylcellulose sodium in 1900 g of purified water to the obtained predetermined 1000 g, the film was coated with a coating machine (Doria coater DRC-300, Faurek) 6% (w / w) based on the predetermined weight. )

(Comparative Example 1)

Using a coating solution in which 140 g of hydroxypropylmethylcellulose, 30 g of talc, and 30 g of titanium oxide were suspended in 1800 g of purified water in a predetermined amount of 1000 g obtained in Example 1, the coating machine (Doria coater DRC-300, Faurek) was 6% by weight. (w / w) coating was carried out to obtain a film-coated tablet (B).

(Test Example 1)

30 tablets of each of the predetermined and film-coated tablets (A) prepared in Example 1 and the film-coated tablets (B) prepared in Comparative Example 1 were placed in a glass bottle and stored at 40 ° C. for 3 hours. The glass bottle was opened, and five test subjects were subjected to the sensory test of odor according to the following evaluation criteria. The results are shown in Table 1.

(Sensory evaluation standard)

<Rating> <contents>

0: no smell

1: Smells a little

2: smells bad

3: pretty stink

Odor evaluation of tablets Subject Prescribed Film coated tablet (A) Film coated tablet (B) One 3 One 3 2 3 0 2 3 3 0 One 4 3 0 One 5 3 0 One Sum 15 One 8

(Example 2)

A coating solution obtained by dissolving 30 g of dextrose and 70 g of carboxymethyl cellulose sodium in 1900 g of purified water was added to the prescribed 1000 g obtained in Example 1, using a coating machine (Doria coater DRC-300, Faurek) 6% (w / w) Coating was carried out to obtain a film coated tablet (C).

(Comparative Example 2)

Using a coating solution in which 140 g of hydroxypropylmethylcellulose, 30 g of talc, and 30 g of titanium oxide were suspended in 1800 g of purified water in a predetermined amount of 1000 g obtained in Example 1, the coating machine (Doria coater DRC-300, Faurek) was 6% by weight. (w / w) coating was carried out to obtain a film coated tablet (D).

(Test Example 2)

30 tablets of the film-coated tablets (C) prepared in Example 1 and the film-coated tablets (D) prepared in Comparative Example 2 were respectively placed in glass bottles, and stored at 40 ° C. for 3 hours. The glass bottle was opened, and five test subjects were subjected to the sensory test of odor according to the following evaluation criteria. The results are shown in Table 2.

(Sensory evaluation standard)

<Rating> <contents>

0: no smell

1: Smells a little

2: smells bad

3: pretty stink

Odor evaluation of tablets Subject Prescribed Film coated tablet (A) Film coated tablet (B) 6 3 One 3 7 3 0 2 8 3 One 2 9 3 One 3 10 3 0 2 Sum 15 3 12

According to this invention, the film coating formulation which is substantially no odor and excellent in a commercial property is obtained.

Claims (16)

A film coating formulation containing olmesaltanmedoxomil in the formulation and sodium carboxymethylcellulose in the film layer. A film coating formulation which simultaneously contains olmesaltanmedoxomil and a medicament in the formulation and contains carboxymethylcellulose sodium in the film layer. 2-amino-5-isobutyl-4- {2- [5- (N, N'-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamide] furanyl} thiazole The film coating formulation which contains and contains sodium carboxymethylcellulose in a film layer. 4. The method according to any one of claims 1 to 3, A film coating formulation which is a coating composition further containing a coating base or excipient in the film layer. 5. The method of claim 4, Coating bases or excipients are hydroxymethylpropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinylalcohol, methylcellulose, ethylcellulose, dextrin, maltodextrin, lactose, D-mannitol, polyvinylalcohol polymer, meta The film coating formulation which is 1 type (s) or 2 or more types of the compound chosen from a crylic acid copolymer, an aminoalkyl methacrylate copolymer, and ethyl acrylate methyl methacrylate copolymer. 6. The method of claim 5, A film coating formulation wherein the coating base or excipient is maltodextrin or dextrin. 4. The method according to any one of claims 1 to 3, Film coating formulation containing a plasticizer further in a film layer. The method of claim 7, wherein Plasticizers include propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, diethyl phthalate and triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, acetyltriethyl citrate, tri The film coating formulation which is 1 type, or 2 or more types of a compound chosen from ethyl citrate, tributyl citrate, and acetyl tributyl citrate. The method of claim 7, wherein A film coating formulation wherein the plasticizer is dextrose. 9. The method of claim 8, A film coating formulation wherein the plasticizer is triacetin. 4. The method according to any one of claims 1 to 3, A film coating formulation wherein the formulation is a tablet. 4. The method according to any one of claims 1 to 3, The film coating formulation whose film layer is 1% (w / w) or more and 50% (w / w) or less with respect to prescription weight. 4. The method according to any one of claims 1 to 3, The film coating formulation whose film layer is 3% (w / w) or more and 50% (w / w) or less with respect to prescription weight. 4. The method according to any one of claims 1 to 3, The film coating formulation whose film thickness of a film layer is 1 micrometer or more and 1000 micrometers or less. 4. The method according to any one of claims 1 to 3, The film coating formulation whose film thickness of a film layer is 20 micrometers or more and 1000 micrometers or less. 9. The method of claim 8, A film coating formulation wherein the polyethylene glycol is Macrogol 6000.