WO2006123765A1

WO2006123765A1 - Film coated preparation

Info

Publication number: WO2006123765A1
Application number: PCT/JP2006/309993
Authority: WO
Inventors: Takeshi Hamaura; Susumu Hasegawa
Original assignee: Daiichi Sankyo Company, Limited
Priority date: 2005-05-20
Filing date: 2006-05-19
Publication date: 2006-11-23
Also published as: KR20080011394A; JP5000491B2; JPWO2006123765A1; TW200719891A; TWI367755B; CN101171006A; CN101171006B; KR101318032B1

Abstract

A film coated preparation which contains a smelling drug in its formulation and further contains sodium carboxymethylcellulose in the film layer thereof.

Description

Specification

Film coating formulation

Technical field

[0001] The present invention relates to a film coating preparation.

Background art

[0002] It is known that some medicinal products have odors that make the user feel uncomfortable, and formulations containing these cause a decrease in compliance of the user. This also has an impact on product value.

[0003] In the prior art, for example, a sugar-coated tablet, which was capable of masking the odor, the sugar-coated tablet had a drawback that the tablet became large and difficult to take. In addition, film-coated tablets coated with a film layer containing hydroxypropyl methylcellulose

Although it is known to mask unpleasant odors of drugs (Japanese Patent Laid-Open No. 2003-300883), the effect of suppressing odors is insufficient.

Patent Document 1: Japanese Patent Laid-Open No. 2003-300883

Disclosure of the invention

Problems to be solved by the invention

[0004] An object of the present invention is to provide a film coating preparation capable of reducing the odor of a drug.

Means for solving the problem

As a result of intensive investigations to achieve the above object, the present inventors have surprisingly found that the odor of the formulation can be reduced by coating with a film layer containing sodium carboxymethyl cellulose, and the present invention has been completed. I let you.

That is, the present invention provides:

(1) A film coating preparation containing a drug having an odor !, in the formulation, and containing carboxymethyl cellulose sodium in the film layer,

(2) Film coating preparation containing olmesartan medoxomil in the formulation and carboxymethyl cellulose sodium in the film layer, (3) Film coating preparation containing olmesartan medoxomil and other drugs at the same time in the formulation, and sodium carboxymethylcellulose in the film layer,

(4) 2-Amino-5-isobutyl-4- {2- [5- (Ν, Ν'-bis ((S) -l-ethoxycarbole) ethyl) phosphonamide] fullerine in the formulation} A film coating preparation containing thiazole and sodium carboxymethylcellulose in the film layer;

(5) The film coating preparation according to any one of (1) and (4) above, which is a coating composition further containing a coating base or an excipient in the film layer,

(6) Coating base or excipient strength Hydroxymethylpropyl methylcellulose, Hydroxypropinoresenorelose, Polyvinylenopyrrolidone, Polyvinylenoreconole, Methinoresenolate, Ethylcellulose, Dextrin, Maltodextrin, Lactose , D-mannthol, polyvinyl alcohol polymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, and ethyl acrylate “methyl methacrylate copolymer” described in (5) above, which is one or more of the selected compounds Film coating formulation,

(7) Coating base or excipient strength Film coating preparation according to (5) above, which is maltodextrin or dextrin,

(8) The film coating preparation according to any one of (1) and (7) above, wherein the film layer further contains a plasticizer,

(9) Plasticizer strength Macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, phthalate, ethyl triethyl thiolate, lauric acid, sucrose, dextrose, sorbitol, triacetin, aceti (1) a film coating preparation according to (8), which is one or more compounds selected from noretretino recitrate, tritino recitrate, tributino recitrate, and acetiltyl butyl titrate;

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

(11) The film coating preparation according to (8), wherein the plasticizer is triacetin,

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

(13) Film laminating force Any of the above (1) and (12), which is 1% (w / w) or more with respect to the prescribed weight A film coating formulation according to any of the above,

(14) Film laminating force The film coating preparation according to any one of (1) and (12) above, which is 3% (w / w) or more with respect to the prescribed weight,

(15) Film layer strength The film coating preparation according to any one of the above (1) and (12), which is 6% (w / w) or more with respect to the prescribed weight,

(16) The film coating preparation according to any one of (1) and (12), wherein the film layer has a film thickness of 1 μm or more.

(17) The film coating preparation according to any one of claims (1) and (12), wherein the film layer has a film thickness force of 5 m or more.

(18) The film coating preparation according to any one of claims (1) and (12), wherein the film layer has a film thickness force of 10 m or more.

(19) The film coating preparation according to any one of claims (1) and (12), wherein the film layer has a film thickness force of 20 m or more.

[0007]

The invention's effect

[0008] According to the present invention, it is possible to provide a film coating preparation having excellent commercial properties, such as a substantially odor!

BEST MODE FOR CARRYING OUT THE INVENTION

[0009] The film coating preparation of the present invention contains sodium carboxymethyl cellulose (CMC-Na) in the film layer. As a result, a film coating preparation that can effectively reduce the odor of the drug and is stable over time can be obtained. The content of sodium carboxymethylcellulose in the film layer is not particularly limited as long as it can effectively reduce the odor of the drug, but usually the lower limit is 20% (w / w) or more. 30% (w / w) or more, more preferably 40% (w / w) or more, and the upper limit is 90% (w / w) or less, preferably 80% (w / w) ) Or less, more preferably 70% (w / w) or less.

[0010] In the film layer, other coating bases or excipients can 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. Can be selected. Such coating bases or excipients include, for example, polyvinylbiridone (PVP), polyvinyl alcohol (PVA), methylcellulose, ethylcellulose, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), dextrin, malto Mention may be made of dextrin, lactose, D-mannthol, polybutyl alcohol polymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer and ethyl acrylate 'methyl methacrylate copolymer.

[0011] Further, if necessary, the coating composition may be added with one or more additives such as plasticizers, excipients, lubricants, hiding agents, colorants, preservatives and the like in the usual amounts. Can be included.

[0012] The type of plasticizer that can be used in the present invention is not particularly limited, and can be appropriately selected by those skilled in the art. Such plasticizers include, for example, Macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, ethyl phthalate and triethyl taenoate, lauric acid, sucrose, dextrose, sonolebithonole, Examples include triacetin, acetinoretretinorecitrate, trietinoretrate, tributyltitrate, and acetitributylbutyrate.

[0013] Examples of excipients that can be used in the present invention include lactose, mannitol, crystalline cellulose, dextrose, maltodextrin, and the like.

[0014] Examples of the lubricant that can be used in the present invention include talc, magnesium stearate, calcium stearate, and stearic acid.

[0015] Examples of the concealing agent that can be used in the present invention include titanium oxide.

[0016] Examples of the colorant that can be used in the present invention include titanium oxide, iron oxide, iron sesquioxide, yellow iron sesquioxide, yellow No. 5 aluminum lake talc and the like.

[0017] Examples of antiseptics that can be used in the present invention include novene and the like.

[0018] In the present invention, the active ingredient contained in the film coating preparation is not limited by the structure, degree, etc. as long as it is a odorous drug, but preferably olmesartan medoxomil or 2-amino-5 -Isobutyl-4- {2- [5- (Ν, Ν'-bis ((S) -l-ethoxycarbol) ethyl) phosphonamide] fuller} thiazole, particularly preferably olmesartan Medoxomil. Olmesartan medoxomil is not suitable for hypertension or hypertension. Diseases derived from blood pressure (more specifically, hypertension, heart disease [angina, myocardial infarction, arrhythmia, heart failure or cardiac hypertrophy], kidney disease [diabetic nephropathy, glomerulonephritis or nephrosclerosis] Or cerebrovascular disease [cerebral infarction or cerebral hemorrhage]

According to the method described in Japanese Patent No. 2082519 (US Pat. No. 5,616,599), etc., it can be easily produced. Also, 2-amino-5-isobutyl-4- {2- [5- (Ν, Ν'-bis ((S) -l-ethoxycarbol) ethyl) phosphonamide] fuller} thiazole is a diabetic It is effective for the prevention or treatment of hyperglycemia, glucose intolerance, obesity, diabetic complications, etc. (preferably prevention or treatment of diabetes), and easily according to the method described in WO 01Z47935 pamphlet etc. Can be manufactured.

[0019] In addition, the film coating preparation of the present invention may contain other effective components as necessary. Examples of the active ingredient include diuretics such as Trichlor omethiazide, Hydrochlorothiazide ^ Benzylhydrochlorothiazide; Azelnidipine, Amlodipine ), Vedipine, -Trendepin, Manidipine, -Cardipine, Nifedipine, Sildidipine, Efonidipine, Calcium antagonists such as rudidipine (Barnidipine) and ferrodipine (Fel odipine); pioglitazone (Rosigl itazone), riboglitazone (Rivoglitazone), MCC-555, NN-2344, BMS-298585, AZ -242, LY-519818, insulin resistance improvers such as TAK-559; pravastatin, simvastatin, atorvastatin HMG-CoA reductase inhibitors such as (Atorvastatin), Rosu vastatin, Cerivastatin, Pitapastatin, Fluvastatin; SMP-797, Pactimibe Ability that can include ACAT inhibitors, etc. The amount of these active ingredients is not particularly limited, and may be the amount used in conventional preparations.

[0020] Examples of the film coating preparation in the present invention include tablets, capsules, powders, fine granules, granules, troches and the like, and tablets are preferred.

[0021] As a method for producing a film coating preparation in the present invention, Powder Technology and Pharmaceutical Processes (D. Chulia et al., Elsevier Science Pub Co (December 1, 1993)).

[0022] The film coating preparation prepared by this method is obtained by spraying a film coating solution containing carboxymethyl cellulose sodium as a coating base onto an object to be coated such as a tablet or drug substance. Can do. The object to be coated may be sub-coated if desired. The film coating solution is obtained by suspending and dissolving sodium carboxymethylcellulose and the above-mentioned additive blended if necessary in water. The spraying of the film coating solution may be performed by a known method such as using a commercially available film coating machine. These production conditions may be the same as those used in the production of ordinary film coating preparations.

[0023] 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, but usually the lower limit is 1% (w / w) or more with respect to the prescription weight, preferably 3% (w / w) or more, more preferably 6% (w / w) or more, and the upper limit is 50% (w / w) or less, preferably 20% (w / w) or less, based on the prescription weight, More preferably, the concentration is 10% (w / w) or less.

[0024] The thickness of the film layer is not particularly limited as long as it can effectively reduce the odor of the drug, but the lower limit is usually 1 m or more, preferably 5 m or more, more preferably 10 m or more. Particularly preferably, it is 20 μm or more, and the upper limit is 1000 μm or less, preferably 500 μm or less, more preferably 200 μm or less, and particularly preferably 100 μm or less.

[0025] The film thickness of the film layer can be measured with an ultra-deep color 3D shape measuring microscope VK-9500 (Keyence Co., Ltd.).

[0026] The film coating preparation of the present invention obtained by caulking may be administered in the same manner as a normal preparation.

[0027]

Example

Hereinafter, the present invention will be described in more detail with reference to examples and the like, but the present invention is not limited thereto.

(Example 1) Olmesartan medoxomil 300g, lactose 1850g, hydroxypropylmethylcellulose 60g, croscarmellose sodium 175g are mixed with a high-speed stirring granulator (VG-10, Baurec), granulated with 500g of purified water, and fluidized bed dryer (Baurec). The granulated product was sized with a sizing machine (Comil, Norrec) and mixed with 15 g of magnesium stearate in a mixer (V-type mixer, Tokuju Seisakusho). Tablets and uncoated tablets were obtained with a rotary tableting machine (Kikusui Seisakusho) using a mortar with a diameter of 7 mm and an R face with a curvature radius of 8 mm so that the weight of each tablet was 160 mg.

[0029] Using a coating solution in which 100 g of sodium carboxymethylcellulose was dissolved in 1900 g of purified water to 1000 g of the obtained uncoated tablet, the coating machine (Driacoater DRC-300, Paulek) was used to measure the weight of the uncoated tablet. 6% (w / w) coating to obtain film-coated tablets (A).

[0030]

(Comparative Example 1)

Using a coating solution in which hydroxypropylmethylcellulose 140 g, talc 30 g, and titanium oxide 30 g are suspended in 1800 g of purified water, 1000 g of the uncoated tablet obtained in Example 1, a coating machine (Driacoater DRC-300, Norec) is used. The film-coated tablet (B) was obtained by coating 6% (w / w) with respect to the uncoated tablet weight.

[0031]

(Test Example 1)

The uncoated tablet and film-coated tablet (A) produced in Example 1 and 30 film-coated tablets (B) produced 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 subjects performed a sensory test of odor according to the following evaluation criteria. The results are shown in Table 1.

[0032]

(Sensory evaluation criteria)

0: Does not smell

1: Slightly smell 2: smell

3: It smells pretty

(Table 1) Tablet odor evaluation

(Example 2)

Using the coating solution obtained by dissolving 30 g of dextrose and 70 g of sodium carboxymethylcellulose in 1900 g of purified water in the plain tablet lOOOOg obtained in Example 1, using a coating machine (Drycoater DRC-300, Purreck) Coating was 6% (w / w) based on the weight to obtain film-coated tablets (c).

[0033]

(Comparative Example 2)

Using the coating solution obtained by suspending 140 g of hydroxypropylmethylcellulose, 30 g of talc, and 30 g of titanium oxide in 1800 g of purified water to the plain tablet lOOOOg obtained in Example 1, it was applied to a coating machine (Driacoater DRC-300, Palek). Then, 6% (w / w) coating was performed on the weight of the uncoated tablet to obtain a film-coated tablet (D).

[0034]

(Test Example 2)

In a glass bottle, the uncoated tablet produced in Example 1 and the film-coated tablet produced in Example 2 ( C), film-coated tablets produced in Comparative Example 2 (D) 30 tablets each, 40 Stored at C for 3 hours. The glass bottle was opened, and the odor sensory test was conducted by the five subjects according to the following evaluation criteria. The results are shown in Table 2.

(Sensory evaluation criteria)

0: Does not smell

1: Slightly smell

2: smell

3: It smells pretty

(Table 2) Tablet odor evaluation

Industrial applicability

According to the present invention, there is virtually no odor! /. A film coating preparation with excellent commercial properties can be obtained.

Claims

The scope of the claims

[1] A film coating preparation containing olmesartan medoxomil in the formulation and carboxymethylcellulose sodium in the film layer.

[2] A film coating preparation containing olmesartan medoxomil and other drugs at the same time in the formulation, and containing strong loxymethylcellulose sodium in the film layer.

[3] 2-Amino-5-isobutyl-4- {2- [5- (Ν, Ν'-bis ((S) -l-ethoxycarbol) ethyl) phosphonamide] fuller } A film coating preparation containing thiazole and carboxymethyl cellulose sodium in the film layer.

4. The film coating preparation according to any one of claims 1 to 3, which is a coating composition further containing a coating base or an excipient in the film layer.

[5] Coating base or excipient strength Hydroxymethylpropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethyl cellulose, dextrin, maltodextrin, lactose, D-mannthol, poly 5. The film coating preparation according to claim 4, wherein the composition is one or two or more selected from the compounds selected from the group consisting of a vinyl alcohol polymer, a methacrylic acid copolymer, an aminoalkyl methacrylate copolymer and an ethyl acrylate acrylate methyl methacrylate copolymer.

[6] The fine rem coating composition according to claim 5, wherein the coating base or excipient is maltodextrin or dextrin.

7. The film coating preparation according to any one of claims 1 to 6, further comprising a plasticizer in the film layer.

[8] The plasticizer is macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, decyl phthalate and triethyl taenoate, lauric acid, sucrose, dextrose, sorbitol, triacetin, aceti 8. The fine remedy coating preparation according to claim 7, wherein the preparation is one or more of compounds selected from noretretino recitrate, tritino recitrate, tributino recitrate, and acetiltributyl citrate.

[9] The film coating preparation according to [7], wherein the plasticizer is dextrose.

10. The film coating preparation according to claim 8, wherein the plasticizer is triacetin.

[11] The film coating preparation according to any one of [1] to [10], wherein the preparation is a tablet.

[12] Film layer strength The film coating preparation according to any one of claims 1 to 11, wherein the film coating strength is 1% (w / w) or more with respect to the prescribed weight.

[13] The film coating preparation according to any one of claims 1 to 11, wherein the film coating strength is 3% (w / w) or more based on the prescribed weight.

14. The film coating preparation according to any one of claims 1 to 11, wherein the film layer has a film thickness force of 1 μm or more.

[15] The film coating preparation according to any one of [1] to [11], wherein the film layer has a film thickness force of 20 m or more.