JPWO2006123765A1 - Film coating formulation - Google Patents

Abstract

A film coating preparation containing an odorous drug in the formulation and carboxymethylcellulose sodium in the film layer.

Description

  The present invention relates to a film coating formulation.

  It is known that some medicines have odors that make the user feel uncomfortable. It has an influence.

In the prior art, for example, a sugar-coated tablet can be used to mask the odor, but the sugar-coated tablet has a drawback that the tablet becomes large and difficult to take. Further, although it is known that a film-coated tablet coated with a film layer containing hydroxypropylmethylcellulose masks an unpleasant odor of a drug (Japanese Patent Laid-Open No. 2003-300883), the effect of suppressing the odor is not good. It was enough.
JP2003-3000883A

  The objective of this invention is providing the film coating formulation which can reduce the smell which a chemical | medical agent has.

  As a result of intensive studies 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 carboxymethylcellulose, and the present invention has been completed.

That is, the present invention
(1) A film coating preparation containing an odorous drug in the formulation and carboxymethylcellulose sodium in the film layer,
(2) A film coating preparation containing olmesartan medoxomil in the formulation and sodium carboxymethylcellulose in the film layer,
(3) A film coating preparation containing olmesartan medoxomil and other drugs at the same time in the formulation, and sodium carboxymethylcellulose in the film layer,
(4) Contains 2-amino-5-isobutyl-4- {2- [5- (N, N′-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamido] furanyl} thiazole in the formulation. A film coating preparation containing sodium carboxymethylcellulose in the film layer,
(5) The film coating preparation according to any one of the above (1) to (4), which is a coating composition further containing a coating base or an excipient in the film layer,
(6) The coating base or excipient is hydroxymethylpropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethylcellulose, dextrin, maltodextrin, lactose, D-mannitol, polyvinyl alcohol polymer, methacrylic acid copolymer, The film coating preparation according to (5) above, which is one or more compounds selected from aminoalkyl methacrylate copolymers and ethyl acrylate / methyl methacrylate copolymers,
(7) The film coating preparation according to the above (5), wherein the coating base or excipient is maltodextrin or dextrin,
(8) The film coating preparation according to any one of (1) to (7), further containing a plasticizer in the film layer,
(9) The plasticizer is macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, diethyl phthalate and triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, acetyl triethyl chito The film coating preparation according to (8), which is one or more of compounds selected from a rate, triethyl titrate, tributyl titrate, and acetyl tributyl 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) The film coating preparation according to any one of (1) to (12), wherein the film layer is 1% (w / w) or more based on the prescription weight,
(14) The film coating preparation according to any one of (1) to (12), wherein the film layer is 3% (w / w) or more based on the prescription weight,
(15) The film coating preparation according to any one of (1) to (12), wherein the film layer is 6% (w / w) or more based on the prescription weight,
(16) The film coating formulation according to any one of claims (1) to (12), wherein the film layer has a thickness of 1 µm or more.
(17) The film coating preparation according to any one of (1) to (12), wherein the film layer has a thickness of 5 μm or more.
(18) The film coating preparation according to any one of (1) to (12), wherein the film layer has a thickness of 10 μm or more.
(19) The film coating preparation according to any one of (1) to (12), wherein the film layer has a thickness of 20 μm or more.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the film coating formulation which is substantially odorless and excellent in commercial property.

  In the film coating formulation in this invention, sodium carboxymethylcellulose (CMC-Na) is contained in a film layer. Thereby, the odor which a chemical | medical agent has can be reduced effectively, and the stable film coating formulation is obtained also with time. Although there is no restriction | limiting in particular as content of sodium carboxymethylcellulose in a film layer if it is the quantity which can reduce the smell which a chemical | medical agent has effectively, Usually, a minimum is 20% (w / w) or more, Preferably it is 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, it is 70% (w / w) or less.

  In the film layer, other coating bases or excipients can be blended as necessary. The kind of coating base or excipient is not particularly limited, and can be appropriately selected by those skilled in the art. Such coating bases or excipients include, for example, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), methylcellulose, ethylcellulose, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), dextrin, maltodextrin, lactose , D-mannitol, polyvinyl alcohol polymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, and ethyl acrylate / methyl methacrylate copolymer.

  If necessary, the coating composition may contain one or more additives such as plasticizers, excipients, lubricants, masking agents, coloring agents and preservatives in the amount usually used. it can.

  The kind 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. Examples of such 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, Examples thereof include acetyl triethyl titrate, triethyl titrate, tributyl titrate, acetyl tributyl titrate and the like.

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

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

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

  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.

  Examples of preservatives that can be used in the present invention include parabens.

  In the present invention, the active ingredient contained in the film coating preparation is not limited by its structure, degree, etc. as long as it is a odorous drug, but preferably olmesartan medoxomil or 2-amino-5-isobutyl- 4- {2- [5- (N, N′-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamido] furanyl} thiazole, particularly preferably olmesartan medoxomil. Olmesartan medoxomil is used for hypertension or a disease derived from hypertension (more specifically, hypertension, heart disease [angina, myocardial infarction, arrhythmia, heart failure or hypertrophy), kidney disease [diabetic nephropathy. , Glomerulonephritis or nephrosclerosis] or cerebrovascular disease [cerebral infarction or cerebral hemorrhage]), and is described in Patent No. 2082519 (US Pat. No. 5,616,599) and the like According to this method, it can be easily manufactured. In addition, 2-amino-5-isobutyl-4- {2- [5- (N, N′-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamide] furanyl} thiazole is used for diabetes and hyperglycemia. , Effective in prevention or treatment of glucose intolerance, obesity, diabetic complications, etc. (preferably prevention or treatment of diabetes), and easily manufactured according to the method described in WO 01/47935 be able to.

  Moreover, the film coating formulation in this invention may contain the other active ingredient as needed. Examples of the active ingredient include diuretics such as trichloromethiazide, hydrochlorothiazide, and benzylhydrochlorothidipine (Azelnidipine). ), Manidipine, nicardipine, nifedipine, cilnidipine, efonidipine, balnidipine, felodipine ( calcium antagonists such as erodipine; pioglitazone, rosiglitazone, riboglitazone, MCC-555, NN-2344, BMS-298585, AZ-242, LY-5198, LY-5198 Insulin resistance ameliorating agents such as: pravastatin, simvastatin, atorvastatin, rosuvastatin, cerivastatin, pitavastatin Co such as pitavastatin, vavastatin F Enzyme inhibitor; SMP- 97, and the like can be mentioned ACAT inhibitors such as pactimibe (Pactimibe), but is not limited thereto. The amount of these active ingredients is not particularly limited, and the amount usually used for a preparation may be used.

  Examples of the film coating preparation in the present invention include tablets, capsules, powders, fine granules, granules, troches, and the like, preferably tablets.

  As a method for producing a film coating preparation in the present invention, a general method described in a publication such as Powder Technology and Pharmaceutical Processes (D. Chulia et al., Elsevier Science Pub Co (December 1, 1993)) is used. There are no special restrictions.

  The film coating preparation prepared by this method can be obtained by spraying a film coating solution containing sodium carboxymethyl cellulose as a coating base onto an object to be coated such as a tablet or drug substance. 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.

  The amount of film coating is not particularly limited as long as it can effectively reduce the odor of the drug, but the lower limit is usually 1% (w / w) or more, 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, more preferably 10 to the prescription weight. % (W / w) or less.

  The thickness of the film layer is not particularly limited as long as the odor of the drug can be effectively reduced, but the lower limit is usually 1 μm or more, preferably 5 μm or more, more preferably 10 μm or more, particularly preferably 20 μm or more. 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.

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

  The film coating preparation of the present invention thus obtained may be administered in the same manner as a normal preparation.

EXAMPLES Hereinafter, although an Example etc. demonstrate this invention further in detail, this invention is not limited to this.
(Example 1)
Olmesartan medoxomil 300 g, lactose 1850 g, hydroxypropyl methylcellulose 60 g, croscarmellose sodium 175 g were mixed with a high-speed stirring granulator (VG-10, Paulek), granulated with 500 g of purified water, and fluidized bed dryer ( (Pauleck). The granulated product was sized with a sizing machine (Comil, Paulek) and mixed with 15 g of magnesium stearate with a mixer (V-type mixer, Tokuju Seisakusho). Tablets and uncoated tablets were obtained from the resulting mixture using a rotary tableting machine (Kikusui Seisakusho) with a 7 mm diameter mortar and a radius of 8 mm, and a curvature of 8 mm so that the weight per tablet was 160 mg.

  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, 6% (w / w) Coating was performed to obtain film-coated tablets (A).

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

(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 each placed in a glass bottle and stored at 40 ° C. for 3 hours. The glass bottle was opened, and the odor sensory test was carried out by five subjects according to the following evaluation criteria. The results are shown in Table 1.

（実施例２）
実施例１で得られた素錠１０００ｇに、デキストロース３０ｇ、カルボキシメチルセルロースナトリウム７０ｇを精製水１９００ｇに溶解させたコーティング液を用い、コーティング機（ドリアコータ−ＤＲＣ−３００、パウレック）にて、素錠重量に対して６％（ｗ／ｗ）コーティングし、フィルムコーティング錠（Ｃ）を得た。(Sensory evaluation criteria)
<Score><Contents>
0: Does not smell 1: Smells slightly 2: Smells 3: Smells quite

(Example 2)
Using a coating solution obtained by dissolving 30 g of dextrose and 70 g of sodium carboxymethyl cellulose in 1900 g of purified water, using 1000 g of the uncoated tablet obtained in Example 1, in a coating machine (Driacoater-DRC-300, POWREC) On the other hand, 6% (w / w) coating was performed to obtain film-coated tablets (C).

(Comparative Example 2)
Using a coating solution in which 140 g of hydroxypropyl methylcellulose, 30 g of talc, and 30 g of titanium oxide are suspended in 1800 g of purified water, 1000 g of the uncoated tablet obtained in Example 1, and using a coating machine (Doria Coater-DRC-300, Paulek) The film-coated tablet (D) was obtained by coating 6% (w / w) with respect to the uncoated tablet weight.

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

(Sensory evaluation criteria)
<Score><Contents>
0: Does not smell 1: Smells slightly 2: Smells 3: Smells quite

  According to the present invention, a film coating preparation having substantially no odor and excellent merchantability can be obtained.

Claims (15)

  A film coating preparation containing olmesartan medoxomil in the formulation and sodium carboxymethylcellulose in the film layer.   A film coating preparation containing olmesartan medoxomil and other drugs at the same time in the formulation, and sodium carboxymethylcellulose in the film layer.   2-amino-5-isobutyl-4- {2- [5- (N, N′-bis ((S) -1-ethoxycarbonyl) ethyl) phosphonamido] furanyl} thiazole in the formulation, film layer A film coating preparation containing sodium carboxymethylcellulose therein.   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.   Coating base or excipient is hydroxymethylpropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethylcellulose, dextrin, maltodextrin, lactose, D-mannitol, polyvinyl alcohol polymer, methacrylic acid copolymer, aminoalkyl methacrylate The film coating preparation according to claim 4, which is one or more compounds selected from a copolymer and an ethyl acrylate / methyl methacrylate copolymer.   The film coating preparation according to claim 5, wherein the coating base or excipient is maltodextrin or dextrin.   The film coating preparation according to any one of claims 1 to 6, further comprising a plasticizer in the film layer.   Plasticizers are macrogol 6000, propylene glycol, polyethylene glycol, polypropylene glycol, glycerin and sorbitol, glycerin triacetate, diethyl phthalate and triethyl citrate, lauric acid, sucrose, dextrose, sorbitol, triacetin, acetyl triethyl titrate, triethyl The film coating preparation according to claim 7, wherein the film coating preparation is one or more compounds selected from titrate, tributyl titrate, and acetyltributyl titrate.   The film coating preparation according to claim 7, wherein the plasticizer is dextrose.   The film coating preparation according to claim 8, wherein the plasticizer is triacetin.   The film coating preparation according to any one of claims 1 to 10, wherein the preparation is a tablet.   The film coating preparation according to any one of claims 1 to 11, wherein the film layer is 1% (w / w) or more based on the prescription weight.   The film coating preparation according to any one of claims 1 to 11, wherein the film layer is 3% (w / w) or more based on the prescription weight.   The film coating preparation according to any one of claims 1 to 11, wherein the film layer has a thickness of 1 µm or more.   The film coating preparation according to any one of claims 1 to 11, wherein the film layer has a thickness of 20 µm or more.