JP2007001873A - Coating composition and coated solid preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a coating composition without having the attachment of preparations each other, excellent in coated film strength and also suitable as a solid preparation containing a medicine unstable with water, and the solid preparation coated with the same. <P>SOLUTION: This coating composition used for the solid preparation containing the medicine unstable with water is characterized by containing hydroxypropylcellulose, talc, propylene glycol, and a polyethylene glycol, and having (75:25) to (98:2) blending mass ratio of the propylene glycol to polyethylene glycol. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a coating composition suitable for a solid preparation containing a water-labile drug and a coated solid preparation.

In the case of producing a solid preparation of a pharmaceutical product, the solid preparation is coated to protect the drug in the preparation.
Conventionally, a method of dissolving and coating a water-soluble polymer in water is generally known as a coating method for solid preparations. However, when a “water-unstable drug” is contained in the solid preparation, the water in the coating solution is transferred to the solid preparation and the content stability of the drug over time is lowered. In order to solve this problem, it is possible to use an organic solvent instead of water. However, since a large amount of the organic solvent is used for the coating solution, there is a concern about adverse effects on the environment and the human body.

In addition, for example, a coating method (Patent Document 1) that improves workability and quality by coating with a powdery polymer and a liquid plasticizer that is compatible with the polymer, and acetylation into a polymer coating agent There is known a solid preparation (Patent Document 2) that does not require a drying step with a high product yield by coating with a plasticizer such as monoglyceride.
However, the former has a problem in workability due to adhesion between tablets at the time of coating, and the latter has water or about 5% aqueous solution directly in order to make a film coated with uncoated tablets more dense and complete. It is necessary to spray the film to swell and then dry it. In this case, there is a problem that water is absorbed by a drug unstable to water, which is not preferable.
JP-A-57-171428 JP-A-10-81620

  Accordingly, an object of the present invention is to provide a coating composition, a coated solid preparation, and a method for producing the same, which are suitable for a solid preparation containing a drug that does not adhere to each other, has excellent film strength, and is unstable to water. It is to provide.

  As a result of diligent studies to find the above-mentioned coating composition, a composition in which hydroxypropylcellulose, talc, propylene glycol and polyethylene glycol are blended and the blending mass ratio of propylene glycol and polyethylene glycol is 75:25 to 98: 2 is obtained. It has been found that by using it, a solid preparation containing a drug that does not adhere to each other, has excellent film strength, and is unstable in water can be obtained, and the present invention has been completed.

  That is, the present invention is a coating composition for a solid preparation containing a water-unstable drug, comprising hydroxypropylcellulose, talc, propylene glycol and polyethylene glycol, and the blending mass of propylene glycol and polyethylene glycol The present invention provides a coating composition having a ratio of 75:25 to 98: 2.

  The present invention also relates to a coated solid preparation containing a water labile drug, which contains hydroxypropyl cellulose, talc, propylene glycol and polyethylene glycol, and a blending mass ratio of propylene glycol and polyethylene glycol is 75. A solid formulation coated with a coating composition that is 25: 98: 2 is provided.

  Further, the present invention relates to a method for producing a coated solid preparation containing a water-labile drug, wherein the uncoated tablet or granulated product is mixed with a propylene glycol / polyethylene glycol mixed solution to the drug-containing uncoated tablet or granulated product. The present invention provides a method for producing a coated solid preparation by coating a surface and then performing a coating process with a hydroxypropylcellulose / talc mixed powder.

  INDUSTRIAL APPLICABILITY The present invention can provide a coated solid preparation containing a drug that does not adhere to each other, has excellent film strength, and is unstable to water.

  The “water-unstable drug” as used in the present invention means a drug that causes undesirable changes such as decomposition and coloring due to moisture during the production of a solid preparation. Specific examples of “water-unstable drugs” include methylmethionine sulfonium chloride, amino acids (aspartic acid, cysteine, etc.), various vitamins (vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, nicotinic acid) Amides, vitamin P and its derivatives, etc.) and enzymes (starch digestive enzymes, protein digestive enzymes, fat digestive enzymes, fibrin digestive enzymes, etc.), herbal medicines (Daegu, oxoamidine, and ogi, sorghum, hops, yokuinin, assembly, rokujou) , Licorice, kyoto, keihi, saishin, peony, sojutsu, shrimp, carrot, etc. or dry extract).

  The coating composition of the present invention contains hydroxypropyl cellulose, talc, propylene glycol and polyethylene glycol, and the blending mass ratio of propylene glycol and polyethylene glycol is 75:25 to 98: 2.

The hydroxypropyl cellulose used in the present invention is preferably a low viscosity type grade (viscosity 2 to 10 CPS, 2% aqueous solution, 20 ° C.), particularly preferably an SSL type (viscosity 2 to 2.9 CPS: manufactured by Nippon Soda). is there.
In this invention, it is preferable that the compounding quantity of a hydroxypropyl cellulose is 30-50 mass% (henceforth only%) with respect to coating composition whole quantity, More preferably, it is 35-45%. If it is less than 30%, the coating cracks, which is not preferable.

The talc used in the present invention may be a normal powder, but those having an average particle diameter of 5 to 15 μm are preferred.
In the present invention, the amount of talc is preferably 30 to 50%, more preferably 35 to 45%, based on the total amount of the coating composition. If it exceeds 50%, the coating cracks, and if it is less than 30%, the preparations adhere to each other, which is not preferable.

  In the present invention, the blending amount of propylene glycol is preferably 15 to 19.5%, more preferably 15.5 to 19.5%, based on the total amount of the coating composition. If it exceeds 19.5%, the preparations adhere to each other, and if it is less than 15.5%, film formation is not preferred.

  In the present invention, the blending amount of polyethylene glycol is preferably 0.5 to 5%, more preferably 0.5 to 4.5%, based on the total amount of the coating composition. If it exceeds 5%, the adhesiveness between the film and the uncoated tablet is deteriorated, and if it is less than 0.5%, the preparations adhere to each other, which is not preferable.

Moreover, it is preferable that the polyethylene glycol used by this invention is a liquid at 25 degreeC, and it is preferable that the molecular weight is 200-500. A molecular weight of 600 or more is not preferable because it is too viscous and semi-solid rather than liquid.
Preferable polyethylene glycols include, for example, Macrogol 200 (Nippon Oils and Fats), Macrogol 300 (Nippon Oils and Fats), Macrogol 400 (Nippon Oils and Fats) and the like.

  The blending mass ratio of propylene glycol and polyethylene glycol in the coating composition in the present invention is preferably 75:25 to 98: 2, more preferably 77:23 to 97: 3.

  The viscosity of the propylene glycol / polyethylene glycol mixed solution in the coating composition of the present invention is not particularly limited, but is preferably 50 to 200 CPS, particularly preferably 50 to 150 CPS at 25 ° C., and 50 to 100 CPS is easy to spray and is dried. Most preferable in terms of speed and the like.

The blending mass ratio of hydroxypropyl cellulose and talc is preferably 40:60 to 60:40, and particularly preferably 50:50.
Furthermore, the blending mass ratio of the hydroxypropyl cellulose / talc mixed powder and the propylene glycol / ethylene glycol mixed liquid is preferably 75:25 to 85:15, and more preferably 80:20.

  The coating composition of the present invention can be blended with a base component such as powder other than hydroxypropylcellulose, talc, propylene glycol and polyethylene glycol, but not necessarily blended. It is not limited to these as possible. Examples of the powder include titanium oxide, yellow iron sesquioxide, iron sesquioxide, legal dyes, light anhydrous silicic acid, hydrous silicon dioxide, and the like.

  The coated solid preparation containing the water-unstable drug of the present invention may be prepared by coating an uncoated tablet or granulated product containing a water-unstable drug with the coating composition. Although not limited, the surface of the uncoated tablet or granulated product is coated with a propylene glycol / polyethylene glycol mixed solution on an uncoated tablet or granulated product containing a water labile drug, and then mixed with hydroxypropyl cellulose / talc. It is preferable to produce by coating with a powder. The propylene glycol / polyethylene glycol mixed solution, hydroxypropyl cellulose / talc mixed powder and the like used for coating are the same as those described in the above coating composition.

  The uncoated tablet or granulated product coated in the present invention is produced by a normal production method. For example, a water-unstable drug and an excipient binder, a disintegrant, a lubricant, etc. are added in a small amount of an organic solvent. Etc., and granulation, drying, sizing and, if necessary, an uncompressed tablet of an appropriate size can be obtained through a tableting process.

  A series of steps of coating the surface of an uncoated tablet or granulated product with a propylene glycol / polyethylene glycol mixed solution and then coating with a hydroxypropylcellulose / talc mixed powder is preferably repeated in order to enhance the coating strength, The number of times is 1 to 50 times, more preferably 3 to 30 times, and particularly preferably 5 to 20 times.

  In addition, although the said coating is normally performed in a sugar-coated bread or a breathable coating apparatus, and it is normal to carry out at room temperature, it can also carry out by heating at 20-200 degreeC depending on the case.

  Examples of the form of the solid preparation to be obtained include coated tablets, coated granules, and coated fine granules.

  Furthermore, the solid preparation obtained in the present invention can be made into sugar-coated tablets and the like. Further, when gloss is required, waxing with carnauba wax or the like can be performed according to a conventional method.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to these.
<Production Example 1>
L-arginine hydrochloride 2000 g, oxoamidin powder 2000 g, gamma-oryzanol 400 g, thiamine nitrate 400 g, riboflavin 160 g, pyridoxine hydrochloride 400 g, L-ascorbic acid sodium 4504 g, nicotinic acid amide 1000 g, anhydrous caffeine 2000 g, low-substituted hydroxypropylcellulose 2400 g In addition, 960 g of corn starch, 960 g of hardened oil, 800 g of calcium silicate, and 640 g of hydroxypropyl cellulose were added with 5200 mL of ethanol and 80 g of vitamin A oil and kneaded. After drying, the resulting dried product was granulated. To the obtained granules, 828 g of tocopherol calcium succinate, 1828 g of crystalline cellulose and 240 g of magnesium stearate were added and mixed, and 270 mg of uncoated tablets per tablet were produced with a tableting machine (Collect 19TU, manufactured by Kikusui Seisakusho).

<Example 1>
In a sugar-coated bread (12 inches), 1300 uncoated tablets produced in Production Example 1 are charged, and a propylene glycol / polyethylene glycol 400 (macrogol 400) mixed solution (blending mass ratio 95: 5) is mixed at a rate of about 1.3 g / min. After spraying for 1 minute so as to cover the surface of the tablet, 5.2 g of hydroxypropylcellulose SSL / talc (average particle system of talc 13 μm) mixed powder (blending mass ratio 50:50) was immediately added. This operation of spraying and adding the mixed powder was repeated 11 times to produce 324 mg coated tablets per tablet.

<Example 2>
A coated tablet was produced in the same manner as in Example 1 except that the blending mass ratio of the propylene glycol / macrogol 400 mixture was 90:10.

<Example 3>
A coated tablet was produced in the same manner as in Example 1 except that the blending mass ratio of the propylene glycol / macrogol 400 mixture was 80:20.

<Comparative Example 1>
A coated tablet was produced in the same manner as in Example 1 except that the blending mass ratio of the propylene glycol / macrogol 400 mixture was 100: 0.

<Comparative example 2>
Coated tablets were produced in the same manner as in Example 1 except that the blending mass ratio of the propylene glycol / macrogol 400 mixture was set to 70:30.

<Comparative Example 3>
Coated tablets were produced in the same manner as in Example 1 except that concentrated glycerin was used in place of Macrogol 400 and the blending mass ratio of the propylene glycol / concentrated glycerin mixture was 90:10.

<Comparative example 4>
Coated tablets were produced in the same manner as in Example 1 except that triacetin was used in place of Macrogol 400 and the blending mass ratio of the propylene glycol / triacetin mixture was 90:10.

<Comparative Example 5>
A coated tablet was produced in the same manner as in Example 1 except that the blending mass ratio of the propylene glycol / macrogol 400 mixture was 90:10 and a mixed powder blended with pullulan instead of hydroxypropylcellulose was used.

<Test example>
The prepared tablets of Examples 1 to 3 and Comparative Examples 1 to 5 were evaluated for adhesion and film properties.
Adhesiveness evaluated the adhesiveness of the tablets at the time of coating, and the formulation which adheres was set to x, and the formulation which does not adhere was set to (circle). The film property was rubbed by hand, and the preparation that peeled off from the uncoated tablet was rated as x, and the preparation that did not peel off was marked as ◯.
Table 1 shows the blending mass ratio (%) of each component with respect to the total amount of the coating composition produced in Examples 1 to 3 and Comparative Examples 1 to 5, and the test results in the test examples.

From Table 1, the coated tablets coated with the coating composition of the present invention (Examples 1 to 3) did not adhere to each other and had excellent film strength compared to those obtained in Comparative Examples 1 to 5. It was a thing.
In addition, the coated tablets obtained in Examples 1 to 3 were able to stably hold water-unstable drugs for a long period of time.
Therefore, it was possible to obtain a coating composition suitable for a solid preparation containing a drug that has no adhesion between preparations, excellent film strength, and is unstable to water.

Claims (7)

  A coating composition for a solid preparation containing a water labile drug, comprising hydroxypropylcellulose, talc, propylene glycol and polyethylene glycol, wherein the blending mass ratio of propylene glycol and polyethylene glycol is 75:25 Coating composition characterized in that it is 98: 2.   A coated solid preparation containing a water labile drug, which contains hydroxypropylcellulose, talc, propylene glycol and polyethylene glycol, with a blending mass ratio of propylene glycol to polyethylene glycol of 75:25 to 98: 2. A solid formulation coated with a coating composition.   In the method for producing a coated solid preparation containing a drug unstable to water, the uncoated tablet or granulated product containing the drug is coated with a propylene glycol / polyethylene glycol mixed solution on the surface of the uncoated tablet or granulated product. A method for producing a coated solid preparation, characterized in that a coating process is carried out with a hydroxypropylcellulose / talc mixed powder after coating.   The method for producing a coated solid preparation according to claim 3, wherein the blending mass ratio of propylene glycol and polyethylene glycol is 75:25 to 98: 2.   The method for producing a coated solid preparation according to claim 3 or 4, wherein the blending mass ratio of hydroxypropylcellulose and talc is 40:60 to 60:40.   The series of steps of coating the uncoated tablet surface with a propylene glycol / polyethylene glycol mixed solution and then coating with a hydroxypropylcellulose / talc mixed powder is repeated. A method for producing a coated solid preparation.   The coated solid preparation according to claim 2, which is obtained by the production method according to claims 3 to 6.