JPS5942325A - Composition for coating and pharmaceutical preparation of coating - Google Patents

Abstract

PURPOSE:The titled composition useful for pharmaceutical preparation of film coating, having improved water vapor barrier characteristics and masking effect, containing a polyvinyl alcohol having a specific degree of saponification, water, and, if necessary, a hydrophilic organic solvent. CONSTITUTION:A composition for coating, containing a polyvinyl alcohol having >=90mol% free hydroxyl group, water, and, if necessary, a hydrophlilic organic solvent (e.g., methanol). Preferably 5-50wt% macrogol and/or polyoxyethylene polyoxypropylene condensate as an anti-blocking agent to prevent the adhesion between solid drugs based on the polyvinyl alcohol is added to it. The use of the composition for coating provides a pharmaceutical preparation of film coating having not only improved masking effect and water vapor barrier characteristics, but also improved glare protection properties, durability, and gas barrier properties.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compositions for film coating solid drugs.

Until now, organic solvents have been used as solvents for film coating, but the use of water is preferred due to economic efficiency, environmental pollution, fire and explosion risks, and safety of residual solvents. There is.

Coating of solid drugs such as fine particles, granules, or tablets is carried out for the following purposes.

1) Make the appearance of the preparation beautiful.

2) Provides a masking effect to prevent the release of drugs with unpleasant taste, odor, irritation to the oral cavity, etc. from the preparation.

3) Provides moisture resistance to prevent deterioration or deliquescence of the drug in the formulation due to moisture absorption.

4) Provides light-shielding properties to prevent the drug in the formulation from being altered or decomposed by light and provides shielding properties to conceal the content of the formulation.

5) Provides air protection to reduce oxygen permeation when the drug in the formulation is susceptible to oxidation.

6) Provide specific efficacy such that the drug is released from the formulation gradually or after a certain period of time.

7) Provide enteric coating so that the drug is not released in the stomach but in the intestines.

Conventionally, the following are known as examples of coating compositions that can or use water as a solvent.

(■) Polyvinyl acetal diethylaminoacetate is used as the coating base, and fumaric acid.

A coating composition obtained by adding a fine powder coating agent of a coating composition containing stearic acid and hydroxypropyl methylcellulose. (Unexamined Japanese Patent Publication No. 54-8
No. 4020) @) A coating composition comprising an aqueous solution of methylcellulose and/or hydroxypropylmethylcellulose. (Japanese Unexamined Patent Publication No. 129728/1982) However, these compositions have the following drawbacks.

That is, although the composition (I) has excellent moisture proofing properties, it has insufficient masking properties. Furthermore, the formed film itself is colored by light. and drugs (especially amino acids) that have an amide 7 group
There are disadvantages such as color change. The composition (II) has the disadvantage that the coating agent must be made into a fine powder with a particle size of 50 μm or less, and the coating film formed is not uniform and brittle. The composition @) has insufficient moisture-proofing properties and masking effects.

The present inventor studied a coating composition based on polyvinyl alcohol (hereinafter referred to as PTA) in order to obtain a coating composition that can use water as a solvent and has excellent moisture-proofing properties and masking effects.

PVA is a sizing agent for textiles, a paper processing agent, an adhesive, a binder,
It is often used as an emulsion stabilizer or a cosmetic thickener. In pharmaceuticals, PTA with less than 90 mol% of free hydroxyl groups is sometimes used as a binder, and there have been attempts to coat it using it as the main component (Japanese Patent Laid-Open No. 50-1
29728), it has been reported that the solid preparations stick to each other during coating, which is undesirable, and even according to the inventor's experiments, it could not be put to practical use on the lateral side. However, one inventor found that the free hydroxyl group was 9
The inventors have discovered that PTA of 0 mol % or more causes almost no adhesion between solid preparations during coating, and that the formed film has excellent moisture-proofing properties and masking effects, and has thus arrived at the present invention.

That is, the present invention is a coating composition consisting of PVA containing 90 mol % or more of free hydroxyl groups and water.

PTA generally has a molecular structure of -(-0H,, -OH'OH
-), but depending on the manufacturing method, not all hydroxyl groups may be in the free form. Generally, polyvinyl acetate is manufactured by saponifying polyvinyl acetate, but in this case, acetic acid residues may be contained up to about 10 mol%, and the degree of hydrolysis of the acetate ester moiety is determined by the degree of saponification (molar %). In the present invention, the mole% of free hydroxyl groups is 5
What is expressed as - corresponds to what is expressed as the degree of saponification (mol %) in general commercial products, and the following description will be made using the degree of saponification.

The PVA used in the present invention has a saponification degree of 91 to 9.
4 mol%, 950-97.0 mol% and 98.5-10
There are various types such as those containing 0 mol%. The content of PVA is preferably in the range of 5 to 30''W/#%9 and usually 7 to 1%.
5%- is appropriate. In this case, the type and content of I'VA may be appropriately combined so that the size of the sprayed droplets is sufficiently small to enable uniform coating and the surface of the prepared film to be smooth and uniform.

A film made of PVA with a degree of saponification of 90 mol% or more has high moisture resistance, and the dissolution of the film is not affected by pH but depends on temperature. In addition, a film made of PVA with a high degree of saponification by mole is difficult to dissolve in drainage water. Therefore, depending on the purpose of coating, PTA with an appropriate degree of saponification can be used.
For example, in the case where the purpose is moisture resistance, PTA with a saponification degree of 91 to 94 mol% is sufficient. In this case, the formed film has high moisture resistance and does not dissolve in cold water, but dissolves in water at physiological body temperature (87°C).

Suitable for purposes of moisture proofing and mild taste masking. Furthermore, when the purpose is to mask highly irritating drugs, it is preferable to use PVR with a degree of saponification of 98.5 mol % or more. in this case.

The formed film does not dissolve in cold water or in water, acid, or alkaline solutions at physiological body temperature, so it is necessary to contain a water-soluble coating agent in order to improve disintegration and drug elution properties. The water-soluble coating agent may be one that dissolves in water at physiological body temperature, such as P'VA or hydroxypropyl methyl cellulose with a degree of saponification of 94 mol% or less.

It is preferable to use one or more of hydroxypropylcellulose, methylcellulose, and polyvinylpyrrolidone. The amount of the water-soluble coating agent is determined depending on the desired degree of masking and the type of water-soluble coating agent.
A range of 10 to 100 w/w% based on PTA is usually sufficient; for example, when hydroxypropyl methylcellulose is used, a range of 40 to 60 w/w% is preferable in terms of masking time and disintegration of the preparation.

Although it is possible to coat solid drugs with a composition consisting only of water and PVA, the coating operation becomes easier if an anti-blocking agent is added to the composition to prevent solid drugs from sticking to each other. Propylene glycol is used as an anti-stick agent.

Examples include ethylene glyfur, macrogol, and hapolyoxyethylene polyoxypropylene condensates (Pluronic type surfactants).

Macrogol and polyoxyethylene polyoxybu-tetrapyrene condensates with low hygroscopicity are preferred, among which Macrogol 6000 and Pluronic 76B (Asahi Denka Kogyo ■
) is particularly preferred. If the amount of anti-blocking agent is too large, it is not preferable from the viewpoint of moisture resistance, and the amount is 5 to 50 with respect to PvA.
A range of 7% is preferable, and a range of around 20W/v% is particularly preferable.

Although the coating composition of the present invention contains water,
A hydrophilic organic solvent such as methanol, ethanol or propatool may be added as necessary to prevent bacterial contamination of the coating composition. The blending amount is 1. For example, when the purpose is to prevent bacterial contamination, the ethanol content may be about 157% based on the total amount of the composition.

■ Also, in the coating composition of the present invention.

Depending on the purpose of coating the solid drug, inorganic compounds such as titanium oxide, red iron oxide or talc can be used as hiding agents.9 Natural pigments or tar-based pigments can be used as coloring agents, and silicone resin can be used as decolorizing agents.

Glycols such as glycerin or ethylene glycol, ethanolamine or surfactants can also be added as plasticizers.

9 tablets to be coated with the composition of the invention;
This may be carried out using a conventional method such as spraying this composition onto fine particles, granules, etc. and drying.

9- As mentioned above, by using the coating composition of the present invention, not only the masking effect and moisture resistance are excellent, but also
A film-coated preparation with excellent light-shielding properties, concealing properties, long-lasting effects, and air-proofing properties can be obtained, and the composition of the present invention can also be used as a protective coating agent when producing sugar-coated tablets.

Next, a detailed explanation will be given with reference to Examples and Comparative Examples.

Example (a) Take 10 g of PVA (Gohsenol AIJ-06 (manufactured by Nippon Gosei Kagaku Kogyo)) with a degree of saponification of 91 to 94 mol%, add water to disperse it, and then heat it to dissolve it. Add water to make 100-. Pour this liquid onto a flat glass plate and dry it to a thickness of 0. A film of IM was prepared.

(+o) ) pv*(
Take Gohsenol AL-06) 1'09, add water to disperse it, and then heat it to dissolve it.
00 Add 29 and dissolve, then add 10- and water to make 100-. This liquid was poured onto a flat glass plate and dried to prepare a film with a thickness of 0.1 layer.

(c) Take 10 g of pvA (Go-Septanol AT, -06) with a degree of saponification of 91 to 94 mol%, add water to disperse it, and then heat it to dissolve it. Add 2 g of hardware [Bulloni, RiF1a (manufactured by Asahi Denka Kogyo Steel 9)] and dissolve, then add water to make 100@t. Pour this liquid onto a glass plate,
Dry to a thickness of 0.1! A film of IB was prepared.

As a comparative example) Hydroxypropyl methylcellulose (TO, -5R (Shin-Etsu Chemical Co., Ltd.) was used as a commercially available water-soluble coating agent.
Take 109 (manufactured by)) and dissolve it in water to make 100gLt. Pour this liquid onto a flat glass plate and dry it to a thickness of 0.
A one-double film was prepared.

(E) As a commercially available water-soluble coating agent: Dowaxybrobyl cellulose [HPC8L (manufactured by Nippon Soda He)]
Take IOG+ and dissolve it by adding water to make it 100-. Pour this liquid onto a flat glass plate and dry it to a thickness of Q, lm.
A film of tn was prepared.

(f) Commercially available water-soluble moisture-proof coating agents such as polyvinyl acetal diethylamino acetate, 7-maric acid,
Take 10 g of a mixture of stearin-low gamma 1 droxypropyl methylcellulose (HA "Sankyo" (manufactured by Sankyo ■)) and dissolve it in water to make a 100-. This liquid was poured onto a flat glass plate and dried to prepare a film having a thickness of 0.1 cm.

Experiment 1 For each film of the prepared Examples and Comparative Examples, J.
Apply the cup method (Z0208) mutatis mutandis.

The moisture permeability was measured under the measurement conditions of 40℃ and 80% relative humidity.
The results shown in Table 1 were obtained.

Table 1 Examples (a), (b) and (c) as shown in Table 1
The film was clearly superior in moisture resistance to the films of Comparative Examples), (E) and (F) obtained using a commercially available coating agent.

Experiment 2 8. Preparation of tablets Composition of tablets (per tablet) Quinine sulfate SMG Lactose
240 ■ Corn starch
51+119 hydroxypropyl cellulose 4
．． 5rn9 Magnesium Stearate 1.5In
9 Using the above ingredients, granules for tabletting are produced by wet granulation, and Humpex-type tablets with a diameter of 9vax and a weight of 300m9 are produced using a tableting machine.

18-B Preparation of coating liquid (g) PTA (Gose/-L AL-06) ・・・・・・・・・・・・・・・ 109 Saponification degree = 91 to 94 mol% Macrogol 6000・・・・・・・・・・・・
・・・・・・ 29 talc ・・・・・・
・・・River......89 water...
...After dispersing the total amount of 100wZPVA in water, 8
The mixture is heated to 0° C. or higher to dissolve it, then Macrogol 6000 is added and dissolved, and talc is further dispersed to form a uniform coating liquid.

(E) PTA (Gose/-/l/NL-05)...
...... Degree of saponification: 98.5 to 100 mol% Hydroxypropyl methyl cellulose (To-5R) ......
・・・・・・ 3g14- Macrogole 6000 ・・・・・・・・・・・・
・・・ 2g talc ・・・・・・
・・・・・・・・・ 3 Risui ・
・・・・・・・・・ Total amount 100 - After dispersing PVA in water, it is heated to 80°C or higher to dissolve it, and then hydroxypropyl methylcellulose and macrogol 6ooot;
: Add and dissolve, and further disperse talc to make a uniform coating liquid.

(Hydroxypropyl methylcellulose (To-5R) ・・・・・・・・・・・・
... 59 Mako Goal 6000 ...
・・・・・・・・・ 19 talc
・・・・・・・・・・・・・・・1.5g water
...... Total amount 100-hydroxypropyl methylcellulose and macrogol 6
After dissolving 000 in water, talc is dispersed to form a uniform coating solution.

C. Coating of tablets 1 kg of the tablets prepared in step A above were transferred to an automatic pan coach (Azusaning device ('I!'M-9 model manufactured by 7 Riint Sangyo Co., Ltd.)).
Spray each coating liquid of B above to increase the amount by 10 to 151119 per tablet (())=1
1m9.6:12m9. (S): 14+119) Coating was performed (spraying for 10 seconds, drying for 80 seconds).

D Characteristic test of coated tablets Appearance of each coated tablet obtained.

■ After the tablet was placed in the oral cavity, the time until the tablet began to taste bitter (attributable to the quinine sulfate in the tablet) was measured.

■ Japanese Pharmacopoeia, disintegration test method, test method for coated tablets (1st liquid).

Table 2 As shown in Table 2, the coated tablets obtained using the coating solutions of Examples (G) and (B) were the same as those of Comparative Example (
Appearance of coated tablets compared to coated tablets obtained using the coating solution of

Although the surface and disintegration tests were equivalent.

The masking effect was clearly superior.

17-

Claims (1)

[Scope of Claims] 1) A coating composition containing polyvinyl alcohol containing 90 mol% or more of free hydroxyl groups, water, and optionally a hydrophilic organic solvent. 2) Macrogol and/or polyoxy as an anti-blocking agent. 5 to 50% of pyrene condensate with ethylene polyoxyb to polyvinyl alcohol
(by weight) The coating composition according to claim 1 3) Claim 1 which contains 10 to 100% (by weight) of one or more water-soluble coating agents based on polyvinyl alcohol Coating composition described in Section 4) Preparation coated with polyvinyl alcohol containing 90 mol% or more of free hydroxyl groups