JPS5818316A - Pharmaceutical preparation with film coating - Google Patents

Abstract

PURPOSE:The titled pharmaceutical preparation preventing the interaction of two medicinal components, obtained by coating a solid agent with a film coating layer containing a medicinal component different from that contained in the solid agent. CONSTITUTION:After a solid agent (e.g., magnesium aluminate metasillicate, etc.) is subjected to a common film coating, a slurry or solution obtained by adding a medicinal component (e.g., pipethanate hydrochloride, etc.) different from that contained in the solid agent to a solution or dispersion of a high polymer substance (e.g., methyl cellulose, etc.) capable of forming a film is sprayed to the solid agent and dried, to give a film coating pharmaceutical preparation. Even if the amount of the medicinal component existing in the coating layer is a small amount, it is dispersed uniformly, and there is no fear of causing the segregation of the content of the medicinal component. The solution or dispersion of the high polymer substance has preferably a concentration of high polymer substance of 0.5-50wt% and the amount of the medicine contained in it is preferably 0.1-50wt%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel film coating formulations.

Conventionally, in solid pharmaceutical preparations containing two or more types of medicinal ingredients, if there are disadvantages such as decreased efficacy due to denaturation or decomposition due to interaction between these different types of medicinal ingredients, it is necessary to prevent the interaction. In order to prevent this and make the preparations stable, coatings are being applied with various polymeric substances. In other words, coating one or both of these pharmaceutical ingredients avoids contact between the two and prevents interactions from occurring. Specifically, solid preparations containing one of the pharmaceutical ingredients are made into granules. Methods of coating this and mixing it with coated or uncoated solid powders or granules containing other pharmaceutical ingredients, or compressing it into tablets are used.

However, in those methods, among the combined pharmaceutical ingredients, U°
Although μ2'1 is small, there are various difficulties involved.

For example, when a medical product is coated in the form of granules and mixed with powder or granules of other ingredients, segregation makes it difficult to maintain a constant content. In addition, in order to avoid segregation, it is necessary to use a large amount of excipients to increase the size of the granules, which results in problems such as the large dosage form, which is inconvenient to take. .

The present inventors investigated methods for stabilizing nuclear bud components in preparations containing bed components that have a low ↑k content and are susceptible to deterioration or decomposition when mixed with carp and other components. The present invention has been completed, and this relates to a film-coated preparation in which a film-coating layer containing a medical ingredient different from the medical label ingredients present in the solid agent is applied on a solid agent.

In the film-coated preparation according to the present invention, even if the pharmaceutical component present in the coating layer is small, it is uniformly dispersed and contained in the film coating, so there is no concern that the pharmaceutical component will be segregated. There are almost no Even if an unfavorable interaction occurs due to direct contact between the medicinal ingredient in the solid preparation and the medicinal ingredient contained in the film coating layer, according to the present invention, one side Since the pharmaceutical ingredients in the film coating layer are isolated from the pharmaceutical ingredients present in the solid dosage form, there is no fear of such interaction and the medicine can be safely stored.

To explain this, the film-coated preparation according to the present invention is produced by applying a conventional film coating to a solid material 1, and then adding a pharmaceutical ingredient to a solution or dispersion of a polymeric substance (film coating base) capable of forming a film. By spraying a slurry or solution obtained from a solid preparation onto a solid preparation using a known coating method and drying by a conventional method, a film enclosing the particles of the pharmaceutical ingredient is formed on the surface of the solid preparation.

Solid preparations to be coated are fine particles, granules, or tablets containing one or more pharmaceutical ingredients and 11
m1: Optionally contains pharmaceutical additives such as a shaping agent, a binder, a disintegrant, a coloring agent, a flavoring agent, and a filler. Not all of these ingredients are necessary;
It is selected depending on the purpose. In addition, it may be a single form of 6+ that does not contain any medicinal ingredients. In particular, when one type of medicinal ingredient is contained in a small proportion, it is not incorporated into a solid formulation, but is coated with a film coating layer as described above. By incorporating it into the liquid, it is possible to significantly reduce the segregation of liquids containing 1<E.

The film-coated preparation according to the present invention basically complies with the Japanese Pharmacopoeia General Rules for Preparations (1st O revision), but the effects of the present invention depend on the particle size of the obtained fine granules or heavy granules or the size of the tablet. Since it has nothing to do with size etc.
There is no problem even if the grain size does not necessarily conform to the regulations.

The polymeric substance capable of forming a film used for forming a film coating layer in the present invention can be obtained as an aqueous solution, an organic solvent solution, or an aqueous dispersion;
Any material that can form a film may be used, but industrially, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylhydroxybutylcellulose, sodium carboxymethylcellulose, ethylcellulose, acetylcellulose, and cellulose acetate are used. Vinyl or acrylic polymers or copolymers having units such as phthalate, cellulose derivatives such as hydroxypropyl methyl cellulose phthalate, vinyl alcohol, vinyl pyrrolidone, acrylic acid, sodium acrylate, acrylic ester, methacrylic acid, methacrylic ester, etc. Natural resins such as gelatin, gum arabic, shellac, one or two polymerizable monomers such as vinyl acetate, acrylic acid, acrylic ester, methacrylic ester, ethylene, maleic acid ester J>J From above The following polymer emulsions are exemplified. Note that these are not limited to use alone, but may be used as a mixture of two or more.

Examples of the solvent used in the film coating base include water, methanol, ethanol, impropatol, acetone, methyl ethyl ketone, methylene chloride, 1,1,1-trichloroethane, chloroform, ethyl acetate, ethylene glycol monoethyl ether, etc. Examples include one type or a mixture of two or more types of solvents, which are of course selected from solvents that dissolve or disperse the coating base used. The drug to be contained in the film coating layer of the film coating preparation may be obtained as a powder, fine particles or granules, and may be either sparsely soluble or soluble in water or organic solvents. Examples include bibesanate hydrochloride, belphenazine, thiamine hydrochloride, provantyline bromide, and diazepam.

- There are no particular restrictions on the type of medicinal ingredients that may be included in the solid dosage form if necessary, but the advantage of the present invention is that the medicinal ingredients in this case come into direct contact with the medicinal ingredients that are included in the film coating layer. Examples of substances that cause undesirable interactions include aluminum silicate, magnesium silicate, and magnesium carbonate. Of course, these bases that are stable even when they come into contact with the drug may be coexisting in the solid balm.

It is desirable that the solution or dispersion (coating liquid) of a polymeric substance prepared for forming a film coating layer has a concentration of the polymeric substance in the range of approximately 0.5 to 50% by weight, Further, the amount of the drug to be pre-contained in the drug is preferably set to a concentration of approximately 1 to 5% ON. In addition, when this film coating liquid is in the form of a slurry, if the bed components or other additives that form the slurry particles are too large, they may clog the nozzle of the gun when spraying. Therefore, these pharmaceutical ingredients and other additives should be prepared in advance from 1410 to
It is preferable to use a powder that has passed through a 149 nm (JIS) sieve. By adding these powders to a solution or dispersion of a polymeric substance and simply stirring the liquid, a slurry-like film coating can be obtained.
This may be carried out using a mixer such as a pony mixer or a dow mixer, or a ball mill, if necessary, and the slurry thus obtained may be filtered using a wire mesh or the like, if necessary.

In order to coat solid drugs such as fine particles, granules, or tablets with this coating liquid containing pharmaceutical ingredients, it is possible to coat not only the conventionally used so-called bread, but also the Axela coater manufactured by Manesty Co., Ltd. in the UK, Freund Sangyo Co., Ltd. Rotating drum type coating equipment such as Hei Coater made by
A Wurster-type fluid coating device developed by the Rice Consin University Foundation in the United States or a fluid coating device manufactured by Blatt Co., Ltd. in West Germany can be used, and there are no restrictions on the equipment. Further, the conditions for the film coating operation are not particularly different in principle from those conventionally performed using the above-mentioned apparatus, and the film coating operation can be performed under the same operating conditions.

The amount of coating applied to a solid drug varies depending on the amount of pharmaceutical ingredients required in the obtained film-coated preparation, so it cannot be generalized, but in general, the amount of coating applied to the solid drug may be reduced due to counterfeit pharmaceutical ingredients in the obtained film-coated layer. 0.01
~5% or 01-20% as coating %t
It is often considered to be in the range of

Among the film-coated preparations thus obtained, fine granules or fine granules may optionally be sieved if necessary. Although they may be taken as is, they may be filled into capsules to make capsules, or if necessary, other ingredients may be added to them and compressed to make tablets. be.

Furthermore, in the present invention, it is free to provide another film layer between the solid agent and the film coating layer containing the pharmaceutical ingredient and/or on the film coating layer.

Next, I will give a concrete example.

Example 1 [Tablet formulation] Magnesium aluminate metasilicate 147.5 fny Licorice active ingredient 35. Low-substituted hydroxypropylcellulose (manufactured by Shin-Etsu Chemical, trade name L-RPC) 23.0q Magnesium stearate 2.25ml Talc
More than 2.25 ingredients were mixed uniformly, and tablets with a diameter of 210 cm and a diameter of 9III11 were produced by direct compression using a rotary tablet press.

This tablet was coated with a coating liquid according to the following formulation, excluding bipesanate hydrochloride as a pharmaceutical ingredient, and coated with air spray using an automatic pan coating device to 2.1 m.
8.3 to 1 tablet was coated in the same manner using a coating solution with the following formulation, and the bipesanate hydrochloride content per tablet was adjusted to 1°5.

[Coating liquid prescription]

-1] - Pipesanate hydrochloride 57.14 parts by weight, product name 'I'C-5R), 240' /
/Methylene chloride 2280//Ethanol 2280 The tablets obtained above were subjected to a disintegration test according to the method of the 10th edition of the Japanese Pharmacopoeia, and met the specifications.

Further, the sample was left under conditions of 40° C. and 75% RH, and the content of bipesanate hydrochloride was measured over time, and the results shown below were obtained. Note that the content of bipesanate hydrochloride is expressed as the residual amount in % with respect to the theoretical amount blended in the tablet.

Immediately after production 60 days later 120 days later Present invention 9B, 7 96,2 93.8
(%) -12= Example 2 [Granule formulation] Magnesium metasilicate aluminate 147.5 parts by weight Licorice effective acid extract 35.0 //
Low-substituted hydroxypropylcellulose 7.5 Hydroxypropylcellulose Granules 5K obtained by wet granulation of a blend consisting of 10.0# or more of each component
First, using a fluid coating device under the following conditions, the coating liquid shown below was prepared using a coating solution excluding bipesanate hydrochloride, which is a pharmaceutical ingredient.
Part by weight of the granules are coated, and then coated using the coating liquid shown below to obtain 100 parts by weight of the granules.
2 parts by weight of bipesanate hydrochloride was contained per part.

Coating equipment Gran) W2O-5 spray gun Brat nozzle Diameter 1.2mm Spray speed 60-70 rpm Spray for 1 hour
2 hours 1 air mixture 50℃ exhaust/! □) Degree 35-40℃ [Coating liquid formulation] Pibesanate hydrochloride 75 parts by weight 41 parts Hydroxypropyl methyl cellulose 500 [Methylene chloride 39] 6//Ethanol
3916//Coating 'I!' obtained above!
N grains are stable even during long-term storage, and when stored in aluminum foil packaging at 40°C and 75% RH, the residual field for the theoretical bipesanate hydrochloride content after 120 days is 87.
It was 5%.

patent applicant Sanya Seikyo Co., Ltd. 15- 93-

Claims (1)

[Scope of Claims] J. A film coating preparation comprising a solid preparation and a film coating layer containing a different pharmaceutical ingredient from that present in the solid preparation. 2. The film-coated preparation according to claim 1, wherein the drug contained in the solid preparation is magnesium aluminate metasilicate, and the drug in the film coating layer is bipesanate hydrochloride. 3. The film coating preparation according to claim 1, wherein the film coating base is hydroxypropyl methylcellulose.