JPH08198776A - Production of emulsion for drug coating - Google Patents

Abstract

PURPOSE: To provide a method of easily producing an emulsion which can coat drugs such as granules even at a cold temperature. CONSTITUTION: At least one selected from among aliphatic alcohols, fatty acids and glycerides of 10 or more carbon atoms in an amount of 100 pts.wt., an anionic surfactant in 10-30 pts.wt., talc in 50-200 pts.wt., and water in more than 10 pts.wt. are mixed, heated over the melting point of the aliphatic alcohol or fatty acid, than the mixture melt is cooled down to give this emulsion for coating drugs.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an emulsion coated on a drug such as granules in order to maintain its pharmacological action for a long period of time.

[0002]

2. Description of the Related Art Medicinal products exert their pharmacological action by being digested in the body. Drugs that can maintain their pharmacological action for a long time
The concentration of the drug in the blood can be kept constant for a long time, and the frequency of taking the drug can be reduced. Therefore, as a drug,
Sustained-release preparations that suppress the elution of medicinal components in the body and maintain the pharmacological action for a long time are widely used.

There are matrix type, coating type, and tablet type pharmaceuticals. Matrix-type drugs are tablets in which the medicinal component is mixed with water-soluble polymer or wax, and coating-type drugs are hydrophobic polymer, enteric polymer or wax on the surface of granules or tablets. The tablet-type drug is prepared by mixing sustained-release or enteric-coated coated granules and immediate-release granules into tablets. Among them, the coated drug is relatively easily manufactured, and therefore, there are many known examples of the manufacturing method thereof.

In the method of coating a granule or the like with a hydrophobic polymer or the like, it is general to spray an organic solvent in which the hydrophobic polymer or the like is dissolved onto the granule and dry the organic solvent. In recent years, the use of organic solvents has tended to be regulated due to environmental problems and the like, and it is becoming popular to carry out the coating treatment in an aqueous system. Japanese Patent Publication No. 56-12614 describes a method of coating with an aqueous solution in which a cellulosic polymer is dispersed. Japanese Patent Examination Sho 60-4
3334 and JP-A-61-100527 describe a method of coating with an aqueous emulsion of a vinyl polymer.

Since these aqueous emulsions may contain unreacted monomers, they are not suitable for use as a coating solution as they are. Since many pharmaceuticals have poor heat stability, coating at low temperature is desired, and heat-melt coating may not be possible depending on the type of drug and wax. In addition, a polymer water-based coating may be insufficient in sustained release or may require a large coating amount, and it is expected that the addition of waxes will improve it, but it can be applied to water-based coating. There was no wax.

[0006]

The present invention has been made to solve the above problems, and an object of the present invention is to provide a method for easily producing an emulsion capable of coating a drug such as a granule even at a low temperature.

[0007]

The method for producing a pharmaceutical coating emulsion of the present invention, which has been made in order to achieve the above object, comprises an aliphatic alcohol having 10 or more carbon atoms,
100 parts by weight of at least one selected from fatty acids and glycerin fatty acid esters, 10 to 30 parts by weight of anionic surfactant, 30 parts by weight or less of nonionic surfactant, 50 to 200 parts by weight of talc, and water. Is mixed with 10 parts by weight or more and heated to a temperature equal to or higher than the melting point of the aliphatic alcohol or fatty acid, and the molten mixture obtained is cooled.

Examples of the aliphatic alcohol having 10 or more carbon atoms include lauryl alcohol, cetyl alcohol and stearyl alcohol. Examples of the fatty acid having 10 or more carbon atoms include lauric acid, myristic acid, palmitic acid, and stearic acid. Examples of the glycerin fatty acid ester having 10 or more carbon atoms include glycerin esters of the above fatty acids, for example, glycerin monostearate. Among these, cetyl alcohol, stearyl alcohol, and stearic acid are particularly preferable. These aliphatic alcohols, fatty acids and glycerin fatty acid esters may be used alone or in combination.

The anionic surfactant is at least one selected from fatty acid sodium, fatty acid potassium, sodium lauryl sulfate and dioctyl sodium sulfosuccinate. Among these, sodium lauryl sulfate and dioctyl sodium sulfosuccinate are particularly preferable from the viewpoint of emulsification. The weight ratio of the anionic surfactant is preferably 10 to 30 parts by weight with respect to 100 parts by weight of the aliphatic alcohol or fatty acid. If it is less than 10 parts by weight, the emulsified state of the emulsion will be poor. If it exceeds 30 parts by weight, the water solubility of the surfactant may adversely affect the coating performance of the emulsion.

The nonionic surfactant is at least one selected from polyoxyethylene fatty acid ester, glycerin ester, polyoxyethylene sorbitan fatty acid ester and polyoxyethylene alkyl ether.
The hydrophilic-lipophilic ratio (hereinafter, HLB) showing the balance between the hydrophilicity and the lipophilicity of the surfactant is preferably 4 to 18.

The weight ratio of the nonionic surfactant is preferably 30 parts by weight or less, more preferably 10 to 15 parts by weight, relative to 100 parts by weight of at least one selected from aliphatic alcohols, fatty acids and glycerin fatty acid esters. Is. If it exceeds 30 parts by weight, the water solubility of the surfactant may adversely affect the performance of the coating emulsion.

The weight ratio of water is preferably 10 parts by weight or more, and more preferably 10 to 30 parts by weight, relative to 100 parts by weight of at least one selected from aliphatic alcohols, fatty acids and glycerin fatty acid esters. If the weight ratio is less than 10 parts by weight, no emulsion is produced. In the case of 10 to 30 parts by weight, cooling the molten mixture gives a solid. The solid matter is easily formed into pellets with a pelleter or the like. The pellets become an emulsion when added to water.

Talc is talc, which is used as an antifriction agent, medicine, cosmetics, etc. after being pulverized into fine particles. The addition of talc facilitates emulsification, and the pellets can be easily re-emulsified when the amount of water is small. The weight ratio is preferably 50 to 200 parts by weight, and more preferably 70 to 150 parts by weight, relative to 100 parts by weight of at least one selected from aliphatic alcohols, fatty acids, and glycerin fatty acid esters. If it is less than 50 parts by weight, the effect is small. If it exceeds 200 parts by weight, the concentration of the obtained emulsion will decrease.

The obtained coating emulsion is added as it is or to an aqueous polymer dispersion to obtain a coating liquid. In the coating process, the coating liquid is sprayed onto the granules or the like by a coating device, and then the liquid is dried to form a film. A pharmaceutically acceptable drug or additive such as a plasticizer, a coloring agent, a pigment or an anti-adhesive agent may be added to the coating liquid. Examples of the plasticizer include triethyl citrate and triacetin. These may be used alone or in combination. Examples of the coating device include a fluidized bed coating device, a pan coating device, and a ventilation type rotary drum coating device. After spraying the coating liquid on the medicine with these devices, when hot air is blown in, the water content in the liquid is diffused and a film for coating the tablets is obtained.

[0015]

According to the production method of the present invention, a coating emulsion containing no unreacted monomers can be easily produced. Granules coated with this emulsion are not decomposed by heat. Therefore, the pharmacological activity of the finally obtained drug is maintained for a long time.

[0016]

EXAMPLES Examples of the present invention will be described in detail below.

Example 1 100 parts by weight of cetyl alcohol, 12 parts by weight of sodium lauryl sulfate, 10 parts by weight of polysorbate 80, 100 parts by weight of talc and 20 parts by weight of water were mixed and then heated to 80 ° C. to obtain a molten mixture. The molten mixture was allowed to cool to 40 ° C. at room temperature and solidified while stirring gently with a stirrer. The obtained solid matter was extruded with Dome Gran DG-L1 type (screen: 0.8 mm made by Fuji Paudal) and pelletized. 2 g of the pellet was placed in a beaker containing 100 ml of water to restore the pellet into liquid fine particles, and the obtained emulsion was used for coating. The emulsion for coating was stirred with a magnetic stirrer to observe the emulsified state, and the evaluation is shown in Table 1.

Example 2 A coating emulsion was prepared in the same manner as in Example 1 except that sodium lauryl sulfate was changed to 15 parts by weight. The emulsified state of the obtained emulsion was observed, and the evaluation is shown in Table 1.

Example 3 A coating emulsion was prepared in the same manner as in Example 1 except that sodium lauryl sulfate was changed to 20 parts by weight. The emulsified state of the obtained emulsion was observed, and the evaluation is shown in Table 1.

Example 4 15 parts by weight of sodium lauryl sulfate and 150 parts of talc
A coating emulsion was prepared in the same manner as in Example 1 except that the amount was changed to parts by weight. The emulsified state of the obtained emulsion was observed, and the evaluation is shown in Table 1.

Comparative Example 1 A coating emulsion was prepared in the same manner as in Example 1, except that sodium lauryl sulfate was changed to 5 parts by weight. The emulsified state of the obtained emulsion was observed, and the evaluation is shown in Table 1.

Comparative Example 2 A coating emulsion was prepared in the same manner as in Example 1, except that 15 parts by weight of sodium lauryl sulfate and talc were not added at all. The emulsified state of the obtained emulsion was observed, and the evaluation is shown in Table 1.

Comparative Example 3 The same experiment as in Example 1 was conducted except that sodium lauryl sulfate was changed to 15 parts by weight and water was changed to 5 parts by weight.
No emulsion was obtained.

[0024]

[Table 1]

As shown in Table 1, in the coating emulsions of Examples 1 to 4, fine particles of cetyl alcohol are well dispersed in water. On the other hand, Comparative Examples 1 and 2
In the coating emulsion, the particles dispersed in water were not uniform, and in Comparative Example 3, the emulsion was not obtained because the ratio of water was small.

Example 5 100 parts by weight of stearic acid, 15 parts by weight of dioctyl sulfosuccinate, 5 parts by weight of sorbitan monolaurate,
100 parts by weight of talc and 20 parts by weight of water were mixed, and the mixture was heated to 90 ° C. to prepare a coating emulsion in the same manner as in Example 1. The emulsified state of the obtained emulsion was good as in Examples 1 to 4.

Example 6 100 parts by weight of cetyl alcohol, 15 parts by weight of sodium lauryl sulfate, 10 parts by weight of polysorbate 80, 100 parts by weight of talc and 200 parts by weight of water were heated to 80 ° C. and dissolved, followed by stirring with a homomixer. Then, an emulsion was prepared. This emulsion was allowed to cool at room temperature to obtain a coating emulsion. The cetyl alcohol particles dispersed in the coating emulsion had a uniform particle size.

Claims (4)

[Claims] 1. 100 parts by weight of at least one selected from aliphatic alcohols having 10 or more carbon atoms, fatty acids and glycerin fatty acid esters, and 1 anionic surfactant.
0-30 parts by weight, nonionic surfactant 30 parts by weight or less, talc 50-200 parts by weight, and water 10 parts by weight or more are mixed and heated to a temperature equal to or higher than the melting point of the aliphatic alcohol or the fatty acid. A method for producing a pharmaceutical coating emulsion, which comprises cooling the obtained molten mixture. 2. The aliphatic alcohol, fatty acid, and glycerin fatty acid ester are at least one selected from lauryl alcohol, cetyl alcohol, stearyl alcohol, lauric acid, myristic acid, palmitic acid, stearic acid, and glycerin monostearate. The method for producing a pharmaceutical coating emulsion according to claim 1, wherein: 3. The medicine according to claim 1, wherein the anionic surfactant is at least one selected from fatty acid sodium, fatty acid potassium, sodium lauryl sulfate, and dioctylsodium sulfosuccinate. Method for producing coating emulsion. 4. The nonionic surfactant is at least one selected from polyoxyethylene fatty acid esters, glycerin esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene alkyl ethers. The method for producing the pharmaceutical coating emulsion according to any one of 1 to 3.