JP2553258B2 - Method for producing wax-coated preparation - Google Patents

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 a wax-coated preparation in which the surface of a drug is coated with waxes, and is particularly suitable for coating fine particles such as microcapsules and fine particles. Is provided.

[0002]

2. Description of the Related Art Conventionally, as a method for producing a wax-coated preparation, a method of heat-treating waxes in a solid preparation not coated with a fluidized bed (Japanese Patent Laid-Open No. 1-287021) and organic waxes are used. It is known to dissolve the solvent in a mixed solvent of water and water, immerse the core substance, and then remove the solvent (Japanese Patent Laid-Open No. 63-151353), but it is difficult to control the temperature and coating of fine particles is difficult. It has the drawbacks that it is impossible, the process is complicated, and it cannot be applied when the core substance is dissolved in a solvent.

[0003]

When waxes are coated on the surface of fine particles, the melting point of the wax itself is low, so that agglomeration of the particles is likely to occur. It was very difficult to apply. Agglomeration of particles is a phenomenon that occurs because the coating agent attached to the core substance does not dry out and maintains its tackiness. Therefore, agglomeration can be prevented by rapidly reducing the adhesiveness of the coating agent attached to the core substance. Focusing on this point, as a result of intensive studies aimed at directly coating the surface of fine particles, the present invention has found that fine particles can be coated without agglomeration of particles.

[0004]

That is, the gist of the present invention is as follows.
A coating raw material containing at least one or more waxes is dissolved in a solvent by heating, and the coating solution is sprayed on the surface of particles serving as a core substance at a temperature of the core substance of 40 ° C. or less, and the temperature difference of the coating solution before and after spraying
And wack in coating solution due to latent heat of vaporization of solvent
Decrease the solubility of waxes and deposit waxes on the particle surface
It is characterized by forming a thin film at the same time as
It exists in a method for producing a wax-coated preparation.

According to the method of the present invention, the coating raw material is dissolved in a solvent by heating and sprayed onto the surface of the particle serving as the core material at a temperature of 40 ° C. or lower, so that the coating material is rapidly coated on the surface of the particle. Because of the precipitation, the latent heat of evaporation of the solvent causes the temperature of the coating material to drop sharply, and at the same time, the solubility to decrease, and at the moment when the waxes reach the surface of the particles, these deposit and form a thin film. According to this method, it is possible to coat fine particles while suppressing the aggregation of particles.

In the present invention, the coating raw material means waxes or a mixture of waxes and coating agents. The waxes used in the present invention include fatty acids such as stearic acid, capric acid, lauric acid, myristic acid, palmitic acid, and undecanoic acid; higher alcohols such as lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, and undecanol. Stearin, myristin, palmitin,
Examples thereof include fatty acid glycerin esters such as laurin. These waxes are used alone or in combination of two or more. Furthermore, it is also possible to use a commonly used coating agent such as ethyl cellulose, hydroxypropyl cellulose, carboxymethyl ethyl cellulose, etc. by mixing with the above waxes.

The solvent in the present invention can be used as long as it can dissolve the coating materials containing waxes under heating, but a chlorine-based solvent is not preferable in consideration of the working environment, and methanol, ethanol, Propanol, acetone, methyl ethyl ketone and the like are preferable. or,
The concentration of the waxes can be adjusted appropriately depending on the solubility in the solvent, but according to the method of the present invention, even if the concentration is 50% or more, the aggregation of the particles does not occur, and the coating can be performed in a short time. The temperature of the core substance during spraying is 40 ° C. or lower, and if it exceeds 40 ° C., the particles are gradually aggregated, which is not preferable. Usually, it is suitable to carry out at 15 to 35 ° C.

In the method of the present invention, since the coating solution is simultaneously sprayed and deposited on the surface of the particles to form a thin film, the coating apparatus used in the present invention is a side spray type or bottom spray type capable of directly spraying the core substance. Type apparatus is preferable, and examples thereof include a fluidized bed granulation coating apparatus, a swirl type fluidized bed granulation coating apparatus, and a centrifugal fluidized type granulation coating apparatus.

The particle size of the core substance used in the present invention is not particularly limited, but it is preferably several tens of microns to 5 mm, and even particles of several tens of microns, which are considered to be particularly difficult to coat, have a small amount of agglomeration. Is possible. As a general method for producing the preparation of the present invention, a core material is charged into a coating apparatus, a predetermined amount of coating raw material is weighed, a solvent is added, and then dissolved by heating (preparation of coating solution). Next, the core substance is kept at 40 ° C or lower (usually at room temperature)
Spray the coating solution while flowing or tumbling. After spraying, dry.

[0010]

The present invention will be described in more detail based on the following examples, but the present invention is not limited to these examples as long as the gist thereof is not exceeded. Example 1 Bitterness masking was performed using anhydrous theophylline having a particle size of approximately 10 to 40 microns. Theophylline is known as an antitussive expectorant, while it is known as a compound with a rather strong bitterness. The method and results are shown below.
3 kg of anhydrous theophylline is charged into a super granulation coating device (SFC-5, manufactured by Freund Sangyo Co., Ltd.). Glycerin monostearate 2.0 kg, and stearic acid 1.
Ethanol (3 kg) is added to 0 kg to dissolve by heating, and coating is performed under the following conditions. On the way, when the coating amount reached 25%, 50%, 75%, and 100% with respect to the core substance, sampling was performed over time to perform a bitterness test and a microscope (100 parts of the core substance, 10 parts of the coating liquid 10
The state where 0 part is coated is 100%. ).
The results are shown in Table 1.

Intake temperature 20 to 30 ° C. (room temperature) Core substance temperature 20 to 25 ° C. Spray flow rate 30 g / min Rotor speed 150 rpm Aggitator speed 150 rpm Spray pressure 3 kg Bitterness test result

[0012]

[Table 1] The bitterness was determined according to the following criteria. Evaluation criteria; 3 Unbearable 2 Unbearable 1 Feeling slightly bitter 0 Not bitter

From the above results, it can be seen that bitterness disappears at a coating amount of 50% with respect to the core substance. Next, the results of the microscope are shown in the photographs of FIGS. 1 and 2. (Minimum scale: 10 microns) From the result of a microscope, even if 50% of wax is coated on 100% of theophylline of 10 to 40 microns, the largest particle size is about 70 microns, and agglomeration etc. You can see that there are very few. According to this method, it becomes possible to perform masking of fine granules having a strong bitterness, which has been very difficult until now, at the stage of the drug substance .

Example 2 Cholestyramine was coated with wax to prepare granules with little swelling when ingested. Cholestyramine is known as an arteriosclerosis agent, but since it is an ion exchange resin, it easily absorbs water and swells significantly when it absorbs water. Therefore, as the present dosage form, only dry syrup which is suspended in water before use is commercially available. Charge 3kg of cholestyramine into a super granulation coating device (SFC-5, manufactured by Freund Sangyo). Glycerin monostearate (0.3 kg) was dissolved in ethanol (0.3 kg) with heating to give Example 1.
Coating was performed under the same conditions as in. 0.3 kg of hydroxypropyl cellulose was added to 3 kg of coating powder, 0.8 kg of ethanol was added after mixing, and kneaded to 0.8 mm
Start with a cylindrical granulator equipped with a diameter screen. After shelf drying, the particles are sized and sieved.

Further, 0.13 kg of glycerin monostearate and 0.15 kg of ethyl cellulose were dissolved in 1.2 kg of ethanol under heating to 3 kg of the elementary granules.
Coating was performed under the same conditions as in. Sodium lauryl sulfate was added to the coated granules in an amount of 0.2% to obtain granules with good ingestibility. The granules were stable under the conditions of 25 ° C. and 75% relative humidity even after being left for 3 months without any change in appearance.

[0016]

EFFECTS OF THE INVENTION According to the present invention, it becomes possible to coat fine particles.
Since it can be processed into various dosage forms, a wide range of coating preparations can be provided.

[Brief description of drawings]

FIG. 1 is a micrograph (× 100) of theophylline drug substance, and one scale in the photograph represents 10 microns.

FIG. 2 is a photomicrograph (× 100) of 50% coated theophylline powder, where 1 scale represents 10 microns.

Claims (2)

(57) [Claims] 1. A coating raw material containing at least one or more waxes is dissolved in a solvent by heating, and the coating solution is applied to the surface of particles to be the core substance at a temperature of the core substance 40.
Spray below ℃ , before and after spraying
Coating due to temperature difference of solution and latent heat of vaporization of solvent
It reduces the solubility of waxes in the solution and causes the wax on the particle surface.
To form a thin film at the same time as depositing
A method for producing a wax-coated preparation, comprising: 2. The method for producing a wax-coated preparation according to claim 1, wherein the waxes are selected from fatty acids, higher alcohols and fatty acid glycerin esters.