JPS6364402B2 - - Google Patents

Description

[Detailed description of the invention]

When formulating pharmaceuticals, especially oral pharmaceuticals whose main ingredient is a viscous substance that cannot be obtained as a crystal or powder, the content of the main ingredient per formulation should be as high as possible, and the content of other excipients should be It is desirable to use soft capsules in order to minimize the amount of Currently, most of the shells of such soft capsules are made of gelatin. However, since gelatin is water-soluble, soft capsules with gelatin shells cannot be used in the past because if an aqueous solution component is used as a filler, the shell will dissolve in water and the soft capsules will be damaged. It was thought that Therefore, only oily substances such as cod liver oil and vitamin A are used as fillers in conventional soft gelatin capsules. However, especially when formulating water-soluble viscous substances such as pantethine, if soft gelatin capsules filled with a concentrated aqueous solution of pantethine were made possible, it would be extremely useful from both the purpose of use and formulation efficiency. desirable. From this point of view, the inventors of the present invention have conducted intensive studies on the realization of soft gelatin capsules that can be filled with an aqueous solution of pantethine, particularly a concentrated aqueous solution, and have found that when polyethylene glycol among various additives is added to an aqueous filler, it is uniquely stable. The present invention was completed by discovering that soft gelatin capsules can be produced. In order to produce the soft gelatin capsules of the present invention, polyethylene glycol may be added to an aqueous solution or dispersion of pantethine, thoroughly mixed, and if necessary, heated to homogenize, and then filled into soft gelatin capsules. The amount of polyethylene glycol to be added may be about 0.5 to 2 times the volume of the aqueous solution or dispersion of pantethine. The polyethylene glycol used in the present invention may be any commercially available polyethylene glycol with a molecular weight of about 200 to 6,000, but when considering mechanical filling of the contents into soft capsules, Molecular weight 200, liquid at room temperature
It is preferable to use ~600. It is of course possible to add appropriate emulsifiers, pH adjusters, stabilizers, etc. to the filler of the present invention, as in the case of ordinary soft capsules. The soft gelatin capsules of the present invention containing polyethylene glycol produced in this manner are uniquely stable, unlike cases in which other commonly used water-retaining agents or humectants are added, and are sufficiently usable as pharmaceutical preparations. This was confirmed as a result of a comparative study using a concentrated aqueous solution of pantethine, a water-soluble viscous substance that is well-known as a lipid-injection improving drug.

[Table] As is clear from the results in Table 1, among the compounds commonly used as water-retaining agents or humectants for pharmaceuticals, adding polyethylene glycol to an aqueous pharmaceutical solution was previously thought to be almost impossible. It has now been found that soft gelatin capsules can be obtained which can be filled with aqueous ingredients. Furthermore, as a result of examining inorganic compounds such as sodium chloride, magnesium chloride, and alum, which are used as water-retaining agents or humectants, it was found that these were difficult to dissolve in a concentrated aqueous solution of pantethine, and uniform dispersion was impossible. It was found that this method could not be used for producing soft gelatin capsules, which is the object of the present invention. Example 1 100 ml of polyethylene glycol (molecular weight 400) was added to 100 ml of a 60 (W/V)% aqueous solution of pantethine and mixed with stirring under heating. Approximately 2 ml of the resulting solution
Divide and fill into 10 soft gelatin capsules. The thus prepared soft capsules were stored at 40° C., room temperature, and cooled at 5° C. for 2 months, respectively, and then examined for changes in shape. As a result, no changes were observed in either case. Reference Example 1 Add 300 ml of polyethylene glycol (molecular weight 400) to 100 ml of a 60 (W/V)% aqueous solution of pantethine and mix with stirring under heating. The stability of the soft gelatin capsules prepared in the same manner as in Example 1 was examined, and no changes were observed in all cases. Reference Example 2 Add 300 ml of glycerin to 100 ml of a 60 (W/V)% aqueous solution of pantethine, and mix with stirring under heating. As a result of examining the stability of soft gelatin capsules prepared in the same manner as in Example 1, it was found that the capsule skin dissolved at 40°C and room temperature, and the liquid content leaked out at 40°C. Softening and deformation of the shell was observed under cooling. Reference Example 3 Add 300 ml of propylene glycol to 100 ml of a 60 (W/V)% aqueous solution of pantethine, and mix with stirring under heating. As a result of examining the stability of gelatin soft capsules prepared in the same manner as in Example 1, it was found that 40
Under conditions of 5°C, the capsule shell dissolved and the liquid content leaked out, and at room temperature and cooling at 5°C, softening and deformation of the capsule shell was observed.

Claims (1)

[Claims] 1 1 volume part of an aqueous solution or dispersion of pantethine
A soft gelatin capsule filled with a uniform mixture of 0.5 to 2 parts by volume of polyethylene glycol.