KR100578669B1 - Transparent soft capsule with ursodeoxycholic acid - Google Patents

Abstract

The present invention relates to a transparent soft capsule containing ursodeoxycholic acid (hereinafter referred to as UDCA) and a transparent soft capsule containing other active ingredients such as UDCA and vitamins, and a method for preparing the same. UDCA) was dissolved in one or more excipients selected from polyethylene glycol, polyvinylpyrrolidone, and unsaturated fatty acids having a molecular weight of 600 or less as a content excipient, and filled into soft gelatin capsules to prepare urethane deoxycholine. It relates to a transparent soft capsule composition containing an acid. The transparent soft capsules prepared in this way are easy to be filled in gelatin cells because the contents of the soft capsules are in a liquid state, and do not have a precipitation phenomenon such as suspension, which is excellent in stability and easily maintains uniformity of the contents of the capsules. After filling the drug, it is rapidly eluted and absorbed after administration, so it can be expected to have a faster effect than other solid preparations.It is a transparent soft capsule that can observe the inside, so it is possible to visually check the state of contents and the state of deterioration. It is also known as, and it is excellent in commerciality.

Description

Transparent soft capsule containing ursodeoxycholic acid (UDCA)

The present invention relates to a transparent soft capsule containing ursodeoxycholic acid (hereinafter referred to as UDCA) and a transparent soft capsule containing other active ingredients such as UDCA and vitamins, and a preparation method thereof. In general, the contents of the soft capsule are liquid and suspended and are filled in a capsule base containing gelatin as a main component. Soft capsules are convenient for the administration of Omi, Odor, or colored medicines, and have the characteristics of solidifying medicines that are difficult to take, such as oil or suspension, and making a constant dose. Soft capsules are mostly opaque soft capsules containing drug suspensions due to the limited content excipients that can be used for soft capsules and the difficulty in solubilizing the capsule contents and the problem of cell composition that can ensure stability. The number is very small.

Furthermore, since urethane deoxycholic acid has a very low solubility, soft capsules containing ursodeoxycholic acid and this component and other active ingredients have not been developed until now.

Transparent soft capsules have the following advantages over opaque soft capsules containing suspension contents.

1. As the contents of the soft capsule are in the liquid state, it is easy to fill in the gelatin cell and there is no precipitation phenomenon such as suspension, so it is excellent in stability and it is easy to maintain the uniformity of the prepared capsules.

2. It is expected to have a faster effect than other solid preparations because it is filled with a liquid drug in a transparent soft capsule and rapidly eluted and absorbed after administration.

3. It is a transparent soft capsule that can observe the inside, so the state of the filled contents and the deterioration state can be seen by the naked eye.

Transparent soft capsules are generally limited to materials such as vegetable oils such as soybean oil and corn oil, polyethylene glycol 400-800, medium chain triglyceride, and polysorbate 20-80. . For this reason, it is difficult to select a content excipient that can dissolve all the main components and does not cause physical stability problems such as phase separation or precipitation generation during the manufacturing process. In order to solve this problem, the present inventors have been conducting a long research, and found a composition of a content excipient capable of dissolving all the main ingredients, and using this content excipient, the production of a transparent soft capsule having no problem in physical and chemical stability. The present invention was completed to find a method.

The present invention is a component of soybean oil, corn oil, etc., which are generally used in the manufacture of soft capsules, has excellent solubilization ability and properties that are hardly mixed with water, and the contents of various soft capsules such as no effect on the human body. Method of making transparent soft capsules containing UDCA and various vitamins with oleic acid, linoleic acid and linolenic acid, which are unsaturated fatty acids that can be used as excipients and various contents An excipient is used to make a transparent soft capsule containing UDCA, which is a poorly soluble drug and has no transparent soft capsule.

The present invention is described in detail as follows.

In the case of the soft capsule containing UDCA, first, the UDCA is dissolved by stirring at least one content excipient selected from polyethylene glycol, polyvinylpyrrolidone, and unsaturated fatty acid having a molecular weight of 600 or less at 90-110 ° C. for a predetermined time, and then cooled to room temperature. This is filled into a soft capsule base containing gelatin as a main component to prepare a transparent soft capsule containing UDCA. In the case of soft capsules containing UDCA and various vitamins, UDCA is dissolved in unsaturated fatty acids (oleic acid, linoleic acid, linolenic acid) at 90-110 ℃, and then cooled to 40-60 ℃. Heat-stable vitamins are added in turn to dissolve and cool to room temperature. Then add vitamins that are relatively unstable to heat and stir for a period of time to dissolve. This is filled with a soft capsule base containing gelatin as a main component to prepare a transparent soft capsule containing UDCA and various vitamins.

Next, the present invention will be described in more detail by way of examples.

Example 1

Prescription (in 1 capsule)

UDCA 100.0mg

Polyethylene Glycol 400 600,0mg

Polyvinylpyrrolidone K30 200.0mg

Gelatin 245.0mg

Concentrated glycerin 90.0 mg

Ethyl Vanillin Proper

0.24 mg of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.06mg

In the above manufacturing prescription, UDCA is dissolved in a molecular weight polyethylene glycol 400 and polyvinylpyrrolidone K30 at 90-100 ° C. for a predetermined time, and then cooled to room temperature. This is filled into a soft capsule base containing gelatin as a main component to prepare a transparent soft capsule.

Example 2

Prescription (in 1 capsule)

Tocopherol 300 I.U

UDCA 30.0mg

Oleic Acid 320.0mg

Gelatin 185.0mg

Concentrated glycerin 60.0 mg

Ethyl Vanillin Proper

0.21 mg of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.06mg

In the above preparation, the UDCA was dissolved in oleic acid, a content excipient having little affinity with water, at a temperature of 90-110 ° C. for a predetermined time to be dissolved, and then cooled at room temperature. Tocophenol was added thereto, stirred for a certain period of time, and then dissolved, and then filled with a soft capsule base containing gelatin as a main component to prepare a transparent soft capsule.

Example 3

Prescription (in 1 capsule)

Tocophenol 300I.U

Tetrabutyric acid riboflavin 2.0mg

Gamma-Orizanol 10.0 mg

UDCA 10.0 mg

Oleic Acid 320.0mg

Gelatin 185.0mg

Concentrated glycerin 60.0 mg

Ethyl Vanillin Proper

Paraoxybenzoic acid propyl 0.06mg

In the preparation of the above, the UDCA was stirred at 90-110 ° C. in oleic acid, a content excipient having little affinity with water, for a predetermined time, and then dissolved at 40-60 ° C. To this, tetrabutyric acid riboflavin is added and dissolved, and after cooling to room temperature, gamma-orizanol and tocopherol are mixed and dissolved at room temperature, and then dissolved by stirring for a predetermined time. This is filled into a soft capsule base containing gelatin as a main component to produce a transparent soft capsule.

Example 4

Prescription (in 1 capsule)

Tocophenol 300 I.U

Tetrabutyric acid riboflavin 12.0 mg

Gamma-Orizanol 10.0 mg

Nicotinic Acid 20.0mg

UDCA 30.0mg

Oleic Acid 320.0mg

Gelatin 185.0mg

Concentrated glycerin 60.0 mg

Ethyl Vanillin Proper

0.24 mg of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.06mg

In the preparation of the above, the UDCA was stirred at 90-110 ° C. in oleic acid, a content excipient having little affinity with water, for a predetermined time, and then dissolved at 40-60 ° C. Tetrabutylriboflavin is added to dissolve it, and after cooling to room temperature, a solution obtained by mixing gamma-orizanol, tocopherol and nicotinamide at room temperature is added and stirred for a predetermined time. This is filled into a soft capsule base containing gelatin as a main component to produce a transparent soft capsule.

Example 5

Prescription (in 1 capsule)

Tocopherol 300 I.U

Tetrabutyric acid riboflavin 10.0 mg

Gamma-Orizanol 10.0 mg

UDCA 30.0mg

Nicotinamide 30.0mg

Cyanocobalamin 50.0ug

Panthenol 20.0mg

Linoleic acid 600.0mg

Gelatin 245.0mg

Concentrated glycerin 90.0 mg

Ethyl Vanillin Proper

0.24 mg of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.06mg

In the preparation of the above, the UDCA was stirred at 90-110 ° C. for a predetermined time in linoleic acid, a content excipient having little affinity with water, and then dissolved first, and then cooled to 40-60 ° C. Heat-stable vitamins gamma-orizanol, tocophenol, nicotinic acid amide, and tetrabutyric acid riboflavin are added in turn to dissolve and cooled at room temperature. Here, the heat-stable vitamins panthenol and cyanocobalamin are dissolved by stirring at room temperature for a certain time. This is filled with a soft capsule containing gelatin as a main component to produce a transparent soft capsule.

Example 6

Ascorbic Acid 50.0mg

Tetrabutyric acid riboflavin 12.0 mg

Gamma-Orizanol 10.0 mg

UDCA 30.0mg

Nitrate Nitrate 12.0mg

Nicotinic Acid 50.0mg

Panthenol 30.0mg

Polyethylene Glycol 400 600.0mg

Polyvinylpyrrolidone K30 100.0mg

Gelatin 245.0mg

Concentrated glycerin 90.0 mg

Ethyl Vanillin Proper

0.24 mg of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.06mg

In the preparation of the above, the mixture was stirred at 90-110 ° C. for UDCA, nitrate ethylene polyethylene glycol 400, polyvinylpyrrolidone K30 for a predetermined time, and then cooled to 40-60 ° C. Heat-stable vitamins gamma-orizanol and nicotinamide amide tetrabutyric acid riboflavin are added sequentially to dissolve and cooled at room temperature. Panthenol and ascorbic acid, which are heat-stable vitamins, are added thereto, stirred at room temperature for a certain time to dissolve, and then filled into a soft capsule base containing gelatin as a main ingredient to prepare a transparent soft capsule.

Experimental Example 1

Physical stability assessment:

According to the formulation and preparation method shown in Example 3, a transparent soft capsule was prepared, stored in a constant storage condition (refrigerated, frozen, 40 ° C.-75% RH), and the characteristics, phase separation, and precipitation generation of the transparent soft capsule at predetermined time intervals. Physical stability was measured and evaluated.

In general, in high humidity conditions (> 60% RH, 21-24 ℃) cells of soft capsules absorb water, so the cells become soft, sticky or swell. When transferred to proper storage conditions, the cells lose their original properties and cling together. Increasing the temperature (> 24 ° C) with increasing humidity (> 45%) causes the cell to melt and burst.

This phenomenon is more pronounced in capsules filled with water-soluble substances than capsules filled with lipophilic substances due to the presence of water remaining in the capsule contents and the thermodynamic relationship between the cells and the capsule contents during the dry process. The transparent soft capsule prepared by the present invention is a fatty acid that has little affinity with water because the content excipient used to solubilize the contents of the capsule not only absorbs water even under high humidity conditions, but also shows the appearance of the cell under normal storage conditions. There was no change and no precipitation occurred. Based on the above experimental results, the transparent soft capsules prepared by the above method were found to be more physically stable than the conventional soft capsules.

Experimental Example 2

Chemical stability evaluation

According to the formulation and preparation method shown in Example 3, the transparent soft capsule was prepared, stored in constant storage conditions (frozen, refrigerated, 40 ° C.-75% RH), and the content of the components contained in the transparent soft capsule at predetermined time intervals. The change was measured over time to evaluate the chemical stability of the clear soft capsule components.

In the embodiments included in the present invention, all of the steps of applying heat in the process of dissolving the main component contained in the capsule are included. In general, since vitamins have a lot of instability in heat, light, air, etc., this is not a method commonly seen in the manufacturing process of the soft capsule, but is a method specifically used only in the present invention. However, when the contents of the main components contained in the transparent soft capsule prepared by the above method were found to be almost unchanged. From the experimental results, it was confirmed that the transparent soft capsule manufactured by the above manufacturing method was chemically stable transparent soft capsule regardless of the process of applying heat during the manufacturing process.

As demonstrated in the above Examples and Experimental Examples, the transparent soft capsule of the present invention is a physically and chemically stable formulation.

Claims (5)

Ursodeoxycholic acid was dissolved in unsaturated fatty acid selected from oleic acid, linoleic acid, and linolenic acid as a content excipient, and filled into soft gelatin capsules to form ursodeoxycholic acid prepared by a conventional method for preparing soft capsules. Transparent soft capsule composition containing. Oleic acid, linoleic acid as contents excipients include urethane deoxycholine acid (UDCA), and at least one component selected from tocopherol, gamma-orizanol, tetrabutyric acid riboflavin, nitrate amine, cyanocobalamin, ascorbic acid and panthenol. A transparent soft capsule composition prepared by dissolving in an unsaturated fatty acid selected from linolenic acid, and filling with a soft gelatin capsule. The transparent soft capsule composition according to claim 1 or 2, wherein the content of the content excipient is 10 to 70% by weight based on the total weight. Ursodeoxycholic acid (UDCA) alone or ursodeoxycholic acid (UDCA) and one selected from tocopherol, gamma-orizanol, tetrabutyric acid riboflavin, nitrate amine, cyanocobalamine, ascorbic acid and panthenol A method of preparing a transparent soft capsule composition by dissolving a phase component in an unsaturated fatty acid selected from oleic acid, linoleic acid and linolenic acid as a content excipient, and filling a soft gelatin capsule. The method for producing a transparent soft capsule composition according to claim 4, wherein the amount of the content excipient is 10 to 70% by weight based on total weight, or ursodeoxycholic acid (UDCA) and other active ingredients.