Banding solution for producing enteric hard capsules and enteric hard capsules produced using the same

Abstract

To provide a banding solution for manufacturing enteric hard capsules and an enteric hard capsule manufactured using the same, and specifically, provide a banding solution for manufacturing enteric hard capsules, which prevent the generation of a gap between the coupled capsule upper portion and capsule lower portion due to gastric acid or the separation of the capsule upper portion and the capsule lower portion during the time the enteric hard capsules stay in the stomach, and an enteric hard capsule subjected to banding treatment using the same.SOLUTION: A banding solution is applied to a region including a boundary 133 of a coupling portion 130 in an enteric hard capsule 100, where a capsule upper portion 110 and a capsule lower portion 120 are coupled to form the coupling portion 130. The banding solution includes 90 to 96 pts.wt. of purified water and 3 to 5 pts.wt. of alginate. The enteric hard capsule 100 has the banding solution applied to the region including the boundary 133 of the coupling portion 130.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a banding solution for producing an enteric hard capsule and an enteric hard capsule banded using the same, and more particularly to a banding solution for producing an enteric hard capsule which prevents the generation of a gap between the upper and lower capsule parts bound together by gastric acid during residence time in the stomach and prevents the upper and lower capsule parts from being separated, and an enteric hard capsule banded using the same. [Background technology]

[0002] People take drugs, health functional foods, etc. to treat illnesses, improve health, etc. The most common dosage form of drugs or health functional foods is tablets, which are broadly divided into tablets and capsules, and capsules are broadly divided into soft capsules and hard capsules.

[0003] Tablets are made by coating solidified drugs so that they dissolve and are absorbed in the body. Soft capsules are generally made using gelatin, and are produced by putting active ingredients and additives between two sheets of gelatin, and then applying pressure to the sheets to form them. Therefore, soft capsules are formed as one piece without any gaps or breaks that can be separated. Hard capsules are produced by having an outer shell with the top and bottom joined together, and putting active ingredients and additives inside. In general, hard capsules are easier to produce than soft capsules, and incur less cost.

[0004] On the other hand, tablets, unless specially treated, disintegrate due to gastric acid during the retention time in the stomach (within 2 hours) and the active ingredient is released in the stomach, so that the active ingredient can be exposed to gastric acid and absorbed in the stomach. However, because the active ingredient loses its activity due to acid, or because it needs to be absorbed in the intestine, or because of other needs, there is a demand for a form of tablet that does not disintegrate in gastric acid. Examples of such active ingredients include aspirin, lactic acid bacteria, omega-3, etc. In the case of aspirin, it needs to be absorbed from the intestine because it can have adverse effects on patients with gastric diseases such as gastritis and gastric ulcers, and in the case of lactic acid bacteria, it must not disintegrate due to gastric acid because it becomes less effective when exposed to gastric acid, and in the case of omega-3, consumers prefer tablets that disintegrate in the intestine rather than the stomach because it has a unique fishy smell. Therefore, it is necessary to manufacture an enteric-coated dosage form, which is a tablet that does not disintegrate due to gastric acid during the 2 hours it stays in the stomach and disintegrates in the intestine within 30 or 60 minutes. Conventional enteric dosage forms include tablets coated with an enteric substance and soft capsules made of an enteric substance. Attempts have been made to produce enteric hard capsules due to their advantages of ease of production and low costs.

[0005] However, in the enteric hard capsules that have been tried in the past, even though the hard capsule itself does not dissolve in stomach acid, the water-soluble ingredients in the part of the hard capsule that comes into contact with stomach acid absorb water and swell, while the inside of the joint part of the hard capsule that does not come into direct contact with stomach acid does not swell, which can lead to structural problems such as gaps forming at the joint between the upper and lower parts of the capsule, or the upper and lower parts separating to allow the active ingredients to leak out. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 2614073 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention provides a banding solution for banding a hard capsule to prevent a gap from being generated at a joint between an upper part and a lower part of the capsule or separation of the upper part and the lower part of the capsule due to gastric acid during residence time in the stomach.

[0008] The present invention provides an enteric hard capsule that has been banded, which prevents gaps from forming at the joint between the upper and lower parts of the capsule and prevents the upper and lower parts from being separated by gastric acid during residence time in the stomach. [Means for solving the problem]

[0009] To achieve the above objectives, a banding solution is provided which is applied to the area including the bond line of the enteric coated hard capsule.

[0010] In the present invention, the banding solution contains 90 to 96 parts by weight of purified water and 3 to 5 parts by weight of an alginate.

[0011] In the present invention, the alginate is at least one selected from the group consisting of sodium alginate, ammonium alginate, calcium alginate, and potassium alginate.

[0012] In the present invention, the banding solution further comprises 1 to 4 parts by weight of a corn starch-based polymer.

[0013] In the present invention, the banding solution further contains 1.5 to 2.5 parts by weight of pectin.

[0014] In the present invention, the banding solution further comprises 1.5 to 2.5 parts by weight of pectin and 1.0 to 3.0 parts by weight of a corn starch-based polymer.

[0015] In the present invention, the banding solution contains 75 to 90 parts by weight of purified water, 2.5 to 6 parts by weight of pectin, 0.05 to 2 parts by weight of a plasticizer, and 10 to 20 parts by weight of alcohol.

[0016] In the present invention, the plasticizer is glycerin and the alcohol is ethanol.

[0017] In the present invention, the banding solution further contains 0.05 to 1.5 parts by weight of a colorant.

[0018] In order to solve the above problems, an enteric hard capsule is provided in which a banding solution is applied to the area including the boundary of the bond. Effect of the Invention

[0019] According to the present invention, a banding solution for producing an enteric capsule can be prepared, which prevents gaps from forming at the boundary of the joint due to stomach acid or the upper and lower parts from separating during the two hours that the hard capsule remains in the stomach after ingestion, thereby preventing the leakage of active ingredients.

[0020] According to the present invention, enteric hard capsules can be prepared by coating and drying a banding solution. [Brief description of the drawings]

[0021] [Figure 1] Enteric-coated hard capsules and their composition. [Diagram 2] 1 shows an enteric coated hard capsule coated with banding solution and dried according to one embodiment. [Diagram 3] 1 shows the results of a disintegration test of an enteric hard capsule coated with a banding solution according to an embodiment and dried under gastric acid conditions for 2 hours. [Figure 4] The results of a disintegration test of hard capsules not coated with a banding solution under gastric acid conditions are shown below. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The present invention can be achieved by the following description. The following description should be understood as describing specific examples of the present invention, and the present invention is not necessarily limited thereto. In addition, it should be understood that the attached drawings are for the purpose of aiding understanding, and the present invention is not limited thereto.

[0023] The embodiments of the present disclosure can be modified in various ways and can be implemented in various forms. Therefore, it should be understood that the present disclosure includes all modifications, equivalents, and alternatives within the scope of the same idea and technical features of the present disclosure.

[0024] First, the enteric hard capsule according to the present invention will be described. FIG. 1 is a schematic diagram of an enteric hard capsule 100 according to the present invention. Referring to FIG. 1, the enteric hard capsule 100 is composed of a capsule upper part 110 and a capsule lower part 120, and the capsule upper part 110 and the capsule lower part 120 are joined to form a joint part 130. The joint part 130 includes an outer joint part 131 that is exposed to the outside and corresponds to a part of the capsule upper part 110, and an inner joint part 132 that is not exposed to the outside and corresponds to a part of the capsule lower part. An active ingredient is present inside the enteric hard capsule 100. Examples of the active ingredient include, but are not limited to, lactic acid bacteria, omega-3, aspirin, and intestinal disease treatment agents. The enteric hard capsule 100 is a hard capsule that does not disintegrate due to gastric acid during its residence time in the stomach (about 2 hours) and disintegrates within 30 to 60 minutes in the intestine. Materials for manufacturing the enteric hard capsule 100 may include, but are not limited to, at least one selected from the group consisting of hydroxypropyl methylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), Eudragit, zein, acrylic acid copolymers, and shellac, pectin, gellan gum, and alginates.

[0025] One of the features of the enteric hard capsule 100 according to the present invention is that a banding solution is applied to an area including a part of the joint 130 of the enteric hard capsule 100, more specifically, an area including the boundary 133 of the joint, and then dried. If such a banding solution is not applied, the hard capsule itself will not dissolve due to gastric acid during the two hours that the enteric hard capsule is retained in the stomach, but the water-soluble components of the outer joint 131 that comes into contact with the gastric acid will absorb water and swell, while the inner joint 132 that does not directly come into contact with the gastric acid will not swell, so that a gap may occur at the joint between the upper and lower capsule portions, or the upper and lower capsule portions may be separated, causing the active ingredients inside the hard capsule to leak out (FIG. 4). However, when the banding solution is applied to an area including a part of the joint 130, the outer joint of the part treated with the banding solution will come into contact with gastric acid while the enteric hard capsule 100 is retained in the stomach, so that it is possible to prevent the outer joint of the part treated with the banding solution from absorbing water-soluble substances and swelling. Therefore, there is an advantage that the active ingredient does not leak out due to a gap occurring at the joint between the upper and lower capsules or due to the upper and lower capsules being separated. In addition, the banding solution is applied only to the area including the joint 130, more specifically, the area including the border 133 of the joint, which is more economical than applying the banding solution to the entire hard capsule, and the increase in volume is small, making it easy to transport and take. In addition, since the banding solution can be applied and dried after the hard capsule is manufactured, the process of applying and drying the banding solution can be easily added to the existing manufacturing process.

[0026] Hereinafter, a banding solution according to an embodiment of the present invention will be described.

[0027] The banding solution according to one embodiment of the present invention contains 90-96 parts by weight of purified water and 3-5 parts by weight of alginate.

[0028] The alginate can increase the viscosity of the banding solution and increase the acid resistance of the banding solution to complement the acid resistance of the enteric coated hard capsule 100. The alginate can be one or more selected from the group consisting of sodium alginate, ammonium alginate, calcium alginate, and potassium alginate.

[0029] Alginic acid, a type of alginate, is a polymeric compound derived from brown algae. It is a weakly acidic uronic acid polymer in which a carboxyl group (-COOH, -CO2H) is introduced in place of the primary alcohol group of aldose by forming a linear covalent bond between β-1,4-linked D-mannuronic acid [β-1,4-D-mannuronic acid] and α-1,4-linked L-guluronic acid [α-1,4-L-guluronic acid].

[0030] Meanwhile, it is very important that the banding solution has an optimal viscosity for preparation and smooth application. In relation to this, the inventors of the present invention conducted numerous experiments and found that when the content of the alginate is less than 3 parts by weight, the required acid resistance is not sufficient, and therefore, even when an enteric hard capsule is prepared using the banding solution, the problem of gaps occurring at the boundary of the joint or separation of the upper and lower parts of the capsule could not be solved. In addition, since the banding solution is thin, even when applied to a hard capsule, the banding solution flows, making it difficult to apply to the desired area, and thus problems occurred in product manufacture. On the other hand, when the content of the alginate exceeds 5 parts by weight, the viscosity becomes too high, and there is a problem that the banding solution does not move smoothly in the machine, or even when applied to a hard capsule by hand, it is not applied to the desired area, and even if applied, it is not dried well, so problems occurred in product manufacture.

[0031] In addition to purified water and alginate, the banding solution according to an embodiment of the present invention may further include a corn starch-based polymer.

[0032] The corn starch-based polymer can complement the acid resistance of the enteric hard capsule 100. Commercially available corn starch-based polymers can be used, for example, Eudraguard® natural by Evonik.

[0033] In one embodiment including a corn starch-based polymer, the banding solution may include 90-96 parts by weight purified water, 3-5 parts by weight alginate, and 1-4 parts by weight corn starch-based polymer.

[0034] The banding solution according to an embodiment of the present invention may further include pectin in addition to purified water and alginate, which can increase the viscosity of the banding solution and increase the acid resistance of the banding solution.

[0035] Pectin is a water-soluble polymeric polysaccharide obtained by extraction from edible plants such as citrus fruits and apples. Pectin is classified according to the degree of esterification (DE), and those with an esterification degree of 50% or more are called HM (high methoxyl) pectin and those with an esterification degree of less than 50% are called LM (low methoxyl) pectin. In addition, pectin obtained by treating LM pectin with ammonia under alkaline conditions is called LM amide pectin. In this case, the pectin used in the banding solution according to one embodiment of the present invention may be LM pectin or LM amide pectin.

[0036] In one embodiment including pectin, the banding solution may include 90-96 parts by weight purified water, 3-5 parts by weight alginate, and 1.5-2.5 parts by weight pectin.

[0037] In addition to purified water and alginate, the banding solution according to an embodiment of the present invention may further include a corn starch-based polymer and pectin.

[0038] In one embodiment including corn starch based polymer and pectin, the banding solution may include 90-96 parts by weight purified water, 3-5 parts by weight alginate, 1.5-2.5 parts by weight pectin, and 1.0-3.0 parts by weight corn starch based polymer.

[0039] Meanwhile, the banding solution according to an embodiment of the present invention may further include a colorant. The colorant may be included in the banding solution in an amount of 0.05 to 1.5 parts by weight. When the colorant is included, a colored banding solution may be prepared, and the portion to which the banding solution is applied may be visualized or the banding solution may be prepared in the same color as the hard capsule. The colorant may be one or more pigments selected from the group consisting of Green No. 3, Red No. 2, Red No. 3, Red No. 40, Red No. 102, Blue No. 1, Blue No. 2, Yellow No. 4, Yellow No. 5, and aluminum lake, but is not limited thereto.

[0040] Hereinafter, a banding solution according to another embodiment of the present invention will be described.

[0041] A banding solution according to another embodiment of the present invention may include 75-85 parts by weight of purified water, 2.5-6 parts by weight of pectin, 0.05-2 parts by weight of plasticizer, and 10-20 parts by weight of alcohol.

[0042] Pectin can increase the viscosity of the banding solution and enhance the acid resistance of the banding solution to complement the acid resistance of the enteric coated hard capsule 100 .

[0043] Meanwhile, it is very important that the banding solution has an optimal viscosity for preparation and smooth application. In relation to this, the inventors of the present invention conducted numerous experiments and found that when the pectin content is less than 2.5 parts by weight, the required acid resistance is not sufficient, and therefore, even when an enteric hard capsule is prepared using the banding solution, the problem of gaps occurring at the boundary of the joint or separation of the upper and lower parts of the capsule could not be solved. In addition, since the banding solution is thin, even when it is applied to the hard capsule, the banding solution flows, making it difficult to apply to the desired area, and thus problems occurred in product manufacture. On the other hand, when the pectin content exceeds 6 parts by weight, the viscosity becomes too high, and there is a problem that the banding solution does not move smoothly in the machine, or even when it is applied to the hard capsule by hand, it is not applied to the desired area, and even if it is applied, it is not dried well, so problems occurred in product manufacture.

[0044] Plasticizers can improve the processability of the banding solution, and examples of plasticizers include, but are not limited to, glycerin, glycerin fatty acid esters, dioctyl adipate, adipate polyester, epoxidized soybean oil, epoxy hexahydrophthalic acid diester, kaolin, and triethyl citrate.

[0045] The alcohol helps dissolve the components of the banding solution and allows for fast drying after the banding solution application process. Examples of alcohols include, but are not limited to, ethanol, methanol, isopropanol, and butanol.

[0046] Meanwhile, the banding solution according to another embodiment of the present invention may further include a colorant. The colorant may be included in the banding solution in an amount of 0.05 to 1.5 parts by weight. When the colorant is included, a colored banding solution may be prepared, and the portion to which the banding solution is applied may be visualized, or the banding solution may be prepared in the same color as the hard capsule. The colorant may be one or more pigments selected from the group consisting of Green No. 3, Red No. 2, Red No. 3, Red No. 40, Red No. 102, Blue No. 1, Blue No. 2, Yellow No. 4, Yellow No. 5, and aluminum lake, but is not limited thereto.

[0047] The enteric hard capsule according to one embodiment of the present invention is manufactured by applying a banding solution to an area including a joint 130 of an acid-resistant hard capsule, more specifically, an area including a border 133 of the joint, and then drying the solution. The acid-resistant hard capsule can be manufactured by a conventional manufacturing method. The banding solution of the sixth invention is a banding solution applied to an area including the boundary of the joint of an enteric hard capsule where the upper and lower parts of the capsule are joined to form the joint, characterized in that the banding solution contains 75 to 85 parts by weight of purified water, 2.5 to 6 parts by weight of pectin, 0.05 to 2 parts by weight of a plasticizer, and 10 to 20 parts by weight of alcohol. The banding solution of the seventh invention is the banding solution of the sixth invention, characterized in that the plasticizer is glycerin and the alcohol is ethanol. The banding solution of the eighth invention is characterized in that the banding solution of the sixth or seventh invention further contains 0.05 to 1.5 parts by weight of a colorant. The enteric hard capsule of the ninth invention is characterized in that the banding solution of the sixth or seventh invention is applied to a region including the boundary of the bonded portion.

[0048] The present disclosure will be described in more detail below with reference to examples and comparative examples, but the present disclosure is not limited to these examples.

[0049] <Experimental Example> A disintegration test was conducted for an acid-resistant hard capsule (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria under gastric acid (pH 1.2) conditions for 1 hour. Figure 4 shows the disintegration test of a hard capsule without a banding solution under gastric acid conditions. The disintegration test confirmed that the upper and lower parts of the hard capsule separated and the formulation inside the capsule leaked out.

[0050] <Examples 1 and 2> Sodium alginate was added to purified water at 70°C and stirred, then colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, it was confirmed that it was well mixed without layer separation. The prepared banding solution was manually applied to acid-resistant hard capsules (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria and then dried. The prepared enteric-coated hard capsules were subjected to a disintegration test for 2 hours under gastric acid (pH 1.2) conditions, and after observation, it was confirmed that the upper and lower parts of the hard capsules did not separate. After a disintegration test under gastric acid conditions, a disintegration test was conducted in purified water, confirming that the capsules disintegrated within 30 minutes.

[0051] <Comparative Examples 1 and 2> Sodium alginate was added to purified water at 70℃ and stirred. Then, colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, the viscosity became too low or too high to apply the banding solution, so a disintegration test could not be performed.

[0052] [Table 1]

[0053] <Examples 3 and 4> Sodium alginate and Eudraguard® natural were added to purified water at 70°C and stirred. Then, colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, it was confirmed that it was well mixed without layer separation. The prepared banding solution was manually applied to acid-resistant hard capsules (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria and then dried. The prepared enteric-coated hard capsules were subjected to a disintegration test for 2 hours under gastric acid (pH 1.2) conditions, and after observation, it was confirmed that the upper and lower parts of the hard capsules did not separate. After a disintegration test under gastric acid conditions, a disintegration test was conducted in purified water, and it was confirmed that the capsules disintegrated within 30 minutes.

[0054] <Comparative Examples 3 and 4> Sodium alginate and Eudraguard® natural were added to purified water at 70°C and stirred. Then, colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, the viscosity was low or high, so the banding solution could not be applied, and a disintegration test could not be performed.

[0055] [Table 2]

[0056] <Examples 5 and 6> Sodium alginate and pectin (LM Amide Pectin) were added to purified water at 70℃ and stirred. Then, coloring (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, it was confirmed that it was well mixed without layer separation. The prepared banding solution was manually applied to acid-resistant hard capsules (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria and then dried. The prepared enteric-coated hard capsules were subjected to a disintegration test for 2 hours under gastric acid (pH 1.2) conditions, and after observation, it was confirmed that the upper and lower parts of the hard capsules did not separate. After a disintegration test under gastric acid conditions, a disintegration test was conducted in purified water, and it was confirmed that the capsules disintegrated within 30 minutes.

[0057] <Comparative Examples 5 and 6> Sodium alginate and pectin (LM Amide Pectin) were added to purified water at 70℃ and stirred. Then, colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, the viscosity was low or high, so the banding solution could not be applied, and a disintegration test could not be performed.

[0058] [Table 3]

[0059] <Examples 7 and 8> Sodium alginate, pectin (LM Amide Pectin), and Eudraguard® natural were added to purified water at 70°C and stirred. Then, coloring matter (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, it was confirmed that it was well mixed without layer separation. The prepared banding solution was manually applied to an acid-resistant hard capsule (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria and then dried. The prepared enteric hard capsule was subjected to a disintegration test for 2 hours under gastric acid (pH 1.2) conditions, and after observation, it was confirmed that the upper and lower parts of the hard capsule did not separate. After the disintegration test under gastric acid conditions, a disintegration test was performed in purified water, and it was confirmed that it disintegrated within 30 minutes.

[0060] <Comparative Examples 7 and 8> Sodium alginate, pectin (LM Amide Pectin), and Eudraguard® natural were added to purified water at 70°C and stirred. Then, colorant (Blue No. 1) was added and stirred. When the prepared banding solution was cooled to room temperature, the viscosity became too low or too high, making it impossible to apply the banding solution, and therefore a disintegration test could not be performed.

[0061] [Table 4]

[0062] <Examples 9 and 10> Pectin (LM Amide Pectin) was added to purified water at 70℃ and stirred. Glycerin was added and stirred, and coloring (Blue No. 1) was added. Then, ethanol was added and stirred while maintaining the temperature at 60℃. It was confirmed that the prepared banding solution was well mixed without layer separation when cooled to room temperature. The prepared banding solution was manually applied to acid-resistant hard capsules (SUHEUNG EMBO CAPS-AP, No. 0) filled with lactic acid bacteria and then dried. The prepared enteric-coated hard capsules were subjected to a disintegration test for 2 hours under gastric acid (pH 1.2) conditions, and after observation, it was confirmed that the upper and lower parts of the hard capsules did not separate. After a disintegration test under gastric acid conditions, a disintegration test was conducted in purified water, and it was confirmed that the capsules disintegrated within 30 minutes.

[0063] <Comparative Examples 9 and 10> Pectin (LM Amide Pectin) was added to purified water at 70°C and stirred. Glycerin was also added and stirred, and coloring (Blue No. 1) was added. After that, ethanol was added and stirred while maintaining the temperature at 60°C. When the prepared banding solution was cooled to room temperature, the viscosity was low or high, making it impossible to apply the banding solution, so a disintegration test could not be performed.

[0064] [Table 5] [Explanation of symbols]

[0065] 100 hard capsules 110 Capsule top 120 Capsule bottom 130 Joint 131 Outer join part 132 Internal joint 133 Joint Boundary

Claims

1. In a banding solution applied to an area including the boundary of the joint of an enteric hard capsule where the capsule upper part and the capsule lower part are joined to form a joint, The banding solution contains 90 to 96 parts by weight of purified water and 3 to 5 parts by weight of an alginate, and is free of an alkaline compound.

2. 2. The banding solution according to claim 1, wherein the alginate is at least one selected from the group consisting of sodium alginate, ammonium alginate, calcium alginate, and potassium alginate.

3. 2. The banding solution of claim 1, further comprising 1.0 to 4.0 parts by weight of a corn starch-based polymer.

4. The banding solution according to claim 1, further comprising 1.5 to 2.5 parts by weight of pectin.

5. 2. The banding solution of claim 1, further comprising 1.5-2.5 parts by weight of pectin and 1.0-3.0 parts by weight of a corn starch-based polymer.

6. The banding solution according to any one of claims 1 to 5, further comprising 0.05 to 1.5 parts by weight of a colorant.

7. 6. An enteric hard capsule, comprising: a banding solution according to claim 1 applied to a region including a boundary of a joint.

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