JP5901998B2 - Soft capsule manufacturing method - Google Patents

Description

The present invention relates to a soft capsule manufacturing how.

  In general soft capsules, a water-insoluble content is filled in a capsule film formed of a water-soluble substance such as gelatin. The contents include an oil-soluble target substance dissolved in an oil or fat as a solvent, a hardly oil-soluble target substance suspended in an oil or fat as a dispersion medium, and DHA (docosahexaenoic acid), When the target substance itself to be filled in the capsule is oily, such as EPA (eicosapentaenoic acid), it is roughly classified. In either case, the contents of a conventional soft capsule can be said to be an “oily liquid”.

  The soft capsule has been regarded as a problem because the capsule coating may be damaged and the contents may leak out. For example, the capsule coating may be damaged by an external impact such as dropping or collision between capsules. In addition, when the soft capsule is refrigerated or frozen, the capsule coating may be cracked due to the low temperature environment. In particular, when a soft capsule film is formed by a rotary die type, the strength of the joint (seam) formed by heat-sealing two sheets formed from the coating liquid is low, and the soft capsule along the joint is formed. There was a tendency for the coating to be damaged and the contents to leak out.

  In the past, attempts have been made to increase the thickness of the capsule coating for the purpose of solving the problem that the contents leak due to the damage of the soft capsule coating. In addition, the capsule coating has a double structure, and the joint portion is reinforced by filling the joint portion of the inner layer with the outer layer, and the content of the plasticizer / water retention agent in the outer layer is made lower than that of the inner layer. A technique for suppressing wetting and softening of the coating has also been proposed (see Patent Document 1).

  However, when the capsule film is thickened, there is a problem that the disintegration property of the soft capsule is lowered. Further, when the capsule coating has a plurality of layers as in the technique of Patent Document 1, in addition to the possibility that the disintegration property of the soft capsule may be lowered, the number of manufacturing steps increases, the labor burden increases, and additional There was a problem of requiring a lot of equipment.

The present invention has been made in view of the above circumstances, the soft capsule leakage is suppressed without fear contents, disintegration properties lowered, to provide a manufacturing how the soft capsules can be manufactured easily, it is an issue.

  In order to solve the above-mentioned problems, a method for producing a soft capsule according to the present invention is described as follows: “After an aqueous solution containing sugar or sugar alcohol is enclosed in a soft capsule film, the aqueous solution is supersaturated with respect to sugar or sugar alcohol. And the contents enclosed in the soft capsule film are made into a solid state.

  The process of “supersaturating the aqueous solution with respect to sugar or sugar alcohol” means that after the aqueous solution of sugar or sugar alcohol is enclosed in the soft capsule film, the solvent (water) in the aqueous solution is evaporated, that is, the content enclosed in the soft capsule film This can be done by reducing the moisture content of the product. Alternatively, by preparing a high concentration of an aqueous solution of sugar or sugar alcohol at a high temperature and reducing the temperature after encapsulating in a soft capsule film, the solubility of the sugar or sugar alcohol can also be reduced. It can be “saturated with respect to sugar or sugar alcohol” and can be used in combination with the above treatment.

  Examples of “sugar or sugar alcohol” include disaccharides such as trehalose, maltose, lactose and cellobiose, monosaccharides such as glucose, mannose and galactose, and sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, maltitol and lactitol. be able to.

  The aqueous solution containing sugar or sugar alcohol can contain a desired component to be ingested by the soft capsule (hereinafter referred to as “ingestion intended component”). Here, as the ingestion intended ingredient, a pharmaceutical ingredient, a herbal medicine ingredient, a health food ingredient, and a nutritional supplement ingredient can be used without particular limitation, but a water-soluble or hydrophilic ingredient is suitable.

  In the method for producing a soft capsule having the above configuration, since the sugar or sugar alcohol is in a liquid (aqueous solution) state when filling the soft capsule film, the filling process into the soft capsule film can be performed without any problem. The aqueous solution of sugar or sugar alcohol is supersaturated after being sealed in the soft capsule film, so that sugar or sugar alcohol is deposited. Therefore, by sufficiently drying and reducing the water content of the contents, the sugar or sugar alcohol can be brought into a solid state. Also, when other components such as ingestion intended components are contained as contents, other components can be incorporated into the solid state sugar or sugar alcohol to bring the entire content into a solid state.

  Thereby, even if a soft capsule film | membrane is damaged, the soft capsule which a content cannot leak easily can be manufactured. In addition, in the conventional soft capsule, since the content is liquid, the content is greatly expanded and contracted due to a change in environmental temperature, and the soft capsule film is easily damaged. In contrast, in the present invention, since the contents are in a solid state, the contents are less likely to expand and contract due to temperature changes, and damage to the soft capsule film itself can be suppressed.

  In contrast to the problem of suppressing leakage of contents, the conventional technique is an approach of improving the capsule film side, whereas in the present invention, the problem is solved by paying attention to the contents. Thereby, the soft capsule in which leakage of the contents is suppressed can be manufactured without affecting the disintegration property of the soft capsule film. Moreover, it can manufacture by the manufacturing process as usual, except that the aqueous solution of sugar or sugar alcohol is contained in the composition encapsulated in the soft capsule film. Therefore, it is possible to easily manufacture a soft capsule in which leakage of contents is suppressed without requiring additional steps and equipment. In addition, the contents of conventional soft capsules are liquid, whereas the present invention can provide a novel soft capsule whose contents are solid.

Next, soft capsules are more produced in the present invention are those "contents containing a sugar or sugar alcohol is encapsulated in a soft capsule film in the solid state."

  The soft capsule of this structure is manufactured by the above-mentioned manufacturing method, and the leakage of the content is suppressed without the possibility of the disintegration being lowered.

As described above, as an effect of the present invention, soft capsules leakage is suppressed without fear contents, disintegration properties lowered, the manufacturing how the soft capsules can be manufactured easily, can be provided.

  Hereinafter, a soft capsule manufacturing method (hereinafter, simply referred to as “manufacturing method”) and a soft capsule manufactured by the manufacturing method according to an embodiment of the present invention will be described. In the production method of the present embodiment, after an aqueous solution containing sugar or sugar alcohol is enclosed in a soft capsule film, the aqueous solution is supersaturated with respect to sugar or sugar alcohol, and sugar or sugar alcohol is precipitated, and the content enclosed in the soft capsule film A thing is made into a solid state.

  More specifically, the manufacturing method of the present embodiment prepares a filling composition preparation step for preparing a filling composition containing an aqueous solution of sugar or sugar alcohol, and a capsule film solution that is a stock solution of the soft capsule film. A coating liquid preparation step, a molding / filling step of filling and encapsulating the filling composition in the soft capsule coating simultaneously with the molding of the soft capsule coating, and a drying step of drying the soft capsule after the molding / filling step are provided.

  In the filling composition preparation step, sugar or sugar alcohol is dissolved in water to obtain an aqueous solution. At this time, by heating, the solubility of sugar or sugar alcohol can be increased, and an aqueous solution containing sugar or sugar alcohol at a high concentration can be obtained. As a solvent of this aqueous solution, a solvent obtained by adding an organic solvent to water in addition to pure water may be used. Then, a filling composition is prepared by adding the ingestion target component to an aqueous solution of sugar or sugar alcohol. The ingestible component can be dissolved or suspended in an aqueous solution of sugar or sugar alcohol, but when suspended, the dispersoid is more likely to precipitate than when the filling composition is oily. Therefore, in order to produce soft capsules of the same quality containing the ingestion target component uniformly, a component that can be dissolved in an aqueous solution of sugar or sugar alcohol is suitable as the ingestion target component.

  In the coating solution preparation step, the coating base is dissolved in a solvent to obtain a capsule coating solution. For example, when gelatin is used as a film base, gelatin is dissolved in water while heating to prepare a capsule film solution having a viscosity suitable for casting. In addition, additives such as a plasticizer, a colorant, a light hiding agent, and an antiseptic can be added to the capsule film solution.

  The molding / filling step can be performed using a rotary die type molding apparatus. Here, a general rotary die type molding apparatus includes a casting drum for forming a capsule coating liquid into a film, a pair of die rolls having a molding mold formed on the outer surface, and a wedge-shaped segment disposed between the die rolls. And a pump that pushes the filling composition into the segment and pushes out the filling composition from the tip of the segment.

  First, the capsule coating liquid held at a high temperature and in a sol state is cast on the surface of the casting drum, cooled, and gelled to form a film. Next, two of the formed films are fed along a segment between a pair of die rolls. Thereafter, with the rotation of the pair of die rolls in opposite directions, the two films are heat sealed to form a soft capsule film that opens upward, and this is filled with the filling composition extruded from the segment. . At the same time, the two films are heat sealed at the top to form a soft capsule in which the filling composition is enclosed in a closed internal space.

  In the drying step, the soft capsules are dried in the dryer until the contents enclosed in the soft capsule film and the moisture content of the soft capsule film reach a predetermined moisture content. By this step, the solvent evaporates from the contents enclosed in the soft capsule film, the aqueous solution of sugar or sugar alcohol becomes supersaturated, and sugar or sugar alcohol is precipitated. Moreover, since the saturated concentration of sugar or sugar alcohol is lowered by lowering the temperature of the aqueous solution as compared with the time when the filling composition is filled and sealed in the capsule film, sugar or sugar alcohol is also precipitated due to this. .

  In this drying step, the contents become solid by being sufficiently dried. Although depending on the type of sugar or sugar alcohol, if the moisture content of the contents is dried to 5 mass% to 15 mass%, the moisture content does not decrease any more. In this state, the moisture remaining in the contents is crystal water, so that moisture does not migrate to the soft capsule film. Therefore, even if the soft capsule film is water-soluble, there is no possibility that the soft capsule film will be softened or deteriorated by the water content.

  Through the above manufacturing process, a soft capsule having a structure in which a content containing sugar or sugar alcohol is enclosed in a soft capsule film in a solid state is manufactured.

  Even if the soft capsule film is damaged, the soft capsule having the above structure is difficult to leak to the outside because the content is a solid having no fluidity. In addition, since the contents are in a solid state, the contents are difficult to expand and contract due to temperature changes, and damage to the soft capsule film itself is suppressed.

  Moreover, since it is an approach which aims at suppression of the leakage of a content from the content side, there is no possibility that the disintegration property of a soft capsule film | membrane may fall. In addition, the soft capsule having the above-described configuration can be easily manufactured without requiring additional steps and equipment as compared with the conventional manufacturing method.

  Furthermore, sugars and sugar alcohols are endothermic reactions that dissolve in water. Therefore, when the soft capsule is disintegrated and dissolved in the oral cavity without being swallowed, a cool texture can be enjoyed. Further, the content of the conventional soft capsule is an oily substance, whereas in this embodiment, the base of the filling composition is an aqueous solution. Thereby, when a soft capsule film | membrane disintegrates, it has the advantage that the solubility of the content is high.

  In addition, since the content is in a solid state and the content hardly expands or contracts due to a temperature change, the soft capsule film may be formed without adding a plasticizer such as glycerin to the capsule film liquid. Since the soft capsule film does not contain a plasticizer, softening of the soft capsule film at high temperatures and high humidity can be suppressed, damage (crushed or torn) due to deformation of the soft capsule film can be reduced, and adhesion between soft capsules can be suppressed. can do.

  Using sorbitol, xylitol, erythritol, and trehalose as sugars or sugar alcohols, respectively, four types of aqueous solutions (samples 1 to 4) were prepared while heating to 70 ° C. Each aqueous solution was filled and sealed in a soft capsule film based on gelatin. The temperature of the aqueous solution in the filling / sealing step was 45 ° C. Table 1 shows the type of sugar or sugar alcohol and the concentration (mass%) of the aqueous solution of the samples 1-4.

  The soft capsules filled with the solutions of Samples 1 to 4 are all dried at room temperature (25 ° C.) until the water content of the content reaches 15% by mass or less, whereby sugar or sugar alcohol precipitates. The thing became a solid state.

  Here, if the solubility of sugar or sugar alcohol is too high, sugar or sugar alcohol does not readily precipitate even if the water content of the content is reduced. On the other hand, if the solubility of sugar or sugar alcohol is too small, the concentration of the original aqueous solution will be low, and the amount of precipitation will be insufficient. In this respect, the sugar or sugar alcohol used in Samples 1 to 4 is a drying process that reduces the moisture content of the contents to at least 15% by mass, and a practical temperature change (filled with a solution at 45 ° C. Encapsulated and cooled to room temperature), a sufficient amount can be deposited to make the contents solid, which can be said to be extremely practical.

  Next, a sorbitol aqueous solution (70% by mass aqueous solution) is used as an aqueous solution of sugar or sugar alcohol, and a filling composition is prepared by adding vitamin C (powder) as a component for ingestion. Soft capsules based on gelatin Soft capsules were manufactured by filling and enclosing the coating. The temperature at which Vitamin C was added to and mixed with the sorbitol aqueous solution was 70 ° C., and the temperature at which the filling composition was filled and sealed in the soft capsule film was 45 ° C. The solubility of Vitamin C was confirmed at both time points. Moreover, in order to evaluate the filling property to a soft capsule film, the viscosity of the composition for filling in the temperature (45 degreeC) with which a soft capsule film is filled and enclosed is measured with a B-type viscometer ((No. 4 rotor, rotational speed 100 rpm)). About the manufactured soft capsule, it dried at normal temperature until the moisture content of the content became 15 mass% or less, and observed precipitation of sorbitol.This examination is different in the blending ratio of sorbitol and vitamin C. It carried out about five types of filling compositions (samples 11-15) The composition of the filling composition of samples 11-15 is shown in Table 2. Moreover, the solubility of vitamin C in 70 degreeC and 45 degreeC, Table 2 shows the viscosity of the filling composition at 45 ° C.

  As shown in Table 2, in sample 15 having a vitamin C ratio of 40% by mass, vitamin C was not completely dissolved in the sorbitol aqueous solution. Further, in the sample 14 in which the proportion of vitamin C was 30% by mass, although vitamin C was dissolved in the sorbitol aqueous solution at 70 ° C., the temperature decreased to 45 ° C., so that precipitation of vitamin C was generated. On the other hand, in the samples 11 and 12 having vitamin C ratios of 10% by mass and 20% by mass, vitamin C was completely dissolved in the sorbitol aqueous solution at 70 ° C. and 45 ° C., respectively. Therefore, in order to produce soft capsules of the same quality that uniformly contain vitamin C, which is an intended ingredient, it is desirable that the proportion of vitamin C in the filling composition be 20% by mass or less. In addition, the viscosity at 45 ° C. of the filling compositions of Samples 11 to 13 in which the proportion of vitamin C was 20% by mass or less was small, and the filling property to the soft capsule film was good.

  Furthermore, the soft capsules filled with the filling compositions of Samples 11 to 13 were all dried at room temperature until the moisture content of the contents became 15% by mass or less, so that sorbitol was precipitated. It became a solid state.

  With respect to these soft capsules (soft capsules filled with the filling composition of Samples 11 to 13), the disintegration property was evaluated. The disintegration property was evaluated by a disintegration test at normal temperature and an accelerated test in which the disintegration property was stored for a predetermined period under a temperature severer than normal storage conditions and the change over time of disintegration property was evaluated. Here, the disintegration test at room temperature is performed in accordance with the disintegration test method prescribed in the Japanese Pharmacopoeia. When the capsule film completely disintegrates within 20 minutes, it is evaluated as “good”, otherwise it is evaluated as “bad”. " In the accelerated test, the storage temperature is set to 40 ° C., and after the storage for a predetermined period, the disintegration test is performed according to the test method prescribed in the Japanese Pharmacopoeia. It was evaluated as “good”, and when it was not, it was evaluated as “bad”. The storage period in the accelerated test was 1 month (corresponding to 6 months of normal temperature storage), 2 months (corresponding to 1 year of normal temperature storage), and 4 months (corresponding to 2 years of normal temperature storage). The evaluation results of disintegration are shown together in Table 2.

  As shown in Table 2, all of the soft capsules filled with the filling compositions of Samples 11 to 13 showed good disintegration, and no deterioration over time with storage was observed.

  Next, a filling composition was prepared by adding vitamin C (powder) as an ingested ingredient to an aqueous solution using sorbitol, xylitol, erythritol, trehalose as sugar or sugar alcohol, respectively, and four kinds of filling compositions (Samples 21 to 24) were prepared. The concentration of vitamin C in the filling composition was 20% by mass. Each filling composition was filled and enclosed in a soft capsule film based on gelatin to produce soft capsules. The temperature when adding and mixing vitamin C to an aqueous solution of sugar or sugar alcohol was 70 ° C., and the temperature when filling and encapsulating the filling composition in the soft capsule film was 45 ° C.

  About each filling composition, the solubility of the vitamin C in 70 degreeC and 45 degreeC was confirmed similarly to the above, and the viscosity of the filling composition in 45 degreeC was measured. In addition, the soft capsules filled and sealed with the respective filling compositions were dried at room temperature until the water content of the contents became 15% by mass or less, and precipitation of sugar or sugar alcohol was observed. Furthermore, by the same method as described above, a disintegration test and an acceleration test at normal temperature were performed to evaluate disintegration. These results are shown in Table 3 together with the composition of the filling composition.

  In the filling compositions of Samples 21 to 24, the solubility of vitamin C in an aqueous solution of sugar or sugar alcohol was good both at 70 ° C. and 45 ° C. Moreover, the viscosities at 45 ° C. of the filling compositions of Samples 21 to 24 were all small, and the filling property to the soft capsule film was good. Furthermore, the soft capsules filled with the filling compositions of Samples 21 to 24 are all dried at room temperature until the water content of the contents is 15% by mass or less, so that sugar or sugar alcohol is sufficiently precipitated. However, the contents became solid. In addition, the soft capsules filled with the filling compositions of Samples 21 to 24 all showed good disintegration properties, and no deterioration over time was observed with storage.

  The present invention has been described with reference to the preferred embodiments. However, the present invention is not limited to the above-described embodiments, and various improvements can be made without departing from the scope of the present invention as described below. And design changes are possible.

  For example, in the above-described embodiment, the case where gelatin is used as the base of the soft capsule film is illustrated, but the present invention is not limited to this. Since the present invention focuses on the contents and suppresses the leakage of the contents, it does not ask the kind of the soft capsule film. For example, a non-gelatin base such as hypromellose (HPMC) or starch is used as the soft capsule film. It can be used as a base for.

JP 2007-320875 A

Claims (1)

After enclosing an aqueous solution containing sugar or sugar alcohol in a soft capsule film, the aqueous solution is supersaturated with respect to sugar or sugar alcohol to precipitate sugar or sugar alcohol, and the content enclosed in the soft capsule film is made solid. A method for producing a soft capsule.