JP2002179560A - Chewable soft capsule with improved ingestibility and its manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a soft capsule preparation excellent in feeling of taking, in which the feeling of discomfort of the skin and the bitterness of the medicine are reduced. SOLUTION: The soft capsule is prepared by filling the contents into a shell, and the contents are solid or semi-solid at room temperature. The soft capsule may be a chewable capsule, the contents of which may contain a low melting point additive. The content of the low melting point additive can be 10% or more based on the total weight of the contents, and its melting point can be about 20-50 ° C. The low melting point additive can be selected from the group consisting of chocolate base, lard, coconut fat, and macrogol (polyethylene glycol), and combinations thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a chewable soft capsule and a method for producing the same, and more particularly, to a soft capsule whose content is solid or semi-solid at room temperature and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, there has been an increasing need for chewable capsules which can be easily taken without water from the viewpoint of improving the ingestibility and portability of pharmaceutical preparations. Chewable capsules that can be taken easily without water are useful as fast-dissolving formulations especially for children or the elderly.

[0003] One of the dosage forms that can be used as a chewable preparation is a soft capsule. As a method of softening the skin of a soft capsule so as to be suitable for mastication, conventionally, concentrated glycerin, glycerin, and D in a skin composition have been used.
-A method of increasing the blending ratio of a plasticizer such as sorbitol is known (for example, see JP-A-10-273436, WO87 / 01034). But,
As the contents of conventional soft capsules, oily solutions or suspensions, solutions containing water or alcohols, and the like are used, and the contents of the soft capsules are not uniform. Therefore, when chewed, the discomfort of the skin,
And the oiliness derived from the oily base of the contents tends to remain. Drugs often exhibit an unpleasant taste, such as characteristic bitterness. In the conventional chewable soft capsule, the content containing the drug is a solution or suspension, so that the content spreads instantaneously in the oral cavity, and the user feels the bitterness of the drug at the same time as taking the drug. This leads to a further reduction in the feeling of taking the soft capsule.

[0004] In the case of tablets, a molding method using granules containing fats and oils to disintegrate quickly in the oral cavity has been reported as a device for improving the feeling of ingestion (JP-A-8-333243). See). However, in the case of soft capsules, no example is known from the above-mentioned viewpoint, in which the feeling of taking is improved.

[0005] Also in the field of foods, the necessity of chewable capsules that can easily supply nutrients has been increasing due to the recent rise in health consciousness. Therefore, soft capsules having excellent feeling of taking are useful not only in medicine but also in application to foods and the like.

[0006]

As described above, the conventional chewable soft capsules are not always satisfactory in the feeling of taking due to the discomfort of the skin and the bitterness of the medicine. The present invention is intended to solve these problems.

[0007]

Means for Solving the Problems As a result of intensive studies, the present inventors have formulated soft capsules so that their contents are solid or semi-solid at room temperature. And that the contents were uniformed and the discomfort of the skin could be reduced. In particular, as the contents of the soft capsule, a low melting point additive is preferable, specifically, cocoa powder, bitter chocolate, by formulating a chocolate base such as cocoa butter to an appropriate mixing ratio,
It has been found that a preparation which can be easily chewed in the mouth without water is obtained. The present invention has been completed based on these findings.

[0008] The present invention provides a soft capsule wherein the contents are filled in a shell and the contents are solid or semi-solid at room temperature.

[0009] In one embodiment, the soft capsule of the present invention is a chewable capsule.

In one embodiment, the content of the soft capsule of the present invention contains a low melting point additive. The content of the low melting point additive is 10% or more based on the total weight of the contents,
Preferably it can be 30% or more, more preferably 50%. Also, the melting point of the low melting point additive may be about 20-50 <0> C.

[0011] The low melting point additive may be selected from the group consisting of chocolate base, lard, coconut fat, and macrogol (polyethylene glycol), and combinations thereof. In particular, preferably a chocolate base, cocoa powder, bitter chocolate, and cocoa butter,
And combinations thereof. Preferably, the cocoa butter comprises a major amount of V-form crystals and a minor amount of V-form.
It may include Form I crystals.

In one embodiment, the content of the soft capsule of the present invention further contains a sweetener. The sweetener may be selected from the group consisting of aspartame, disodium glycyrrhizinate, sodium saccharin, stevia, and thaumatin, and combinations thereof.

[0013] In one embodiment, the soft capsule of the present invention may have a content comprising cocoa butter as a chocolate base, which is a low melting point additive, and aspartame as a sweetener.

In one embodiment, the content of the soft capsule of the present invention further contains a saccharide in addition to the sweetener. The saccharide may be selected from the group consisting of sucrose, D-mannitol, xylitol, erythritol, D-sorbitol, maltose, reduced maltose syrup, and maltitol, and combinations thereof.

In one embodiment, the content of the soft capsule of the present invention further contains a flavoring agent in addition to the sweetener. The flavor may be a chocolate flavor.

[0016] In one embodiment, the soft capsule of the present invention has a shell containing the following components (A) and (B): (A) gelatin; and (B) gelatin 100
100 to 600 parts by weight of plasticizer in total with respect to parts by weight, and one or more plasticizers selected from (b1) to (b3): (b1) glycerin, (b2) sucrose,
Fructose, D-mannitol, xylitol, erythritol, D-sorbitol, maltose, reduced maltose starch syrup, maltitol, sucrose alcohol and isomerized sugar,
And a saccharide plasticizer selected from the group consisting of combinations thereof, and (b3) propylene glycol and polyethylene glycol, and glycols selected from the group consisting of combinations thereof. The plasticizer (B) is (b)
1) It may contain glycerin. The coating may further contain, in addition to (A) and (B), 5 to 100 parts by weight of water-insoluble cellulose per 100 parts by weight of (C) gelatin.

In one embodiment, the soft capsule of the present invention further comprises (D) a sweetener in addition to (A) and (B). The sweetener of (D) may be selected from the group consisting of saccharin sodium, stevia, and thaumatin, and combinations thereof.

In one embodiment, the content of the soft capsule of the present invention contains a drug. The drug content can be up to 60% by total weight of the contents.

In one embodiment, the drug of the soft capsule of the present invention is selected from the group consisting of an antipyretic analgesic component, a rhinitis component, an antitussive expectorant component, and a vitamin component, and a combination thereof.

In one embodiment, the content of the soft capsule of the present invention contains a food.

[0021] The present invention also provides a method for producing the soft capsule according to any of the above, which comprises a step of filling the contents with a coating.

[0022] In one embodiment, the method comprises the steps of: wherein the content comprises cocoa butter as a chocolate base, a low melting point additive;
The method further includes aging at a temperature of 0 ° C. Aging can take place for more than 10 hours.

[0023]

DETAILED DESCRIPTION OF THE INVENTION Hereinafter, further details of the present invention will be described.

The soft capsule of the present invention is characterized in that the contents containing a drug or food are filled in the skin, and the contents are solid or semi-solid at room temperature. “Room temperature” refers to about 1-30 ° C. "Solid or semi-solid" means that the contents show substantially no fluidity at room temperature. The content can be a powder, but more preferably an integrated solid or semi-solid.

According to the present invention, since the content of the soft capsule is solid or semi-solid, the content and the skin are entangled in the mouth when chewed. Therefore, the feeling of incongruity peculiar to the skin is reduced, the oily base is not oily, and the feeling of taking can be remarkably improved.

The soft capsule of the present invention, whose content is solid or semi-solid at room temperature, is novel and its use is not particularly limited, but is preferably a chewable capsule.

The content of the soft capsule of the present invention may contain a low melting point additive. By adding an appropriate amount of the low melting point additive, the entire content dissolves without requiring excessive heating. Therefore, a soft capsule can be easily produced without causing denaturation or decomposition of components such as medicines and foods or poor adhesion of capsules.

Although the content of the low melting point additive is not particularly limited, it is typically at least 10%, preferably at least 20%, more preferably at least 30%, more preferably at least 40%, based on the total weight of the contents. , More preferably 50% or more, more preferably 60% or more. The low-melting-point additive has a dissolution temperature of the entire base of the content containing the same, which is higher than room temperature, and typically about 70 ° C. or lower, preferably about 60 ° C. or lower, more preferably about 50 ° C. or lower. It is preferred that the additive can be adjusted to even less than about 45 ° C. The “base” refers to, for example, components other than the drug in the case of a soft capsule containing a drug, and the components of the content other than the food in the case of a soft capsule containing a food.

[0029] The low melting point additive can be any additive that is pharmaceutically acceptable or suitable for food as long as the above objects can be achieved. The melting point of such low melting point additives is typically about 20-50 ° C, preferably about 2 ° C.
It can range from 5 to 45C, more preferably from about 30 to 40C.

Examples of preferred low melting point additives include chocolate base, lard, coconut fat, and macrogol (polyethylene glycol), and any combination thereof. In particular, when macrogol is used, the solubility and dissolution of a poorly soluble drug can be improved, and the absorbability of a poorly absorbable drug can be improved. These additives are commercially available or can be easily obtained by known preparation methods. Examples of commercially available macrogol that can be suitably used in the present invention include macrogol 600 and macrogol 100.
0, Macrogol 1500, and Macrogol 154
There is 0.

[0031] Chocolate base refers to known ingredients that can be used as raw materials for chocolate and combinations thereof. Representative chocolate bases include cocoa powder, bitter chocolate, and cocoa butter, and combinations thereof. Cocoa powder, bitter chocolate, and cocoa butter are all known as pharmaceutical additives.

By appropriately incorporating the chocolate base into the contents, it is possible to provide a chocolate-flavored preparation which maintains the appearance of the capsule and can be easily chewed in the mouth without water. Also, unpleasant tastes such as drugs and foods are masked.

The soft capsules of the present invention may also contain any sweetening ingredients whose contents are pharmaceutically acceptable or suitable for food use (herein referred to as "sweetening agents"). Examples of preferred sweeteners include aspartame, disodium glycyrrhizinate, sodium saccharin, stevia, and thaumatin, and any combination thereof. For convenience, saccharides that can be contained in the contents described later are excluded from the definition of the sweetener.

By appropriately adding a sweetener to the contents, a preparation can be provided which further suppresses unpleasant tastes such as bitterness of drugs and foods.

The present inventors have found that an effect of stabilizing aspartame can be obtained by combining cocoa butter as a chocolate base with aspartame as a sweetener. Accordingly, soft capsules whose contents include cocoa butter as a chocolate base and aspartame as a sweetener are a preferred embodiment of the present invention. The above-mentioned stabilizing effect is achieved in such a manner that the mixing ratio of cocoa butter is typically about 5% or more, preferably about 10% to 50%, based on the total weight of the contents, or 1 part by weight of aspartame. , Typically about 3 to 15 parts by weight, preferably about 3 to 12 parts by weight.

[0036] The soft capsules of the present invention may also contain, in addition to the sweetener, any saccharide that is pharmaceutically acceptable or suitable for food use, in addition to the sweetener. Examples of preferred saccharides include sucrose, D-mannitol, xylitol, erythritol, D-sorbitol, maltose, reduced maltose starch syrup, and maltitol, and any combination thereof. Sugar alcohols are particularly preferred examples of sugars because they are generally stable to drugs and foods. For the sake of convenience, glycosides exhibiting sweetness such as the aforementioned stevia are excluded from the definition of sugars.

[0037] The soft capsules of the present invention may also contain, in addition to the sweetening agent, any flavoring that is pharmaceutically acceptable or suitable for food use. Examples of preferred flavors include chocolate flavor, peppermint flavor, and vanilla flavor, and any combination thereof.

By appropriately adding sugars and / or flavors to the contents in addition to the sweetener, it is possible to provide soft capsules with a further improved feeling of taking.

[0039] The contents of the soft capsule of the present invention typically contain a drug or food.

In the soft capsule of the present invention, the content of the drug is typically 60% or less, preferably 50% or less, more preferably 30% or less, and still more preferably 15% or less, based on the total weight of the contents. It can be: By regulating the prescription amount of the drug to a low level as described above, it is possible to provide a drug product in which the unpleasant taste of the drug is particularly reduced.

Non-limiting examples of drugs used in the soft capsules of the present invention include antipyretic analgesic, rhinitis, antitussive expectorant, and vitamin components, and combinations thereof. Examples of antipyretic analgesic components include acetaminophen, aspirin, etensamide,
Salicylamide, lactylphenetidine and the like; examples of rhinitis drug components include phenylpropanolamine hydrochloride, d-
Chlorpheniramine maleate, dipotassium glycyrrhizinate, total alkaloids of belladonna, etc .; Examples of antitussive expectorants include dextromethorphan hydrobromide, codeine phosphate, methoxyphenamine hydrochloride, ephedra, licorice, etc .; and vitamin components Examples are water-soluble vitamins such as vitamins B and vitamin C, and fat-soluble vitamins such as vitamin A and vitamin D. As described above, the present invention can be suitably used for a soft capsule containing a drug exhibiting an unpleasant taste, particularly a bitter taste.

In the soft capsule of the present invention, the content of the food is typically 80% or less, preferably 70% or less, more preferably 50% or less, and even more preferably 30% or less, based on the total weight of the contents. It can be:

Non-limiting examples of foods used in the soft capsules of the present invention include any protein, peptide, lipid (including steroids, carotenoids and terpenoids), and saccharides, and derivatives thereof;
Dry powders and extracts of any edible plants, animals, fungi, fungi and the like; and combinations thereof.

Examples of proteins include enzymes, antibodies, and collagen. Examples of enzymes include pepsin, trypsin, amylase, lipase, ribonuclease and the like.

Examples of peptides include metabolic regulatory peptides, antimicrobial peptides, antiviral peptides, antitumor peptides and the like.

As an example of a lipid, docosahexaenoic acid (D
HA) and highly unsaturated fatty acids such as eicosapentaenoic acid (EPA).

Examples of steroids include cholesterol,
Sex hormones, corticosteroids, sapogenins, digitoxins and the like.

Examples of carotenoids include lycopene, β-
There are carotene and lutein.

Examples of carbohydrates include oligosaccharides (eg lactose, trehalose, maltose) and polysaccharides (starch, starch hydrolyzate, chondroitin sulfate, hyaluronic acid).

Examples of edible plants include plants used as vegetables, fruits and vegetables (eg, peppers, carrots, tomatoes, watermelons, melons, apples, konjac, blueberries, etc.) and plants used as medicinal plants (eg, , Korean carrots, ginkgo, saw palmetto, Arhat fruit, Garcinia, etc.).

Examples of edible animals include mammals, birds, reptiles, arthropods, fish and the like. Examples of mammals include pigs and cows. Examples of birds include chickens. Examples of reptiles include turtles, turtles,
There are snakes. Examples of arthropods include centipedes and millipedes. Examples of fish include eels.

Examples of fungi include bifidobacteria.

Examples of fungi include yeast and mushrooms. Examples of mushrooms include arboretum, cordyceps,
Agaricus.

As described above, the present invention can be suitably used for soft capsules containing foods exhibiting an unpleasant taste, such as health foods, functional foods, and dietary supplements. The invention also has the flavor of a chocolate base,
It can also be suitably used as a soft capsule-type palatable food that gives a unique chewing feeling.

The soft capsule of the present invention has a total coating of 100 to 60 parts by weight based on 100 parts by weight of the following components (A) and (B): (A) gelatin; and (B) gelatin.
It may contain 0 parts by weight of a plasticizer. The plasticizer is typically one or more selected from the following (b1) to (b3): (b1) glycerin, (b2) sucrose, fructose, D-mannitol, xylitol, A saccharide selected from the group consisting of erythritol, D-sorbitol, maltose, reduced maltose syrup, maltitol, sucrose alcohol and isomerized sugar, and combinations thereof (herein referred to as "sugar plasticizer"); (B
3) Glycols selected from the group consisting of propylene glycol and polyethylene glycol, and combinations thereof.

In the present invention, "gelatin" includes any of gelatin, acidic gelatin, alkaline gelatin, peptide gelatin, low molecular gelatin, derivatives of gelatin (for example, succinated gelatin) and the like. Any of these gelatins can be used alone or in combination as the component (A) of the coating in the present invention.

As the plasticizer of the component (B) of the coating, (b)
One or more selected from 1) glycerin, (b2) saccharide plasticizer and (b3) glycols are used. In the present invention, at least (b)
1) It is preferable to use glycerin. In particular, considering the ease of molding, (b1) glycerin and at least one of (b2) a saccharide plasticizer and (b3) glycol which are other plasticizer components are used. It is preferable to use them in combination.

The amount of the plasticizer in the coating is 10% gelatin.
The total amount of the plasticizer is preferably 100 to 600 parts by weight based on 0 part by weight. If the compounding amount is less than 100 parts by weight, the capsule becomes hard, and if it exceeds 600 parts by weight, it becomes soft but molding tends to be difficult.

When glycerin (b1) is used alone as the component (B), the amount of glycerin used is 100 to 300 parts by weight, especially 12 to 100 parts by weight of the gelatin of the component (A).
0 to 200 parts by weight is preferred.

In the present invention, (b2) sugar plasticizers include sucrose, fructose, D-mannitol, xylitol, erythritol, D-sorbitol, maltose,
What is selected from reduced maltose water candy, maltitol, sucrose alcohol, isomerized sugar, and combinations thereof is used. To impart sweetness during chewing, D
-Sorbitol, sucrose and mannitol are preferred. From the point of low adhesiveness when added at a high concentration,
D-sorbitol and mannitol are preferred.

When (b1) glycerin is used in combination with (b2) a saccharide plasticizer, the compatibility with gelatin is excellent, and the concentration of the plasticizer in the coating can be increased. When glycerin and a saccharide plasticizer are used in combination, glycerin is added in an amount of 50 to 300 parts by weight, especially 5 to 100 parts by weight of gelatin.
0 to 250 parts by weight, and 30 to 3 parts of a saccharide plasticizer.
It is preferable to add 00 parts by weight, especially 50 to 150 parts by weight.

In the present invention, as the glycol (b3), a glycol selected from propylene glycol and polyethylene glycol is used. As the polyethylene glycol, those having a weight average molecular weight of 400 to 4000 are particularly preferred. Since these glycols have a high hygroscopicity and tend to be difficult to handle after molding, it is preferable that the amount added is not too large.

When (b1) glycerin and (b3) glycol are used in combination, a very soft gelatin coating can be obtained. When glycerin and propylene glycol are used in combination, glycerin is mixed with 40 to 200 parts by weight, particularly 50 to 120 parts by weight, based on 100 parts by weight of gelatin,
And it is preferable to mix 20 to 300 parts by weight, especially 40 to 100 parts by weight of propylene glycol. When using glycerin and polyethylene glycol together,
Glycerin is 50 to 1 with respect to 100 parts by weight of gelatin.
00 parts by weight, especially 60 to 80 parts by weight, and 40 to 200 parts by weight, especially 50 to 200 parts by weight of polyethylene glycol.
It is preferable to mix 100 parts by weight.

When the glycerin (b1), the saccharide (b2) and the glycol (b3) are used together, glycerin is added in an amount of 50 to 200 parts by weight based on 100 parts by weight of gelatin.
Parts by weight, especially 60 to 150 parts by weight, and 30 to 130 saccharides
Parts by weight, especially 40 to 80 parts by weight,
It is preferable to add 120 parts by weight, particularly 50 to 100 parts by weight.

In the soft capsule of the present invention, the skin may contain water-insoluble cellulose as the component (C) in addition to the gelatin as the component (A) and the plasticizer as the component (B). Examples of water-insoluble cellulose include crystalline cellulose, ethyl cellulose, low substituted hydroxypropyl cellulose, and starches, and combinations thereof. Crystalline cellulose is particularly preferred for the reason of preventing adhesion between soft capsules. The amount of the water-insoluble cellulose is based on 100 parts by weight of gelatin.
5 to 100 parts by weight, especially 25 to 75 parts by weight, is preferred.
If the amount of the water-insoluble cellulose is less than 5 parts by weight with respect to 100 parts by weight of gelatin, the adhesion of the capsules is not sufficiently suppressed, and the capsules or the capsule and the container adhere to each other during storage, and a feeling of adhesion in the mouth occurs. Tends to be easy. If the amount of the water-insoluble cellulose exceeds 100 parts by weight based on 100 parts by weight of gelatin, molding tends to be difficult.

The soft capsule of the present invention may further contain any sweet component (herein referred to as “sweetener”) as the component (D) in the skin. The sweetener can be any sweetening substance so long as it is pharmaceutically acceptable or suitable for food use and is compatible with the manufacture of soft capsules. Examples of preferred sweeteners include saccharin sodium, stevia, and thaumatin, and any combination thereof.

By appropriately adding a sweetener to the skin, it is possible to provide a preparation which can be chewed extremely easily in the oral cavity even when taken without water.

The soft capsule of the present invention contains
In addition to the above components (A) to (D), a coloring agent, a preservative, a disintegrating agent, a surfactant, a fragrance, a flavoring agent, a flavoring agent, and the like can be added as necessary. In addition, from the viewpoint of enhancing the ingestibility, the weight ratio of the contents to the skin is typically about 1: 1 to about 4: 1, preferably about 3: 2 to about 3: 1. Size 3-20, preferably 5-1
No. 5.

The soft capsule of the present invention can be produced by any appropriate method, including a step of filling the contents into a shell. The filling of the contents into the coating may utilize equipment and procedures known in the field of conventional production of soft capsules. (See, for example, Yamada, Monthly Pharmaceutical Affairs, Vol. 28, No. 4, pp. 713-717 (1986).)
FIG. 2 is a process chart showing one example of the production of the soft capsule of the present invention. First, the chocolate base (or other low melting point additives) is heated and dissolved. A mixture of a drug (or food), a sweetener and a saccharide and, if necessary, a flavor are added to the melt while heating is continued to obtain a homogeneous suspension. Separately, a coating material mainly composed of gelatin and a plasticizer is mixed and dissolved by heating. This coating material is filled with the contents in which the fluidity is maintained by heating using a suitable filling machine (for example, a rotary automatic molding machine), molded, and then dried at an appropriate temperature as needed. The desired soft capsule is obtained by drying in a room.

By continuing the drying step at a desired temperature for a certain period of time or more, the effect of aging the contents may be obtained. Here, "aging"
By maintaining at a desired temperature for a certain period of time or more, it means that the physicochemical properties of the contents are improved. For example, if the content contains a chocolate base, especially cocoa butter,
By performing aging, the crystal form of cocoa butter contained in the chocolate base can be controlled.

The cocoa butter has a polymorph, and when the melted cocoa butter is slowly cooled, the stable forms V and VI are obtained.
Type crystals are precipitated, and the hardness increases. VI type crystal
Although the hardness is higher than that of the type crystal, it is thought that it is likely to become coarse and to reduce the ingestibility (melting in the mouth) (Hachiya et al., New Food Industry, 31).
(9), 65-74 (1989);
42, 50-58 (1989)).

In the production of soft capsules using cocoa butter as a low-melting point additive, the present inventors perform aging so as to increase the hardness appropriately and precipitate an appropriate amount of type VI crystal which does not decrease the ingestibility. As a result, it has been found that a soft capsule in which the feeling of unity between the shell and the contents is further improved can be obtained. The aging temperature to achieve the desired hardness is typically between 20 and 40C, preferably between 25 and 40C, more preferably between 30 and 40C, more preferably between 32 and 38C, more preferably about 35C. ° C. The aging time is generally at least 5 hours, preferably at least 10 hours, more preferably at least 15 hours. There is no particular upper limit on the aging time, but if it exceeds a certain time, the effect does not change even if it continues for a longer time.

Accordingly, in a preferred embodiment of the present invention,
The cocoa butter contained in the contents as a low melting point additive contains a major amount of type V crystals and a small amount of type VI crystals. Here, the “major amount” refers to the amount of the crystal form that is most frequently present among the cacao butter crystals that can be observed by X-ray diffraction. The term "small amount" refers to an amount in which the amount of the crystal is relatively smaller than the main amount but equal to or more than the lower limit that can be observed by X-ray diffraction.

The control of the crystal form by aging can be applied to the case where bitter chocolate containing a small amount of cocoa butter is used as a low melting point additive. Further, the present invention can be applied to a case where a low melting point additive exhibiting polymorphism other than cocoa butter is used.

The soft capsule of the present invention obtained as described above can be suitably used as various foods such as medicines, preparations, confectionery and health foods.

[0076]

The following is a specific example for further disclosing the present invention. They do not limit the scope of the invention.

(Production of Soft Capsules) All the soft capsules in the examples were produced as follows: the content was a chocolate base (or a substitute thereof).
Is dissolved at about 40 ° C. and the drug, sugars, sweeteners and, if necessary, flavorings are prepared by suspending, while maintaining the heating at about 40 ° C. The skin is gelatin, plasticizer,
And optionally, dissolving the sweetener at about 60 ° C. Rotary automatic molding machine (LEINER & SON
After filling and filling the contents into the skin using
A soft capsule is produced by drying in a drying room at 0 to 35 ° C (humidity of about 10 to 30%).

(Evaluation Method of Taste Test) The taste test of the soft capsules in the examples was carried out as follows: The first sample was taken without water, using five volunteers as controls. Evaluate taste. Four hours after dosing, the second sample is similarly dosed and evaluated. If there is a third or fourth sample, the next day, the samples are taken without water at intervals of 4 hours and evaluated. If there is a fifth sample, the next day, the sample is taken without water and evaluated. (The samples shown in the table below were
From the right side to the left side, the first, second, ...
Call. ) The taste of the sample is evaluated according to the criteria shown in Table 1 below.

[0079]

[Table 1]

(Production Examples 1 to 5: Examination of base) The contents of each formulation shown in Table 2 were produced by the above method without encapsulation.

[0081]

[Table 2]

The results of the taste test are shown in Table 3 as an average value of five volunteers. In addition, Comparative Example 1 and Production Examples 1 and 2 and Production Examples 3 to 5 were evaluated separately.

[0083]

[Table 3]

In Comparative Example 1 using an oily base (medium-chain fatty acid triglyceride) which is a conventional formulation, the bitterness of the drug and the oily base peculiar oiliness are instantly felt upon taking the drug, and the feeling of taking the drug is considerably poor. Was. In Production Example 2 in which the oily base and the cocoa butter were added in equal amounts, the contents became semi-solid, and the feeling of taking was slightly improved. Production Example 1 in which only cocoa butter, which is a chocolate base, was added, became solid and had a bitter taste when taken,
I didn't feel much oily.

When bitter chocolate having bitter taste and / or cocoa powder was used among the chocolate bases based on the prescription of Production Example 1 having a good feeling of taking as described above, the bitter taste of the drug was further suppressed, and The feeling was improved (Production Examples 3 to 5). Among them, Production Example 3 using bitter chocolate alone was the best.

(Production Examples 6 to 13: Investigation of sweetener and flavor) The contents of each formulation shown in Table 4 were produced in the same manner as in Production Example 1 and the like.

[0087]

[Table 4]

The results of the taste test are shown in Table 5 as an average value of five volunteers. In addition, Production Examples 6 to 10,
Production Examples 11 to 13 were separately evaluated.

[0089]

[Table 5]

When aspartame, sodium saccharin, thaumatin, dipotassium glycyrrhizinate, and stevia were used as sweeteners based on the formulation of the above Preparation Example 3 which gave a good feeling of taking, the bitterness of the drug was further suppressed.
The feeling of taking was improved. Among them, Production Example 6 using aspartame was the best. When chocolate flavor, peppermint flavor and vanilla flavor were used as flavors based on the formulation of Production Example 6, the bitterness of the drug was further suppressed, and the feeling of taking was also improved. Among them,
Production Example 11 using chocolate flavor was the best.

(Production Examples 14 to 18: Examination of drug content) The contents of each formulation shown in Table 6 were produced in the same manner as in Production Example 1 and the like.

[0092]

[Table 6]

A taste test was conducted using five volunteers in the same manner as described above. (Results are not shown.) Using acetaminophen, which has relatively strong bitterness of the drug,
When we examined how much the main drug concentration felt the strong bitterness, the main drug concentration was 50% (Production Example 17).
To some extent, bitterness could be suppressed. Among them,
When the main drug concentration was 20% (Production Example 14), bitterness was significantly suppressed.

(Production Examples 19 to 24: Examination of stability of aspartame as a sweetener) The contents of each formulation shown in Table 7 were produced in the same manner as in Production Example 1 and the like.

[0095]

[Table 7]

As Preparation Example 20, Preparation Example 6 was prepared again and subjected to a stability test with time (45 ° C., 1 month). In addition, the same study was conducted by changing the mixing ratio of the cocoa butter. When the mixing ratio of cocoa butter is 10% or more of the content weight,
Aspartame stability over time was ensured.
In addition, even in the case of Production Example 24 in which the blending ratio of cocoa butter was 0%, the residual ratio of aspartame to the initials was about 9%.
Since the content of cocoa butter can be 10%
% Or more, there was a possibility that the content of aspartame could be sufficiently ensured.

(Production Examples 25 to 28: Classification of semi-solid and solid contents) The contents of each formulation shown in Table 8 were used in Production Example 1 described above.
Manufactured in a similar manner. At a standard temperature (about 20 ° C.), the state of the contents was observed.

[0098]

[Table 8]

Even when a liquid oily base such as a medium-chain fatty acid triglyceride is used as the base, the content is determined by the amount of the constant melting point additive such as cocoa butter and bitter chocolate. About 10% to about 36 of the entire contents
%, It was semi-solid, and about 36% or more, it was completely solid. .

(Examples 1-3: Comprehensive evaluation of soft capsules) From the contents and skin of each formulation shown in Table 9,
No. 7.5 Oval-type soft capsules were produced. In Examples 1 to 7, the drying conditions after molding were 25
C., humidity 20%, 64 hours.

[0101]

[Table 9]

The results of the taste test are shown in Table 10 as an average value of five volunteers.

[0103]

[Table 10]

In Comparative Example 2, since the contents are liquid,
There was also a feeling of incongruity of the skin, and the feeling of taking the drug tended to be considerably worse. Example 1 in which the content was changed to cocoa butter and solidified
Although the feeling of incongruity of the skin was reduced, the bitter taste of the drug remained slightly, and the feeling of taking was somewhat poor. In Example 2 in which bitter chocolate was added, bitterness was also suppressed, and the feeling of taking was considerably improved. It was also found that the addition of a sweetener to the skin (Example 3) further improved the feeling of taking.

(Examples 4 to 7: Comprehensive Evaluation of Rhinitis Drug Formulations) From the contents and skin of each formulation shown in Table 11, 7.
No. 5 Oval-type soft capsules were produced.

[0106]

[Table 11]

The results of the taste test are shown in Table 12 as an average value of five volunteers.

[0108]

[Table 12]

In Example 4, since the content was only cocoa butter, there was little discomfort in the skin, but the bitter taste of the drug remained slightly, and the feeling of taking was somewhat poor. In Examples 5 and 6 to which bitter chocolate was added, bitterness was also suppressed, and the feeling of taking was considerably improved. Among them, in Example 6 in which the amount of bitter chocolate added was increased, the bitterness was further suppressed and the feeling of taking was also improved. In Example 7 in which the sweetener was added to the skin, it was found that the feeling of taking was further improved as in Example 3 above.

(Evaluation Criteria for Usability) In the following examples, the usability of the soft capsule was evaluated according to the criteria shown in Table 13 below.

[0111]

[Table 13]

(Examples 8 to 11: Comprehensive evaluation of water-insoluble cellulose-containing formulation) (a) Antipyretic analgesic formulation No. 7.5 Oval-type soft capsule from the contents and skin of each formulation shown in Table 14 Was manufactured.

[0113]

[Table 14]

The results of the taste test and the usability test are shown in Table 15 as an average value of five volunteers.

[0115]

[Table 15]

In Comparative Example 3, since the contents are liquid,
There was also a feeling of incongruity of the skin, and the feeling of taking the drug tended to be considerably worse. PTP (Press Through Pac)
k) There was also a tendency that the extrusion of the soft capsule from the packaging became difficult.

In Examples 8 and 9 in which the base was changed to cocoa butter and bitter chocolate or cocoa powder was added to make the contents solid, the discomfort of the skin was reduced, the bitter taste was suppressed, and Feeling improved. In the soft capsules of Examples 8 and 9 in which the shell contains microcrystalline cellulose, which is a kind of water-insoluble cellulose, there is almost no uncomfortable feeling of the shell, and the capsules are sealed with glass bottles at 40 ° C for one month. Almost no adhesion was observed. Further, since the contents are solid, P
Extrusion of the soft capsule from the TP package was easy. Therefore, it was shown that the formulations of these examples were excellent in practicality as products.

(B) Rhinitis drug formulation No. 7.5 Oval-type soft capsules were produced from the contents and skin of each formulation shown in Table 16.

[0119]

[Table 16]

The results of the taste test and the usability test are shown in Table 17 as the average value of five volunteers.

[0121]

[Table 17]

In the rhinitis drug formulations of Examples 10 and 11,
As in Examples 8 and 9, the unpleasant sensation of the skin was reduced, the bitterness was suppressed, and the overall feeling of taking was very good. The evaluation of usability was also high, indicating that the product was excellent in practicality.

(Production Examples 29 and 30: Examination of Aging) (a) Examination of Aging Temperature After the content (Production Example 29) having the same formulation as in Example 8 was prepared and melted in the same manner as in Production Example 1, etc. In the drying room, 25
Aged at 30 ° C, 30 ° C, 35 ° C, 37 ° C, and 40 ° C for 16 hours. As a control, the same operation was performed using cocoa butter alone. After aging, it was cooled and solidified into a capsule. The hardness of the solid content and the short form (short axis direction) of the cocoa butter were measured using a manual tablet hardness tester (Pfize).
r company).

The results are shown in FIG. In both capsule contents and cocoa butter, the hardness gradually increased as the aging temperature was increased, and showed a tendency to decrease with a peak at 35 ° C. Since the change in the hardness of the capsule content and the change in the hardness of the cocoa butter alone show the same temperature dependence, it was found that the physical properties of the cocoa butter were dominant in the increase in the hardness of the capsule content. Here, the cacao butter aged at 35 ° C. was mainly composed of V-type crystals and contained a small amount of VI-type crystals by X-ray diffraction.

(B) Examination of aging time The content (Preparation Example 30) having the same formulation as in Example 8 was prepared and melted in the same manner as in Preparation Example 1 and the like, and then melted in a drying chamber.
0 ° C, 2 hours, 6 hours, 8 hours, 12 hours, 1 hour
Aged for 6 hours and 64 hours. The same operation was performed with cocoa butter alone as a control. After aging, it was cooled and solidified into a capsule. The hardness of the solidified contents and cocoa butter was measured in the same manner as in (a) above.

The results are shown in FIG. In both the capsule contents and the cocoa butter, the hardness gradually increased as the aging time was increased up to 16 hours, and no difference was observed between 16 hours and 64 hours. From this, it was found that when aging was performed at 35 ° C. for 16 hours or more, almost the maximum hardness was obtained.

(Example 12: Comprehensive evaluation of aged soft capsules) A soft capsule was produced from the same formulation and skin as in Example 8. 35 ° C after molding
A group (Example 12) aged for 16 hours,
It was divided into a group cooled at 25 ° C. without aging (Example 13). A taste test and a usability test were performed on each of the obtained soft capsules.

FIG. 4 shows the results. The aged soft capsules further reduced the discomfort of the skin, further suppressed the bitterness of the contents, and further improved the overall feeling of use and the evaluation of usability, as compared with the soft capsules that were not aged. From this, it has been found that, for a formulation whose content contains cocoa butter, aging can provide a particularly good soft capsule.

[0129]

According to the present invention, a soft capsule is
By prescribing the contents to be solid or semi-solid at room temperature, the skin and the contents are homogenized when chewed, and the discomfort of the skin can be reduced. In particular, by appropriately formulating a low melting point additive such as a chocolate base as the content of the soft capsule, a preparation that can be easily chewed in the mouth without water can be obtained. Such chewable soft capsules are particularly useful as fast-dissolving pharmaceutical preparations for pediatric or elderly people or for food.

By making the contents solid, a soft capsule preparation which is easy to take out from the packaging container and has a good feeling in use can be obtained. By including the water-insoluble cellulose in the coating, there is obtained an effect that the capsules hardly adhere to each other during storage or the like. Thus, according to the present invention,
A soft capsule excellent in practicality as a product can be provided.

When a chocolate base, particularly cocoa butter, is used as the low-melting point additive, aging is performed after the contents are filled in the shell to obtain a soft capsule preparation with particularly improved feel and usability. Can be

[Brief description of the drawings]

FIG. 1 is a process chart showing one example of the production of the soft capsule of the present invention.

FIG. 2 is a graph showing hardness changes of capsule contents and cocoa butter according to aging temperature. The vertical axis indicates hardness (kgs), and the horizontal axis indicates aging temperature (° C.). The black triangles show the results for the capsule contents, and the black diamonds show the results for cocoa butter alone.

FIG. 3 is a graph showing hardness changes of capsule contents and cocoa butter according to aging time. The vertical axis indicates hardness (kgs), and the horizontal axis indicates aging time (h) at 35 ° C. The black triangles show the results for the capsule contents, and the black diamonds show the results for cocoa butter alone.

FIG. 4 is a graph showing the results of a taste test and a usability test for soft capsules produced with or without aging. The vertical axis indicates the average value of judgments by five volunteers for each item in the five-step evaluation. The four columns on the left (unmodified) show the results without aging, and the four columns on the right (improved) show the results with aging. From the left side, the evaluation of the skin discomfort, the bitterness of the contents, the overall feeling of taking, and the usability are shown.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4B035 LC04 LE12 LG12 LP35 4C076 AA56 BB01 CC01 CC04 CC10 DD46 DD66 EE53 EE54 EE58 FF02 FF31 FF33 FF52 FF68

Claims (3)

[Claims] 1. A chewable soft capsule, wherein the contents are filled in a shell, the contents being solid or semi-solid at room temperature, and containing a low melting point additive. 2. The chewable soft capsule according to claim 1, wherein the low melting point additive is selected from the group consisting of coconut oil, lard, and combinations thereof. 3. The low melting point additive is coconut oil.
A chewable capsule according to item 1.