KR20140013411A

KR20140013411A - Aqueous composition for hard capsule, method of preparing the aqueous composition and hard capsule prepared thereof

Info

Publication number: KR20140013411A
Application number: KR1020120080258A
Authority: KR
Inventors: 손진열; 이상엽; 전정희; 방성환; 신주희
Original assignee: 삼성정밀화학 주식회사
Priority date: 2012-07-23
Filing date: 2012-07-23
Publication date: 2014-02-05
Also published as: KR102013296B1

Abstract

Disclosed are an aqueous composition for a hard capsule, a production method thereof, and the hard capsule produced by using the aqueous composition. The aqueous composition for the hard capsule contains water soluble cellulose ether, alcohol, and water. The aqueous composition for the hard capsule contains 10-25 wt% of water soluble cellulose ether, and 5-30 wt% of alcohol. [Reference numerals] (AA) Example 2-5; (BB) Example 2-4; (CC) Drying rate(wt%); (DD) Drying time(min)

Description

Aqueous composition for hard capsules, method of preparing the aqueous composition and hard capsule prepared according to the present invention

Disclosed are an aqueous composition for hard capsules, a method for preparing the same, and a hard capsule prepared using the aqueous composition. More specifically, an aqueous composition for hard capsules comprising a water-soluble cellulose ether and alcohols, and hard capsules prepared using the aqueous composition are disclosed.

Generally, hard capsules have been prepared using gelatin derived from cattle or pigs.

The aqueous composition comprising gelatin can dissolve the gelatin directly in water of high temperature (eg, 60 ° C.), so that the preparation time of the aqueous composition is short, and after immersing the mold pin in the aqueous composition, it is removed and applied to the mold pin. When the aqueous composition is dried, the drying time is short, a high quality hard capsule having excellent elasticity, gloss and disintegration can be obtained, and the yield of the hard capsule is also very high. However, since the use of gelatin has been limited due to problems such as mad cow disease, a capsule manufactured using cellulose ether, which is a vegetable material that does not use gelatin, is in the spotlight.

However, although the cellulose ether is dissolved in water at room temperature (25 캜), most of the cellulose ether is aggregated immediately after it is added to water to form an aggregate, which takes a long time to be completely dissolved. In order to prevent this, when preparing an aqueous composition for hard capsules, cellulose ether is added to high temperature (eg, 80 ° C. or higher) water to disperse well, and then dispersed well to prepare a dispersion, and then the dispersion is After cooling to a first temperature (eg, 40-50 ° C.), the dispersed cellulose ether is dissolved in water. Thereafter, the resultant is heated to a second temperature (for example, 55 to 65 ° C), and a gelling agent and optionally a gelling aid are added to the resultant. At this time, the reason for raising the temperature of the resultant to the second temperature is to prevent the gelling agent and the gelling aid from hardening. However, at the second temperature, the cellulose ether is not completely dissolved in water, so that the aqueous composition comprising the cellulose ether and the final hard capsule have the following disadvantages:

(1) The aqueous composition is not uniform in viscosity depending on the position, and layer separation occurs when stored for a long period of time.

(2) In the aqueous composition, the degree of mixing of the cellulose ether and the gelling agent (and the optional gelling aid) is reduced, so that the amount of the gelling agent (and the optional gelling aid) is to be increased.

(3) The aqueous composition has low filtration efficiency in a subsequent filtration step to remove foreign matter (eg, fibers) therefrom.

(4) Even after the filtration process, foreign substances remain in the water-based composition to weaken the function of the encapsulating agent and / or the capsule auxiliary agent, and thus the capsule formability is deteriorated.

(5) The drying speed is slow when the drying process for evaporating moisture in the aqueous composition applied to a substrate (for example, a mold pin) in the capsule forming process is carried out.

(6) The production time of the aqueous composition and the drying time are so long that the production yield of the hard capsule is low.

(7) Foreign matter remaining in the aqueous composition is incorporated into the hard capsule, which is the final product, and the foreign matter thus incorporated lowers the quality (elasticity, glossiness, disintegration, etc.) of the hard capsule, and the quality of each manufacturing unit of the hard capsule. This is hard to keep constant.

One embodiment of the present invention provides an aqueous composition for hard capsules comprising a water-soluble cellulose ether and alcohols.

Another embodiment of the present invention provides a method of preparing the aqueous composition.

Another embodiment of the present invention provides a hard capsule prepared using the aqueous composition.

According to an aspect of the present invention,

Water-soluble cellulose ethers;

Alcohols; And

An aqueous composition for hard capsules comprising water.

The content ratio of the water-soluble cellulose ether in the hard capsule aqueous composition may be 10 to 25% by weight, and the content ratio of the alcohols may be 5 to 30% by weight.

The water-soluble cellulose ether may include hydroxypropylmethylcellulose (HPMC), hydroxyethylmethylcellulose (HEMC), methylcellulose (MC), or a mixture of two or more thereof.

The alcohols may include ethanol, methanol, isopropanol, butanol, or a mixture of two or more thereof.

The hard capsule aqueous composition may further include a gelling agent having a content ratio of 0.05 to 5.0% by weight.

The gelling agent includes a water soluble gum, and the water soluble gum may include carrageenan, gellan gum, xanthan gum, pectin, or a mixture of two or more thereof.

The hard capsule aqueous composition may further include a gelling aid having a content ratio of more than 0% by weight and 1.0% by weight or less.

The gelling aid may include potassium chloride, potassium acetate, calcium chloride or a mixture of two or more thereof.

Another aspect of the invention,

It provides a method for producing an aqueous composition for hard capsules comprising water, alcohols, and water-soluble cellulose ethers, the method comprising preparing a cellulose ether solution maintained at a first temperature higher than atmospheric temperature.

The first temperature may be 40 ~ 70 ℃.

The method for preparing an aqueous composition for hard capsules may further include the step of aging the cellulose ether solution, and adding a gelling agent to the resultant.

The aging step of the cellulose ether solution may be performed for 2 to 12 hours at a temperature of 40 ~ 70 ℃.

According to another aspect of the present invention,

It provides a hard capsule prepared using the aqueous composition for the hard capsule.

The aqueous composition for hard capsules according to one embodiment of the present invention includes water-soluble cellulose ethers and alcohols, so that the water is not only low temperature (eg, 0 to 40 ° C.) but also high temperature (eg, 40 to 70 ° C.) water. It is possible to directly dissolve the cellulose ether to shorten the manufacturing time of the aqueous composition, the drying time in the drying process during the capsule molding, it is also possible to improve the production yield of the final product of the hard capsule. In addition, the mixing of the cellulose ether and the gelling agent (and optional gelling aid) is improved so that a high quality hard capsule can be obtained even with a small amount of gelling agent (and optional gelling aid).

1 is a graph showing the change in drying rate over time of the aqueous compositions prepared in Examples 2-5 and Comparative Examples 2-4.

Hereinafter will be described in detail an aqueous composition for hard capsules according to an embodiment of the present invention.

The aqueous composition for hard capsules according to one embodiment of the present invention includes a water-soluble cellulose ether, alcohols and water.

The water soluble cellulose ether is the main component of the aqueous composition for hard capsules. These water-soluble cellulose ethers are derived from cellulose, which is a vegetable material, and are harmless to the human body. As used herein, the term " cellulose ether " means a cellulose derivative etherified by using an etherifying agent for the hydroxy group of cellulose.

The content ratio of the water-soluble cellulose ether in the aqueous composition for hard capsules may be 10 to 25% by weight. When the content ratio of the water-soluble cellulose ether is within the above range, the viscosity is appropriate, bubbles are easily removed, and a capsule having a suitable thickness can be obtained.

The alcohols serve to help the water-soluble ether to liquefy (ie, dissolve) in the aqueous composition for hard capsules. Specifically, the water-soluble cellulose ether is dissolved in a portion which is in direct contact with water when it is added to water at low temperature (20 to 30 ° C.), but the remaining portion that is not in direct contact with water aggregates to form agglomerates. When it is added to high temperature (40 ~ 70 ℃) water, even if the part is in direct contact with water has a property that does not dissolve well. By the way, the alcohols are mixed with water to form an aqueous alcohol solution, and the water-soluble cellulose ether is well dissolved not only in the low-temperature (20-30 ° C) alcohol solution but also in the high-temperature (40-70 ° C) alcohol solution.

The content ratio of the alcohols may be 5 to 30% by weight. When the content ratio of the alcohols is within the above range, the solubility of the cellulose ether is increased and the evaporation rate of the alcohols at the time of capsule manufacture is moderate, thereby obtaining a smooth capsule membrane without wrinkles.

The hard capsule aqueous composition may further include a gelling agent having a content ratio of 0.05 to 5.0% by weight. When the content ratio of the gelling agent is within the above range, the viscosity of the aqueous composition for hard capsules is moderately increased, so that the elongation at break of the hard capsules formed using the same is high and the brittleness is low.

The gelling agent may include water-soluble gums.

The water-soluble gum may include Carrageenan, Gellan gum, Xanthan gum, Pectin or a mixture of two or more thereof.

The hard capsule aqueous composition may further include a gelling aid having a content ratio of more than 0% by weight and 1.0% by weight or less. When the content ratio of the gelling aid is within the above range, the gelling ability of the gelling agent may be improved to obtain an aqueous composition for hard capsules having excellent capsule moldability, and hard capsules without generation of haze may be obtained.

The hard capsule aqueous composition may further include a plasticizer having a content ratio of 0.05 to 5.0% by weight. When the content ratio of the plasticizer is within the above range, a hard capsule having a high elongation at break can be obtained.

The plasticizer may include glycerol, sorbitol, propylene glycol, polyethylene glycol or a mixture of two or more thereof.

The aqueous composition for hard capsules has the following advantages when complete dissolution of the water-soluble cellulose ether when heated to the capsule molding temperature (40 ~ 70 ℃): First, the production time is shortened. Second, homogeneity is high, viscosity is uniform, and layer separation does not occur even after long-term storage. Third, the viscosity is maintained constant for each manufacturing unit. Fourth, there is no undissolved substance (e.g., cellulose ether) that inhibits the function of the gelling agent and the optional gelling aid, so that the capsule formability is high. Fifth, the mixing degree of the cellulose ether and the gelling agent (and the optional gelling aid) is high, so that the amount of the gelling agent (and the optional gelling aid) is reduced. Sixth, the filtration efficiency is high in a subsequent filtration process for removing foreign matter from the aqueous composition for hard capsules. Seventh, the drying speed is high when the drying process for removing the solvent component in the aqueous composition applied to the substrate (for example, mold pin) in the capsule molding process. Eighth, the production time and drying time of the aqueous composition for hard capsules is short, the production yield of hard capsules is high.

Another aspect of the present invention provides a hard capsule prepared using the aqueous composition for hard capsules. For example, the hard capsule is obtained by immersing a mold pin at room temperature (20 to 30 ° C.) in an aqueous composition for hard capsules heated to a high temperature (40 to 70 ° C.), and then removing the mold pin from the aqueous composition and drying it. Can be prepared (called a 'cold pin process').

The hard capsule has a high quality (elasticity, glossiness, disintegration, etc.) because the aqueous composition for the hard capsule does not contain foreign substances such as fibers, and the quality is kept constant for each manufacturing unit.

The hard capsule may be gastric juice soluble.

Hereinafter, the manufacturing method of the aqueous composition for hard capsules will be described in detail.

The method for producing an aqueous composition for hard capsules comprises water, alcohols and water-soluble cellulose ethers, and to prepare a cellulose ether solution maintained at a first temperature (40 to 70 ° C.) higher than atmospheric temperature (0 to 39 ° C.). Steps. Specifically, the method for producing an aqueous composition for hard capsules is prepared by mixing water and alcohols to prepare an aqueous solution of alcohol (S1), heating the aqueous solution of alcohol (S2), the water-soluble cellulose ether in the heated aqueous alcohol solution It may comprise the step of preparing a cellulose ether solution by dissolving (S3), the step of aging the cellulose ether solution (S4) and the step of adding a gelling agent to the resultant (S5).

In the step (S2), the alcohol aqueous solution may be heated from room temperature (20 to 30 ° C) to a temperature of 40 to 70 ° C. This step (S2) is intended to allow the water-soluble cellulose ether to be well dispersed in the aqueous alcohol solution and to be dissolved well in the non-agglomerated state in the step (S3). When the heating temperature is within the above range, it is possible to obtain an aqueous composition for hard capsules, which has a high capsule moldability without hardening the gelling agent (and optional gelling aid) described later, and minimizes an increase in energy cost due to unavoidable heating. have.

The step (S3) may be carried out by slowly (for example, 1 to 2 hours) injecting the water-soluble cellulose ether to the heated aqueous alcohol solution under stirring (for example, 300rpm).

However, the present invention is not limited thereto. Instead of the above steps S1 to S3, the first cellulose ether solution is prepared by dissolving the water-soluble cellulose ether in water (or alcohols), and then the alcohol (Or water) may be added to prepare a second cellulose ether solution. In this case, the first cellulose ether solution is prepared by using water and / or alcohols heated in the course of preparing the cellulose ether solution or by dissolving the water-soluble cellulose ether in water (or alcohols) to form a first cellulose ether solution, After the ether solution is heated, an alcohol (or water) is added to the first cellulose ether solution to prepare a second cellulose ether solution.

The aging step (S4) of the cellulose ether solution may be performed at a temperature of 40 to 70 ° C for 2 to 12 hours. When the execution time of the step (S4) (i.e., the ripening time) is within the above range, the bubbles are sufficiently removed from the resultant product and the composition thereof becomes uniform.

In the step (S4) it may be further added to the resulting gelation aid and / or plasticizer in addition to the gelling agent.

At least one of the steps S1 to S5 may be performed under stirring.

After the step (S5) may further comprise the step of removing bubbles from the aqueous composition for hard capsules. This step S5 may be carried out by stirring.

Since the functions, types and content ratios of the alcohols, water-soluble cellulose ethers, gelling agents, gelling aids and plasticizers are the same as those described above, detailed descriptions thereof will be omitted.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these embodiments.

Example

Example 1-1 to 1-4 and Comparative Example 1-1: High Temperature Solubility Evaluation of Cellulose Ether

Ethanol and water (purified water) were mixed in the ratios shown in Table 1 below to prepare an aqueous ethanol solution. Thereafter, the ethanol aqueous solution was heated to the temperature of Table 1, and then hydroxypropyl methyl cellulose (HPMC) (Samsung Fine Chemical, AW4) was added to the ethanol aqueous solution in the ratio of Table 1 to dissolve. After 4 hours after completion of the dissolution, the appearance of the result was visually observed and evaluated in four steps as follows. In addition, the evaluation results are shown in Table 1 below.

(Method of evaluating the property of the result)

(Double-circle): HPMC melt | dissolves very quickly, and the result appearance is clear and transparent.

○: HPMC dissolves relatively quickly, and the result is clear and transparent.

(Triangle | delta): HPMC melt | dissolves a little late and the appearance of the result looks a little whitish.

X: HPMC is not dissolved, and the appearance of the result is very whitish.

Content ratio (% by weight) Temperature (° C) of aqueous ethanol solution Appearance water ethanol HPMC Example 1-1 60 20 20 60 ◎ Examples 1-2 65 15 20 60 ◎ Example 1-3 70 10 20 60 ○ Example 1-4 75 5 20 60 △ Comparative Example 1-1 80 0 20 60 ×

Referring to Table 1, the results prepared in Examples 1-1 to 1-4 are HPMC is well dissolved and good properties and viscosity, while the results prepared in Comparative Examples 1 to 1 are not HPMC dissolved It exists as a condition and appears to be bad.

Example 2-1 to 2-5: of aqueous composition Gelation degree And drying rate evaluation

To the resultant prepared in Example 1-2 was added K-carrageenan (K-Carrageenan, HG404) and the gelling aid of potassium chloride in the ratio of the following Table 2 to obtain an aqueous composition. Thereafter, the gelation degree of each of the aqueous compositions was measured by the following method, and the results are shown in Table 2 below. In addition, the drying rate of the aqueous composition prepared in Example 2-5 was measured in the following manner, and the results are shown in Table 3 below.

(Gel degree evaluation method)

Each of the aqueous compositions was sampled with a 2 ml syringe and then sprayed on a glass plate standing upright. When the flow of each of the aqueous compositions flowing along the glass plate after the injection was stopped, the length of each of the aqueous compositions flowed along the glass plate was measured. Here, the shorter the length means that the degree of gelation is larger.

(Drying Speed Evaluation Method)

Mold pins were immersed in the aqueous composition prepared in Example 2-5. The mold pin was then removed from the aqueous composition and the weight change of the mold pin was measured over time in a state left at 25 ° C. and 55% RH (relative humidity). The drying rate of the aqueous composition was then calculated from the weight change of the mold pins. Here, the larger the drying rate change over time, the higher the drying rate. The weight change and drying rate change of the mold pin over time are shown in Table 3 below. In addition, the drying rate change of the aqueous composition over time is shown graphically in FIG.

Comparative Example 2-1 to 2-3: of an aqueous composition Gelation degree And drying rate evaluation

Examples 2-1 to 2-5, except that the resultant prepared in Comparative Example 1-1 was used instead of the resultant prepared in Example 1-2, and the amount of K-carrageenan and selective potassium chloride was changed. An aqueous composition was prepared in the same manner as described above, and the gelation degree of the prepared aqueous composition was evaluated and the results are shown in Table 2 below. In addition, except that the aqueous composition prepared in Comparative Example 2-4 was used instead of the aqueous composition prepared in Example 2-5, the drying rate over time of the aqueous composition in the same manner as in Example 2-5 To evaluate the results are shown in Table 3 below. In addition, the drying rate change of the aqueous composition over time is shown graphically in FIG.

Content ratio (% by weight) Gelation degree (cm) K-carrageenan Potassium chloride Example 2-1 2.0 0.0 7.0 Example 2-2 1.5 0.0 7.5 Example 2-3 1.0 0.0 9.0 Examples 2-4 0.8 0.0 10.0 Example 2-5 1.0 0.1 7.5 Comparative Example 2-1 2.0 0.0 10.0 Comparative Example 2-2 1.5 0.0 11.1 Comparative Example 2-3 1.0 0.1 11.5 Comparative Example 2-4 1.0 0.5 7.5

Referring to Table 2, the aqueous compositions prepared in Examples 2-1 to 2-5 are gelling agents (K-carrageenan) and gelling aids (potassium chloride) as compared to the aqueous compositions prepared in Comparative Examples 2-1 to 2-3. The gelation degree was excellent when the content ratio of) is the same or similar. Therefore, when the aqueous composition is prepared according to one embodiment of the present invention, the amount of the gelling agent and the gelling aid may be reduced as compared with the case of preparing the aqueous composition according to the prior art. In addition, it can be seen that there are suitable content ratios and mixing ratios of the gelling agent and the gelling aid that can increase the degree of gelation of the aqueous composition. On the other hand, the aqueous composition prepared in Comparative Example 2-4 has a high degree of gelation, but as shown in Table 1, HPMC is present in an undissolved state, not only the capsule formability is lowered, but also a hard capsule having low quality is obtained.

Time (min) Weight of mold pin (g) Mold Pin + Weight of Aqueous Composition (g) Weight of aqueous composition (g) Drying rate (% by weight) Example 2-5 Comparative Example 2-4 Example 2-5 Comparative Example 2-4 Example 2-5 Comparative Example 2-4 Example 2-5 Comparative Example 2-4 0 12.54 12.54 13.30 13.19 0.76 0.65 0.0 0.0 20 12.54 12.54 13.25 13.18 0.71 0.64 6.58 1.54 40 12.54 12.54 13.19 13.14 0.65 0.60 14.47 7.69 60 12.54 12.54 13.09 13.09 0.55 0.55 27.63 15.38 120 12.54 12.54 12.98 13.04 0.44 0.50 42.11 23.08

Referring to Table 3 and FIG. 1, the aqueous composition prepared in Example 2-5 was found to have a faster drying rate than the aqueous composition prepared in Comparative Example 2-4.

Example 3-1 and Comparative Example 3-1: solubility of hard capsules and Hayes evaluation

Mold pins were immersed in the aqueous compositions (temperature: 60 ° C.) prepared in Examples 2-5 and Comparative Examples 2-4. Thereafter, the mold pin was taken out of the aqueous composition and left for 1 hour under 25 ° C. and 55% RH (relative humidity) to obtain a hard capsule by drying the solvent component in the aqueous composition. Thereafter, the solubility and the haze of the hard capsules were evaluated in the following manner, and the results are shown in Tables 4 and 5, respectively.

Evaluation of Dissolution Rate of Hard Capsules

50 ml of water (purified water) was added to a 100 ml Erlenmeyer flask, and the temperature of the water was maintained at 37 ° C. Thereafter, the keratoplasty capsule was placed in the Erlenmeyer flask, and the erlenmeyer flask was intermittently shaken to confirm the dissolution state of the keratoplasty capsule. The time (ie dissolution time) that elapsed from the time when the hard capsule was added to the Erlenmeyer flask and the time when the hard capsule was completely dissolved is recorded and shown in Table 4 below. Here, the shorter the dissolution time, the faster the dissolution rate.

Example 3-1 Comparative Example 3-1 Dissolution time 6 minutes 15 seconds 8 minutes 26 seconds

Referring to Table 4, the hard capsules prepared in Example 3-1 was found to have a faster dissolution rate than the hard capsules prepared in Comparative Example 3-1.

(Haze evaluation of hard capsule)

After the hard capsules were placed in a 40 ml vial, the vials were placed in a constant temperature and humidity chamber at 40 ° C. and 75% RH (relative humidity). Thereafter, the hard capsules were visually observed every week, and the degree of haze was evaluated in three steps as follows. The results are shown in Table 5 below.

◎: no change (ie transparent).

(Circle): It turns into partly whitish.

(Triangle | delta): It turns white generally.

Elapsed time Example 3-1 Comparative Example 3-1 Early ◎ ◎ 1 week ◎ ◎ 2 weeks ◎ ◎ 3 weeks ◎ ○ 4 weeks ◎ △

Referring to Table 5, the hard capsules prepared in Example 3-1 did not appear to have a haze even when stored for a long time, whereas the hard capsules prepared in Comparative Example 3-1 had a haze after three weeks. appear.

Although the present invention has been described with reference to the drawings and embodiments, it is to be understood that various modifications and equivalent embodiments may be made by those skilled in the art. Accordingly, the true scope of the present invention should be determined by the technical idea of the appended claims.

Claims

Water-soluble cellulose ethers;
Alcohols; And
An aqueous composition for hard capsules comprising water.

The method of claim 1,
The aqueous composition for hard capsules is an aqueous composition for hard capsules comprising 10 to 25% by weight of the water-soluble cellulose ether, and 5 to 30% by weight of the alcohol.

The method of claim 1,
The water-soluble cellulose ether is hydroxypropyl methyl cellulose (HPMC), hydroxyethyl methyl cellulose (HEMC), methyl cellulose (MC) or an aqueous composition for hard capsules comprising a mixture of two or more thereof.

The method of claim 1,
The alcohol is an aqueous composition for hard capsules containing ethanol, methanol, isopropanol, butanol or a mixture of two or more thereof.

The method of claim 1,
The hard capsule aqueous composition may be added as a gelling agent to carrageenan, gellan gum, xanthan gum, xanthan gum, pectin, or two or more water-soluble gums thereof in a content ratio of 0.05 to 5.0% by weight. Aqueous composition for hard capsules comprising a.

6. The method of claim 5,
The hard capsule aqueous composition further comprises potassium chloride, potassium acetate, calcium chloride or a mixture of two or more thereof as a gelling aid in an amount ratio of more than 0% by weight to 1.0% by weight.

Dissolving a water-soluble cellulose ether in water and alcohols, the method for producing an aqueous composition for hard capsules comprising the step of preparing a cellulose ether solution for 2 to 12 hours at a temperature of 40 ~ 70 ℃.

8. The method of claim 7,
The method of producing an aqueous composition for hard capsules further comprising the step of adding a gelling agent to the cellulose ether solution.

Hard capsules prepared using the aqueous composition for hard capsules according to any one of claims 1 to 6.