KR20130077373A - Water stable film-coating tablet comprising alginic acid and sodium carboxymethylcellulose - Google Patents

Abstract

PURPOSE: A film-coated tablet including alginic acid and carboxymethylcellulose sodium is provided to prevent the rupture of the film of a tablet from moisture effect occurs by long period storage or during circulation. CONSTITUTION: A film-coated tablet includes alginic acid or pharmaceutically-acceptable salt, and carboxymethylcellulose alkaline salt as active ingredients. Polyvinyl alcohol is used as a coating base. Hydroxypropylmethylcellulose is used as an additional coating base. A coating solvent for coating the film is water, not an organic solvent. The film-coated tablet is secondarily coated with the coating solution including ethyl cellulose as a coating base after coating with the coating solution including polyvinyl alcohol.

Description

Water stable film-coating tablet comprising alginic acid and sodium carboxymethylcellulose

The present invention relates to a film-coated tablet containing alginic acid or a pharmaceutically acceptable salt thereof and an carboxymethyl cellulose alkali salt, and more particularly, to a film-coated tablet having improved storage stability such as moisture.

Alginic acid and carboxymethylcellulose sodium complex have been used as an adjunct to weight loss through reduced food intake.

However, alginic acid / carboxymethyl cellulose sodium composites have high hygroscopicity, which not only has to reduce the use of water during film coating, but also has a difficulty in finding a means of inhibiting the penetration of water during storage for product stability and quality assurance. .

Thick film coatings may be applied to prevent the ingress of moisture during storage, but film coatings used to prevent the ingress of moisture often delay the disintegration of tablets, which is problematic for product efficacy and conventional test methods.

Therefore, the technical problem to be achieved by the present invention is a tablet coating under the influence of moisture during long-term storage and distribution in tablets containing alginic acid or its pharmaceutically acceptable salts and carboxymethylcellulose alkali salts (preferably sodium salts). The occurrence of breakage is to provide an improved film coated tablet.

In order to achieve the above technical problem, the present invention is a film-coated tablet containing alginic acid or a pharmaceutically acceptable salt thereof and carboxymethyl cellulose alkali salt as an active ingredient, polyvinyl alcohol or polyvinyl alcohol and hydroxy as a coating base It provides a tablet characterized in that the use of propyl methyl cellulose.

The present invention is based on the surprising fact that the use of polyvinyl alcohol as a periodic agent among a wide variety of coating bases significantly increases the water stability of the alginic acid / carboxymethyl cellulose alkali salt-containing film coating tablets.

Preferably, in the film coating using the polyvinyl alcohol as the main coating base, water, not an organic solvent, is used as the coating solvent.

More preferably, the alginic acid / carboxymethyl cellulose alkali salt-containing film coating tablet according to the present invention is first coated with a coating liquid containing polyvinyl alcohol, and then secondly coated with an coating liquid containing ethyl cellulose as a coating base. Through this secondary coating it is possible to further increase the water stability of the alginic acid / carboxymethyl cellulose alkali salt film coating tablets.

The coating liquid containing such ethyl cellulose may further include hydroxypropyl methyl cellulose in addition to the ethyl cellulose as a coating base.

In the film coating tablet according to the present invention, it is most preferable for the purpose of the present invention that the primary coating amount is 3-10% by weight of the uncoated mass, and the secondary coating amount is 3-10% by weight of the uncoated mass. That is, in the case of such a coating amount it may have an appropriate disintegration time while ensuring stability for moisture.

In the film coating according to the present invention, the film coating liquid, in addition to the above-mentioned coating bases within the scope of not impairing the object of the present invention, polyethylene glycol, diethphthalate, glycerin, triacetin, propylene glycol, acetyl triethyl sheet Plasticizers such as late, triethyl citrate, glyceryl triacetate and dibutyl sebacate; Lubricants such as talc, stearic acid and silicon dioxide; Coloring agents such as titanium oxide, aluminum lake, iron oxide, and natural pigments; Anti-sticking agents such as lecithin, glycerin, acetylated monoglycerides, mineral oils, carnauba wax; Suspending agents such as hydroxypropylmethyl cellulose, hydroxypropyl cellulose, xanthan rubber, natural rubber, and carboxymethyl cellulose; It may further include a flow aid such as lactose, starch, talc, fumed silica and the like.

The film coating tablet according to the present invention does not serve to delay the disintegration of the tablet because the film of the film coating is ruptured within 5 minutes in water.

The present invention provides a film containing alginic acid or a pharmaceutically acceptable salt thereof and an carboxymethylcellulose alkali salt (preferably sodium salt), which is improved in the occurrence of breakage of tablets under the influence of moisture during long-term storage and distribution. Provide a coated tablet.

Figure 1 is a photograph of the appearance after storing the film coated tablet prepared in Example 11-1 under accelerated conditions for 6 months.
Figure 2 is a photograph of the appearance after storing the film coated tablet prepared in Example 11-2 under accelerated conditions for 6 months.
Figure 3 is a photograph of the appearance after storing the film coated tablet prepared in Example 12-1 under accelerated conditions for 6 months.
Figure 4 is a photograph of the appearance after storing the film coated tablet prepared in Example 12-2 under accelerated conditions for 6 months.
5 is a photograph of the appearance after storing the film coated tablet prepared in Example 13-1 under accelerated conditions for 6 months.
Figure 6 is a photograph of the appearance after storing the film coated tablet prepared in Example 13-2 under accelerated conditions for 6 months.
Figure 7 is a photograph of the appearance after storing the film coated tablet prepared in Example 14-1 under accelerated conditions for 6 months.
Figure 8 is a photograph of the appearance after storing the film coated tablet prepared in Example 14-2 under accelerated conditions for 6 months.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Alginic acid and Carboxymethylcellulose Sodium  contain Undefined  Produce

Alginic acid, carboxymethyl cellulose sodium, microcrystalline cellulose, crospovidone, sodium starch glycolate, corn starch, citric acid (hydrate), sodium lauryl sulfate, and precipitated calcium carbonate are mixed, and povidone is dissolved in purified water and used as a binder liquid. The granules were prepared by the formulation technique. To prepare the granules in Table 1 to prepare a conventional tableting method by separately mixing the glidant hard anhydrous silicic acid and magnesium stearate.

Raw material name Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Alginic acid 35.4% 36.0% 37.7% 35.4% 35.4% 35.4% 35.4% Carboxymethylcellulose sodium 17.7% 18.0% 18.9% 17.7% 17.7% 17.7% 17.7% Microcrystalline cellulose 101 5.3% × × 1.8% 1.8% × × Crospovidone 7.1% 7.1% Starch glycolate sodium × × × 4.4% × 4.4% 4.4% Corn starch × × × × 4.4% × × Citric acid hydrate 8.8% 9.0% 9.4% 8.8% 8.8% 5.3% 3.5% Light anhydrous silicic acid 4.4% 20.0% 3.8% 3.5% 3.5% 3.5% 3.5% Povidone K30 2.7% 4.5% 2.8% 2.7% 2.7% 2.7% 2.7% Sodium lauryl sulfate 5.3% 5.4% 5.7% 5.3% 5.3% 3.5% 5.3% Precipitated calcium carbonate 17.7% 18.0% 18.9% 17.7% 17.7% 15.9% 15.9% Magnesium stearate 2.7% 5.4% 2.8% 2.7% 2.7% 4.4% 4.4% Mass ratio total 100.0% 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Alginic acid and Carboxymethylcellulose Sodium  contain Definition of film coating  Produce

To the uncoated tablet of Table 1 was prepared a coating base in the composition of Table 2.

Example Purpose of blending Raw material name Furtherance(%) Example 8 Coating agent Hypromellose 2910 76.5 Diacetyl monoglycerides 5.9 Talc 8.8 Polyethylene Glycol 6000 8.8 Mass ratio total 100.0 Coating Solvent ethanol qs Dichloromethane qs Example 9 Coating agent Polyvinyl alcohol 24.0 Hypromellose 2910 11.0 Polyethylene Glycol 4000 15.0 Talc 8.0 Titanium oxide 42.0 Mass ratio total 100.0 Coating Solvent Purified water qs Example 10 Coating agent Hypromellose 2910 58.1 Ethyl Cellulose 8.0 Diethylphthalate 8.9 Talc 8.0 Titanium oxide 17.0 Mass ratio total 100.0 Coating Solvent ethanol qs Purified water qs

According to the composition and weight of Table 2 to prepare a film coated tablet of Table 3.

Example Used uncoated tablet Coating base: Composition Example 11-1 Example 1 Example 8: 2% Example 11-2 Example 1 Example 8: 5% Example 12-1 Example 1 Example 8: 2%
Example 10: 4% Example 12-2 Example 1 Example 8: 2%
Example 10: 3% Example 13-1 Example 1 Example 9: 2% Example 13-2 Example 1 Example 9: 5% Example 14-1 Example 1 Example 9: 2%
Example 10: 4% Example 14-2 Example 1 Example 9: 2%
Example 10: 3%

Experimental Example 1 Appearance Evaluation

The film-coated tablets prepared in Table 3 were stored for 6 months under accelerated conditions at 45 ° C. and 75% relative humidity. At this time, according to the degree of maintaining the properties of the tablet according to the degree of breakage of the tablet and the film was evaluated by assigning from the lowest 1 point to the maximum 5 points.

Example Score according to the degree of retention Example 11-1 One Example 11-2 2 Example 12-1 One Example 12-2 2 Example 13-1 3 Example 13-2 4 Example 14-1 5 Example 14-2 5

The change in appearance according to the composition and coating rate of the coating agent was different according to the embodiment, and the properties of Examples 13 and 14 were the best. This was found to be a tablet coated with the composition of Examples 9 and 10. As a result of Table 4, it was found that the use of a mixture of polyvinyl alcohol, hypromellose, and ethyl cellulose was more effective in the stability of the formulation than the use of hypromellose alone in the coating composition. In addition, it was found that the use of a coating agent composed of a mixture of polyvinyl alcohol, hypromellose, and ethyl cellulose in a constant ratio was more effective for stability of the quality of the formulation than the use alone.

Experimental Example 2 Evaluation of Film Break Time and Disintegration

The film rupture time and degree of disintegration of the tablets prepared in Example 11-14 were evaluated according to the pharmacopeia dissolution test method. The disintegration evaluation medium was purified water. The results are shown in Table 5 below.

Example Early 6 months Rupture of the film Disintegration Rupture of the film Disintegration Example 11-1 Within 5 minutes Within 38 minutes Within 5 minutes Within 5 minutes Example 11-2 Within 5 minutes Within 38 minutes Within 5 minutes Within 5 minutes Example 12-1 Within 5 minutes Within 38 minutes Within 5 minutes Within 5 minutes Example 12-2 Within 5 minutes Within 38 minutes Within 5 minutes Within 5 minutes Example 13-1 Within 5 minutes Within 38 minutes Within 5 minutes Within 45 minutes Example 13-2 Within 5 minutes Within 38 minutes Within 5 minutes Within 45 minutes Example 14-1 Within 5 minutes Within 38 minutes Within 5 minutes Within 45 minutes Example 14-2 Within 5 minutes Within 38 minutes Within 5 minutes Within 45 minutes

As a result of Table 5, the film rupture time did not differ from the initial result. On the other hand, tablets that showed disintegration time within 45 minutes at the beginning of the experiment showed different disintegration times depending on the composition of the coating after 6 months. This seems to be related to the appearance shown in Table 4 above. The disintegration time was also faster due to the larger change in appearance. It is believed that the coating did not block the water, weakening the uncoated bond strength, which lowered the hardness of the tablet, resulting in faster disintegration time.

Claims (8)

In the film-coated tablet containing alginic acid or a pharmaceutically acceptable salt thereof and carboxymethyl cellulose alkali salt as an active ingredient,
Tablets, characterized in that the use of polyvinyl alcohol as a coating base. The tablet of claim 1, wherein the film-coated tablet further uses hydroxypropylmethylcellulose as a coating base. The tablet according to claim 1 or 2, wherein in the film coating, water, not an organic solvent, is used as a coating solvent. The tablet according to claim 1 or 2, wherein the film-coated tablet is first coated with a coating solution containing polyvinyl alcohol and then secondly coated with a coating solution containing ethylcellulose as a coating base. 6. The tablet according to claim 5, wherein the coating liquid containing ethyl cellulose further comprises hydroxypropyl methyl cellulose as a coating base. The tablet according to claim 5, wherein the primary coating amount is 3-10% by weight of the uncoated mass, and the secondary coating amount is 3-10% by weight of the uncoated mass. The tablet according to claim 1 or 2, wherein the film of the film coating ruptures in water within 5 minutes. The tablet according to claim 5, wherein the film-coated film ruptures in water within 5 minutes.

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