KR102265977B1 - Composition for film-coating having improved damp-proof property and tablet coated with the composition - Google Patents

Abstract

The present invention relates to a composition for film coating capable of rapid coating, which is advantageous for securing stability of a coated tablet, and improved stability of the appearance of the coating layer such as cracking, and a tablet coated with the composition for film coating . In particular, the composition for film coating of the present invention is more effective in preventing moisture absorption.

Description

Composition for film coating with improved moisture-proof properties and tablets coated therewith {Composition for film-coating having improved damp-proof property and tablet coated with the composition}

The present invention relates to compositions for film coating tablets and tablets coated with such film coating compositions. In particular, the present invention relates to a film coating composition and tablets coated with the composition, which can be coated at a high speed, which can dramatically reduce the time required for coating, and the coating has excellent moisture resistance.

Recently, aqueous film coating using a water-soluble polymer as a coating agent is often performed for the purpose of protecting the uncoated tablet and improving stability and appearance. For the purpose of such film coating, the film coating composition should have a desirable effect on securing the stability of the coated tablet.

On the other hand, if the film to be coated is thick, it takes too much time to complete the coating process, which is uneconomical, and this coating process itself may adversely affect the properties and stability of the uncoated tablet, so shortening the coating process is of great economic value have

In particular, since there are many drugs that are unstable to moisture, it is a very big advantage if the film coating has excellent moisture resistance. However, excellent moisture resistance and coating speed are often arranged, so it is difficult to shorten the coating process and at the same time have excellent moisture resistance.

Republic of Korea Patent Publication No. 10-2016-0111375

Therefore, the problem to be solved by the present invention is to provide a composition for film coating that enables rapid coating, is advantageous in securing stability of a coated uncoated tablet, and has improved stability of the appearance of the coating layer such as cracking.

In particular, the present invention is to provide a film coating composition capable of providing excellent moisture-proof ability while allowing rapid coating.

An additional problem to be solved by the present invention is to provide a tablet coated with such a composition for film coating.

In order to solve the above problems, the present application contains a polymer for coating of 35-55% by weight based on the total weight of the composition, and the polymer for coating is polyvinyl alcohol, polyvinylpyrrolidone and a methacrylic acid copolymer, and the poly The content of the vinyl pyrrolidone and the methacrylic acid copolymer is 0.35 to 0.65 parts by weight relative to the polyvinyl alcohol content, respectively. A composition for film coating, preferably a tablet film coating composition, is provided. Preferably, in the composition, the content of polyvinylpyrrolidone and methacrylic acid copolymer in the composition is 0.4 to 0.6 parts by weight relative to the content of polyvinyl alcohol, respectively. More preferably, polyvinyl alcohol, polyvinylpyrrolidone and methacrylic acid copolymer are used in parts by weight of 2:0.9-1.1:0.9-1.1 (polyvinyl alcohol: polyvinyl pyrrolidone: methacrylic acid copolymer) as the coating polymer. do.

Preferably, as the methacrylic acid copolymer in the film coating composition of the present invention, methacrylic acid copolymer type C, type B, type A, or a mixture thereof may be used, and type C is most preferred for the purpose of the present invention. .

There are many substances known to be similar to polyvinyl alcohol, such as copovidone (vinylpyrrolidone-vinyl acetate copolymer), but these are not suitable for the purpose of the present invention because they have a sticky property, and the temperature during coating is too high. There is a possibility of causing a problem in the stability of the drug by increasing it a lot, and the moisture-proof ability was not very desirable.

Preferably, in the present application, in the composition for film coating, 35-55% by weight of the coating polymer (polyvinyl alcohol, polyvinylpyrrolidone and methacrylic acid copolymer), 13-33% by weight of oxidation based on the total weight of the composition Provided is a composition for film coating comprising titanium, 15-30% by weight of talc, and 0.2-8% by weight of a plasticizer.

Preferably, in the present application, in the composition for film coating, 35-55% by weight of the coating polymer (polyvinyl alcohol, polyvinylpyrrolidone and methacrylic acid copolymer), 13-33% by weight of oxidation based on the total weight of the composition Titanium, 15-30% by weight of talc, 0.2-8% by weight of a plasticizer, and the remaining amount (eg, 0.1-8% by weight) of other additives (any one or more selected from the group consisting of pigments, lecithin, etc.) It provides a composition for film coating.

The composition for film coating according to the present invention may increase the content of the composition in the coating solution for the purpose of shortening the coating time and to form a good film coating layer. Preferably, the composition is used by mixing with the coating solvent so as to be 25-35 wt% based on the final coating solution. More preferably, the composition is used by mixing with the coating solvent so as to be 28-32 wt% based on the final coating solution. Most preferably, the composition is used by mixing with a coating solvent so as to be 29-31 wt% based on the final coating solution.

For the film coating composition according to the present invention, a coating solution is prepared using water, preferably purified water, as a coating solvent, and the mixing ratio of the coating solvent and the composition is as described above.

As a result of conducting various studies, the present inventors completed the present invention by confirming that the film coating speed can be dramatically increased during film coating using the film coating composition, and there is a great improvement in maintaining the stability and appearance of the coated tablet. did. In particular, the composition for film coating of the present invention is excellent in preventing moisture absorption.

Preferably, the composition for film coating according to the present invention contains lecithin, which serves to smooth the surface of the film coating with the other additives and to soften the film.

Optionally, the film coating composition of the present invention may further include a colored pigment in addition to titanium oxide, which is a white-based colorant. As such a colorant, aluminum lake-based pigments may be used.

In the composition for film coating according to the present invention, polyethylene glycol, triethyl citrate, propylene glycol, and the like may be used as the plasticizer.

In the film coating composition according to the present invention, the polyethylene glycol is preferably polyethylene glycol 4000, polyethylene glycol 6000, and the like, and particularly, polyethylene glycol 6000 is more preferred for various purposes of the present invention. In the composition for film coating according to the present invention, the polyvinyl alcohol is preferably polyvinyl alcohol having a viscosity of 4-6 mPas when the viscosity is measured with a 4 wt% aqueous solution at 20°C. In the film coating composition according to the present invention, the polyvinylpyrrolidone is preferably polyvinylpyrrolidone K-15, K-17, K-25, K-30, or the like. In the composition for film coating according to the present invention, the hypromellose is preferably hypromellose 2910, and the hypromellose has a viscosity of 10-20 mPas when measured with a 2 wt% aqueous solution at 20°C. is more preferred for several purposes of the present invention.

The present invention provides a composition for film coating capable of rapid coating, which is advantageous for securing stability of a coated tablet, and improved stability of the appearance of the coating layer such as cracking, and a tablet coated with the composition for film coating .

The following drawings attached to this specification illustrate preferred embodiments of the present invention, and serve to further understand the technical spirit of the present invention together with the above-described content of the present invention, so the present invention is limited to the matters described in those drawings It should not be construed as being limited.
1 to 3 are stability evaluation results of Samples A to E of Experimental Example 1. 1 is a photograph of the external change of the tablet, FIG. 2 is a result of measuring the degree of discoloration of the tablet, and FIG. 3 is a result of measuring the degree of cracking of the tablet.
4 to 6 are evaluation results of the composition for quick plus film coating. 4 is a photograph of their external changes, FIG. 5 is a measurement result of discoloration of the tablet, and FIG. 6 is a result of evaluating their moisture absorption.

Hereinafter, examples and the like will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art to which the present invention pertains.

The viscosity mentioned below is the viscosity of the solution obtained by measuring the viscosity for about 1 minute with a BROOKFIFLD DVE viscometer (spindle RV S02, 60 rpm).

Comparative Example 1: Tab Shield White 21W002

Comparative Example 1, a composition for film coating, was prepared with the composition and content of Table 1 below.

Raw material name purpose of mixing amount polyvinyl alcohol coating agent 40.0 titanium oxide colorant (pigment) 25.0 Polyethylene glycol 3350 skinning aid 20.2 talc skinning aid 14.8 total 100

Film coating was attempted while mixing the composition with purified water to find a suitable coating solution concentration, and when the composition exceeds 25% by weight relative to the total weight of the coating solution, the viscosity increases and spraying is difficult. did. A suitable concentration of the coating solution of Comparative Example 1 was about 20% by weight based on the total weight of the coating solution, and the viscosity at that time was about 90 cp.

A coating solution was prepared by mixing 50 parts by weight of the coating composition and 200 parts by weight of purified water, and the sample tablets were coated as shown in Table 2 below using BGB-1 as a coating machine.

The coating weight was 10 mg, the coating weight gain was 2%, and the tablet weight was 537 mg after coating from 527 mg. The total coating time was 15 minutes and the average spray rate was 4.8 g/min. As a result, it took about 15 minutes to coat 10 mg with the composition.

Comparative Example 2: Tab Shield Orange 22O048

Comparative Example 2, which is a composition for film coating, was prepared with the composition and content shown in Table 3 below.

Raw material name purpose of mixing amount polyvinyl alcohol coating agent 45.5 titanium oxide colorant (pigment) 28.0 lecithin skinning aid 2.0 talc skinning aid 20.0 xanthan gum skinning aid 0.5 aluminum lake coloring agent remaining amount total 100

A coating solution was prepared by mixing 15 parts by weight of the coating composition and 35 parts by weight of purified water, and the sample tablets were coated as shown in Table 4 below using BGB-1 as a coating machine.

The coating weight was 36 mg, the coating weight gain was 5%, and the tablet weight was 750 mg after coating from 714 mg. The total coating time was 35 minutes and the average spray rate was 7.2 g/min. As a result, it took about 35 minutes to coat 36 mg with the composition. During the coating process, a lot of sticking occurs, so it is not easy to set the coating process, and it takes a relatively long time for coating.

Example 1: Tab Shield Orange 71O154

Example 1, which is a composition for film coating, was prepared with the composition and content shown in Table 5 below.

Raw material name purpose of mixing amount remark titanium oxide colorant (pigment) 23.0 Polyethylene glycol 6000 skinning aid 20.2 polyvinyl alcohol coating agent 20.0 polyvinylpyrrolidone coating agent 20.0 talc skinning aid 14.8 hypromellose coating agent 1.0 Degree of substitution: 2910, Viscosity: 15 mPas aluminum lake pigment colorant (pigment) remaining amount Yellow No. 4 total 100

Film coating was attempted while mixing the composition with purified water to find a suitable coating solution concentration, and the composition was suitable for film coating at about 30% by weight based on the total weight of the coating solution. The viscosity of the coating solution was about 99 cp.

A coating solution was prepared by mixing 50 parts by weight of the coating composition and 116 parts by weight of purified water, and the sample tablets were coated as shown in Table 6 below using BGB-1 as a coating machine.

The coating weight was 35 mg, the coating weight gain was 5%, and the tablet weight was 742 mg after coating from 707 mg. The total coating time was 9 minutes and the average spray rate was 8.0 g/min. As a result, it took about 9 minutes to coat 35 mg with the composition.

Example 2: Tab Shield Orange 71O155

Example 2, a composition for film coating, was prepared with the composition and content shown in Table 7 below.

Raw material name purpose of mixing amount remark titanium oxide colorant (pigment) 24.5 polyvinyl alcohol coating agent 22.76 polyvinylpyrrolidone coating agent 22.76 K-30 talc skinning aid 21.5 lecithin skinning aid 2.0 Soy Lecithin xanthan gum skinning aid 0.48 aluminum lake pigment colorant (pigment) remaining amount total 100

Film coating was attempted while mixing the composition with purified water to find a suitable coating solution concentration, and the composition was suitable for film coating at about 30% by weight based on the total weight of the coating solution. The viscosity of the coating solution was about 120 cp.

A coating solution was prepared by mixing 50 parts by weight of the coating composition and 116 parts by weight of purified water, and the sample tablets were coated as shown in Table 8 using BGB-1 as a coating machine.

The coating weight was 35 mg, the coating weight gain was 5%, and the tablet weight was 742 mg after coating from 707 mg. The total coating time was 9 minutes and the average spray rate was 8.0 g/min. As a result, it took about 9 minutes to coat 35 mg with the composition.

Example 3: Tab Shield Orange 71O156

Example 3, which is a composition for film coating, was prepared with the composition and content shown in Table 9 below.

Raw material name purpose of mixing amount remark titanium oxide colorant (pigment) 24.5 polyvinyl alcohol coating agent 22.76 polyvinylpyrrolidone coating agent 22.76 K-30 talc skinning aid 21.5 Polyethylene glycol 6000 skinning aid 2.48 aluminum lake pigment colorant (pigment) remaining amount Red No. 40 total 100

Film coating was attempted while mixing the composition with purified water to find a suitable coating solution concentration, and the composition was suitable for film coating at about 30% by weight based on the total weight of the coating solution. The viscosity of the coating solution was about 125 cp.

A coating solution was prepared by mixing 50 parts by weight of the coating composition and 116 parts by weight of purified water, and the sample tablets were coated as shown in Table 9 using BGB-1 as a coater.

The coating weight was 35 mg, the coating weight gain was 5%, and the tablet weight was 742 mg after coating from 707 mg. The total coating time was about 9 minutes and the average spray rate was 8.0 g/min. As a result, it took about 9 minutes to coat 35 mg with the composition.

Experimental Example 1: Evaluation of the effect of polyvinylpyrrolidone mixing ratio (weight ratio)

Comparative Example 1 Uncoated tablet film coating was performed in the same manner as in Comparative Example 1 while replacing a certain portion of polyvinyl alcohol with polyvinylpyrrolidone in the prescription. The substitution ratio of polyvinylpyrrolidone was shown in Table 11 below.

sample name Polymer percentage (%) solute ratio
(%) solution viscosity
(cp) Coating amount
(%) polyvinyl alcohol polyvinylpyrrolidone sample A
(Comparative Example 1) 100 0 20 90.0 4 sample B 75 25 20 120.0 4 sample C 50 50 30 352.0 4 sample D 25 75 30 208.0 4 sample E 0 100 30 152.0 4

Thereafter, the stability of the film-coated tablet was evaluated while being stored in a thermo-hygrostat (model name: YHS-250SC) at a temperature of 40° C. and a humidity of 75 RH. Specifically, discoloration and cracking of the tablets were observed at 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours after the start of storage.

The results are shown in FIGS. 1 to 3 . 1 is a photograph of the external change of the tablet, FIG. 2 is a result of measuring the degree of discoloration of the tablet, and FIG. 3 is a result of measuring the degree of cracking of the tablet.

As can be seen from the results of FIGS. 1 and 2 , polyvinylpyrrolidone was found to be somewhat vulnerable to discoloration. However, when the content of polyvinyl alcohol and polyvinylpyrrolidone were mixed in a similar ratio, discoloration stability was relatively good.

As shown in FIGS. 1 and 3, samples A, B, and C did not crack, and the coating substrate melted and cracked only in samples D and E, which had a very high content of polyvinylpyrrolidone than polyvinyl alcohol. seemed

Experimental Example 2: Tab Shield Quick Plus Evaluation

Comparative Examples and Examples were prepared as shown in Table 12 below, and for the comparative evaluation, the same uncoated tablets (unripe tablets of Impactamine premium tablets, a multivitamin preparation, were used) were used. Each coating composition is shown in Tables 13 (primary coating material) and 14 (secondary coating material). Water was used as a coating solvent for dissolving or finely suspending the composition.

The coating solution was prepared by mixing with water so that the tab shield clear (71C152) was 8.5 wt%, tab shield white 20 wt%, tab shield quick 30 wt%, and tab shield quick plus 30 wt% relative to the total weight of the coating solution.

sample name primary coating Coating amount (%) secondary coating Coating amount (%) A Tap Shield Clear (71C152) 0.75% Tap Shield White (11W001) 5.0% B Tap Shield White (21W002) C Tap Shield White (22W005) D tap shield quick E Tap Shield Quick Plus

Raw material name Tap Shield Clear (71C152) Hypromellose 2910 6mPas 90.000 Polyethylene glycol 3350 5.000 talc 3.000 Ethyl Cellulose 10mPas 1.000 Polyvinylpyrrolidone K-30 1.000 total 100

Raw material name tap shield white
(11W001) tap shield white
(21W002) tap shield white
(22W005) tap shield quick Tap Shield Quick Plus Hypromellose 6mPas 62.500 - - - - Polyethylene glycol 400 6.250 - - - - titanium oxide 31.250 25.000 32.000 22.760 22.760 polyvinyl alcohol - 40.000 45.520 22.760 22.760 talc - 14.800 20.000 26.000 26.000 lecithin - - 2.000 3.500 3.500 xanthan gum - - 0.480 - - polyvinylpyrrolidone - - - 22.760 11.380 Methacrylic acid copolymer TYPE C (Eudragit L100-55) - - - - 11.380 Polyethylene glycol 3350 - 20.200 - - - Polyethylene glycol 6000 - - - 2.220 2.220 total 100 100 100 100 100

Each coating condition was shown in Table 15 below.

Item
(Average) tap shield clear
(71C152) Tab Shield White (11W001)
tap shield white
(21W002) tap shield white
(22W005) tap shield quick
Tap Shield Quick Plus Inlet temperature about 64℃ Approx. 74℃ About 85℃ Approx. 74℃ Exhaust temperature About 33℃ Approx. 40℃ Approx. 43℃ Approx. 40℃ spray rate Approx. 8.0 g/min Approx. 7.2 g/min Approx. 7.2 g/min Approx. 7.2 g/min Pump Speed about 9 rpm about 8 rpm Approx. 7.9 rpm about 8 rpm Pan speed about 15 rpm about 16 rpm about 13 rpm about 16 rpm Atomizing air pressure about 0.4 bar about 1.0 bar Approx. 1.1 bar Approx. 1.1 bar Pattern Air pressure about 0.4 bar about 1.0 bar Approx. 1.1 bar Approx. 1.1 bar air flow Approx. 180 m ³ /hr Approx. 180 m ³ /hr Approx. 180 m ³ /hr Approx. 180 m ³ /hr coating weight 7 mg 35 mg 35 mg 35 mg Coating Weight Gain 1% by weight 5% by weight 5% by weight 5% by weight

In the case of Tab Shield Clear (71C152), the tablet weight was 707 mg after coating at 700 mg. The total coating time was about 9 minutes. As a result, about 9 minutes were required to coat 7 mg with the composition.

For Tab Shield White (11W001), the tablet weight was 742 mg after coating at 707 mg. The total coating time was about 40 minutes. As a result, it took about 40 minutes to coat 35 mg with the composition. In the case of the tab shield white (11W001) coating composition, when the content of the coating composition in the coating solution exceeds 12% by weight, the spraying was not good and the sticking phenomenon occurred, and the moisture-proof ability was also not very good.

For Tab Shield White (21W002), the tablet weight was 742 mg after coating at 707 mg. The total coating time was about 20 minutes. As a result, it took about 20 minutes to coat 35 mg with the composition. In the case of the tab shield white (21W002) coating composition, a sticking phenomenon occurred during coating, and it was difficult to further increase the spray rate due to poor coating quality.

For Tab Shield White (22W005), the tablet weight was 742 mg after coating at 707 mg. The total coating time was about 40 minutes. As a result, it took about 20 minutes to coat 35 mg with the composition. In the case of the tab shield white (22W005) coating composition, a sticking phenomenon occurred during coating, and it was difficult to further increase the spray rate due to poor coating quality.

For TabShield Quick and TabShield Quick Plus, tablet weights ranged from 707 mg to 742 mg after coating. The total coating time was about 9 minutes. As a result, it took about 9 minutes to coat 35 mg with the composition.

While the Comparative Examples and Examples samples were stored in a thermo-hygrostat (model name: YHS-250SC) (40° C., 75 RH), discoloration and moisture absorption of the tablets were observed at 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. did. The results are shown in FIGS. 4 to 6 .

As shown in FIGS. 4 to 6 , the film coating composition according to the present invention can be coated within a short time, so that the coating process can be dramatically shortened, and at the same time, it shows excellent stability in protecting the uncoated tablet.

Claims (8)

Contains 35-55% by weight of the polymer for coating based on the total weight of the composition,
The coating polymer is polyvinyl alcohol, polyvinylpyrrolidone and methacrylic acid copolymer,
The content of the polyvinylpyrrolidone and the methacrylic acid copolymer is each 0.35 to 0.65 parts by weight relative to the content of polyvinyl alcohol, the composition for coating a moisture-proof film of the tablet. According to claim 1, wherein the methacrylic acid copolymer is methacrylic acid copolymer type C, the film coating composition. According to claim 1, wherein the composition comprises 35-55% by weight of the coating polymer, 13-33% by weight of titanium oxide, 15-30% by weight of talc and 0.2-8% by weight of a plasticizer based on the total weight of the composition , a composition for film coating. According to claim 1, wherein the composition comprises 0.1-8% by weight of any one or more selected from the group consisting of a pigment and lecithin based on the total weight of the composition, the composition for film coating. [Claim 5] The composition for film coating according to any one of claims 1 to 4, wherein the composition is mixed with a coating solvent in an amount of 25-35 wt% based on the final coating solution. [Claim 6] The composition for film coating according to claim 5, wherein the composition is mixed with a coating solvent so as to be 28-32 wt% based on the final coating solution. The composition for film coating according to claim 5, wherein the coating solvent is water. The method according to any one of claims 1 to 4, wherein the content of polyvinyl alcohol, polyvinylpyrrolidone and methacrylic acid copolymer in the composition is 2:0.9-1.1:0.9-1.1 (polyvinyl alcohol: polyvinyl) Pyrrolidone: methacrylic acid copolymer), a composition for film coating.

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