KR20200059771A - Bilayer coated tablet comprising choline alfoscerate and a method for producing the same - Google Patents

Abstract

The present invention relates to a bilayer-coated tablet containing choline alfoscerate and a method for manufacturing the same. The bilayer-coated tablet containing choline alfoscerate of the present invention exhibits satisfactory dissolution properties while improving storage stability by effectively shielding moisture.

Description

Bilayer coated tablet comprising choline alfoscerate and a method for producing the same}

The present invention relates to a two-layer coated tablet comprising choline alfoscerate and a method for manufacturing the same.

Choline is one of the most useful nutrients for improving brain metabolism and improving mental ability. Choline alfoscerate is a substance naturally found in the body, and is known as L-alpha Glycerylphosphorylcholine.

Choline alfoscerate passes through the brain vascular barrier and enters the brain, and choline alfoscerate introduced into the brain is broken down into choline and glycerin phosphate dehydrogenase, and choline is used as a precursor to biosynthesize acetylcholine. Acetylcholine normalizes the neurotransmitter function that has been reduced due to brain nerve damage, and glycerin phosphate dehydrogenase is metabolized to phospholipids, a component of the nerve cell membrane, to normalize the damaged neuron function.

Therefore, choline alfoscerate is known to be effective not only for improving and treating perception or brain function in the elderly, but also for reducing concentration, emotional anxiety, irritability, and depression.

When formulating choline alfoscerate into tablets, choline alfoscerate has a problem of poor storage stability due to a strong water adsorption tendency, and coating can be considered to improve it, but it is difficult to have the desired moisture-proof properties as well as coating. There was a problem that the dissolution rate of the tablet was lowered.

Accordingly, it is intended to provide a novel tablet having a satisfactory dissolution rate while improving storage stability by effectively shielding choline alfoscerate having a moisture adsorption tendency.

One object of the present invention is to improve the storage stability of a tablet containing choline alfoscerate, while showing a satisfactory dissolution rate of the active ingredient, and to provide a tablet that is coated evenly on the tablet surface so that no picking occurs in the tablet during the process. do.

Another object of the present invention is to provide a method for preparing the tablet.

One aspect of the present invention, a tablet containing choline alfoscerate and a pharmaceutically acceptable additive;

A primary coating layer containing polyvinylpyrrolidone on the tablet; And

It relates to a two-layer coating tablet comprising a second coating layer comprising polyvinyl alcohol and talc on the primary coating layer.

Choline alfoscerate as the active ingredient may be included in the range of 50 to 80% by weight of the total tablet weight, specifically 55 to 75% by weight, more specifically 58 to 70% by weight.

The pharmaceutically acceptable additive may be an additive that can be used in the manufacturing process of tablets, and may include one or more of excipients, disintegrants, lubricants, binders, or plasticizers. Examples of excipients include microcrystalline cellulose, starch, low-substituted hydroxypropyl cellulose, polyethylene glycol, dextrose, lactose, or mannitol, and disintegrants include carboxymethylcellulose calcium, croscarmellose sodium, and sodium starch glycolate. , Crospovidone, pregelatinized starch, or low-substituted hydroxypropyl cellulose. In particular, it is preferable to include polyethylene glycol and microcrystalline cellulose as an excipient, crospovidone, and croscarmellose sodium as a disintegrant. The total amount of the disintegrant may be 10 to 30 parts by weight based on 100 parts by weight of choline alfoscerate, specifically 10 to 20 parts by weight. The excipient may be 10 parts by weight to 35 parts by weight based on 100 parts by weight of choline alfoscerate, and the microcrystalline cellulose content in the excipient may be 70% or more. The above range is advantageous in terms of moisture resistance and release rate.

   As the lubricant, magnesium stearate, sodium lauryl sulfate, sodium stearate fumarate, colloidal silicon dioxide, talc, aluminum magnesium silicate, stearic acid, sucrose fatty acid ester and the like can be used. In particular, as a lubricant, it is preferable to use magnesium stearate, sodium lauryl sulfate, colloidal silicon dioxide, and the like. The lubricant may be 1 part by weight to 20 parts by weight based on 100 parts by weight of choline alfoscerate, specifically 5 parts by weight to 15 parts by weight, and sodium lauryl sulfate content in the lubricant may be 40% or more. As the binder, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hypromellose, povidone, methyl cellulose, or gelatin can be used. Povidone can be used especially as a binder. The binder may be 1 part by weight to 25 parts by weight based on 100 parts by weight of choline alfoscerate, and specifically 1 part by weight to 20 parts by weight. Polysorbate etc. are mentioned as a plasticizer.

The tablet comprises a primary coating layer comprising polyvinylpyrrolidone on the tablet. Since polyvinylpyrrolidone is hygroscopic, it can protect choline alcocerate from moisture. To this end, polyvinylpyrrolidone is 10% by weight or more, specifically 10% by weight to 30% by weight of the total weight of the primary coating solution. It can be included as Moisture-proof effect and release characteristics in the above range may be good. The primary coating layer weight is 0.5% to 3% by weight based on the total tablet weight, specifically 0.6% to 2% by weight. Polyvinylpyrrolidone may be included in an amount of 80% by weight or more, specifically 90% by weight or more based on the total weight of the primary coating layer, and good moisture-proof properties may be obtained in the above range.

On the primary coating layer, a secondary coating layer comprising polyvinyl alcohol and talc is included. The weight ratio of the primary coating and the secondary coating may be 1: 2 to 1: 6, specifically 1: 2 to 1: 5. Elution and moisture-proof properties in the above range may be good. The secondary coating layer may include polyvinyl alcohol and talc at least 50% by weight of the total weight of the secondary coating layer, specifically 50% to 80% by weight, and more specifically 60% to 70% by weight. Can be. If it is within the above range, it may have good moisture resistance and good release characteristics. The weight ratio of polyvinyl alcohol and talc may be in the range of 7: 3 to 3: 7, specifically 6: 4 to 4: 6. The secondary coating layer may include an additional coating agent in addition to polyvinyl alcohol and talc, and examples of the additional coating agent include glycerol monocaprylocaprate, sodium lauryl sulfate, polyethylene glycol, and HPMC. The secondary coating layer may further include a colorant, and examples of the colorant include black iron oxide, titanium oxide, and yellow iron oxide. The secondary coating layer weight is 0.5% to 5% by weight based on the total tablet weight, specifically 0.6% to 4% by weight.

In another aspect of the present invention, a tablet is prepared from choline alfoscerate and a pharmaceutically acceptable additive, a primary coating solution containing polyvinylpyrrolidone is prepared, and the primary coating solution is coated onto the tablet. Forming a primary coating layer, preparing a secondary coating solution comprising polyvinyl alcohol and talc, and coating the secondary coating solution on the primary coating layer to form a secondary coating layer, A manufacturing method is provided. The detailed description of each component, content, weight ratio, etc. in the above aspect is the same as that of the above-described two-layer coated tablet, so reference is made to this, but only those portions that do not overlap or require explanation are described below.

Preparation of the tablet may include mixing and tableting one or more components of choline alfoscerate and a pharmaceutically acceptable additive, specifically, a binder, an excipient, a disintegrant, a lubricant, or a plasticizer. The preparation of the tablet may include preparing dry granules or wet granules and tableting the prepared granules. Granule production may use a granulator used in the art, for example, a high shear mixer. For wet granulation, a solvent such as water, ethanol or a mixture thereof may be used for association of the mixture, or a binding solution obtained by dissolving the binder in the solvent may be used. The obtained granules can be dried using a dryer such as a conventional dryer, for example, a fluid bed dryer. It can be further formulated to obtain granules of a certain size. The prepared granules can be prepared by mixing with a pharmaceutically acceptable additive and then tableting. Pharmaceutically acceptable additives that can be used in this process can be lubricants, disintegrants, or binders.

Thereafter, a primary coating solution containing polyvinylpyrrolidone is prepared. Since polyvinylpyrrolidone is hygroscopic, it can protect choline alcocerate from moisture. To this end, polyvinylpyrrolidone is 30% by weight or less of the total weight of the primary coating solution, specifically 10% by weight to 20% by weight It can be included as Moisture-proof effect and release characteristics in the above range may be good. The primary coating solution may include, for example, water (purified water), ethanol, or a mixture thereof. The primary coating is, for example, a solvent coating using ethanol, and although it is a solvent coating, it has a feature of improving the moisture resistance of the active drug. The coating method is not particularly limited, and a method of forming a coating layer, for example, dip coating or spray coating, may be used.

Subsequently, a secondary coating layer may be formed on the primary coating layer. The secondary coating layer includes polyvinyl alcohol and talc. By including polyvinyl alcohol and talc as a secondary coating layer at the same time, a synergistic effect can be obtained in terms of the moisture blocking effect compared to the case where only one is included alone. The secondary coating solution may include polyvinyl alcohol and talc at 5% to 20% by weight of the total weight relative to the total secondary coating solution weight. Polyvinyl alcohol and talc in the total weight of the secondary coating layer may be included in the range of 40% to 80% by weight, specifically 50% to 70% by weight. The coating solution may include water, ethanol, or a mixture thereof. The secondary coating solution may include an additional coating agent in addition to polyvinyl alcohol and talc, and examples of the additional coating agent include glycerol monocaprylocaprate, sodium lauryl sulfate, polyethylene glycol, and HPMC. The secondary coating solution may further include a colorant, and examples of the colorant include black iron oxide, titanium oxide, and yellow iron oxide.

The two-layer coated tablets containing choline alfoscerate of the present invention effectively shield moisture and improve storage stability, and at the same time exhibit satisfactory dissolution characteristics, and also have a smooth coating surface, which is advantageous in the process and simple manufacturing method, thereby reducing production cost. There is.

1 is a graph showing the dissolution rate results of tablets of one embodiment and a comparative example of the present invention.
Figure 2 is a photograph showing the results of the state in the long-term storage conditions of the tablets of the Examples and Comparative Examples of the present invention.
Figure 3 is a photograph showing the surface state of the tablets of Examples and Comparative Examples of the present invention.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1: 2nd floor  Preparation of coated tablets 1

With the same prescription as in Table 1, tablets were prepared. That is, powdered choline alfoscerate, microcrystalline cellulose, and croscarmellose sodium were added to the high-speed coalescer and mixed at high speed. Povidone was dissolved in anhydrous ethanol, and a binding solution made therein was added to combine. After drying the lysate and sifting, crospovidone, sodium lauryl sulfate, polyethylene glycol 6000, colloidal silicon dioxide, and magnesium stearate were added to the sizing product, followed by mixing to prepare tablets. Polyvinylpyrrolidone (povidone) was dissolved in anhydrous ethanol at a concentration of 15.0 w / w% to prepare a primary coating solution, and the primary tablet was coated therewith to prepare the primary coating tablet.

Subsequently, a second coating solution was prepared by dissolving Opadry AMBII 88A620001 having the composition shown in Table 2 in water to a concentration of 20.0 w / w%, and coating it to prepare a two-layer coating tablet (containing 400 mg of choline alfoscerate).

Raw material name amount unit Choline alfoscerate 59.61 Mass percentage Microcrystalline cellulose 13.11 Mass percentage Croscarmellose sodium 1.79 Mass percentage Polyvinylpyrrolidone 2.98 Mass percentage Crospovidone 7.45 Mass percentage Sodium lauryl sulfate 3.73 Mass percentage Polyethylene glycol 6000 2.98 Mass percentage Colloidal silicon dioxide 1.79 Mass percentage Magnesium stearate 2.24 Mass percentage 1st coating 0.89 Mass percentage Second coating 3.43 Mass percentage Tablet Total 100.0 Mass percentage

Raw material name Purpose of blending amount unit Polyvinyl alcohol Coating 37.000 Mass percentage Talc Coating 31.000 Mass percentage Titanium oxide Coloring agent (pigmentation) 16.470 Mass percentage Yellow iron oxide Coloring agent (pigmentation) 8.500 Mass percentage Glycerol monocaprylocaprate Coating 4.000 Mass percentage Sodium lauryl sulfate Coating 3.000 Mass percentage Black iron oxide Coloring agent (pigmentation) 0.030 Mass percentage

Example 2: 2nd floor  Preparation of coated tablets 2

Prepared in the same manner as in Example 1, the tablets were prepared in the same manner as Table 3, primary coated tablets, two-layer coated tablets. Here, the primary coating solution was used by dissolving in anhydrous ethanol at a concentration of 12.5 w / w% of povidone and 2.5 w / w% of talc, and the secondary coating solution watered Opadry AMBII 88A620001 having the composition of Table 2 above at a concentration of 20.0 w / w%. It was used to dissolve in.

Raw material name amount unit Choline alfoscerate 59.61 Mass percentage Microcrystalline cellulose 13.11 Mass percentage Croscarmellose sodium 1.79 Mass percentage Polyvinylpyrrolidone 2.98 Mass percentage Crospovidone 7.45 Mass percentage Sodium lauryl sulfate 3.73 Mass percentage Polyethylene glycol 6000 2.98 Mass percentage Colloidal silicon dioxide 1.79 Mass percentage Magnesium stearate 2.24 Mass percentage 1st coating 0.90 Mass percentage Second coating 2.56 Mass percentage Tablet Total 100.0 Mass percentage

Example 3: 2nd floor  Preparation of coated tablets 3

Prepared in the same manner as in Example 1, a tablet, a primary coating tablet, and a secondary coating tablet were prepared according to the prescription shown in Table 4, wherein the primary coating solution was povidone 12.5 w / w%, talc 2.5 w / w%. It was used by dissolving in anhydrous ethanol at a concentration, and the secondary coating solution was used by dissolving Opadry AMBII 88A620001 having the composition in Table 2 above in water at a concentration of 20.0 w / w%.

Raw material name amount unit Choline alfoscerate 59.70 Mass percentage Microcrystalline cellulose 13.13 Mass percentage Croscarmellose sodium 1.79 Mass percentage Polyvinylpyrrolidone 2.99 Mass percentage Crospovidone 7.46 Mass percentage Sodium lauryl sulfate 3.73 Mass percentage Polyethylene glycol 6000 2.99 Mass percentage Colloidal silicon dioxide 1.79 Mass percentage Magnesium stearate 2.24 Mass percentage 1st coating 0.60 Mass percentage Second coating 3.58 Mass percentage Tablet Total 100.0 Mass percentage

Example 4: 2nd floor  Preparation of coated tablets 4

Prepared in the same manner as in Example 1, a tablet, a primary coating tablet, and a secondary coating tablet were prepared according to the prescription shown in Table 5, wherein the primary coating solution was povidone 10.0 w / w%, talc 5.0 w / w%. It was used by dissolving in anhydrous ethanol at a concentration, and the secondary coating solution was used by dissolving Opadry AMBII 88A620001 having the composition of Table 2 above in water at a concentration of 25.0 w / w%.

Raw material name amount unit Choline alfoscerate 59.61 Mass percentage Microcrystalline cellulose 13.11 Mass percentage Croscarmellose sodium 1.79 Mass percentage Polyvinylpyrrolidone 2.98 Mass percentage Crospovidone 7.45 Mass percentage Sodium lauryl sulfate 3.73 Mass percentage Polyethylene glycol 6000 2.98 Mass percentage Colloidal silicon dioxide 1.79 Mass percentage Magnesium stearate 2.24 Mass percentage 1st coating 0.89 Mass percentage Second coating 3.43 Mass percentage Tablet Total 100.0 Mass percentage

Comparative example  One

Prepared in the same manner as in Example 1, the first coating on tablets prepared by coating a tablet prepared by dissolving Opadry AMBII 88A620001 of Table 2 in water at a concentration of 20.0 w / w% in a formulation as shown in Table 6 below to prepare a single-layer coated tablet It was prepared.

Raw material name amount unit Choline alfoscerate 60.15 Mass percentage Microcrystalline cellulose 13.23 Mass percentage Croscarmellose sodium 1.80 Mass percentage Polyvinylpyrrolidone 3.01 Mass percentage Crospovidone 7.52 Mass percentage Sodium lauryl sulfate 3.76 Mass percentage Polyethylene glycol 6000 3.01 Mass percentage Colloidal silicon dioxide 1.80 Mass percentage Magnesium stearate 2.26 Mass percentage 1st coating 3.46 Mass percentage Tablet Total 100.0 Mass percentage

Comparative example  2

A tablet (choline alfoscerate containing 400 mg) was prepared according to the formulation shown in Table 7 below. That is, powdered choline alfoscerate and microcrystalline cellulose were added to a high-speed coalescer and mixed at high speed. Here, a polyvinylpyrrolidone was dissolved in anhydrous ethanol to introduce a binding solution. After drying the lysate and sifting, crospovidone, sodium lauryl sulfate, polyethylene glycol 6000, colloidal silicon dioxide, and magnesium stearate were added to the sizing product, followed by mixing to prepare tablets.

The crude tablets were coated with a primary coating solution prepared by dissolving in povidone 10.0 w / w%, talc 2.0 w / w% concentration in anhydrous ethanol, and then polyethylene glycol 6000 1.33 w / w%, Opadry 03F620050 10.0 w / w% concentration A second coating solution was prepared by dissolving in 80% ethanol, and coated with it to prepare a two-layer coated tablet. The composition of Opadry 03F620050 is shown in Table 8 below.

Raw material name amount unit Choline alfoscerate 61.26 Mass percentage Microcrystalline cellulose 15.31 Mass percentage Polyvinylpyrrolidone 3.06 Mass percentage Crospovidone 7.66 Mass percentage Sodium lauryl sulfate 3.83 Mass percentage Polyethylene glycol 6000 3.06 Mass percentage Magnesium stearate 2.30 Mass percentage 1st coating 0.92 Mass percentage 2nd coating 2.61 Mass percentage Tablet Total 100.00 Mass percentage

Reference amount Raw material name Purpose of blending amount unit 100 HPMC 2910 Coating 70.000 Mass percentage 100 PEG 6000 Coating 13.333 Mass percentage 100 Titanium oxide Coloring agent (pigmentation) 8.676 Mass percentage 100 Yellow iron oxide Coloring agent (pigmentation) 4.587 Mass percentage 100 Talc Coating 3.334 Mass percentage 100 Black iron oxide Coloring agent (pigmentation) 0.070 Mass percentage

Comparative example  3

A tablet (choline alfoscerate containing 400 mg) was prepared according to the prescription shown in Table 9 below. That is, powdered choline alfoscerate and microcrystalline cellulose were added to a high-speed coalescer and mixed at high speed. Here, a polyvinylpyrrolidone was dissolved in anhydrous ethanol to introduce a binding solution. After drying the lysate and sifting, crospovidone, sodium lauryl sulfate, polyethylene glycol 6000, colloidal silicon dioxide, and magnesium stearate were added to the sizing product, followed by mixing to prepare tablets.

The crude tablet was coated with a primary coating solution prepared by dissolving in povidone 10.0 w / w%, talc 2.0 w / w% concentration in anhydrous ethanol, and then polyethylene glycol 6000 1.00 w / w%, Opadry 03F620050 15.0 w / w% concentration Secondary coating tablets were prepared by dissolving in 80% ethanol to prepare a secondary coating solution. The composition of Opadry 03F620050 is shown in Table 8 above.

Raw material name amount unit Choline alfoscerate 61.26 Mass percentage Microcrystalline cellulose 15.31 Mass percentage Povidone 3.06 Mass percentage Crospovidone 7.66 Mass percentage Sodium lauryl sulfate 3.83 Mass percentage Polyethylene glycol 6000 3.06 Mass percentage Magnesium stearate 2.30 Mass percentage 1st coating 0.92 Mass percentage 2nd coating 2.61 Mass percentage Tablet Total 100.00 Mass percentage

Comparative example  4

Prepared in the same manner as in Example 1, the tablets were prepared as shown in Table 10, primary coated tablets, two-layer coated tablets. Here, the primary coating solution was used by dissolving in anhydrous ethanol at a concentration of 12.5 w / w% of povidone and 2.5 w / w% of talc, and the secondary coating solution was dissolved in water at a concentration of 20.0 w / w% with the composition of Table 11 below. Did. The coating agent was prepared by subtracting talc from the composition of Opadry AMBII 88A620001.

Raw material name amount unit Choline alfoscerate 59.61 Mass percentage Microcrystalline cellulose 13.11 Mass percentage Croscarmellose sodium 1.79 Mass percentage Polyvinylpyrrolidone 2.98 Mass percentage Crospovidone 7.45 Mass percentage Sodium lauryl sulfate 3.73 Mass percentage Polyethylene glycol 6000 2.98 Mass percentage Colloidal silicon dioxide 1.79 Mass percentage Magnesium stearate 2.24 Mass percentage 1st coating 0.89 Mass percentage Second coating 3.43 Mass percentage Tablet Total 100.0 Mass percentage

Raw material name Purpose of blending amount unit Polyvinyl alcohol Coating 56.623 Mass percentage Titanium oxide Coloring agent (pigmentation) 8.153 Mass percentage Yellow iron oxide Coloring agent (pigmentation) 2.193 Mass percentage Glycerol monocaprylocaprate Coating 0.522 Mass percentage Sodium lauryl sulfate Coating 0.196 Mass percentage Black iron oxide Coloring agent (pigmentation) 0.001 Mass percentage

Comparative example  5

Commercially available tablets (Preparation: Prime Pharmaceutical) were used as tablets of Comparative Example 5.

Test example

Test example  1 Evaluation of long-term storage conditions

The prepared tablets were evaluated for long-term storage conditions. When left at 25 ° C and 60% relative humidity, a phenomenon in which the symptoms of water condensation on the tablet surface worsened (ie, deliquescent and / or hygroscopic) was observed. In order to evaluate the possibility of blocking the deliquescent / hygroscopicity, a time point in which the property is inappropriately deformed in the case of using various film coating agents was confirmed. In Comparative Example 2, it was confirmed that the property was deformed in less than 9 hours, and in Comparative Example 1, when coated with Opadry 88A620001, stability was improved compared to Comparative Example 2, but the property was inappropriately modified in less than 23 hours. Was confirmed. The two-layer coated tablets of Examples 1 to 4 can be confirmed that the properties are more stable than the one-layer coated tablets or the two-layer coated tablets of Comparative Examples 1 to 3, and in particular, the two-layer coated tablets of Example 1 are It was confirmed that the properties did not deform until 7 days (see [Table 12] results).

Long-term test storage conditions (temperature 25 ℃ ± 2 ℃ / relative humidity 60% ± 5%) Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Early 9 hours ● ● 23 hours ● 70 hours ● 73 hours ● 80 hours ● 7 days ●

※ ● When the tablet bursts

The stability test results after 80 hours under the above long-term conditions (temperature 25 ℃ ± 2 ℃ / relative humidity 60% ± 5%) are as shown in FIG. 2 below.

Test example  2. Dissolution rate test

Comparative dissolution test results in pH 1.2 eluate, the standard for pharmaceutical equivalence in Korea, are shown in Table 13 below. On the other hand, in order to compare the dissolution pattern and the dissolution rate, the data in Table 13 below is shown graphically in FIG. 1. It was confirmed that the tablets of Comparative Example 5 had a low initial dissolution rate, whereas the tablets of Examples of the present application had a high initial dissolution rate.

Test solution Test group Average dissolution rate (%) (mean ± standard deviation) 5 minutes 10 minutes 15 minutes 30 minutes pH1.2 Example 1 25.9 ± 3.3 55.2 ± 5.1 77.7 ± 5.9 99.8 ± 1.0 Example 2 28.8 ± 4.1 58.1 ± 7.0 80.4 ± 8.2 99.7 ± 0.7 Example 3 22.4 ± 4.7 53.4 ± 5.5 78.2 ± 6.1 101.3 ± 1 Example 4 25.8 ± 3.0 58.4 ± 3.8 81.1 ± 6.0 98.1 ± 0.8 Comparative Example 5 13.1 ± 1.5 34.7 ± 8.3 64.5 ± 9.3 97.1 ± 3.3

Test example  3. In the secondary coating Talc  Confirmation of coating properties depending on the use

Tablets of Comparative Example 4 were prepared to compare the coating process problems and tablet stability when talc was excluded from the second coating agent Opadry AMBII 88A620001 of Example 1 among the tablets. When the second coating was performed except for talc, a picking phenomenon occurred in the tablet during the coating process, resulting in a problem that the tablet surface was not coated evenly. Pictures after the second coating of the tablets of Example 1 and Comparative Example 4 tablets are shown in FIG. 3.

Claims (15)

A tablet containing choline alfoscerate and a pharmaceutically acceptable additive;
A primary coating layer containing polyvinylpyrrolidone on the tablet; And
A two-layer coated tablet comprising a second coating layer comprising polyvinyl alcohol and talc on the first coating layer.
According to claim 1, The weight ratio of the primary coating layer and the secondary coating layer is 1: 2 to 1: 6, two-layer coating tablets.
The two-layer coated tablet of claim 1, wherein the pharmaceutically acceptable additive is selected from one or more of excipients, disintegrants, lubricants, binders, or plasticizers.
The two-layer coated tablet according to claim 3, comprising both polyethylene glycol and microcrystalline cellulose.
According to claim 1, The polyvinylpyrrolidone is 80% by weight or more based on the weight of the primary coating layer, the two-layer coating tablets.
According to claim 1, The polyvinyl alcohol and talc is 50% by weight or more based on the weight of the secondary coating layer, two-layer coating tablets. The two-layer coated tablet of claim 1, wherein the primary coating layer further comprises talc.
According to claim 1, The weight ratio of the polyvinyl alcohol and talc is 7: 3 to 3: 7, two-layer coating tablets.
Choline alfoscerate and a pharmaceutically acceptable additive are mixed and compressed into tablets to obtain uncoated tablets,
A primary coating solution is prepared by dissolving polyvinylpyrrolidone in an alcoholic aqueous solvent,
The primary coating solution is first coated onto the bare tablet,
A second coating solution is prepared by dissolving polyvinyl alcohol and talc in a non-alcoholic aqueous solvent,
A method of manufacturing a two-layer coated tablet comprising coating a second layer with the second coating solution on the first coating.
10. The method of claim 9, wherein the production of the tablet further comprises the production of dry granules or wet granules.
The method of claim 9, wherein the polyvinylpyrrolidone in the primary coating solution is contained in an amount of 30% by weight or less.
The method of claim 9, wherein the polyvinyl alcohol and talc in the secondary coating solution are 5% to 20% by weight.
The method of claim 9, wherein the secondary coating solution comprises an additional coating agent. The method according to claim 13, wherein the additional coating agent is at least one of glycerol monocaprylocaprate, sodium lauryl sulfate, polyethylene glycol, or HPMC.
The method according to claim 9, wherein the weight ratio of the polyvinyl alcohol and talc is 7: 3 to 3: 7.

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