KR101826994B1 - Composition containing ascorbic acid for oral administration with controlled release property and method of analyzing the same - Google Patents

Abstract

The present invention relates to an ascorbic acid-containing sustained-release tablet composition capable of constantly and continuously maintaining the blood concentration of ascorbic acid once or twice daily. The composition of the present invention is characterized by containing a high viscosity hydroxypropylmethylcellulose to control the release of the active drug.
In addition, the present invention provides an analytical method capable of performing a dissolution test of sustained release by stabilizing ascorbic acid eluted in an eluent in the course of analyzing an ascorbic acid-containing tablet composition, and an eluent used therefor.

Description

[0001] The present invention relates to a controlled-release oral ascorbic acid-containing oral tablet composition and its analytical method,

The present invention relates to an oral tablet composition having controlled release properties containing ascorbic acid and an analytical method thereof. The ascorbic acid-containing tablet composition of the present invention comprises a release-controlling polymer for controlled release, and in the course of its analysis, an antioxidant that delays or suppresses the oxidation of ascorbic acid to secure the stability of ascorbic acid Provides analysis methods to use.

Ascorbic acid is a known compound having the following structural formula and is used for the prevention and treatment of scurvy and is useful for the prevention or treatment of consumable diseases in which the requirement of ascorbic acid is increased such as physical strength loss during pregnancy, Is used. It is also used for the treatment of ascorbic acid deficiency due to capillary hemorrhage such as gum bleeding, non-hemorrhage, hematuria, and pigmentation (spots and freckles) due to sunlight and skin diseases and malabsorption. In addition, ascorbic acid acts as an antioxidant, such as vitamin E, beta-carotene, to prevent damage to the body caused by the body's active oxygen (which promotes senescence and affects health such as cancer, heart disease and arthritis) It plays a role.

[Chemical Formula 1]

L-Ascorbic acid is a chemical name for vitamin C, which is white crystalline and structurally linked to a monosaccharide. In the natural world, there are two types of L-ascorbic acid, which is reduced form, and dehydroascorbic acid, which is oxidized form. These two substances are reversible and physiological activities are the same.

Ascorbic acid reaches its peak blood concentration 30 minutes after intravenous injection, and excreted ex vivo after 4 hours in the urine and respiratory tract. Therefore, absorption at regular intervals is most important for maintaining blood concentration. When administered orally, it is absorbed through the mucous membranes of the digestive tract such as the mouth, stomach, small intestine and the like.

Ascorbic acid exhibits a variety of clinical features, including: 1) It is an essential ingredient in the synthesis of collagen (collagen - a protein in the body), an important component of blood vessels, muscles, ligament bones, Scurvy (collagen tissue collapse between cells, bleeding at the pressure applied - subcutaneous tissue pressure drops as the capillary wall weakens and breaks) - there are fibroblasts between cells and cells, There is no collagen fiber. When ascorbic acid is administered, collagen is produced within a few hours. 2) Ascorbic acid is closely related to tooth structure, bone formation, and normal retention of capillary walls. Therefore, when ascorbic acid is deficient, bones are broken and growth is stopped. In normal tissues, calcified cartilage is replaced with connective tissue, and anemia occurs due to poor hematopoiesis. 3) Ascorbic acid also affects the absorption of iron, which changes the structure of the dentin part of the teeth, causing the gums to sponge and bleed. 4) It strengthens connective tissues between cells and cells to accelerate wound and burn healing, and maintains a constant heart rate by constantly activating the arterial blood vessel walls, and it has the effect of improving peripheral blood vessels which are easily damaged. 5) It is involved in the synthesis of norepinephrine, a neurotransmitter. This neurotransmitter is an essential component for brain function. 6) It is involved in the synthesis of carnitine. This protein carries the role of carnitine as it moves from cell tissue to mitochondria to convert fat into energy. 7) As an antioxidant, ascorbic acid may reduce progression of arteriosclerosis. It prevents the risk from LDL cholesterol and gives arterial blood vessel flexibility. It is involved in the metabolism of cholesterol into bile acid, which affects blood cholesterol regulation and gallstones and digestibility.

In the modern world, there are not many serious deficiencies of ascorbic acid, but most people have weak deficits. Smoking decreases the amount of ascorbic acid in the body and increases the risk of deficiency. Dryness and damage of the scalp, gingivitis, gum bleeding, dry skin, scaly skin, reduced wound healing rates, nosebleeds, bruises and decreased resistance to infection in the body. Low intake of ascorbic acid is associated with hypertension, cholelithiasis, stroke, cancer and atherosclerotic disease, and regular intake of ascorbic acid may reduce this risk.

According to the recommended dietary allowances (RDA) for ascorbic acid, adult daily intake is 90 mg for men and 75 mg for women, 120 mg for breast-feeding women and 35 mg for smokers. However, the above amounts are the minimum intakes. In order to prevent and treat diseases, absorption rate and loss amount are different for each person, but the recommended recommended daily dose is about 500 to 1000 mg per day. However, the higher the dose, the lower the absorption rate, so that absorption at a constant time interval is most important for maintaining the blood concentration. However, taking a small amount of ascorbic acid continuously at regular intervals to absorb about 500-1000 mg of ascorbic acid per day may cause inconvenience in compliance with the medication, and is practically impossible. In addition, taking a high dose of ascorbic acid in consideration of the actual absorption rate can lead to overeating and it can also lead to economic loss.

Ascorbic acid is stable under dry conditions but easily oxidized in humid environments. Oxidation is accelerated by heat, light, alkaline substances, copper and zinc, oxidizing enzymes, and so on. Also, because it is soluble, it is likely to be lost when exposed to moisture, and may be lost even in the storage of fresh fruits and vegetables.

The present invention seeks to provide an ascorbic acid-containing sustained-release tablet composition having controlled release properties, wherein the blood concentration of ascorbic acid can be kept constantly constant by once or twice daily administration.

The present invention also provides a method for stably analyzing the elution amount of an effective drug by preventing the oxidation of ascorbic acid during the analysis of the sustained-release tablet composition containing ascorbic acid.

The present invention relates to a pharmaceutical composition comprising 40 to 70% by weight of ascorbic acid, 10 to 30% by weight of hydroxypropylmethylcellulose having a high viscosity as a release controlling polymer, 10 to 30% by weight of an excipient, 3 to 7% % Of an oral ascorbic acid-containing tablet composition.

Preferably, the high viscosity hydroxypropyl methylcellulose has a viscosity of from 4,000 cps to 200,000 cps.

Preferably, the binder is hydroxypropylmethylcellulose having a viscosity of from 4 cps to 10 cps.

Preferably, the excipient is at least one selected from lactose, mannitol and microcrystalline cellulose.

Preferably, the lubricant is one or a mixture of two or more selected from the group consisting of silicon dioxide, talc, stearic acid, and magnesium stearate.

Preferably, the ascorbic acid is in powder form or granular form.

According to another embodiment of the present invention, the above ascorbic acid-containing sustained-release tablet composition is eluted into an elution solution containing at least one antioxidant selected from sodium sulfite, sodium hypophosphite, potassium pyrosulfite and sodium pyruvate, A method of analyzing an ascorbic acid-containing sustained-release tablet composition is provided.

Preferably, the antioxidant is used in an amount of 0.03 to 1.5% by weight based on the eluent.

According to another embodiment of the present invention, there is provided an ascorbic acid-containing sustained-release tablet characterized by comprising 0.03 to 1.5% by weight of at least one antioxidant selected from sodium sulfite, sodium hypophosphite, potassium pyrosulfite and sodium pyrosulfite An eluate for the analysis of the composition is provided.

The sustained-release pharmaceutical composition according to the present invention exhibits a zero-order release pattern irrespective of the gastro-intestinal peristaltic movement in the release of an effective drug, and can maintain a constant effective drug concentration by continuously maintaining an effective blood concentration.

The composition of the present invention has an effect of improving the convenience of taking by ascorbic acid in the body by increasing the rate of ascorbic acid in the body by taking twice a day or once a day with an ascorbic acid content of 500 mg to 1000 mg.

Further, according to the present invention, it is possible to easily analyze the dissolution rate by stabilizing the unstable ascorbic acid component in the dissolution test of the sustained-release tablet composition containing ascorbic acid.

Fig. 1 shows the results of analysis performed in Examples 2-1 to 2-4 of the present invention.
Fig. 2 shows the results of the analyzes conducted in Examples 2-5 to 2-7 of the present invention and in Examples 2-3 for comparison.
FIG. 3 shows the results of the analyzes performed in Examples 2-3 and 2-9 of the present invention and in Examples 2-3.
FIG. 4 shows the results of the analyzes performed in Examples 3-1 to 3-3 of the present invention and in Example 2-3 for comparison.
Fig. 5 shows the results of the analysis performed in Comparative Example 1, Comparative Example 2 and Example 2-3 for comparison.

The present invention relates to an ascorbic acid-containing sustained-release tablet composition capable of exhibiting an effect of sustained absorption of ascorbic acid.

To this end, the tablet composition of the present invention contains 40 to 70% by weight of ascorbic acid, 10 to 30% by weight of release-controlling polymer, 10 to 30% by weight of excipient, 3 to 7% by weight of binder and 0.5 to 2% . In the present invention, hydroxypropylmethylcellulose having a high viscosity is preferably used as a polymer for emission control. Hydroxypropylmethylcellulose (HPMC) is a compound represented by the following general formula (1), in which H, -CH ₃ and -CH ₂ CH (CH ₃ ) OH are substituted with a substituent R to cellulose which is a main chain.

[Chemical Formula 1]

The high viscosity hydroxypropyl methylcellulose has a relatively long dissolution time and can be controlled at a relatively constant dissolution rate as compared with general release control polymers such as methyl cellulose and polyvinyl acetate.

The controlled release system of the present invention using high viscosity hydroxypropyl methylcellulose as a release controlling polymer is a drug release control system by corrosion of the matrix.

In other words, hydroxypropylmethylcellulose is a water-soluble polymer having the property of absorbing water to form a gel after swelling. As the gel becomes thicker, the gel layer becomes thicker. As a result, the drug dissolves through this layer and the drug is liberated through a constant speed diffusion mechanism . Thus, controlling the viscosity of hydroxypropylmethylcellulose is a means of controlling release. The hydroxypropylmethylcellulose used in the present invention has a viscosity of 4,000 cps to 200,000 cps and a viscosity of 90,000 cps to 110,000 cps.

On the other hand, when the gel which can be expressed in hydroxypropylmethylcellulose reaches a certain level, the gel layer begins to erosion (erosion). When the amount of hydroxypropylmethylcellulose is increased, erosion starts later. This means that the effect of the diffusion mechanism is increased, and the emission control effect can be taken longer. In the present invention, high viscosity hydroxypropyl methylcellulose is preferably used in an amount of 10 to 30% by weight based on the weight of the tablet composition. Addition of less than 10% by weight of high viscosity hydroxypropylmethylcellulose results in a rapid drug dissolution rate, and if added in an amount of more than 30% by weight, there is a problem of increasing the total weight of the composition.

In the present invention, hydroxypropylmethylcellulose having a high viscosity is preferably used as a release-controlling polymer, and hydroxypropylmethylcellulose having a low viscosity is used as a binder.

The viscosity of hydroxypropylmethylcellulose used as a binder is preferably 4 to 10 cps, more preferably 4 cps, and is used in an amount of 3 to 7% by weight of the composition. When less than 3% by weight of low-viscosity hydroxypropyl methylcellulose is added, tableting is difficult to be performed due to a weak binding force, and when the binder is added in an amount of more than 7% by weight, a swollen state occurs on the tablet surface.

The excipient serves to improve the ease of tableting and maintain the tablet form. As the excipient, at least one selected from lactose, mannitol and microcrystalline cellulose is used. In the present invention, the three excipients are mixed with hydroxypropylmethylcellulose having a high viscosity so that ascorbic acid and hydroxypropylmethylcellulose can be uniformly mixed. The excipient is preferably added in an amount of 10 to 30% by weight based on the weight of the oral tablet composition containing ascorbic acid. When the excipient is used in an amount of less than 10% by weight of the composition, it is difficult to uniformly mix hydroxypropylmethylcellulose and ascorbic acid having a high viscosity, and the mixture may not exhibit proper binding force during tablet preparation to cause capping If it is used in an amount exceeding 30% by weight, there is a problem that the total weight of the composition increases.

The lubricant improves the fluidity of the powder and increases the filling of the die, which is the lower part of the tablet machine. The friction between the powder and the punch-die, which is the upper part of the powder and granulator, To facilitate compression and release of the tablet. As such a lubricant, one or a mixture of two or more selected from the group consisting of silicon dioxide, talc, stearic acid and magnesium stearate is used. The lubricant is preferably added in an amount of 0.5 to 3% by weight based on the weight of the tablet composition. When the lubricant is added in an amount of less than 0.5% by weight, tableting of the tablets becomes difficult. When the lubricant is added in an amount of more than 3% by weight, the binding force is weakened and capping phenomenon occurs. This is because it affects the dissolution profile.

On the other hand, in order for the sustained-release formulation to maintain its effective blood concentration continuously for more than 12 hours in vivo, a certain release and absorption should occur in the digestive tract, in vitro) should be representative of the 0th emission pattern. Also, referring to the Guideline for dissolution of oral medicines, which is presented by the KFDA as a guideline, the timing of dissolution of the sustained - release formulation is selected as the point at which more than 80% of the effective drug is eluted.

In the composition of the present invention, as the 0th-order emission pattern, ascorbic acid which is an effective drug elutes at least 80% at the time of 13 hours.

The present invention relates to a method for analyzing an ascorbic acid-containing sustained-release tablet composition, which accurately estimates the dissolution rate of ascorbic acid from the sustained-release tablet composition using an antioxidant so as to prevent oxidation of ascorbic acid in the eluent of the tablet composition . ≪ / RTI >

Ascorbic acid is easily oxidized by moisture, heat, light, alkaline substance, copper or zinc, oxidizing enzyme, etc., and proper pretreatment is required for analysis. In the elution test from the commercially available ascorbic acid tablet sold in the market, the elution is completed within about 1 hour, so the quantitative analysis can be performed before the reduction type ascorbic acid is oxidized. However, as in the present invention, In the case of sustained release formulations that require testing, the stability of ascorbic acid in the effluent must be ensured. To this end, the present invention provides a method for analyzing an ascorbic acid-containing sustained-release pharmaceutical composition characterized by securing stability using an antioxidant capable of preventing oxidation of ascorbic acid in an effluent.

As the antioxidant, those selected from sodium sulfite, sodium hypophosphite, potassium pyrosulfite and sodium pyrophosphate are used. The antioxidant is preferably added in an amount of 0.03 to 1.5% by weight based on the weight of the eluant of the tablet composition. When the antioxidant is added in an amount less than 0.03% by weight, oxidation of ascorbic acid can not be prevented. When the antioxidant is added in an amount exceeding 1.5% by weight, the structure of ascorbic acid is deformed due to the acid base reaction in the eluent, Because.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, these embodiments are not intended to limit the scope of the present invention.

≪ Examples 1-1 to 1-9 >

Preparation of a composition comprising a release-controlling polymer

Powdered ascorbic acid (DSM) was prepared by homogenizing particles with a 40 mesh sieve, and then hydroxypropyl methylcellulose (Samsung Fine Chemicals) as a release controlling polymer, microcrystalline cellulose (FMC biopolymer) as an excipient, low molecular weight hydroxypropylmethylcellulose (Samsung Fine Chemicals) were mixed well, magnesium stearate (BASF) was further added as a lubricant, and the mixture was compressed into tablets according to the weight per tablet.

(1) Viscosity control of polymer for emission control

As shown in Table 1, ascorbic acid-containing sustained-release tablet compositions (Examples 1-1 to 1-4) were prepared by varying the viscosity of hydroxypropylmethylcellulose used as a release-controlling polymer.

Classification ingredient Example 1-1 Examples 1-2 Example 1-3 Examples 1-4 content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) Active ingredient L-ascorbic acid 500 62.5 500 62.5 500 62.5 500 62.5 Emission control
Polymer Hydroxypropylmethyl
cellulose
(4,000 cps) 120 15.0 - - - - - - Hydroxypropylmethyl
cellulose
(15,000 cps) - - 120 15.0 - - - - Hydroxypropylmethyl
cellulose
(100,000 cps) - - - - 120 15.0 - - Hydroxypropylmethyl
cellulose
(200,000 cps) - - - - - - 120 15.0 Binder Hydroxypropylmethyl
Cellulose (4 cps) 40 5.0 40 5.0 40 5.0 40 5.0 Excipient Microcrystalline cellulose 132 16.5 132 16.5 132 16.5 132 16.5 Lubricant Magnesium stearate 8 1.0 8 1.0 8 1.0 8 1.0 1 Total weight 800 100 800 100 800 100 800 100

(2) Control of the amount of polymer used for emission control

Next, ascorbic acid-containing sustained-release tablet compositions (Examples 1-5 to 1-7) were prepared by varying the amount of hydroxypropylmethylcellulose having a viscosity of 100,000 cps for release control as shown in Table 2 below.

Classification ingredient Examples 1-5 Example 1-3 Examples 1-6 Examples 1-7 content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) Pharmacological
Active ingredient L-ascorbic acid 500 62.5 500 62.5 500 62.5 500 62.5 Emission control polymer Hydroxypropylmethyl
cellulose
(100,000 cps) 80 10.0 120 15.0 160 20.0 240 30.0 Binder Hydroxypropylmethyl
Cellulose (4 cps) 40 5.0 40 5.0 40 5.0 40 5.0 Excipient Microcrystalline cellulose 172 21.5 132 16.5 92 11.5 12 1.5 Lubricant Magnesium stearate 8 1.0 8 1.0 8 1.0 8 1.0 1 Total weight 800 100 800 100 800 100 800 100

(3) Types of excipients

Next, ascorbic acid-containing sustained-release tablet compositions (Examples 1-8 and 1-9) were prepared with different excipients as shown in Table 3 below.

Classification ingredient Example 1-3 Examples 1-8 Examples 1-9 content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) content
(mg) Content ratio
(%) Pharmacological
Active ingredient L-ascorbic acid 500 62.5 500 62.5 500 62.5 Emission control
Polymer Hydroxypropylmethyl
cellulose
(100,000 cps) 120 15.0 120 15.0 120 15.0 Binder Hydroxypropylmethyl
Cellulose (4 cps) 40 5.0 40 5.0 40 5.0 Excipient Microcrystalline cellulose 132 16.5 - - - - Lactose - - 132 16.5 - - Mannitol - - - - 132 16.5 Lubricant Magnesium stearate 8 1.0 8 1.0 8 1.0 1 Total weight 800 100 800 100 800 100

≪ Examples 2-1 to 2-9 >

Analysis of ascorbic acid purification compositions - Na ₂ SO ₃ ≪ / RTI >

Each of the ascorbic acid sustained-release tablet compositions prepared in Examples 1-1 to 1-9 was subjected to a dissolution test using an eluent containing Na ₂ SO ₃ .

An aqueous Na ₂ SO ₃ solution at a concentration of 0.05 w / w% was used as the eluent. The paddle method was used for the elution, the eluent was 900 ml, the stirring speed was 50 rpm, and the elution temperature was 37 ± 0.5 ° C. 3 mL of the sample solution was taken at 1, 3, 5, 7, 10, 13 and 24 hours after the start of the dissolution test and the same amount of the eluate was added and mixed.

The dissolution rate of the obtained mixed solution was analyzed by the following method.

(1) Assay using HPLC

The mixture was filtered through a 0.45 ㎛ membrane filter, and ascorbic acid was quantified by HPLC using a 1: 1 dilution with 10% metaphosphoric acid solution. The analytical wavelength was 254 nm and the mobile phase was a mixture of 0.05 M KH ₂ PO ₄ : acetonitrile (60:40) and octadecylsilylated column.

(2) Analysis using UV

The mixture was filtered with a 10.0 ㎛ probe filter and diluted 30 times with purified water. The ascorbic acid was quantitated at 260 nm of the analytical wavelength using UV.

The results of the analysis are shown in Tables 4 to 6 and Figs.

time Dissolution rate (%) Example 2-1 Example 2-2 Example 2-3 Examples 2-4 1 hr 21.11 21.40 17.60 16.53 3 hr 44.52 42.16 39.99 39.76 5 hr 58.41 55.19 52.97 51.56 7 hr 70.34 68.62 65.84 64.61 10 hr 84.48 83.86 79.69 79.44 13 hr 93.64 93.67 87.84 87.35 24 hr 97.16 97.11 97.23 97.15

Referring to Table 4 and FIG. 1, as the viscosity of the polymer for emission control increases, the release property is shown. This is because, as described above, ascorbic acid dissolves as the viscosity of hydroxypropylmethylcellulose, which is a release-controlling polymer, becomes higher, and the gel layer, in which a diffusion mechanism at a constant rate is formed, becomes thicker.

time Dissolution rate (%) Example 2-5 Example 2-3 Examples 2-6 Examples 2-7 1 hr 20.62 17.60 16.70 16.12 3 hr 42.57 39.99 36.92 34.04 5 hr 57.48 52.97 49.07 45.80 7 hr 70.25 65.84 62.45 58.22 10 hr 85.46 79.69 76.85 71.03 13 hr 92.45 87.84 85.01 80.59 24 hr 97.43 97.23 96.84 96.64

Referring to Table 5 and FIG. 2, as the use of the polymer for emission control increases, the release property is shown. As described above, when the amount of hydroxypropylmethylcellulose is increased, the corrosion of the matrix is delayed and the release control effect can be prolonged.

time Dissolution rate (%) Example 2-3 Examples 2-8 Examples 2-9 1 hr 17.60 15.12 17.43 3 hr 39.99 36.77 40.56 5 hr 52.97 52.76 54.65 7 hr 65.84 63.76 67.45 10 hr 79.69 76.72 81.65 13 hr 87.84 86.77 89.84 24 hr 97.23 96.98 98.70

Referring to Table 6 and FIG. 3, there was almost no difference in dissolution rate depending on the type of excipient.

≪ Examples 3-1 to 3-3 >

Analysis of ascorbic acid purification composition - pH  adjustment

The dissolution test according to pH was carried out on the ascorbic acid-containing sustained-release tablets prepared in Example 1-3.

An aqueous solution of 0.1 w / w% Na ₂ SO ₃ of pH 1.2 (disintegration test method 1), pH 6.8 (disintegration test method 2 solution) described in the pharmacopoeial dissolution test described in the dissolution solution and 1.0 w / w% Na ₂ SO ₃ aqueous solution was used in place of the aqueous solution of the sample solution and the elution solution.

The dissolution rate of the obtained mixed solution was analyzed by the following method.

(1) Assay using HPLC

The mixture was filtered through a 0.45 ㎛ membrane filter, and ascorbic acid was quantified by HPLC using a 1: 1 dilution with 10% metaphosphoric acid solution. The analytical wavelength was 254 nm and the mobile phase was a mixture of 0.05 M KH ₂ PO ₄ : acetonitrile (60:40) and octadecylsilylated column.

(2) Analysis using UV

In the eluent of pH 1.2, the resulting mixture was filtered through a probe filter of 10.0 ㎛ and diluted 20 times with purified water. The ascorbic acid was quantitatively analyzed by UV at 244 nm.

In the eluent of pH 4.0, the resulting mixture was filtered through a 10.0 ㎛ probe filter and diluted 30 times with purified water. The ascorbic acid was quantitatively analyzed by UV at 264 nm.

In the eluate of pH 6.8, the obtained mixture was filtered with a probe filter of 10.0 ㎛, diluted 30 times with purified water, and ascorbic acid was quantified by UV at an analysis wavelength of 266 nm.

The results of the analysis are shown in Table 7 and FIG.

time Dissolution rate (%) Example 2-3 Example 3-1
(pH 1.2) Example 3-2
(pH 4.0) Example 3-3
(pH 6.8) 1 hr 17.60 21.82 22.22 17.77 3 hr 39.99 41.76 42.51 41.14 5 hr 52.97 57.24 54.48 54.29 7 hr 65.84 67.91 66.04 68.22 10 hr 79.69 82.18 78.61 82.57 13 hr 87.84 88.22 86.72 90.92 24 hr 97.23 93.79 93.54 96.58

Referring to Table 7 and FIG. 4, the dissolution rates were almost similar regardless of the pH of the eluate until 13 hours, which is the time point when the elution was terminated.

≪ Comparative Example 1 &

Preparation and analysis of purification compositions without release control polymer

As shown in Table 8 below, an ascorbic acid-containing sustained-release tablet composition containing no hydroxypropyl methylcellulose as a release-controlling polymer was prepared.

Classification ingredient Content (mg) Content ratio (%) Pharmacologically active ingredient L-ascorbic acid 500 62.5 Binder Hydroxypropylmethylcellulose (4 cps) 40 5.0 Excipient Microcrystalline cellulose 252 16.5 Lubricant Magnesium stearate 8 1.0 1 Total weight 800 100

Then, the dissolution rates were evaluated in the same manner as in Examples 2-1 to 2-9, except that the sample solution was taken at 15, 30, 60 and 90 minutes after the start of the dissolution test, and the results are shown in Table 9 and FIG. .

≪ Comparative Example 2 &

Analysis of ascorbic acid purification compositions - Na ₂ SO ₃ Use of an effluent that does not contain

The same procedure as in Examples 2-1 to 2-9 was repeated except that water for general dissolution test without addition of Na ₂ SO ₃ as the eluent was used for the ascorbic acid sustained-release tablets prepared in Example 1-3. The results are shown in Table 9 and FIG. 5 below.

time Dissolution rate (%) Comparative Example 1 Comparative Example 2 Example 2-3 0.25 hr 42.78 - - 0.5 hr 58.27 - - 1 hr 79.50 17.64 17.60 1.5 hr 97.13 - 3 hr - 39.47 39.99 5 hr - 52.94 52.97 7 hr - 65.61 65.84 10 hr - 51.50 79.69 13 hr - 20.85 87.84 24 hr - 0.00 97.23

Referring to Table 9 and FIG. 5, in the tablet composition of Comparative Example 1 which did not contain the release-controlling polymer of the present invention, the dissolution rate reached almost 80% after 1 hour of the dissolution test, Respectively.

In order to secure the stability of ascorbic acid, in Comparative Example 2 using Na ₂ SO ₃ -free eluate as compared with Example 2-3, which was analyzed with an elution solution containing Na ₂ SO ₃ as an antioxidant, elution test for 24 hours The dissolution rate of 90% or more was not measured, and oxidation of ascorbic acid occurred from about 6 hours after the start of the dissolution test, and the analysis became impossible.

Claims (9)

10 to 30% by weight of high viscosity hydroxypropylmethylcellulose having a viscosity of 4,000 cps to 200,000 cps as a release controlling polymer, 10 to 30% by weight of an excipient, 4 to 10 cps By weight of hydroxypropylmethylcellulose having a viscosity of 3 to 7% by weight and a lubricant of 0.5 to 2% by weight based on the total weight of the tablet. delete delete The method of claim 1,
Wherein the excipient is at least one selected from lactose, mannitol and microcrystalline cellulose. The method of claim 1,
Wherein the lubricant is one or a mixture of two or more selected from the group consisting of silicon dioxide, talc, stearic acid, and magnesium stearate. The method of claim 1,
Wherein the ascorbic acid is in the form of a powder or a granule. delete delete delete

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