KR101485421B1 - Controlled-release Oral Drug Preparations and it's Manufacturing Process Containing Itopride Hydrochloride - Google Patents

Abstract

The present invention relates to a method for preparing a sustained-release tablet containing itopride hydrochloride as an active substance. More specifically, the present invention relates to a method for preparing a sustained release tablet containing itopride hydrochloride as an active substance, And provides a sustained release that can improve compliance.
The Ito-Pride sustained-release tablet according to the present invention can effectively control the release of itopride hydrochloride for 24 hours at a rate close to zero order without leaning deviation, thereby solving the inconvenience of eating three times a day once per day , Since the tablet size is small because the weight per tablet is 450 mg, the loss of medicinal efficacy and deterioration of symptoms can be prevented because the patient's compliance with the medicines is high.

Description

FIELD OF THE INVENTION [0001] The present invention relates to controlled release oral formulations containing itopride hydrochloride,

The present invention relates to a method for preparing a sustained-release tablet containing itopride hydrochloride as an active substance. More specifically, the present invention relates to a method for preparing a sustained release tablet containing itopride hydrochloride as an active substance, And provides a sustained release that can improve compliance.

Ito pride hydrochloride (N - [[4- (2-dimethylaminoethoxy) phenyl] methyl] -3,4-dimethoxybenzamide) inhibits acetylcholine esterase and antagonizes dopamine D2 receptor To increase the amount of acetylcholine, and this acetylcholine promotes gastrointestinal peristalsis, which is a drug used for digestive symptoms due to functional dyspepsia, abdominal bloating, abdominal pain, anorexia, chest pain, and vomiting. This drug is a peripheral selective dopamine D2 antagonist that has the advantage of being suitable for long-term use because it has little side effects such as gynecomastia and lactation secretion, which are side effects of gastrointestinal function improvers such as Dom Peridone.

Itopride Hydrochloride (N - [[4- (2-Dimethylaminoethoxy) phenyl] methyl] -3,4-dimethoxybenzamide has a time of 30 minutes or less when administered orally, ~ 1.5 hours, and the duration is about 12 hours. The Ito Pride is known to elicit about 80% of its urine when administered orally, and its excretion rate (half-life) is known to be about 6 hours.

Despite the fact that patients with poor digestive function have to take long-term use due to the frequent occurrence of symptoms due to stress, development has not yet been made into a form that can be taken once a day. Thus, patients taking long-term use of Itopride And may lead to inconvenience in the administration of the medication and compliance with the medication. The present invention can help prevent the loss of medicinal properties and the deterioration of symptoms by allowing the patient to take the medication once per day by allowing the preparation to take itfridide hydrochloride three times a day to be sustained.

The present invention is characterized by a matrix tablet comprising itopride hydrochloride as an active ingredient. The drug is administered in a dose of 150 mg once a day for 24 hours, The present invention provides a sustained-release tablet containing itopride hydrochloride which improves the convenience of medication and compliance of the patient by simplifying the formulation therapy of patients with gastrointestinal diseases by effectively controlling the release of the drug so as to be sustained.

According to a preferred embodiment of the present invention, in the itopride hydrochloride sustained release comprising itopride hydrochloride, water-soluble additive, disintegrant, filler, release controlling polymer and glidant, the release controlling polymer is hydroxypropylmethylcellulose Itopride Hydrochloride is characterized by a sustained release.

According to another preferred embodiment of the present invention, the weight ratio of the hydroxypropylmethylcellulose is preferably 10% to 45% of the total weight.

According to another preferred embodiment of the present invention, the disintegrant is selected from the group consisting of Croscamellose Sodium, Sodium Starch Glycolate, Pregelatinized Starch (Starch 1500 or Premojel) , Microcrystalline cellulose, crospovidone (cross-linked povidone), polyvinylpyrrolidone (PVP), povidone, low substituted hydroxypropylcellulose (Low substituted), alginic acid calcium carbonate and sodium salt of carboxymethylcellulose, fumed silica, colloidal silica, guar gum, magnesium aluminum silicate, methylcellulose, One or two selected from the group consisting of powdered cellulose, starch, and sodium alginate. And more thereof, wherein the filler is one or a mixture of two or more selected from microcrystalline cellulose, gyeoljil silicic acid anhydride, the group consisting of before the gelling starch and lactose and the lubricant is magnesium stearate (magnesium stearate), silica oxide (SiO ₂₎ , Colloidal silicon dioxide, colloidal silica, and talc.

According to another preferred embodiment of the present invention, it is preferable that the dissolution rate of the sustained-release tablet shows elution of 10 to 30% in 1 hour, 55 to 75% in 12 hours, and 85% or more in 24 hours.

The Ito-Pride sustained-release tablet according to the present invention can effectively control the release of itopride hydrochloride for 24 hours at a rate close to zero order without leaning deviation, thereby solving the inconvenience of eating three times a day once per day , Since the tablet size is small because the weight per tablet is 450 mg, the loss of medicinal efficacy and deterioration of symptoms can be prevented because the patient's compliance with the medicines is high.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows the results of a dissolution test (eluent: purified water) of the preparations described in Examples 1 to 10 of the present invention.
Fig. 2 shows the results of the dissolution test (effluent: purified water) of the preparations described in Comparative Examples 1 to 2 and Example 10 of the present invention.
Fig. 3 shows the results of the scratch test of the preparations described in Examples 1 to 10 of the present invention.
4 shows results of hardness tests of the preparations described in Examples 1 to 10 of the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. However, the embodiments according to the present invention can be modified in various forms, and the scope of the present invention is not limited to the embodiments described below. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

The present invention relates to an oral composition comprising an itopride hydrochloride (N - [[4- (2-dimethylaminoethoxy) phenyl] methyl] -3,4-dimethoxybenzamide which is a drug useful for treating gastrointestinal disorders, More particularly, the present invention relates to an oral sustained-release composition which exhibits a sufficient therapeutic effect by once-daily dosing of itopride hydrochloride at a constant rate for 24 hours, and which reduces the weight of tablets and increases ease of administration.

The itopride hydrochloride sustained-release tablet of the present invention has the advantage that the active ingredient can be slowly released at a release rate almost similar to that of the 0th dose by administration once a day, even though the biological activity is the same, I have.

The composition for sustained release tablets according to the present invention comprises 30% by weight of a pharmacologically active ingredient, itopride hydrochloride, 45% by weight of hydroxypropylmethylcellulose, 5% by weight of microcrystalline cellulose, 6% by weight of lactose, 5% by weight of low-substituted hydroxypropylcellulose %, 3% by weight of povidone, and 1% by weight of a lubricant.

In the composition of the present invention, the sustained-release base must form a hydrogel matrix so as to effectively release and control itopride hydrochloride having a very high water solubility, and have an appropriate viscosity range. Because of the 24-hour release control, the pH of the sustained-release system of patients should be adjusted so that the viscosity and release pattern of the sustained-release system change with pH. Hydroxypropyl methylcellulose is suitable as a sustained-release agent which satisfies the above conditions and is capable of controlling a relatively constant dissolution rate with a long elution time. When the viscosity of the composition of the present invention is 2% by weight aqueous solution of hydroxypropylcellulose and the viscosity is measured at 20 캜, when the viscosity is 80,000 cps or less, highly effective water-soluble iupofride hydrochloride is effectively released In case of 120,000 cps or more, hydroxypropylmethylcellulose having a viscosity in the range of 80,000 cps to 120,000 cps is suitable because the initial gel hydration time is delayed and the elution deviation increases.

Also, in the composition of the present invention, when hydroxypropylmethylcellulose is contained in an amount of less than 10% by weight based on the total composition, itopride hydrochloride having extremely high water solubility can not be effectively controlled to be released for 24 hours, It is preferable that 10 to 45% by weight of the total composition is contained.

In the composition of the present invention, it is preferable to use a binder in order to make the tablets preferably formed. In particular, it is very important to use a binder having an appropriate binding force because it is desirable to minimize the size and weight of the final sustained release agent and to minimize the amount of excipient added to the tablet in order to improve patient compliance with the medication. In the present invention, polyvinylpyrrolidone (commonly known as povidone and having a molecular weight of 30, povidone K-30 is used), which is preferably added in an amount of 3 to 5% by weight of the tablet, The addition of more than 5% by weight of the binding agent lowers the initial dissolution rate of the drug, and it is difficult to expect a quick effect after the administration of the drug.

In the compositions of the present invention, the disintegrant is used to absorb moisture and promote initial disintegration of the formulation and to facilitate dissolution of itopride hydrochloride, examples of disintegrants that may be used in the formulations of the invention include croscarmellose Sodium Starch Glycolate, Pregelatinized Starch (Starch 1500 or Premojel), microcrystalline cellulose, crospovidone (cross-linked), cross-linked povidone) and other commercially available polyvinylpyrrolidone (PVP, Povidone), and low substituted hydroxypropylcellulose (Low substituted).

Preferably, the disintegrant is at least one selected from the group consisting of croscarmellose sodium, sodium starch glycolate, pregelatinized starch, microcrystalline cellulose, crospovidone and commercially available low substituted hydroxypropylcellulose And mixtures thereof.

The lubricant in the present invention is characterized by being a mixture of at least one selected from the group consisting of silicon dioxide, stearic acid and magnesium stearate, and magnesium stearate is preferably used. The lubricant improves the fluidity of the powder to be refined to increase the filling of the tablet into the die and the friction between the powder and the punch-die, which is the upper part of the powder and the powder, To facilitate compression of the tablet. The lubricant is preferably added in an amount of 1 to 3% by weight based on the weight of the tablet. When the lubricant is added in an amount of less than 1% by weight, tableting becomes difficult. When the lubricant is added in an amount of more than 3% by weight, Which affects the dissolution profile of the active ingredient.

In the present invention, one or more excipients selected from the group consisting of lactose, glucose, mannitol, white sugar, sorbitol, microcrystalline cellulose, calcium phosphate, calcium monohydrogen phosphate and dextrin may be added in a usual amount and used. Coating agents may be used for preventing the active ingredients, sustained-release agents, binders and lubricants, and improving appearance. Additives commonly used in the pharmaceutical field such as surfactants, stabilizers, and preservatives can also be added. However, the addition of other excipients increases the bulk of the final formulation and reduces the convenience of taking the patient, which is an advantage of the slow release formulation, so that the active ingredient, the sustained release agent, the binder, the lubricant and the excipient, It is most ideal not to add it.

The method for preparing the oral preparation of Itoferide sustained-release according to the present invention comprises the steps of (1) mixing itopride hydrochloride with microcrystalline cellulose, lactose and hydroxypropylmethylcellulose as a pharmacologically active ingredient; (2) a granulation step of producing a wet granule by adding a liquid solvent in which a binder is dissolved to the mixture obtained in the mixing step; (3) a milling step of milling said western granule; (4) a step of mixing and then calibrating the lubricating flux; (5) coating with a suitable coating agent. All of the above steps are economical because there is no additional facility cost and can be easily formulated with high productivity since they can be easily formulated using conventional equipments such as mixer, crusher tablet machine, and coater. .

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

≪ Test Example 1 >

The following tests were conducted to confirm the interaction and suitability of itopride hydrochloride with excipients.

After mixing 150 mg of itopride hydrochloride and each of the excipients, the mixture was accelerated for 1 hour at room temperature and then left for 1 month in an environment of 45 ° C and 75% humidity. The results are shown in Table 1.

Excipient Initial content test Content test after accelerated test standard result Judgment standard result Judgment Microcrystalline cellulose 95 to 105% 99.7% fitness 95 to 105% 99.4% fitness Lactose Monohydrate 95 to 105% 99.1% fitness 95 to 105% 99.2% fitness Sorbitol 95 to 105% 99.8% fitness 95 to 105% 99.7% fitness Pregelatinized Starch 95 to 105% 99.3% fitness 95 to 105% 99.1% fitness PVP K-30 95 to 105% 99.1% fitness 95 to 105% 99.3% fitness Hydroxypropyl cellulose 95 to 105% 99.5% fitness 95 to 105% 99.4% fitness Crospovidone 95 to 105% 99.7% fitness 95 to 105% 99.8% fitness Croscarmellose sodium 95 to 105% 99.7% fitness 95 to 105% 99.9% fitness Low-substituted 95 to 105% 99.3% fitness 95 to 105% 99.4% fitness Methocel K4M 95 to 105% 99.2% fitness 95 to 105% 99.1% fitness Methocel K15M 95 to 105% 99.8% fitness 95 to 105% 99.2% fitness Methocel K100M 95 to 105% 99.9% fitness 95 to 105% 99.3% fitness Sodium Starch Glycolate 95 to 105% 99.2% fitness 95 to 105% 99.7% fitness Magnesium stearate 95 to 105% 99.4% fitness 95 to 105% 99.9% fitness Stearic acid 95 to 105% 99.2% fitness 95 to 105% 99.4% fitness SiO ₂ 95 to 105% 99.4% fitness 95 to 105% 99.0% fitness

≪ Example 1 >

The contents of the components and contents described in Table 2 below were used to prepare itopride hydrochloride sustained release tablets. Itoferpride hydrochloride, microcrystalline cellulose, lactose and hydroxypropylmethylcellulose are mixed, and the povidone K-30 solution dissolved in ethanol is added and granulated, followed by drying in a fluidized bed dryer at 50 ° C for 1 hour. After granulating the obtained granules, the crude glutamate was mixed and compressed, and then film-coated with Opadyl-OY-C-7000A (trade name of Colorcon) to give Itopride hydrochloride sustained release containing 150 mg of itopride hydrochloride in one tablet I make it. The weight percentages of these components are shown in Table 2.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itopride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 120 26.1 Emission control
Polymer HPMC
(Methcel K100M) 35 7.6 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

≪ Example 2 >

The weight of each component is the same as in Example 1 except that the weight of each component is as shown in Table 3.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 110 23.9 Emission control
Polymer HPMC
(Methcel K100M) 45 9.8 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 50 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

≪ Example 3 >

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 4.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 100 21.7 Emission control
Polymer HPMC
(Methcel K100M) 55 12.0 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

<Example 4>

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 5.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 90 19.6 Emission control
Polymer HPMC
(Methcel K100M) 65 14.1 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 5 >

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 6.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 75 16.3 Emission control
Polymer HPMC
(Methcel K100M) 80 17.4 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 6 >

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 7.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 65 14.1 Emission control
Polymer HPMC
(Methcel K100M) 90 19.6 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 7 >

The weight ratio of each component was the same as in Example 7, except that the weight ratio of each component was as shown in Table 8.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 35 7.6 Emission control
Polymer HPMC
(Methcel K100M) 120 26.1 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 8 >

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 9.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 100 21.7 Excipient Lactose monohydrate 15 3.3 Emission control
Polymer HPMC
(Methcel K100M) 140 30.4 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 9 >

The weight ratio of each component is the same as in Example 1, except that the weight ratio of each component is as shown in Table 10.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 45 9.8 Excipient Lactose monohydrate 30 6.5 Emission control
Polymer HPMC
(Methcel K100M) 180 39.1 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Example 10 >

The weight ratio of each component was the same as in Example 1, except that the weight ratio of each component was as shown in Table 11.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 25 5.4 Excipient Lactose monohydrate 30 6.5 Emission control
Polymer HPMC
(Methcel K100M) 200 43.5 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Comparative Example 1 &

Comparative Examples were prepared by the ingredients and contents shown in Table 12 below. After the mixture of itopride hydrochloride, lactose, carboxymethylcellulose and colloidal silicon dioxide, the cornstarch solution dissolved in purified water is added and granulated, and dried in a fluidized bed dryer at a temperature of 50 ° C for 6 hours. After the obtained granules were formulated, the remaining colloidal silicon dioxide and magnesium stearate were mixed and compressed, and then film-coated with Opadry-OY-C-7000A (trade name of Colorcon) to give an isotopeptide hydrochloride salt containing 50 mg of itopride hydrochloride Pride Hydrochloride Generates a regular tablet. Table 12 shows the weight percentages of the above components.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itopride HCI 50.0 38.5 Excipient Lactose 35.0 26.9 Binder Corn starch 15.0 11.5 Disintegration Carboxymethylcellulose 20.0 15.4 Disintegration Colloidal silicon dioxide 4.0 3.1 Lubricant St-Mg 1.0 0.8 Coating agent Opadry OY-C-7000A 5.0 3.8 Sum 130.00 100.0

&Lt; Comparative Example 2 &

The same as Example 1, except that the viscosity unit of hydroxypropylmethylcellulose used as a sustained-release agent was different. The weight percentages of the above components are shown in Table 13.

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 25 5.4 Excipient Lactose monohydrate 30 6.5 Emission control
Polymer HPMC
(Methcel K4M) 200 43.5 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Comparative Example 3 &

The same as Example 1, except that the viscosity unit of hydroxypropylmethylcellulose used as a sustained-release agent was different. The weight percentages of these components are shown in Table 14

Classification ingredient Weight (mg) weight% Pharmacological
Active ingredient Itoride HCI 150 32.6 Excipient MCC pH102 25 5.4 Excipient Lactose monohydrate 30 6.5 Emission control
Polymer HPMC
(Methcel K15M) 200 43.5 Disintegration L-HPC 25 5.4 Binder PVP K-30 15 3.3 Lubricant St-Mg 5 1.1 Coating agent Opadry OY-C-7000A 10 2.2 Sum 460 100.0

&Lt; Dissolution test >

The dissolution test of itopride hydrochloride was carried out in the following conditions.

▶ Temperature: 37 ± 0.5 ℃

▶ Dissolution method: Korean Pharmacopoeia dissolution test Method 2 (Paddle method)

▶ Eluent: Purified water, 900 mL

Stirring speed: 50 rpm

▶ Analysis method: The eluate was collected at the time after the elution test, and the absorbance of the eluate was measured at 266 nm wavelength using a 0.45 μm membrane filter using the filtrate as the sample solution and using an ultraviolet absorption spectrophotometer.

Elution Time (hr) 0.25 0.5 One 1.5 2 3 5 6 8 10 12 24 for
Out
rate
(%) Example 1 8.1 13.5 21.0 27.2 32.6 43.7 60.1 67.3 84.3 93.7 97.2 98.8 Example 2 8.1 13.1 20.3 26.6 31.3 41.3 56.6 63.0 74.1 83.4 91.7 98.8 Example 3 8.1 13.0 19.9 26.1 31.2 41.1 56.0 62.3 73.3 82.6 90.3 98.1 Example 4 8.6 13.6 20.8 26.6 31.6 40.6 53.3 59.2 70.3 78.4 86.2 104.1 Example 5 8.8 13.7 21.2 26.7 32.0 41.0 58.3 65.4 75.0 82.9 88.1 103.5 Example 6 8.2 12.7 19.2 24.3 29.2 37.3 57.2 64.1 73.9 83.4 89.1 103.0 Example 7 8.1 12.1 18.2 23.3 27.8 35.2 47.9 53.9 63.6 73.1 81.5 103.8 Example 8 7.8 11.4 17.0 21.6 25.8 32.6 44.2 50.2 59.0 68.5 76.6 101.6 Example 9 7.3 10.7 15.8 20.3 24.3 31.5 43.0 48.8 58.8 68.0 76.9 101.1 Example 10 6.8 9.9 14.6 18.8 22.7 29.2 40.2 45.5 54.9 64.1 72.5 101.7

Elution Time (hr) 0.25 0.5 One 1.5 2 3 5 6 8 10 12 24 for
Out
rate
(%) Comparative Example 1 12.5 21.2 32.6 45.5 52.9 65.1 71.3 79.8 85.2 90.6 98.4 99.5 Comparative Example 2 8.5 12.5 20.1 30.1 38.9 45.1 52.5 60.1 69.8 75.9 81.5 99.8 Example 10 6.8 9.9 14.6 18.8 22.7 29.2 40.2 45.5 54.9 64.1 72.5 101.7

<Property Test>

The samples prepared in Examples 1 to 10 and Comparative Examples 1 to 3 were placed in a hardness meter (Pharmatest, Germany) six times for each sample, and the hardness, thickness and diameter of the tablet were measured. The mean and standard deviation of the results are shown in Table 17 below.

Furtherance Diameter (mm) Thickness (mm) Hardness (kg / cm2) Marson (%) Weight change (mg) Example 1 10.64 ± 0.03 5.49 + 0.02 10.6 ± 0.25 0.96 451.6 ± 2.3 Example 2 10.67 ± 0.02 5.47 ± 0.05 11.2 ± 0.43 0.91 452.1 ± 3.5 Example 3 10.71 + 0.04 5.46 + 0.04 11.9 ± 0.65 0.85 453.2 + 4.1 Example 4 10.69 ± 0.06 5.47 ± 0.06 12.8 ± 0.47 0.78 449.3 ± 2.3 Example 5 10.62 + 0.04 5.48 ± 0.03 13.2 ± 0.21 0.74 452.4 + - 4.9 Example 6 10.65 ± 0.05 5.51 + 0.06 13.7 ± 0.81 0.65 451.6 ± 5.1 Example 7 10.69 ± 0.07 5.45 + 0.04 14.2 ± 0.36 0.62 453.1 + - 4.8 Example 8 10.67 ± 0.03 5.47 ± 0.09 14.9 ± 0.42 0.54 449.4 ± 3.6 Example 9 10.63 + 0.02 5.46 + 0.03 15.3 + - 0.51 0.31 456.3 ± 4.3 Example 10 10.62 ± 0.09 5.48 ± 0.07 16.7 ± 0.64 0.21 452.1 + - 3.4

<Stability test>

The stability test of itopride hydrochloride was carried out under the conditions of 1 to 4.

standard 0 weeks 2 weeks 4 weeks 6 weeks Properties White fitness fitness fitness fitness Confirmation test IR fitness fitness fitness fitness HPLC fitness fitness fitness fitness Dissolution test
(Purified water) 180 minutes
20.2% to 40.0% 97.0% 97.6% 97.1% 96.8% 720 minutes
55.0% to 75.0% 71.0% 71.5% 72.1% 72.8% 1440 minutes
More than 80.0% 99.4% 99.5% 98.2% 99.5% Content test 90 to 110% 100.2% 101.3% 99.6% 99.9%

▶ Condition 1: circulation from minus 20 ℃ to 40 ℃ and confirmation for 6 weeks

standard 0 weeks 2 months 4 months Properties White fitness fitness fitness Confirmation test IR fitness fitness fitness HPLC fitness fitness fitness Dissolution test
(Purified water) 180 minutes
20.0 to 40.0% 97.0% 97.2% 96.9% 720 minutes
55.0 to 75.0% 71.0% 72.0% 70.0% 1440 minutes
More than 80.0% 99.4% 99.8% 98.5% Content test 90 to 110% 100.2% 101.5% 99.8%

Condition 2: confirmed at 4 ℃ / RH 60% for 4 months

standard 0 weeks 2 months 4 months Properties White fitness fitness fitness Confirmation test IR fitness fitness fitness HPLC fitness fitness fitness Dissolution test
(Purified water) 180 minutes
20.0 to 40.0% 97.0% 96.2% 95.4% 720 minutes
55.0 to 75.0% 71.0% 73.1% 72.5% 1440 minutes
More than 80.0% 99.4% 98.2% 97.5% Content test 90 to 110% 100.2% 100.1% 99.8%

Condition 3: confirmed for 4 months at 25 ° C / RH 60%

standard 0 weeks 2 months 4 months Properties White fitness fitness fitness Confirmation test IR fitness fitness fitness HPLC fitness fitness fitness Dissolution test
(Purified water) 180 minutes
20.0 to 40.0% 97.0% 96.8% 96.4% 720 minutes
55.0 to 75.0% 71.0% 72.2% 71.5% 1440 minutes
More than 80.0% 99.4% 99.2% 98.3% Content test 90 to 110% 100.2% 100.2% 99.5%

Condition 4: 4 months at 40 ° C / RH 75%

Claims (11)

In the itopride hydrochloride sustained release characterized in that it comprises an itopride hydrochloride, a polymer for release control, an excipient, a disintegrant, a binder and a glidant,
Wherein the release controlling polymer is hydroxypropyl methylcellulose in an amount of 10 to 45 wt% based on the total weight of the sustained release tablet, the binder is 3 to 5 wt% based on the total weight of the sustained release tablet, and the sustained release tablet is administered once a day Itopride hydrochloride.
The method according to claim 1,
The dissolution rate of the sustained-release tablet is 10 to 30% in 1 hour, 55 to 75% in 12 hours, And at least 85% elution at 24 hours.
The method according to claim 1,
Wherein the hydroxypropyl methylcellulose has a viscosity of 80,000 to 120,000 cps.
The method according to claim 1,
Wherein the binding agent is polyvinylpyrrolidone.
The method according to claim 1,
Wherein the hydroxypropylmethylcellulose is 43.5% by weight based on the total weight of the sustained-release tablet.
The method according to claim 1,
The excipient is selected from the group consisting of microcrystalline cellulose or Itofridide hydrochloride is characterized by being lactose.
The method according to claim 1,
Wherein the disintegrant is at least one selected from the group consisting of croscarmellose sodium, sodium starch glycolate, pregelatinized starch, crospovidone and low-substituted hydroxypropylcellulose. .
The method according to claim 1,
Wherein the lubricant is at least one selected from the group consisting of silicon dioxide, stearic acid, and magnesium stearate.
32.5% by weight of itopride hydrochloride, 43.5% by weight of hydroxypropylmethylcellulose having a viscosity of 100,000 cps, 5.4% by weight of microcrystalline cellulose, 6.5% by weight of lactose, 5.4% by weight of low substituted hydroxypropylcellulose, (Povidone), 1.1% by weight of magnesium stearate, and 2.2% by weight of opaque dry.
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