KR100502505B1 - Manufacturing Method of Omeprazole oral dosage forms - Google Patents

Abstract

The present invention prepares inert microgranules having a particle size of about 0.2 to 0.7 millimeters in diameter using starch and sugar or only sugar, and is an active pharmacologically active ingredient omeprazole or lansoprazole and its salts and hydroxypropylmethylcellulose or hydroxy. The binder selected from propyl cellulose and its derivatives is dissolved or dispersed in a mixed solvent of purified water, acetone, and ethanol, and then the solution is combined with talc in the fine granules to prepare granules in which omeprazole or lansoprazole are combined. A method for preparing an oral preparation containing omeprazole or lansoprazole, which comprises enteric pellets having a particle size of 0.3 to 2.5 millimeters by protective coating and enteric coating with a coating agent and an enteric coating agent with a plasticizer. Omeprazole with gastric secretion Or by employing a relatively simple method of dissolving or dispersing lansoprazole with a suitable solvent, granulating and spheronizing with various seeds, and then carrying out protective and enteric coating. The advantage is that the yield can be overcome and a more stable formulation can be prepared.

Description

Manufacturing method of omeprazole oral preparations {Manufacturing Method of Omeprazole oral dosage forms}

The present invention relates to a method for preparing a stable oral preparation containing an effective gastric acid secretion inhibitor omeprazole or lansoprazole and its pharmacologically active salts. It is to effectively protect the gastrointestinal cells from ulcers.

In particular, omeprazole and its salts are susceptible to degradation and modification over time in acid and neutral, and have a half-life of less than 10 minutes at pH 4 or less, and are also very unstable compounds of about 14 hours at neutral pH. However, when the pH value is alkaline (pH 10), it is known to be somewhat stable and about 300 days. The degradation of omeprazole remains a major problem in formulation because it is rapidly degraded by the acid medium. The stability of omeprazole is also affected by moisture and organic solvents.

Stable formulations containing omeprazole have been developed and used to date, but there is a need for further development of stabilization methods. The present invention has been made possible to solve this problem of the currently developed omeprazole-containing formulations and to innovatively shorten the process time.

       The present invention maximizes the therapeutic effect by providing a more stable formulation containing the omeprazole or lansoprazole as described above, an object of the present invention is to block the loss of activity by gastric acid during oral administration of the formulation and to absorb the drug in the small intestine It is to provide a method for preparing a pharmaceutically stable new oral formulation that can facilitate.

The present invention was able to achieve the above object by dissolving or dispersing an active active material omeprazole or lansoprazole using a suitable solvent and then realizing granulation and spheronization using various seeds. It is possible to minimize the loss of raw materials by overcoming low yields in the preparation of analogous preparations. The present invention also facilitated dissolution by adding suitable excipients and solvents. In addition, the present invention is a technique for carrying out protective coating and enteric coating of granulated and spherical drugs using a suitable base, the process can be very simple.

          In the present invention, by using omeprazole dissolved or dispersed using only water and alcohol or water, solubility can be adjusted by varying the mixing ratio. In the present invention, the ratio of alcohol and water was used in various ways such as 1: 1, 0.8: 1, 0.6: 1, 0.5: 1, 0.4: 1, 0.2: 1, 0: 1, and solubility was slightly increased as the amount of alcohol increased. Although it increased gradually, the stability was insufficient, so that the talc was added as a stabilizing excipient to ensure the stability of the formulation.

          On the other hand, talc is a natural hydrous magnesium silicate and is white to gray fine crystalline powder, which is hardly soluble in water, ethanol or ether, and is known as an excipient with neutral glidability that does not affect the titer of the active substance.

The present invention consists of the following processes.

Inert microgranules having a particle size of 0.2 to 0.7 mm in diameter are prepared using only starch and sugar or sugar, and a binder selected from omeprazole or lansoprazole and hydroxypropyl methyl cellulose, or hydroxypropyl cellulose and its derivatives is purified water, acetone. After dissolving or dispersing in a mixed solvent of ethanol, the solution is combined with talc in the fine granules to prepare granules in which omeprazole or lansoprazole is combined, followed by protective coating with a film coating base, and an enteric coating base and a plasticizer. The enteric coating was performed to prepare an enteric pellet having a particle size of about 0.3 to 2.5 millimeters in diameter, and the potency of the active substance per gram was 80 to 100 milligrams.

In the present invention, the insoluble microgranules are preferably in the form of spherical granules, and the enteric coating base is selected from hydroxy propyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate or methacrylic acid copolymer, and as a plasticizer, polystyrene is used. Choose from Glycol 6000, Triacetin or Triethyl Citrate.

Omeprazole oral preparations of the present invention are convenient formulations by filling a fixed amount of hard gelatin capsules with enteric-coated microgranules containing omeprazole or lansoprazole as active ingredients.

The present invention is explained in more detail by the following examples.

Example 1 Omeprazole-Containing Oral Preparation

200 grams of sugar selected to have a certain size is used as an inert granule by itself. Usually, the particle size of sugar is about 0.2 to 0.7 millimeters in diameter. This example is useful when the omeprazole content is 80-100 milligrams per gram.

(Unit: weight%)

Name Primary coating Secondary coating Enteric coating Omeprazole Hydroxypropyl Methyl Cellulose Polyethylene Glycol 6000 Corn Starch Phthalate Hydroxypropyl Methyl Cellulose Triacetin Talc Titanium Ethanol Purified Water Acetone Chloride Methylene Sugar 4.42.20.210.5--5.5-27.611.027.6-11.0 -3.60.49.4 ---- 43.3-43.3-- ---- 4.70.5--47.4--47.4- Sum 100 100 100

Dissolve or disperse 80 grams of omeprazole, 30-50 grams of hydroxypropyl methyl cellulose or its derivatives using a mixture of 200 grams of purified water, 500 grams of acetone and 500 grams of ethanol, and apply it together with 100 grams of talc to the fine granules of sugar. To prepare an omeprazole pellet having a particle size of about 0.3 to 2.5 millimeters in diameter. Subsequently, a protective coating was performed with a secondary coating base to prevent contact with the enteric coating base, and an enteric coating for complete blockage from gastric fluid was applied to give a more stable condition under acidic conditions. Enteric coating was prepared by coating the surface of the omeprazole pellets to have a thickness of about 0.01 ~ 0.05mm.

Example 2 Lansoprazole-Containing Oral Formulations

This example is a very useful example when the formulation is configured to be 160-180 milligrams per gram as lansoprazole content.

(Unit: weight%)

Name Primary coating Secondary coating Enteric coating Lansoprazole Hydroxypropyl Methyl Cellulose Polyethylene Glycol 6000 Corn Starch Phthalate Hydroxypropyl Methyl Cellulose Triacetin Talc Titanium Dioxide Purified Water Acetone Chloride Methylene Sugar 9.62.20.2 2.0--8.8-27.611.027.6-11.0 -3.60.49.4 ---- 43.3-43.3-- ---- 4.70.5--47.4--47.4- Sum 100 100 100

After dissolving or dispersing 174 grams of lansoprazole as in Example 1, it is applied with 160 grams of talc to prepare omeprazole pellets. 30-50 grams of starch is suspended in purified water and then coated with the remaining amount of talc. Prepare granules. Protective coating and enteric coating are carried out in the same manner as in Example 1.

Comparative Example 1

This comparative example was prepared after constituting the formulation to be 80 to 100 milligrams per gram as the omeprazole content.

          80 grams of omeprazole is completely dissolved or dispersed as in Example 1 and then applied to prepare omeprazole pellets. Herein, 276 grams of starch is suspended in a binding solution prepared from a mixture of purified water and ethanol, and then applied to microgranules coated with omeprazole to prepare spherical granules. Protective coating and enteric coating are carried out in the same manner as in Example 1.

                                                (Unit: weight%)

Name Primary coating Secondary coating Enteric coating Omeprazole Hydroxypropyl Methyl Cellulose Polyethylene Glycol 6000 Corn Starch Phthalate Hydroxypropyl Methyl Cellulose Sodium Hydrogen Phosphate Sodium Triacetin Titanium Ethanol Purified Water Acetone Chloride Methylene Sugar 4.52.20.215.3-0.2--27.711.127.7-11.1 -3.60.49.4 ---- 43.3-43.3-- ---- 4.7-0.5-47.4--47.4- Sum 100 100 100

Test Example 1

The stability test results of the omeprazole enteric pellets prepared in Examples and Comparative Examples are as follows.

        Each test method was carried out by the Korean Pharmacopoeia test method.

(Unit: weight%)

   (-): No change

The present invention is a relatively simple method of dissolving or dispersing omeprazole or lansoprazole having an effect of gastric acid secretion, which is an active active substance, using a suitable solvent, granulating and spheronizing with various seeds, and then performing protective coating and enteric coating. By adopting the method, it is possible to overcome the low yield in the preparation of the preparations according to the prior art, and has the advantage of producing a more stable formulation, it can be seen that the invention is very useful industrially.

Claims (4)

Spherical inert microgranules having a particle size of 0.2 to 0.7 millimeters in diameter using starch and sugar or sugar alone are prepared, and the active pharmacologically active ingredient omeprazole or lansoprazole and its salts and hydroxypropylmethylcellulose or hydroxypropyl The binder selected from cellulose and its derivatives is dissolved or dispersed in a mixed solvent consisting of 1: 2.5: 2.5 weight ratio of purified water, acetone, and ethanol, and the solution corresponds to 5.5-8.8% by weight of the primary coating solution in the fine granules. In combination with talc to prepare granules combined with omeprazole or lansoprazole, protective coating with hydroxy propylmethyl cellulose, a conventional film coating base and enteric coating with phthalic acid hydroxy propyl methyl cellulose, an enteric coating base and triacetin, a plasticizer Particle size 0.3-2.5 mm Which manufacturing method of an oral preparation containing omeprazole or lansoprazole, characterized in that the manufacture of an enteric pellet. delete. delete. delete.